1.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.
2.Antiosteoporosis effect of conventional treatment combined with Denosumab after percutaneous kyphoplasty for osteoporotic vertebral compression fractures
Chenyang WU ; Yiping GU ; Xueli QIU ; Huajian SHAN ; Xiang GAO ; Lide TAO ; Yingzi ZHANG ; Bingchen SHAN ; Xiaozhong ZHOU ; Jinyu BAI
Chinese Journal of Trauma 2024;40(9):787-792
Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.
3.Study on anti-adhesion effect and mechanism of dynamic and static stress stimulation during early healing process of rat Achilles tendon injury.
Jiani WU ; Yingzi JIANG ; Guanyu WANG ; Liliao WANG ; Jie BAO ; Jun WANG
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(11):1391-1398
OBJECTIVE:
To investigate the anti-adhesive effect and underlying mechanism of dynamic and static stress stimulation on the early healing process of rat Achilles tendon injury.
METHODS:
Achilles tendon tissues of 15 male Sprague Dawley (SD) rats aged 4-6 weeks were isolated and cultured by enzyme digestion method. Rat Achilles tendon cells were treated with tumor necrosis factor α to construct the Achilles tendon injury cell model, and dynamic stress stimulation (dynamic group) and static stress stimulation (static group) were applied respectively, while the control group was not treated. Live/dead cell double staining was used to detect cell activity, ELISA assay was used to detect the expression of α smooth muscle actin (α-SMA), and real-time fluorescence quantitative PCR was used to detect the mRNA expression of collagen type Ⅰ (COL1A1), collagen type Ⅲ (COL3A1), and Scleraxis (SCX). Thirty male SD rats aged 4-6 weeks underwent Achilles tendon suture and were randomly divided into dynamic group (treated by dynamic stress stimulation), static group (treated by static stress stimulation), and control group (untreated), with 10 rats in each group. HE staining and scoring were performed to evaluate the healing of Achilles tendon at 8 days after operation. COL1A1 and COL3A1 protein expressions were detected by immunohistochemical staining, α-SMA and SCX protein expressions were detected by Western blot, and maximum tendon breaking force and tendon stiffness were detected by biomechanical stretching test.
RESULTS:
In vitro cell experiment, when compared to the static group, the number of living cells in the dynamic group was higher, the expression of α-SMA protein was decreased, the relative expression of COL3A1 mRNA was decreased, and the relative expression of SCX mRNA was increased, and the differences were all significant ( P<0.05). In the in vivo animal experiment, when compared to the static group, the tendon healing in the dynamic group was better, the HE staining score was lower, the expression of COL1A1 protein was increased, the expression of COL3A1 protein was decreased, the relative expression of SCX protein was increased, the relative expression of α-SMA protein was decreased, and the tendon stiffness was increased, the differences were all significant ( P<0.05).
CONCLUSION
Compared with static stress stimulation, the dynamic stress stimulation improves the fibrosis of the scar tissue of the rat Achilles tendon, promote the recovery of the biomechanical property of the Achilles tendon, and has obvious anti-adhesion effect.
Animals
;
Achilles Tendon/injuries*
;
Male
;
Rats
;
Rats, Sprague-Dawley
;
Collagen Type I/metabolism*
;
Collagen Type III/metabolism*
;
Tendon Injuries/therapy*
;
Wound Healing
;
Stress, Mechanical
;
Actins/metabolism*
;
Cells, Cultured
;
Tissue Adhesions/prevention & control*
;
Tumor Necrosis Factor-alpha/metabolism*
;
RNA, Messenger/genetics*
;
Disease Models, Animal
;
Collagen Type I, alpha 1 Chain/metabolism*
;
Biomechanical Phenomena
;
Basic Helix-Loop-Helix Transcription Factors
4.On Privacy Protection of Electronic Health Records
Qiang GUAN ; Yanling WU ; Huiqiang HAN ; Zhanhui WANG ; Ya GAO ; Yingzi MA ; Feng WEI
Chinese Medical Ethics 2022;35(6):613-618
With the continuous advancement of health informatization and the wide application of medical big data, electronic health records came into being and spread rapidly. However, because electronic health records contain a large amount of private information, privacy protection is the primary consideration for the sustainable development of electronic health records. By analyzing the shortcomings of privacy protection of electronic health records in law, technology, management and protection consciousness, this paper put forward some countermeasures, such as perfecting the relevant laws and regulations of privacy protection of electronic health records, improving the technical level, improving the management defects of electronic health records, and cultivating the privacy protection consciousness of professionals and the public, so as to improve the overall privacy protection level of China’s health records information management system and provide effective protection for the privacy information of Chinese residents’ electronic health records.
