1.Mechanism of Xielitang Against Ulcerative Colitis in Mice Based on "Intestinal Flora-bile Acid" Axis
Xiaotian WANG ; Yaning BIAO ; Yixin ZHANG ; Jian CHEN ; Ya GAO ; Yufang ZHANG ; Muqing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):30-38
ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group, a model group, a sulfasalazine group (0.6 g·kg-1), and low-, medium-, and high-dose Xielitang groups (1.67, 3.34, 6.68 g·kg-1). After treatment for 42 d, the colon length was recorded, and the disease activity index (DAI) score was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). Hematoxylin-eosin (HE) staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), liver receptor homolog-1 (LRH-1), cholesterol 7α-hydroxylase (CYP7A1), and fibroblast growth factor receptor 4 (FGFR4) in liver and FXR, sodium-dependent bile acid transporter (ASBT), and fibroblast growth factor 15 (FGF15) in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover, ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group, the model group showed significantly decreased colon length, IL-10 content, α-diversity index, abundance of Firmicutes and Lactobacillus, and content of deoxycholic acid (DCA) and lithocholic acid (LCA) (P<0.01), significantly increased DAI score, IL-6 and TNF-α content, abundance of Bacteroidetes, and the content of cholic acid (CA), chenodeoxycholic acid (CDCA), and taurocholic acid (TCA) (P<0.05, P<0.01), significantly down-regulated protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver (P<0.01). In addition, the structure of colonic mucosa was destroyed, and inflammatory cells infiltrated in the model group. Compared with the model group, Xielitang could significantly increase the colon length, IL-10 content, α-diversity index, the abundance of Firmicutes and Lactobacillus, and DCA and LCA content (P<0.05, P<0.01), decrease DAI score, abundance of Bacteroidetes, and the content of IL-6, TNF-α, CA, CDCA, and TCA (P<0.01), up-regulate the protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and down-regulate the protein expression of LRH-1 and CYP7A1 in liver (P<0.01). The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis, regulating intestinal flora imbalance, and maintaining bile acid homeostasis.
2.Effects of the prolyl hydroxylase 2 inhibitor cpd17 on mouse osteogenic precursor cells
Zhongqiu DU ; Xiaoyang QI ; Ping YANG ; Jianglin YU ; Yixin CHEN ; Linjian ZHANG ; Xusheng QIU
Chinese Journal of Tissue Engineering Research 2025;29(2):238-244
BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.
3.Risk Identification Model of Coronary Artery Stenosis Constructed Based on Random Forest
Yongfeng LV ; Yujing WANG ; Leyi ZHANG ; Yixin LI ; Na YUAN ; Jing TIAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):138-146
ObjectiveTo establish a risk recognition model for coronary artery stenosis by using a machine learning method and to identify the key causative factors. MethodsPatients aged ≥18 years,diagnosed with coronary heart disease through coronary angiography from January 2013 to May 2020 in two prominent hospitals in Shanxi Province, were continuously enrolled. Logistic regression,back propagation neural network (BPNN), and random forest(RF)algorithms were used to construct models for detecting the causative factors of coronary artery stenosis. Sensitivity (TPR), specificity (TNR), accuracy (ACC), positive predictive value (PV+), negative predictive value (PV-), area under subject operating characteristic curve (AUC), and calibration curve were used to compare the discrimination and calibration performance of the models. The best model was then employed to predict the main risk variables associated with coronary stenosis. ResultsThe RF model exhibited superior comprehensive performance compared to logistic regression and BPNN models. The TPR values for logistic regression,BPNN,and RF models were 75.76%, 74.30%, and 93.70%, while ACC values were 74.05%, 72.30%, and 79.49%, respectively. The AUC values were:logistic regression 0.739 9; BPNN 0.723 1; RF 0.752 2. Manifestations such as chest pains,abnormal ST segments on ECG,ventricular premature beats with hypertension, atrial fibrillation, regional wall motion abnormalities(RWMA) by color echocardiography, aortic regurgitation(AR), pulmonary insufficiency (PI), family history of cardiovascular diseases,and body mass index(BMI)were identified as top ten important variables affecting coronary stenosis according to the RF model. ConclusionsRandom forest model shows the best comprehensive performance in identification and accurate assessment of coronary artery stenosis. The prediction of risk factors affecting coronary artery stenosis can provide a scientific basis for clinical intervention and help to formulate further diagnosis and treatment strategies so as to delay the disease progression.
