1.Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis
Chao XU ; Xiaoping TAN ; Jie LI ; Minghua AI ; Yueyue LU ; Chaoyong LIU
China Pharmacy 2025;36(2):166-171
OBJECTIVE To investigate the effects and mechanism of asperuloside (Asp) on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis (UC). METHODS The male SD rats were randomly divided into Control group, model group (UC group), ASP low-dose and high-dose groups [Asp-L, Asp-H groups, Asp 35, 70 mg/(kg·d)], ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group, Asp 70 mg/(kg·d)+Compound C 0.2 mg/(kg·d)], with 12 rats in each group. Except for Control group, the other groups were injected with 50% ethanol (0.25 mL)+5% 2,4, 6- trinitrobenzene sulfonic acid solution (2 mL/kg) into the intestinal cavity to construct UC model. After modeling, the rats in each drug group were given corresponding drug solution by gavage or (and) tail vein injection, once a day, for 14 consecutive days. After the last administration, the weight of rats in each group was measured, and the length of their colons was measured; disease activity index (DAI) score and colonic mucosal damage index (CMDI) score were performed, and the serum levels of inflammatory factors (interleukin-18, -1β, -6) were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1, gasdermin D (GSDMD)] in colon tissue, and pathway-related proteins such as adenosine monophosphate-activated protein kinase (AMPK), thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a CARD (ASC) were all detected. RESULTS Compared with Control group, the colon tissue structure of rats in UC group was damaged, with obvious infiltration of inflammatory cells and edema. Their body weight, colon length and phosphorylation level of AMPK protein were significantly reduced or shortened; DAI and CMDI scores, serum levels of inflammatory factors, and the protein expressions of caspase-1, GSDMD, TXNIP, NLRP3 and ASC in colon tissue were increased or upregulated significantly (P<0.05). Compared with UC group, the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups, and all quantitative indicators were significantly improved (P<0.05); the improvement effect of Asp-H group was more significant (P<0.05). Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats (P<0.05). CONCLUSIONS Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats, which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.
2.Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis
Chao XU ; Xiaoping TAN ; Jie LI ; Minghua AI ; Yueyue LU ; Chaoyong LIU
China Pharmacy 2025;36(2):166-171
OBJECTIVE To investigate the effects and mechanism of asperuloside (Asp) on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis (UC). METHODS The male SD rats were randomly divided into Control group, model group (UC group), ASP low-dose and high-dose groups [Asp-L, Asp-H groups, Asp 35, 70 mg/(kg·d)], ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group, Asp 70 mg/(kg·d)+Compound C 0.2 mg/(kg·d)], with 12 rats in each group. Except for Control group, the other groups were injected with 50% ethanol (0.25 mL)+5% 2,4, 6- trinitrobenzene sulfonic acid solution (2 mL/kg) into the intestinal cavity to construct UC model. After modeling, the rats in each drug group were given corresponding drug solution by gavage or (and) tail vein injection, once a day, for 14 consecutive days. After the last administration, the weight of rats in each group was measured, and the length of their colons was measured; disease activity index (DAI) score and colonic mucosal damage index (CMDI) score were performed, and the serum levels of inflammatory factors (interleukin-18, -1β, -6) were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1, gasdermin D (GSDMD)] in colon tissue, and pathway-related proteins such as adenosine monophosphate-activated protein kinase (AMPK), thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a CARD (ASC) were all detected. RESULTS Compared with Control group, the colon tissue structure of rats in UC group was damaged, with obvious infiltration of inflammatory cells and edema. Their body weight, colon length and phosphorylation level of AMPK protein were significantly reduced or shortened; DAI and CMDI scores, serum levels of inflammatory factors, and the protein expressions of caspase-1, GSDMD, TXNIP, NLRP3 and ASC in colon tissue were increased or upregulated significantly (P<0.05). Compared with UC group, the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups, and all quantitative indicators were significantly improved (P<0.05); the improvement effect of Asp-H group was more significant (P<0.05). Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats (P<0.05). CONCLUSIONS Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats, which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.
