1.Synthesis, preclinical evaluation and pilot clinical study of a P2Y12 receptor targeting radiotracer 18FQTFT for imaging brain disorders by visualizing anti-inflammatory microglia.
Bolin YAO ; Yanyan KONG ; Jianing LI ; Fulin XU ; Yan DENG ; Yuncan CHEN ; Yixiu CHEN ; Jian CHEN ; Minhua XU ; Xiao ZHU ; Liang CHEN ; Fang XIE ; Xin ZHANG ; Cong WANG ; Cong LI
Acta Pharmaceutica Sinica B 2025;15(2):1056-1069
As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an 18F-labeled PET tracer (QTFT) that targets the P2Y12, a receptor highly expressed on anti-inflammatory microglia. [18F]QTFT exhibited high binding affinity to the P2Y12 (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [18F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y12 antagonist. Furthermore, [18F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y12 in anti-inflammatory microglia. In a pilot clinical study, [18F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [18F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y12 overexpressed in anti-inflammatory microglia.
2.Development of five grading standards and visual assessment tools for the elderly disability with dementia and its reliability and validity testing
Cheng CHEN ; Xin JIAO ; Yixiu WANG ; Qin ZHANG ; Xiang LU ; Wenwen LI ; Zhongli JIANG
Chinese Journal of Geriatrics 2024;43(5):616-622
Objective:To establish Chinese grading standards for elderly disability and dementia, in accordance with the International Classification of Functioning, Disability and Health(ICF)items, and to develop visual assessment tools that can be easily understood by patients, family members, and health workers.The aim is to verify the reliability and validity of these tools.Methods:In this study, we established five categories of elderly disability classification, along with corresponding ICF items and visual evaluation tools.The appropriateness and compatibility of the tools were assessed using questionnaires, which included illustrations, GIF dynamic pictures, and ICF items.Correlation analysis was conducted to screen the items, and the validity of the visual evaluation tools was determined through a picture-text matching validity test.Reliability was evaluated using internal consistency or test-retest reliability, and validity was assessed through content validity.Results:Each grade of disability was initially divided into five levels.However, after expert consultations and classification revision, each level was ultimately simplified into four levels with clearer descriptions.The Pearson correlation coefficients between all items and the total scores of each part were found to exceed 0.3, and the difference was statistically significant(all P<0.05).The average and mode of the illustrations and GIF dynamic pictures, when matched with related descriptions, were both above 3, with consistency rates surpassing 50%.Statistical differences were observed in eight items between the two visual assessment tools.The Cronbach's α coefficients, which reflect internal consistency, were all above 0.60.The intra-group correlation coefficients, which indicate test-retest reliability, were all greater than 0.70.The content validity index of the questionnaire at the overall level was above 0.90, while the item-level content validity index was more than 0.78. Conclusions:The Chinese grading standards for elderly disability and dementia, which are aligned with the ICF, have been preliminarily established.Visual assessment tools have also been developed, which demonstrate good reliability and validity.Among the two visual assessment tools, GIF dynamic pictures were found to be more popular and easier to understand.
3.The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling.
