1.Establishment of an Intestinal Fibrosis Model Associated with Inflammatory Bowel Disease in VDR-/- Mice Induced by Helicobacter hepaticus Infection and Mechanism Exploration
Zhihao WU ; Shuyang CAO ; Zhengyu ZHOU
Laboratory Animal and Comparative Medicine 2025;45(1):37-46
ObjectiveTo employ Helicobacter hepaticus (H.hepaticus, H.h) to induce intestinal fibrosis in vitamin D receptor deletion (VDR-/-) mice, thereby establishing a model of inflammatory bowel disease to investigate its pathological characteristics and underlying mechanisms. MethodsFive male WT and five male VDR-/- mice were orally administered a suspension containing 2×108 CFU of H.hepaticus (referred to as the WT+H.h group and the VDR-/-+H.h group, respectively), with treatments occurring every other day for three administrations. Concurrently, two uninfected control groups were established, consisting of five WT and five VDR-/- mice, which were administered an equivalent volume of PBS. Seven days after the final administration, the infection status of the mice was assessed, and their body weight was recorded weekly. At the 16th week post-infection, the mice were dissected, and the length of the colon tissue was measured, with fecal moisture content analyzed. The colon tissue was partitioned into four parts: one for paraffin embedding for HE, alcian blue-periodic acid Schiff (AB-PAS), Masson's trichrome staining, and immunohistochemical analysis; one for DNA extraction to evaluate the colonization levels of H.hepaticus through real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR), thereby assessing the impact of the infection; one for RNA extraction to analyze cytokine expression via reverse transcription-PCR (RT-PCR); and one for protein extraction to measure the expression levels of alpha smooth muscle actin (α-SMA) and interleukin (IL)-33 using Western blotting. Results All mice in the infected groups successfully were infected with H. hepaticus after three oral gavages. Compared to VDR-/- control group, VDR-/- mice exhibited significant weight loss (P<0.05), intestinal hemorrhage, and higher fecal water content after 16 weeks of H. hepaticus infection than the uninfected control group and the WT+H.h group (P<0.05). Compared to the WT+H.h group, HE staining of the VDR-/-+H.h group showed inflammatory cell infiltration, AB-PAS staining revealed irregular atrophy of intestinal glands and reduced acini, and Masson staining showed increased collagen area. RT-PCR demonstrated that the transcription levels of inflammation and fibrosis-related genes, including IL-6, IL-33, tumor necrosis factor-α (TNF-α), and α-SMA (P < 0.000 1), were significantly upregulated in the colon tissues of VDR-/-+H.h group. Additionally, immunohistochemical analysis and Western blotting showed that the protein expression levels of IL-33 and α-SMA were markedly increased (P<0.001) in the VDR-/-+H.h group. ConclusionVDR-/- mice infected with H.hepaticus exhibit more severe inflammatory responses, including mucosal inflammatory infiltration, impaired mucosal tissue function, and collagen deposition, indicating successful construction of the inflammatory bowel disease model. Further research suggests that VDR deficiency may exacerbate the intestinal fibrosis process associated with inflammatory bowel disease by affecting IL-33 expression.