3.Genetic analysis of cases from a family with reduced B antigen expression in ABO blood group system
Taimei ZHOU ; Yingchun YANG ; Zihao ZHAO ; Weizhen XU ; Zishan JIAN ; Tongping YANG
Chinese Journal of Blood Transfusion 2025;38(5):717-722
Objective: To classify the ABO blood group phenotypes of 5 cases from a family, and to explore the molecular mechanism for reduced B antigen expression in ABO blood group system. Methods: Serological identification of the ABO blood group was performed using microcolumn gel assay and saline tube method. The soluble antigens in saliva were detected by the agglutination inhibition assay. The full-length sequences and upstream promoter regions of ABO gene were sequenced for genotyping using PacBio SMRT sequencing technology. Results: The results of serological tests indicated the expression of B antigen decreased in 3 out of 5 blood samples. A mixed-field agglutination was observed with anti-B antibody. B antigen was not detected in all 5 saliva samples. The ABO genotype for all samples were ABO
B.01/ABO
O.01.02, and a novel mutation c. 28+5875C>T within the DNA-binding region of RUNX1 in +5.8-kb site were found in the B allele for 3 samples with reduced expression of B antigen. Conclusion: Results of serological and genetic analyses classify the 3 cases with reduced B antigen expression as B
phenotype. The novel mutation c. 28+5875C>T of RUNX1 could be the key reason for reduced B antigen expression in 3 cases with B
phenotype.
4.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
5.Molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches
Zelin ZHU ; Xia ZHANG ; Junyi HE ; Ying CHEN ; Weisi WANG ; Hehua HU ; Chunli CAO ; Ziping BAO ; Suying GUO ; Liping DUAN ; Yi YUAN ; Jing XU ; Shizhu LI ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2024;36(5):527-530
Objective To evaluate the molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches. Methods A semi-dry and semi-wet ditch with O. hupensis snails was selected in the second branch field of Jiangbei Farm, Jiangling County, Hubei Province in May 2023, and divided into 4 experimental areas, named groups A1, A2, B1 and B2. Environmental cleaning was performed in groups A1 and B2, and was not conducted in groups A2 or B2. Then, 50% wettable powder of niclosamide ethanolamine salt was sprayed with drones at an effective dose of 2 g/m2 in groups A1 and A2, and 5% niclosamide ethanolamine salt granule was sprayed with drones at an effective dose of 2 g/m2 in groups B1 and B2. O. hupensis snails were surveyed using the systematic sampling method 1, 3, 5, 7, 14 days after spraying, and the natural mortality and corrected mortality of O. hupensis snails were calculated. Results The occurrence of frames with living snails, mean density of living snails and natural mortality of snails were 97.50% (117/120), 6.30 snails/0.1 m2 and 1.18% (9/765) in the test ditch before spraying, respectively. There were significant differences in the mortality of snails among four groups 1, 3, 5, 7 and 14 days after spraying niclosamide formulations with drones (χ2 = 17.230, 51.707, 65.184, 204.050 and 34.435, all P values < 0.01). The overall mortality rates of snails were 94.51% (1 051/1 112), 79.44% (908/1 143), 96.54% (977/1 012) and 88.55% (1 021/1 153) in groups A1, A2, B1 and B2 (χ2 = 207.773, P < 0.05), respectively. In addition, there was no significant difference in the overall snail mortality between groups A1 and B1 (P > 0.05), and the snail mortality in groups A1 and B1 were both statistically different from that in groups A2 and B2 (all P values < 0.05). Conclusion Both 50% wettlable powder of niclosamide ethanolamine salt and 5% niclosamide ethanolamine salt granule sprayed with drones are active against O. hupensis snails in ditches, and environmental cleaning may improve the molluscicidal effect.
6.Correlation of milk tea consumption with comorbid overweight/obesity and depressive symptoms among college students
LI Shengpeng, LIANG Dingxiong, SU Fan, SONG Yongjing, SHA Mian, XU Jiali, SONG Jiancai, GONG Ling
Chinese Journal of School Health 2024;45(11):1644-1647
Objective:
To explore the association of milk tea consumption with comorbid of overweight/obesity and depressive symptoms among college students, so as to provide a reference for promoting the physical and mental health of college students.