Yixiu ZHAO ; Zhiqi WANG ; Jing REN ; Huan CHEN ; Jia ZHU ; Yue ZHANG ; Jiangfei ZHENG ; Shifeng CAO ; Yanxi LI ; Xue LIU ; Na AN ; Tao BAN ; Baofeng YANG ; Yan ZHANG
Frontiers of Medicine 2024;18(6):1068-1086
Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals
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Atherosclerosis/prevention & control*
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Mice
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Receptor, Fibroblast Growth Factor, Type 1/metabolism*
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Signal Transduction/drug effects*
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Anthraquinones/pharmacology*
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Humans
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Integrin beta1/metabolism*
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Epithelial-Mesenchymal Transition/drug effects*
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Male
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Transforming Growth Factor beta/metabolism*
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Disease Models, Animal
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Mice, Inbred C57BL
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Human Umbilical Vein Endothelial Cells/drug effects*
4.A cross-sectional investigation on the detection of colorectal cancer and adenoma in adults under colonoscopy in Shihezi in recent ten years
Yuanmao XIE ; Miaomiao LUO ; Mengzhen SHI ; Xueping WANG ; Huizhu CHEN ; Yang LI ; Yixiu LIN ; Weigang CHEN
Chinese Journal of Digestive Endoscopy 2022;39(6):472-478
Objective:To investigate the change of the detection rate of colorectal cancer (CRC), colorectal adenoma and advanced adenoma in adults under colonoscopy in Shihezi in the past ten years.Methods:Data of patients who completed colonoscopy in the First Affiliated Hospital of Shihezi University School of Medicine from January 1, 2010 to December 31, 2019 were investigated. The medical records were collected by consulting the electronic medical record system, including the age and sex of patients and the location, quantity, size and pathological type of lesions. The detection rates, including the overall detection rate in the past 10 years, those in the first 5 years (from 2010 to 2014) and the second 5 years (from 2015 to 2019) of colorectal adenomas, advanced colorectal adenomas and CRC, were studied.Results:A total of 50 645 cases were included, 14 931 cases were excluded by the exclusion criteria, and finally a total of 35 714 cases were included in the data analysis. The 10-year overall detection rates of colorectal adenoma, advanced colorectal adenoma and CRC were 17.65% (6 302/35 714), 4.45% (1 589/35 714) and 3.71% (1 324/35 714), respectively. The overall detection rates of colorectal adenoma and advanced colorectal adenoma in the second 5 years were higher respectively than those in the first 5 years [20.33% (4 565/22 457) VS 13.10% (1 737/13 257), 4.69% (1 053/22 457) VS 4.04% (536/13 257)]. The overall detection rate of CRC in the second 5 years [3.30% (741/22 457)] was lower than that in the first 5 years [4.40% (583/13 257)].Conclusion:Compared with 2010 to 2014, the detection rate of colorectal adenoma in Shihezi area in 2015 to 2019 increased significantly, the detection rate of advanced colorectal adenoma increased slightly, and the detection rate of CRC decreased slightly. Therefore, the detection and resection of colorectal adenoma by colonoscopy may be important in reducing the incidence of CRC.
5.Diagnostic value of CT thin-section target reconstruction technique in patients with pulmonary small size ground glass nodules
Biao WU ; Changyi MA ; Yixiu HAO ; Liebin HUANG ; Yueyue LI ; Jintang CHEN ; Wansheng LONG ; Xiangmeng CHEN ; Enming CUI
Journal of Practical Radiology 2018;34(5):769-772
Objective To investigate the diagnostic value of CT thin-section target reconstruction technique in patients with pulmonary small size groud glass nodules (sGGN).Methods A total of 109 patients with pulmonary sGGN certified post-operation and/or follow up were analyzed retrospectively,and the clinical and CT images of all patients were completely collected.There were 23 cases of benign group,21 cases of adenocarcinoma in situ group,29 cases of minimally invasive adenocarcinoma group and 36 cases of invasive adenocarcinoma group,respectively.The differential diagnostic value using CT thin-section target reconstruction technique was analyzed between the benign and malignant pulmonary sGGN groups,and the CT feature detection rates were compared between CT thin section target and common reconstruction techniques.Results The CT thin-section target reconstruction technique had improved the diagnostic efficiency of pulmonary sGGN.The diagnostic accuracy,area under curve(AUC),sensitivity and specificity were 85.32 %,0.679,90.80 %,63.64 % in malignant group and 77.06%,0.764,83.72%,52.17% in benign pulmonary sGGN group,respectively.The CT features as solid component in whole nodule,"halo sign",speculation sign,pleural retraction sign,lobulation sign were more detected by using the thin-section target reconstruction technique than that by using the common reconstruction among adenocarcinoma in situ group,minimally invasive adenocarcinoma group and invasive adenocarcinoma group (P<0.05) but not speculation sign in the invasive adenocarcinoma group(P=0.126).Conclusion The CT thin section target reconstruction technique can improve the diagnostic value of pulmonary sGGN.