2.Analysis of the efficacy of fiber laser stapes fenestration in the treatment of 58 cases of otosclerosis and ossicular malformation
Yuna ZHANG ; Shijie QIU ; Bing CAO ; Zhengyu WEI ; Zhisen SHEN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(8):797-802
Objective:To explore the surgical efficacy of conductive deafness caused by otosclerosis and ossicular malformation with 980 nm fiber laser stapedial floor fenestration.Methods:Data of 58 patients (ears) who were diagnosed with conductive deafness caused by otosclerosis (49 ears) and ossicular malformation (9 ears) treated by 980 nm Diode laser small-fenestra stapedotomy were retrospectively analyzed. Air conduction (AC) thresholds, bone conduction (BC) thresholds, and air-bone gap (ABG) at 0.5, 1, 2, 4 kHz pure tone frequencies were compared before and 3 months after surgery, and the advantages and precautions of 980 nm fiber laser were summarized. Paired t-test (SPSS 26.0 software) was use to analyze the listening data. Results:Fiber optic laser stapes fenestration and artificial stapes implantation were successfully completed in all 57 cases (ears), the hearing of another one patient (ear) with floating malformation of detachment of stapedial floor was lower than that before surgery. Preoperative at 0.5, 1, 2, 4 kHz frequencies of AC thresholds, BC thresholds, and ABG were (65.4±9.7) dB, (27.2±8.9) dB, and (38.2±9.8) dB respectively. Postoperative 3 months at the same frequency of AC thresholds, BC thresholds, and ABG were (42.1±11.3) dB, (26.9±6.6) dB, and (15.2±9.1) dB. Preoperative and postoperative of AC threshold and ABG were statistically significant at 0.5, 1, 2, 4 kHz ( t value was 13.270 and13.948, both P<0.01), and yet the BC threshold was not statistically significant before and after surgery at the same frequency ( t=0.418, P>0.05). Conclusions:980 nm fiber laser stapes floor fenestration is an effective treatment for conductive deafness caused by otosclerosis and ossicular malformation.
3.Tetrahedral DNA nanostructures synergize with MnO2 to enhance antitumor immunity via promoting STING activation and M1 polarization.
Siping LIANG ; Jiaying LI ; Zhengyu ZOU ; Miao MAO ; Siqi MING ; Fan LIN ; Ziyan ZHANG ; Can CAO ; Jinyu ZHOU ; Yuanqing ZHANG ; Jiaping LI ; Minhao WU
Acta Pharmaceutica Sinica B 2022;12(5):2494-2505
Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.
4.The feasibility of assessing left ventricular global and regional myocardial strain in patients with heart failure based on coronary CT angiography
Likun CAO ; Peijun LIU ; Yun WANG ; Xiao LI ; Lu LIN ; Matai ZHU ; Shenghui YU ; Yining WANG ; Zhengyu JIN
Chinese Journal of Radiology 2022;56(4):385-391
Objective:To investigate the feasibility of coronary CT angiography(CCTA)-feature tracking(FT) for assessing global and regional myocardial strain in patients with heart failure(HF).Methods:From July 2019 to December 2020, twenty-five patients diagnosed with HF from Peking Union Medical College Hospital were prospectively enrolled into the study. All patients underwent retrospective electrocardiogram-gated CCTA and cardiac MR (CMR) imaging within 7 days. CCTA-FT and CMR-FT were undertaken using cvi 42 dedicated commercial software to measure global and regional strain parameters, including global peak radial strain (GPRS), global peak circumferential strain (GPCS) and global peak longitudinal strain (GPLS), as well as peak radial strain (PRS), peak circumferential strain (PCS) and peak longitudinal strain (PLS) of left ventricular basal segment, middle segment and apical segment. Conventional left ventricular functional parameters were also calculated, including left ventricular ejection fraction (LVEF), left ventricular stroke volume (LVSV) and left ventricular mass index (LVMI). Paired t test or Wilcoxon signed-rank test was used to compare the differences of measurements between CCTA group and CMR group. Pearson or Spearman correlation analysis was used to analyze the correlation between the two groups. Inter-and intra-observer consistence in CCTA group was evaluated by intraclass correlation coefficient (ICC) analysis. Results:The effective radiation dose of CCTA examination was 6.00 (4.86,7.63) mSv. Inter-and intra-observer consistence in CCTA group was excellent, and the ICC value was 0.85-0.98. In the overall strain parameters, GPCS in CCTA group[-8.10%(-10.32%, -5.20%)] was significantly lower than that of CMR group[-8.49%(-13.79%, -5.95%)] ( Z=-2.15, P=0.031). There was no significant difference in GPRS and GPRS between the two measurement methods ( P>0.05). Strong correlations were observed between GPRS, GPCS and GPLS ( r=0.65, 0.63, 0.71,all P<0.001). For local strain parameters, PCS in the middle segment and apical segment of CCTA group were lower than those of CMR group ( Z=-2.17, -2.62, all P<0.05). There were no significant differences in PCS of basal segment, PRS and PLS of all segments between groups (all P>0.05). The PCS and PLS of basal segment, PRS of middle segment and PRS of apical segment were moderately correlated ( r=0.46, 0.52, 0.58, 0.53, P<0.05); The other local strain parameters were strongly correlated, the range of r value was from 0.64 to 0.70 (all P<0.001). For left ventricular functional parameters, LVEF, LVSV and LVMI showed no significant differences between groups ( P>0.05), and the correlation was extremely strong ( r=0.90, 0.89, 0.96, all P<0.001). Conclusions:The repeatability of CCTA-FT technique in measuring myocardial strain was good, and the correlation of parameters measured by CCTA-FT technique and CMR-FT technique was excellent. Therefore, CCTA-FT technique can be used as a new noninvasive and simple method to evaluate myocardial motor function.