4.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.
5.Cognition and Attitude of Chinese Medical Researchers towards Scientific Research Ethics: Based on the Results of a National Sample Survey
Guangxi HE ; Xinqing ZHANG ; Yandong ZHAO ; Yixin GUI
Chinese Medical Ethics 2024;35(1):26-32
Based on the sampling survey data of 11 164 medical researchers in China, this paper analyzed the understanding, attitude and compliance of medical researchers on scientific research ethics in China. The survey found that although most medical researchers claim to have more understanding of scientific research ethics, the level of understanding of scientific research ethics is not optimistic; the channels to scientific research ethics knowledge are diversified, but the standardized training channels are insufficient; most researchers held the positive attitude toward following the ethical norms, but those male, youth under 35, with senior professional titles, or from northeast China held negative attitude relatively; more than half of the researchers claimed that the supervision of research ethics in China was basically in place, but some people said that the violation of scientific research ethics was common, and some researchers reported that there was a phenomenon of "direct seal consent and reply" in ethical review. Compared with medical institutions, enterprises and universities are the weak links of scientific research ethics training, education and review. Based on the above actuality, it puts forward policy suggestions to strengthen the scientific research ethics training and ethics review requirements.
6.Status risk factors and prevention and control strategies of familial aggregation of Helicobacter pylori infection
Lihua SONG ; Sijing HAN ; Shuqin REN ; Wen YANG ; Sihong DING ; Yixin ZHONG ; Yao QIN ; Huiyue ZHANG ; Yang ZHANG
Journal of Public Health and Preventive Medicine 2024;35(2):148-151
Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ2=9.719, P=0.008), marital status (χ2=8.496, P=0.014), occupations (χ2=19.462, P<0.001), frequencies of dining out (χ2=5.457, P=0.019), previous Hp test results (χ2 =4.131, P=0.042) and test results after treatment (χ2=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.
7.Analysis of cases of reinfection of past SARS-CoV-2 patients in Pudong New Area of Shanghai
Ge ZHANG ; Anran ZHANG ; Yilin JIA ; Li ZHANG ; Lipeng HAO ; Hongmei XU ; Yuanping WANG ; Chuchu YE ; Bo LIU ; Weiping ZHU ; Yixin ZHOU
Shanghai Journal of Preventive Medicine 2024;36(2):117-122
ObjectiveTo identify the rate, population characteristics, and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai, and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics, nucleic acid or antigen test results, and symptoms after infection. The repeat infection rates among different populations were compared, and logistic regression was used to analyze the impact of gender, age, and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males (53.40%) and 3 528 females (46.60%), with a median age of 34 years old (P25, P75: 7, 61). The overall vaccine uptake rate was 59.44% (4 500/7 571). In December of 2022, there were 563 cases of repeat infection, with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group (2.86%) and the highest rate in the 30‒ year-old group (12.42%), with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower (6.57%) compared to those who had not (7.11%). The age groups of 3‒ years, 70‒79 years, as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant, and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots, it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.