5.Efficacy of Qingqi Huatan Decoction combined with western medicine in the treatment of severe pneumonia and its influence on the level of inflammatory factors
Yingzi WU ; Weihou FANG ; Meixiu LIU
International Journal of Traditional Chinese Medicine 2022;44(4):371-374
Objective:To evaluate the efficacy of Qingqi Huatan Decoction combined with conventional western medicine therapy in the treatment of severe pneumonia with phlegm-heat obstructing the lung syndrome.Methods:A total of 84 patients with severe pneumonia with phlegm-heat obstructing lung syndrome admitted to Zhangjiagang Hospital of Traditional Chinese Medicine from February 2018 to June 2020 were randomly divided into two groups, 42 in each group. The control group was treated with bronchoalveolar lavage (BAL) on the basis of routine treatment, and the combined group was treated with Qingqi Huatan Decoction on the basis of the control group. Both groups were treated for 7 days. The Clinical Pulmonary Infection Score (CPIS) was used to evaluate the degree of pulmonary infection, and the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) was used to evaluate the severity of the disease. The Serum CRP and IL-6 levels were detected by ELISA, and procalcitonin (PCT) levels were detected by electrochemiluminescence method to evaluate clinical efficacy.Results:The total effective rate was 88.1% (37/42) in the combined group and 69.0% (29/42) in the control group, with a statistically significant difference between the two groups ( χ2=4.53, P=0.033). After treatment, the CPIS (2.19±0.42 vs. 3.66±0.69, t=11.79) and APACHE Ⅱ (9.84±1.31 vs. 11.25±3.22, t=2.63) in the combination group were significantly lower than those in the control group. The serum CRP, PCT, and IL-6 levels in the combination group were significantly lower than those in the control group ( t=30.32, 8.59, 6.08, all Ps<0.001). During the treatment period, there was no obvious abnormality of liver and kidney function in both groups. Conclusion:Qingqi Huatan Decoction combined with conventional western medicine therapy can reduce the degree of pulmonary infection in patients with severe pneumonia with phlegm-heat obstructing the lung syndrome, reduce the level of inflammatory cytokines, and improve clinical efficacy.
6.A prospective multi-center cross-sectional study of urethral mobility in normal parous women in China
Shuangyu WU ; Ying CHEN ; Kun WANG ; Huihuan ZHU ; Suzhen RAN ; Aihua WEI ; Yingzi XU ; Xudong WANG ; Jiawei TIAN ; Xinling ZHANG
Chinese Journal of Ultrasonography 2021;30(4):299-305
Objective:To assess the urethral mobility of normal parous women in China and explore the impacts of related risk factors on it using translabial ultrasound.Methods:Females who met the inclusion criteria in 37 tertiary hospitals from February 2017 to August 2018 were included. All women underwent standardized translabial ultrasound examination and the urethral rotation angle (URA), bladder neck position at maximum Valsalva maneuver (BNP-V) and bladder neck descent (BND) were measured. Questionnaires were used to collect basic information including age, height, weight, body mass index (BMI), past medical history, maternity history, and urinary incontinence related history. Mann-Whitney U test and multiple linear regression analysis were adopted to explore the influences of age, BMI, delivery mode and parity on normal parous women′s urethral mobility. Then, the study subjects were divided into different groups and the corresponding values of URA, BNP-V and BND were compared. Results:Compared with parous women with normal BMI and no history of vaginal delivery, those who were overweight and/or had a history of vaginal delivery were more likely to gain greater URA and BND ( P<0.05). The URA and BND were not significantly different between women with different times of cesarean sections ( P>0.05); while for women with a history of vaginal delivery, these two parameters increased with the increase of the number of transvaginal deliveries ( P<0.05). Conclusions:BMI and vaginal delivery are important risk factors for the urethral mobility of normal parous women. The urethral mobility increases with the increase of BMI and the number of vaginal deliveries.
7.Epidemiological survey of an outbreak of acute gastroenteritis caused by norovirus G type II in a school in Wujin District in Changzhou
Hui WU ; Hengtai XYU ; Jiahui WU ; Xuewu ZHAO ; Yingzi PAN
Journal of Public Health and Preventive Medicine 2021;32(5):130-133
Objective To investigate an outbreak of norovirus GII gastroenteritis in a school, and explore the causes, transmission routes and risk factors of the outbreak, and to provide a scientific basis and experience for effective control of outbreaks of acute gastroenteritis in schools. Methods A case study of an acute gastroenteritis outbreak in a school in Wujin District, Changzhou was conducted by field epidemiological investigation. Anal swab samples of patients and controls were collected, and enterovirus nucleic acid was detected by real-time fluorescent PCR. Results From December 12 to December 17, 2019, a total of 185 cases were identified, all of them from students of the school, with an incidence rate of 3.84% (185/4,822). All of the cases were distributed in three (7th/8th/9th) grades of the school, with attack rates of 5.38% (31 / 576), 18.71% (104 / 556) and 9.06% (50 / 552) in 7th, 8th and 9th grade, respectively, showing a significant difference among the grades (χ2=54.47,P<0.05). The attack rate of each floor of the teaching building from the first to fifth floor was 2.17% (5/230), 7.51% (26/346), 15.77% (53/336), 17.11% (65/380), and 6.38% (25/392), respectively, showing a statistically significant difference among different floors (χ2=55.66,P<0.05). A total of 32 anal swabs were collected, including 12 patients, 10 control students and 10 workers in the canteen. Of them, 9 specimens of the patients and 1 specimen of the workers were positive for norovirus type GII. Conclusion The school outbreak of acute gastroenteritis was caused by norovirus GII. Close contact between students was the main mode of transmission. A hidden infection of canteen staff may be related to this outbreak. It is important to promote popular science of norovirus prevention and to enhance the awareness of the risks of the virus.