6.Analysis of TCM single disease nursing quality indicators of cervical spondylosis
Yixiu CHEN ; Yanxia CAO ; Jingyun WANG ; Jie SONG
Chinese Journal of Modern Nursing 2017;23(16):2109-2114
Objective To establish traditional Chinese medicine (TCM) dominant disease nursing quality management specification to be suitable for the demand of curative effects of spinal disease cervical spondylosis.Methods The basic frame of cervical spondylosis TCM nursing quality indicators was established using the theory structure of "framework-process-result",learning from modern nursing program and based on the literature research method,clinical research and the semi-structured interview method. The Delphi expert consultation and expert argumentation method were used to formulate the final system of cervical spondylosis TCM nursing quality indicators.Results After two rounds of Delphi procedure, cervical spondylosis of TCM nursing quality indicator system was established including the first grade indexes (3 items),the second grade indexes (21 items) and the third grade indexes (111 items).Conclusions Establishment of TCM nursing quality indicators of cervical spondylosis provides a standard to specify TCM nursing process and objectively evaluate TCM nursing quality of single disease,and has an important clinical significance.
7.Effects of rheum officinale midnight-noon and ebb-flow doctrine acupoint application on bowel preparation before colonoscopy among constipation patients
Chinese Journal of Modern Nursing 2016;22(12):1642-1645
Objective Toobserve the effects of rheum officinale midnight-noon and ebb-flow doctrine (MNEFD) acupoint application on bowel preparation before colonoscopy for constipation patients.Methods A total of 66 cases met the inclusion criteria were collected and divided into control and observation groups with 33 cases in each group using randomized controlled method .Rhubarb MNEFD acupoint application and routine bowel preparation were used for observation group , while routine bowel preparation alone was employed in the control group.The intestinal cleansing effects , the first exhaust and defecation time , the time required to reach a fecal residue-free level and the patients′tolerance to bowl preparation were observed .Meanwhile, the safety of bowl preparation for colonoscopy among constipation patients was assessed as well after the intervention .Results In observation group , 31 cases of patients were confirmed with intestinal cleansing grade I and II , and 32 cases of patients were with intestinal tolerance grade I and II; while they were 30 and 31 in the control group .The difference of satisfaction and intestinal tolerance level of bowl preparation between two groups were significant (χ2 =12.321,9.524;P <0.01).The first exhaust and defecation time were (74.73 ±44.634) min and (75.79 ±46.219)min for patients in the observation group without significant difference compared with that of control group (P>0.05).The bowl preparation time for patients in the observation group was (251.79 ± 72.738)min, shorter than that of control group (294.06 ±55.411)min (P<0.05); intestinal tolerance level was better than that of control group ( P <0.01 ) .Conclusions Rhubarb MNEFD acupoint application can improve the effects of intestinal cleansing and increase the tolerance level of patients for bowl preparation with respect to a shortened time for fecal to reach residue-free at certain level .
8.An investigation of the necessity on performing preoperative trachea and esophageal pushing in cervical operation using anterior approach
Yixiu CHEN ; Xiaojing SU ; Ziming YAO
Chinese Journal of Practical Nursing 2015;31(27):2046-2049
Objective To investigate the influence of preoperative training of pushing trachea and esophagus or not on cervical operation by anterior approach.Methods All patients were randomly divided into two groups:experimental group and control group (56 cases,respectively).Patients in the former group had no training of pushing trachea and esophagus,while patients in the latter group had,recording the data of surgery duration,operator's degree of satisfaction,blood loss,blood pressure,heart rate,and oxygen saturation during operation,hospital stay and cost.Meanwhile,we observed and compared the VAS scores and the complication rate etc.between two groups.Results There were no differences between two groups in surgery duration,operator's degree of satisfaction,blood loss,blood pressure,heart rate,and oxygen saturation during operation,hospital stay and cost,nor in the VAS scores and the throat-related complications rate.The hospital stay and cost of patients in experimental group were longer and higher than that of patients in control group,(7.3±1.6) d vs (5.8±1.4) d,(48 468.3±4 313.8) vs (45 228.4±4 124.6) yuan,t=5.280,4.062,P<0.05.Conclusions Training of pushing trachea and esophagus has no influence in the throat-related complications rate,VAS scores and operator's degree of satisfaction.Instead,training of pushing trachea and esophagus increases hospital stay and cost and amount of nurse's work.So,it's not necessary to undertake the preoperative training before cervical operation by anterior.