8.Regularity and mechanism of medicinal and edible herbs in the treatment of myelosuppression
Yiqiao GAO ; Yixin ZHANG ; Yuye YANG ; Zhaowei WEI
Journal of Xinxiang Medical College 2024;41(3):221-226,231
Objective To explore the regularity and potential mechanisms of medicinal and edible herbs(MEHs)in the treatment of myelosuppression through the retrieval,summary,sorting and visual analysis of relevant literature.Methods Literature about MEHs treatment for myelosuppression was reviewed in document databases,such as Web of Science,CNKI,Wanfang Data Knowledge Service Platform,China Science and Technology Journal Database,and China Biology Medicine Disc.Multivariate statistical analysis was performed using the SPSS and CiteSpace software to explore the frequency,efficacy and correlation of MEHs,as well as the potential mechanisms of MEHs in treating myelosuppression.Results A total of 123 recipes involving 170 traditional Chinese medicines(including 38 MEHs)were screened out.Five pairs of MEHs core combinations in the treatment of myelosuppression were obtained by cluster analysis.Their main functions included benefiting qi and nourishing blood,invigo-rating spleen and dispelling dampness,replenishing qi and solidifying kidney.The potential mechanisms were associated with many related signal pathways,such as Janus kinase 2-signal transducer and activator of transcription 5 andβ-catenini.Conclusion MEHs such as radix astragali combined with angelica sinensis,poria cocos and codonopsis pilosula are mainly used clinically to treat myelosuppression induced by chemotherapy.They play their therapeutic effects by promoting proliferation and delaying senescence of hematopoietic stem cells.
9.Danggui Shaoyaosan Regulates Autophagy via AMPK/mTOR/ULK1 Signaling Pathway in Rat Model of Metabolism-associated Fatty Liver Disease
Yaning BIAO ; Chenxu LIU ; Yixin ZHANG ; Yi XIAO ; Ziheng WEI ; Zehe YU ; Ran CAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):9-16
ObjectiveTo investigate the regulatory effect of Danggui Shaoyaosan on adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase-1 (ULK1) signaling pathway in the rat model of metabolism-associated fatty liver disease (MAFLD). MethodSixty SD rats were randomized into control, model, western medicine (polyene phosphatidylcholine capsules,0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, 9.76 g·kg-1, respectively) Danggui Shaoyaosan groups. After being fed with a high-fat diet for 8 weeks, the rats in each group were administrated with corresponding drugs for 4 weeks. At the end of drug treatment, serum and liver tissue were collected for subsequent determination of related indicators. ResultCompared with the control group, the model group showed increased contents of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, increased contents of TC, TG, and free fatty acids (FFAs) in the liver (P<0.01), and decreased content of high-density lipoprotein cholesterol (HDL-C) in the serum (P<0.01). Furthermore, the model group showed down-regulated protein levels of p-AMPK, microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ, Beclin1, and ULK1 (P<0.01) and up-regulated protein levels of p-mTOR and ubiquitin-binding protein p62 in the liver (P<0.01). The hepatic steatosis was obvious and the NAFLD activity score (NAS) and oil red O staining area increased in the model group, (P<0.05, P<0.01). Compared with the model group, Danggui Shaoyaosan reduced the contents of TC and TG and the activities of ALT and AST in the serum, lowered the levels of TC, TG, and FFA in the liver, down-regulated the protein levels of p-mTOR and p62 (P<0.01), elevated the serum HDL-C level, and up-regulated the protein levels of p-AMPK, LCBⅡ, Beclin1, and ULK1 in the liver (P<0.05, P<0.01). Moreover, it alleviated hepatic steatosis and decreased the NAS and oil red O staining area (P<0.05, P<0.01). ConclusionDanggui Shaoyaosan has therapeutic effect on MAFLD rats by regulating AMPK/mTOR/ULK1 signaling pathway to enhance autophagy.
10.Advances in chiral analysis and stereoselective pharmacokinetics of dihydropyridine calcium antagonists
Yixin ZHANG ; Xinyi GUAN ; Boning WANG ; Jun WEN ; Zhanying HONG
Journal of Pharmaceutical Practice and Service 2024;42(8):319-324
Chiral drugs are closely related to the safety and effectiveness of drug use.Most dihydropyridine drugs have chiral carbon atoms,which are used as racemes and produce stereoselective disposal characteristics after entering the body,and may affect the safety and effectiveness of drugs.Therefore,based on the chiral resolution and pharmacokinetic characteristics of this class of drugs,the selection rules of chiral HPLC and CE methods and in vivo analysis applications of this class of drugs in recent years were reviewed.The stereoselective pharmacokinetics of this class of drugs were listed and compared.It was found that some of these drugs had obvious differences in stereoselective pharmacokinetics,and the pharmacokinetics and toxicity in vivo were also different.


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