Methods:
A questionnaire survey was conducted from August to October 2023 using convenience sampling among 13 920 students from nine universities in Shanghai, Jiangxi, and Hubei provinces (municipality directly under the central government). Information on college students demographic characteristics, milk tea consumption, overweight/obesity status, and depressive symptoms was collected. Chi square tests were used to compare the association between different demographic characteristics and milk tea consumption with comorbid overweight/obesity and depressive symptoms. Multivariate Logistic regression analysis was performed to infer the strength of the association.
Results:
The detection rate of comorbidity of overweight/obesity and depressive symptoms was 5.8% among college students. The univariate analysis revealed statistically significant differences in the detection rate of comorbidity of overweight/obesity and depressive symptoms among various groups, including gender, grade, parents education level, only child status, family economic status, meeting moderate to high levels of physical activity standards, sleep quality, and frequent fast food consumption ( χ 2= 82.10, 23.07, 8.91, 10.87 , 4.56, 47.60, 17.60, 386.74, 96.61, P <0.05). There were also statistically significant differences between groups based on milk tea consumption frequency and quantity ( χ 2=42.12, 38.76, P <0.01). Compared with the group of without consuming milk tea, Logistic regression analysis showed that college students who consumed milk tea 4-5 times and ≥6 times had higher risk of comorbid overweight/obesity and depressive symptoms ( OR =1.98, 2.46), and college students who consumed 1-1 500 mL and ≥3 000 mL of milk tea also had higher comorbidity risk ( OR =1.52, 1.22) ( P <0.05).
Conclusions
Frequent and excessive milk tea consumption among college students may increase the risk of comorbid of overweight/obesity and depressive symptoms. It is recommended to reduce the frequency and quantity of milk tea consumption to improve college students physical and mental health.
7.Automated identification and localization of inferior vena cava based on ultrasound images
Jinghan YANG ; Ziye CHEN ; Jingyuan SUN ; Wen CAO ; Chaoyang LÜ ; Shuo LI ; Mingqiu LI ; Pu ZHANG ; Jingzhou XU ; Chang ZHOU ; Yuxiang YANG ; Fu ZHANG ; Qingli LI ; Ruijun GUO ; Jiangang CHEN
Academic Journal of Naval Medical University 2024;45(9):1107-1112
Objective To explore the automated identification and diameter measurement methods for inferior vena cava (IVC) based on clinical ultrasound images of IVC. Methods An automated identification and localization method based on topology and automatic tracking algorithm was proposed. Tracking algorithm was used for identifying and continuously locating to improve the efficiency and accuracy of measurement. Tests were conducted on 18 sets of ultrasound data collected from 18 patients in intensive care unit (ICU),with clinicians' measurements as the gold standard. Results The recognition accuracy of the automated method was 94.44% (17/18),and the measurement error of IVC diameter was within the range of±1.96s (s was the standard deviation). The automated method could replace the manual method. Conclusion The proposed IVC automated identification and localization algorithm based on topology and automatic tracking algorithm has high recognition success rate and IVC diameter measurement accuracy. It can assist clinicians in identifying and locating IVC,so as to improve the accuracy of IVC measurement.
8.Prognosis analysis of multi-indicator combined with sequential organ failure assessment in patients with sepsis.
Lilin ZHANG ; Jinpeng ZHANG ; Lyu JIN ; Hongyue XU ; Xiaohui ZHAO ; Yadong YANG
Chinese Critical Care Medicine 2023;35(12):1245-1249
OBJECTIVE:
To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients.
METHODS:
A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis.
RESULTS:
A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05).
CONCLUSIONS
The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.