5.Preliminary Study on Clinical Features and CT Findings of Common-type Coronavirus Disease 2019 Patients in Peking Union Medical College Hospital.
Lan SONG ; Wei SONG ; Xin SUI ; Tiekuan DU ; Wu LIU ; Baiyu WANG ; Xiaoping LU ; Yan XU ; Qiwen YANG ; Wei CAO ; Zhengyu JIN
Acta Academiae Medicinae Sinicae 2020;42(3):376-382
To summarize the clinical characteristics and chest CT findings of coronavirus disease 2019(COVID-19)patients in Peking Union Medical College Hospital(PUMCH). A total of 13 patients with COVID-19 confirmed at PUMCH from January 20 to February 6,2020 were selected as the research subjects.Their epidemiological histories,clinical characteristics,laboratory tests,and chest CT findings were analyzed retrospectively.The location,distribution,density,and other accompanying signs of abnormal lung CT lesions were recorded,and the clinical types of these patients were assessed. The clinical type was "common type" in all these 13 patients aged(46.8±14.7)years(range:27-68 years).Ten patients had a travel history to Wuhan or direct contact with patients from Wuhan,2 cases had recent travel histories,and 1 case had a travel history to Beijing suburb.The white blood cell(WBC)count was normal or decreased in 92.3% of the patients and the lymphocyte count decreased in 15.4% of the patients.Twelve patients(92.3%)had a fever,among whom 11 patients were admitted due to fever and 2 patients(15.4%)had low fever.Eight patients(61.5%)had dry cough.The CT findings in these 13 patients were all abnormal.The lesions were mainly distributed along the bronchi and under the pleura.The lesions were relatively limited in 8 patients(affecting 1-3 lobes,predominantly in the right or left lower lobe),and diffuse multiple lesions of bilateral lungs were seen in 5 patients.The CT findings mainly included ground glass opacities(GGOs)(=10,76.9%),focal consolidation within GGOs(=7,53.8%),thickened vascular bundle passing through the lesions(=10,76.9%),bronchial wall thickening(=12,92.3%),air bronchogram(=10,76.9%),vacuole signs in the lesions(=7,53.8%),fine reticulation and interlobular septal thickening(=3,23.1%),reversed halo-sign(=2,15.4%),crazy-paving pattern(=2,15.4%),and pleural effusion(=2,15.4%). Most of our patients diagnosed with COVID-19 at PUMCH had a travel history to Wuhan or direct contact with patients from Wuhan.The first symptoms of COVID-19 mainly include fever and dry cough,along with normal or reduced counts of WBC and lymphocytes.CT may reveal that the lesions distribute along the bronchi and under the pleura;they are typically localized GGOs in the early stage but can become multiple GGOs and infiltrative consolidation in both lungs in the advanced stage.Scattered vacuole signs may be visible inside the lesions in some patients.