9.Prenatal diagnosis of fetal dysplastic kidney with normal amniotic fluid volume by ultrasonography
Hua MENG ; Yuxin JIANG ; Qing DAI ; Meng YANG ; Yixiu ZHANG ; Qingli ZHU ; Yan CHEN
Chinese Journal of Ultrasonography 2008;17(3):227-230
Objective To determine the diagnostic value and clinical significance of sonographically detected fetal dysplastic kidney with normal amniotic fluid volume. Methods At the 2nd or 3rd trimester of gestation,the fetuses with unilateral or bilateral renal anomalies (ahnormal size,echo,shape or cyst of the kidney) and normal amniotic fluid volume received systemic ultrasound examination,autopsy or follow-up until after birth. The fetus with only dilated renal pelvis was not included. Results Eleven fetuses of dysplastic renal anomalies with normal amniotic fluid volume were identified by prenatal ultrasound. Among the five fetuses affected by unilateral multicystic kidney dysplasia (MCKD),the renal anomaly was isolated in four fetuses,and the other one was complicated with absence of the ipsilateral hand. One of the two fetuses of unilateral renal agenesis had no other associated anomaly and the other one was complicated with hydrocephalus,spina bifida,ipsilateral absent radius and single umbilical artery,correspongding to the VACTERL syndrome. Two fetuses of pelvic kidney and horseshoe kidney respectively was proved by postnatal ultrasound. One fetus was diagnosed as autosomal dominant polycystic kidney disease(ADPKD)on the basis of multiple renal cysts and a positive family history,the fetus also had cardiac rhabdomyoma. One fetus of bilateral normal sized hyperechoic kidneys was proved to be renal dysplasia by autopsy. Conclusions Unilateral MCKD is the most common type of fetal renal dysplasia which can be detected by prenatal ultrasound with normal amniotic fluid volume. Based on the sonographic characteristics and the family history,most of the dysplastic renal anomalies can be diagnosed prenatally and the prognosis can be predicted.
10.WWOX gene expression and aberrant CpG island hypermethylation of WWOX gene in breast cancer
Xiao WANG ; Jingzhong SUN ; Liansheng CHEN ; Bin TIAN ; Tao SUN ; Guangchao JIN ; Guohui MA ; Yixiu ZANG
Chinese Journal of General Surgery 2008;23(5):380-383
Objective To evaluate the expression of WWOX gene in breast cancer and its relation to hypermethylation of WWOX gene CpG island. Methods The expression of WWOX protein was evaluated by immunohistochemical staining in breast cancer cell line and breast cancer tissues.Methylation specific PCR(MSP)was used to check whether it Was methylated in the promoter and exon 1 of WWOX.Results Deletion in the WWOX expression was observed more frequently in invasive breast tumors,(32.2%)than normal breasttissues(5.4%)(P<0.01).20.3% of premenopause eases were completely negative for WWOX expression compared to 57.2% of postmenopause breast carcinomas(P<0.01).Furthermore,23.1% of Stage Ⅰ(6/26),28.6%of Stage Ⅱ(10/35),46.2%of Stage Ⅲ(12/26)tunlors showed negative WWOX protein expression.In breast cancer specimens.methylation rate of promoter and exon 1 CpG island of WWOX gene was 55%and 45%respectively.Whereas.WWOX CpG islands of normal mammary tissues were completely unmethylated in all cases.CpG islands of WWOX promoter and exon 1 were methylated in MDA-MB-231 cell line but not MCF-7 cell.Conclusions Some deletion in WWOX expression is common in breast cancer and methylation of WWOX DNA CpG islands plays a crucial role in the silence of WWOX.WWOX may play a role in the carcinogenesis and development of breast cancer.

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