8.Preliminary study on deoxyribonucleic acid methylation of breast cancer anti-resistance 1, phospho-diesterase 1C, opioid receptor delta 1 and neurexin 1 in gout and hyperuricemia
Yong CHEN ; Xiaoke LI ; Ying YING ; Yuhan WU ; Rongxin ZOU ; Zanbo CHU ; Yingzi PAN
Chinese Journal of Rheumatology 2020;24(10):676-680
Objective:To provide a preliminary theoretical basis for gout and hyperuricemia of Deoxyribonucleic acid (DNA) methylation.Methods:Breast cancer anti-resistance 1(BCAR1), phospho-diesterase 1C (PDE1C), opioid receptor delta 1(OPRD1) and neurexin 1(NRXN1) methylation levels were measured by bisulfite pyrosequencing in 50 gout patients, 30 hyperuricemia patients and 50 matched healthy controls. Comparisons between groups were evaluated by F-test and Nonparametric tests. Results:Receiver operating characteristic showed that the methylation of PDE1C(pos4, pos5, pos6)(AUC: 0.712, 0.772, 0.775; all P values<0.05) had higher accuracy for diagnosis of gout, and OPRD1 pos4 (AUC=0.733, P<0.05) had higher accuracy for hyperuricemia. Conclusion:DNA methylation may play a role in the development of gout and hyperuricemia, however, further studies are needed.
9.Research progress on fatigue in recipients of renal transplantation
Yue LI ; Yingzi MING ; Quan ZHUANG ; Xiaoxia WU ; Dongfang YIN ; Lifang LIU ; Jia LIU
Organ Transplantation 2020;11(2):311-
Renal transplantation is one of the most effective treatment methods for end-stage renal diseases. However, some recipients present with fatigue symptoms after renal transplantation. Fatigue not only affects the quality of life, but also reduces the compliance of recipients with immunosuppressive agents. To strengthen the attention of medical staff to the fatigue, make early diagnosis and deliver effective interventions for renal transplant recipients, the current situation, risk factors and intervention methods of fatigue in renal transplant recipients were reviewed in this article.
10.Study on the Active Ingredients and Mechanism of Alpinia officinarum in the Treatment of Gastric Ulcer Based on Network Pharmacology
Zhenmiao QIN ; Lili ZHANG ; Demei CHEN ; Ning WANG ; Yingzi CHEN ; Xinfu WU ; Junqing ZHANG
China Pharmacy 2020;31(12):1440-1439
OBJECTIVE:To explore the potential active ingredients and mechanism of Alpinia officinarum in the treatment of gastric ulcer. METHODS :By network pharmacology method ,the active ingredients and action targets of A. officinarum were screened through TCMSP and TCMID database retrieval [oral bioavailability (OB)≥30% and drug like (DL)≥0.18] and literature mining. Targets of gastric ulcer were obtained in the TTD ,CTD,OMIM,PubMed,DrugBank and DisGeNet databases. Venny 2.1 software was used to screen common targets for the active ingredients of A. officinarum and gastric ulcer. Then ,the protein-protein interaction(PPI)of the common targets was obtained by STRING database ,and the PPI network was constructed and analysed by using Cytoscape 3.7.1 software. GO function and KEGG pathway enrichment analysis of the common targets were performed by using ClusterProfiler R package. Finally ,Cytoscape 3.7.1 software was used to construct and analyze the network diagram of “active ingredients-targets-pathways ”. RESULTS :Totally 19 active ingredients of A. officinarum ,209 active ingredients targets and 195 gastric ulcer related targets ,involving 35 common targets ,were screened out. The average node degree of PPI network of common targets was 18,and the average intermediate number was 16.9. There were 11 key targets ,i.e. PTGS2,VEGFA,IL6, IL1B,CCL2,MYC,MMP9,EGFR,HIF1A,ESR1,BCL2L1. The common targets were mainly concentrated in the cell constituents such as the platelet α granule lumen and mitochondria outer membrane ,involved in the biological processes as oxidative stress ,inflammatory response regulation ,and molecular functions as protein phosphatase binding ,growth factor receptor binding. They were also enriched in the signal pathways such as PI3K/Akt,HIF-1. The network of“active ingredients- targets-pathways”showed the active ingredients such as quer- cetin,apigenin,kaempferol and galangin in A. officinarum played an anti-gastric ulcer effect by acting on PTGS2,NOS2, BCL2, IL6, VEGFA, IL1B, MMP9, BCL2L1 and other targets to jointly regulate PI 3K-Akt,HIF-1,TNF,IL-17, NF-κB and other cell proliferation,angiogenesis,and infla- 163.com mmation related pathways. CONCLUSIONS :A. officinarum shows anti-gastric ulcer effect with the characteristics of multi-ingredient ,multi-target and multi-path.


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