Adult
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Aged
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Betacoronavirus
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Coronavirus Infections
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diagnostic imaging
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Humans
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Lung
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Middle Aged
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Pandemics
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Pneumonia, Viral
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diagnostic imaging
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Retrospective Studies
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Tomography, X-Ray Computed
6.Chemical constituents of Uvaria grandiflora
Qian ZHU ; Qilong HUANG ; Chunlei ZHANG ; Zhengyu CAO
Journal of China Pharmaceutical University 2019;50(6):666-671
Chemical investigation of the roots of Uvaria grandiflora by repeated column chromatography(CC)over silica gel, ODS, Sephadex LH-20, and HPLC resulted in the isolation of twelve compounds. Their structures were identified as: epicatechin-(4β→1′, 2→O→2′)-phloroglucinol(1), proanthocyanidin A-1(2), proanthocyanidin A-2(3), epicatechin(4), phlorizin(5), eriodictyol(6), erythro-guaiacylglycerol-8-O-4′-(coniferyl alcohol)ether(7), threo-guaiacylglycerol-8-O-4′-(coniferyl alcohol)ether(8), erythro-guaiacylglycerol-8-O-4′-(sinapyl alcohol)ether(9), threo-syringylglycerol-8-O-4′-(sinapyl alcohol)ether(10), burselignan(11)and icariol A2(12). Compounds 1 to 12 were all isolated from this plant for the first time, and compound 1 was a new natural product.
7.TIPS access to portal vein thrombolysis
Gaopo CAI ; Zhaohui HUA ; Peng XU ; Zhouyang JIAO ; Hui CAO ; Shirui LIU ; Jing YUAN ; Zhengyu PENG ; Zhen LI
Chinese Journal of General Surgery 2019;34(4):336-339
Objective To evaluate the clinical efficacy of portal venous thrombolysis by way of TIPS.Methods The clinical data of 40 patients with portal venous system thrombosis treated by TIPS at our department from May 2012 to May 2018 were retrospectively analyzed.There were 34 cases of via catheterdirected thrombolysis(7 cases by catheter-directed thrombolysis alone and 27 cases by way of TIPS before catheter-directed thrombolysis),and 6 cases via pharmaco mechanical thrombectomy (AngioJet);the postoperative complications of the two methods were followed up.Results The portal vein was opened in all 40 patients,and there were no major complications during the operation.One patient in the catheter-directed thrombolysis group developed acute liver failure after surgery.In the mechanical thrombolysis group,1 patient was discharged after small intestinal necrosis resection and intestinal fistula reconstruction.After 6-24 months of postoperative follow-up,6 patients in the group of thrombolysis suffered from shunt canal stricture.Conclusions It is a safe and minimally invasive method to treat portal venous system thrombosis through TIPS.Mechanical thrombolysis is more direct and rapid than catheter thrombolysis.
8.Application of 70 kV Third-generation High-pitch Dual-source Coronary CT Angiography in Patients with Different Body Mass Index.
Yan YI ; Jian CAO ; Lu LIN ; Lingyan KONG ; Shu JIANG ; Xiao LI ; Peijun LIU ; Ming WANG ; Man WANG ; Yun WANG ; Zhengyu JIN ; Yining WANG
Acta Academiae Medicinae Sinicae 2017;39(1):42-48
Objective To investigate the optimized range of body mass index (BMI) selection for patients undergoing 70 kV high-pitch dual-source coronary CT angiography (CCTA) on the third-generation dual-source CT (DSCT). Methods Patients undergoing prospective high-pitch ultra-low contrast media (CM) CCTA on the third-generation DSCT using the automatic tube voltage selection at 70 kV were included and divided into three groups:group A,with BMI≤24 kg/m;group B,with 24 kg/m
Body Mass Index
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China
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Computed Tomography Angiography
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methods
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Contrast Media
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Heart Rate
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Humans
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Prospective Studies
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Radiation Dosage
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Radiographic Image Interpretation, Computer-Assisted
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Signal-To-Noise Ratio
9.Application of the Low-dose One-stop-shop Cardiac CT Protocol with Third-generation Dual-source CT.