Humans
;
Organ Dysfunction Scores
;
Retrospective Studies
;
C-Reactive Protein
;
ROC Curve
;
Sepsis/metabolism*
;
Prognosis
;
Anticoagulants
;
Antithrombin III
;
Intensive Care Units
9.Long-term prognostic value of coronary CT angiography-derived fractional flow reserve in elderly patients with CHD
Jingzhou JIANG ; Xiang GUO ; Rui ZUO ; Qian CHEN ; Hongyan QIAO ; Bangjun GUO ; Pengpeng XU ; Tongyuan LIU ; Longjiang ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2023;25(12):1255-1259
Objective To evaluate the long-term prognostic value of coronary CT angiography-derived fractional flow reserve(CT-FFR)in elderly patients with coronary heart disease(CHD).Methods A retrospective analysis was performed on 1133 patients with clinically suspected CHD from a prospective observational study based on coronary CTA and CT-FFR at the General Hos-pital of Eastern Theater from April 2018 to March 2019,and 330 elderly CHD patients were even-tually included.According to major adverse cardiovascular events(MACE)occurred or not,295 patients were assigned into non-MACE group and 35 patients into the MACE group.Based on cor-onary CTA data,plaque features were analyzed and CT-FFR values were measured in all lesioned vessels.The relationship of plaque features and CT-FFR with MACE was evaluated by using Cox proportional risk regression model,Kaplan-Meier survival curve,and ROC curve analyses.Results The patients with coronary stenosis(≥50%)or CT-FFR value ≤0.8 had a higher risk of MACE(P<0.01).Univariate Cox analysis showed that coronary stenosis ≥50%and CT-FFR value 0.8 were risk factors of MACE(P<0.01).After adjusting confounding factors,multivariate Cox analysis indicated that CT-FFR ≤0.8(HR=17.037,95%CI:5.060-57.358,P=0.000)was only independent predictor for MACE.The risk prediction model based on CT-FFR presented better performance than the model based on coronary CTA stenosis(C-index:0.820 vs 0.696,P=0.000).Conclusion CT-FFR≤0.8 is an important independent predictor for long-term MACE in elderly CHD patients.Clinical risk stratification based on CT-FFR may optimize prognostic man-agement strategies in these patients.
10.A study on the first-order interaction of diagnostic performance of coronary CT angiography-derived fractional flow reserve
Pengpeng XU ; Jingzhou JIANG ; Xiaolei ZHANG ; Mengdi JIANG ; Longjiang ZHANG
Chinese Journal of Internal Medicine 2023;62(12):1451-1457
Objective:To investigate the effect of image quality, degree of stenosis, calcification, and their first-order interactions on diagnostic performance of coronary computed tomography (CT) angiography-derived fractional flow reserve (CT-FFR).Methods:This is a reanalysis of data from a multi-center retrospective cross-sectional study of CT-FFR in China. A total of 522 patients with suspected or known coronary heart disease [mean age: 61.6 (34.0-83.0) years, 71.8% (354/493) were male] from 11 medical centers including the General Hospital of Eastern Theater Command from May 2015 to October 2019 were enrolled. All patients underwent coronary CT angiography (CCTA), CT-FFR, and invasive FFR examination. Subjective image quality scores of target vessels were recorded on CCTA images, and stenosis was visually assessed at the lesion level. Calcification arc and calcification remodeling index (CRI) were recorded for each lesion. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were compared. Two-way analysis of variance was used to analyze the first-order interaction effects of image quality, degree of stenosis, and calcification.Results:A total of 493 patients with 629 lesions with invasive FFR as a reference were included in the study. The overall sensitivity, specificity, and accuracy of CT-FFR were 80.4%, 93.8%, and 88.6%, respectively. The specificity (95.0% vs. 87.3%, χ2=4.11, P=0.043); accuracy (90.1% vs. 81.9%, χ2=6.22, P=0.013); and NPV (89.7% vs. 80.9%, χ2=4.25, P=0.039) of the group with image quality ≥3 was higher than the group with image quality <3. The degree of stenosis affected the sensitivity, PPV, and NPV of CT-FFR and the calcification arc affected the specificity of CT-FFR (all P>0.05). The specificity (95.8% vs. 90.5%, χ2=4.23, P=0.040); accuracy (91.0% vs. 86.1%, χ2=4.01, P=0.045); and NPV (91.1% vs. 83.8%, χ2=5.10, P=0.024) of the group with CRI<1 were higher than that of the group with CRI≥1. In the subgroup of mild and severe stenosis, no calcification, and CRI<1, the accuracy of CT-FFR with image quality ≥3 points were higher than that with image quality <3 points. The accuracy of CT-FFR in the moderate stenosis group was mainly affected by CRI; the accuracy of CT-FFR in the group with CRI<1 was higher than that in the group with CRI≥1 (after Bonferroni correction, P values between groups were statistically significant). Conclusion:Subjective image quality, degree of stenosis, calcification of lesions, and their first-order interactions can all negatively affect the diagnostic performance of CT-FFR.


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