Lu LIN ; Yining WANG ; Yan YI ; Jian CAO ; Lingyan KONG ; Hao QIAN ; Hongzhi ZHANG ; Wei WU ; Yun WANG ; Zhengyu JIN
Acta Academiae Medicinae Sinicae 2017;39(1):34-41
Objective To evaluate the feasibility of a low-dose one-stop-shop cardiac CT imaging protocol with third-generation dual-source CT (DSCT). Methods Totally 23 coronary artery disease (CAD) patients were prospectively enrolled between March to September in 2016. All patients underwent an ATP stress dynamic myocardial perfusion imaging (MPI) (data acquired prospectively ECG-triggered during end systole by table shuttle mode in 32 seconds) at 70 kV combined with prospectively ECG-triggered high-pitch coronary artery angiography (CCTA) on a third-generation DSCT system. Myocardial blood flow (MBF) was quantified and compared between perfusion normal and abnormal myocardial segments based on AHA-17-segment model. CCTA images were evaluated qualitatively based on SCCT-18-segment model and the effective dose(ED) was calculated. In patients with subsequent catheter coronary angiography (CCA) as reference,the diagnosis performance of MPI (for per-vessel ≥50% and ≥70% stenosis) and CCTA (for≥50% stenosis) were assessed. Results Of 23 patients who had completed the examination of ATP stress MPI plus CCTA,12 patients received follow-up CCA. At ATP stress MPI,77 segments (19.7%) in 13 patients (56.5%) had perfusion abnormalities. The MBF values of hypo-perfused myocardial segments decreased significantly compared with normal segments [(93±22)ml/(100 ml·min) vs. (147±27)ml/(100 ml·min);t=15.978,P=0.000]. At CCTA,93.9% (308/328) of the coronary segments had diagnostic image quality. With CCA as the reference standard,the per-vessel and per-segment sensitivity,specificity,and accuracy of CCTA for stenosis≥50% were 94.1%,93.5%,and 93.7% and 90.9%,97.8%,and 96.8%,and the per-vessel sensitivity,specificity and accuracy of ATP stress MPI for stenosis≥50% and ≥70% were 68.7%,100%,and 89.5% and 91.7%,100%,and 97.9%. The total ED of MPI and CCTA was (3.9±1.3) mSv [MPI:(3.5±1.2) mSv,CCTA:(0.3±0.1) mSv]. Conclusion The third-generation DSCT stress dynamic MPI at 70 kV combined with prospectively ECG-triggered high-pitch CCTA is a feasible and reliable tool for clinical diagnosis,with remarkably reduced radiation dose.
Computed Tomography Angiography
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methods
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Coronary Artery Disease
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diagnostic imaging
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Heart
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diagnostic imaging
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Humans
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Myocardial Perfusion Imaging
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Prospective Studies
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Radiation Dosage
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Sensitivity and Specificity
10.Alkaloid constituents from Corydalis decumbens
Qilong HUANG ; Wanjin ZHANG ; Yan LI ; Juan CHEN ; Baoping ZHOU ; Xiaohan ZOU ; Chunlei ZHANG ; Zhengyu CAO
Journal of China Pharmaceutical University 2017;48(5):563-567
To study alkaloid constituents in Corydalis decumbens,thirteen compounds were isolated from 95% ethanol extracts of Corydalis decumbens (Thunb) Pers.by silica gel,RP-C1s,Sephadex LH-20 column chromatographer,recry stallization,thin-layer chromatography and HPLC.Their structures were elucidated on the basis of spectral data combined with physiochemical properties as tetrahydropalmatine (1),oxyhydrastinine (2),doryanine (3),palmatine (4),bicuculline (5),canadine (6),tetrahydrocoptisine(7),corydaldine (8),epicorynoxidine (9),N-methylcorydaldine (10),(+)-corlumine (11),N-methyl-6,7-dimethoxyisoquinolone (12) and oxysanguinarine (13).Compounds 2,3,6,7,and 9-13 were isolated from this plant for the first time.In addition,compounds 2,3,and 9-13 were obtained firstly from this genus.Pharmacological experiments showed that tetrahydropalmatine (1) might have analgesic or sedative effects,and the bicuculline (5) could probably induce epilepsy.

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