1.Right ventricular-pulmonary artery connection for palliative treatment of pulmonary atresia with ventricular septal defect in children: A single-center retrospective study
Shuai ZHANG ; Jianrui MA ; Hailong QIU ; Xinjian YAN ; Wen XIE ; Qiushi REN ; Juemin YU ; Tianyu CHEN ; Yong ZHANG ; Xiaohua LI ; Furong LIU ; Shusheng WEN ; Jian ZHUANG ; Qiang GAO ; Jianzheng CEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):366-371
Objective To compare the benefits and drawbacks of primary patch expansion versus pericardial tube right ventricular-pulmonary artery connection in patients diagnosed with pulmonary atresia with ventricular septal defect (PA/VSD). Methods A retrospective study was conducted on patients diagnosed with PA/VSD who underwent primary right ventricular-pulmonary artery connection surgery at our center between 2010 and 2020. Patients were categorized into two groups based on the type of right ventricular-pulmonary artery connection: a pericardial tube group and a patch expansion group. Clinical data and imaging findings were compared between the two groups. Results A total of 51 patients were included in the study, comprising 31 males and 20 females, with a median age of 12.57 (4.57, 49.67) months. The pericardial tube group included 19 patients with a median age of 17.17 (7.33, 49.67) months, while the patch expansion group consisted of 32 patients with a median age of 8.58 (3.57, 52.72) months. In both groups, the diameter of pulmonary artery, McGoon index, and Nakata index significantly increased after treatment (P<0.001). However, the pericardial tube group exhibited a longer extracorporeal circulation time (P<0.001). The reoperation rate was notably high, with 74.51% of patients requiring further surgical intervention, including 26 (81.25%) patients in the patch expansion group and 12 (63.16%) patients in the pericardial tube group. No statistical differences were observed in long-term cure rates or mortality between the two groups (P>0.005). Conclusion In patients with PA/VSD, both patch expansion and pericardial tube right ventricular-pulmonary artery connection serve as effective initial palliative treatment strategies that promote pulmonary vessel development and provide a favorable foundation for subsequent radical operations. However, compared to the pericardial tube approach, the patch expansion technique is simpler to perform and preserves some intrinsic potential for pulmonary artery development, making it the preferred procedure.
2.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
3.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.
4.Flavones in pomelo peel resist fibril formation of human islet amyloid polypeptide.
Cuiyun GAO ; Zhiruo WAN ; Yan LIU ; Yuting MENG ; Xu CHEN ; Xiaohan TANG ; Lingyu HANG ; Hailong YUAN
Chinese Herbal Medicines 2025;17(1):166-177
OBJECTIVE:
Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated.
METHODS:
The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation.
RESULTS:
The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers.
CONCLUSION
A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.
5.Effects of tumor location on the prognosis of upper tract urothelial carcinoma and development and validation of a prognostic nomogram
Zewei WANG ; Hailong LI ; Gang LI ; Zhimin GAO ; Rumin WEN
Journal of Modern Urology 2024;29(2):146-153
【Objective】 To investigate the prognostic value of tumor location in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU), and to develop and validate a nomogram model for predicting the overall survival (OS). 【Methods】 UTUC patients undergoing RUN at our hospital during Jan.2010 and Dec.2022 were retrospectively collected, 70% of whom were included in the training group and 30% in the validation group.According to the tumor location, patients were divided into renal pelvis tumor (RPT) group and ureteral tumor (UT) group.The differences in clinicopathological features and prognosis were analyzed.Based on multivariate Cox results, a nomogram model for predicting OS was developed and validated. 【Results】 A total of 366 patients (196 RPT and 170 UT) were included in this study.There were statistically significantly differences in urine cytology (P=0.001), hydronephrosis (P<0.001), history of bladder tumor (P=0.021), pathological T stage (P<0.001) and histological structure (P=0.037) between the two groups.Multivariate Cox results showed that patients with UT had a worse prognosis (HR=2.00, 95%CI: 1.22-3.27, P=0.006).Factors of the nomogram for predicting OS included age, tumor location, lymphovascular invasion and pathological T stage.The model showed good discrimination and calibration, and performed well in internal verification. 【Conclusion】 Compared with RPT, UT has a worse prognosis and the fat around the tumor should be surgically removed more thoroughly to avoid micro-residual.We successfully coustructed a nomogram model that can be used to predict the OS of UTUC patients after RNU surgery.
6.Establishing and validating a nomogram model for predicting the prognosis of bladder cancer patients based on the score of systemic inflammatory markers before radical cystectomy combined with pathological T stage
Gang LI ; Hailong LI ; Zewei WANG ; Zhimin GAO ; Rumin WEN
Journal of Modern Urology 2024;29(6):533-539
Objective To evaluate the value of systemic inflammatory markers(SIM)in the prognosis of patients with bladder cancer undergoing radical cystectomy.Methods Clinical data of 233 patients with bladder cancer who underwent radical cystectomy in the Affiliated Hospital of Xuzhou Medical University during Dec.2011 and Nov.2020 were retrospectively collected,the SIM score was calculated and patients were grouped.Progression-free survival(PFS)was assessed with Kaplan-Meier analysis,and differences between groups were compared with log-rank test.Factors affecting PFS were analyzed with Cox proportional risk model.The patients were randomly divided into a training set(n=164)and a verification set(n=69)according to 7:3 ratio,and a nomogram model was established and verified.Results Cox regression analysis showed that SIM score and pathological T staging were independent predictors of PFS(P<0.05).A predictive model was established based on SIM score and pathological T staging.The area under the receiver operating characteristic(AUC)curve for predicting 1-year,3-year,and 5-year PFS were 0.939,0.943,and 0.943,respectively.After the model was applied to evaluate the validation set,the performance was still stable.Conclusion The prediction model based on SIM score and clinicopathological T staging can accurately predict the survival of patients with bladder cancer after radical cystectomy,and can be used to guide individualized treatment of patients.
7.Recombinant human CC16 inhibits senescence in human bronchial epithelial cells induced by cigarette smoke extract
Ting LI ; Xiaoxue YANG ; Rui GAO ; Xinyang LI ; Hailong WANG ; Min PANG
Journal of Army Medical University 2024;46(12):1410-1416
Objective To investigate the effect and mechanism of recombinant human CC16 protein(rhCC16)on cigarette smoke extract(CSE)-induced senescence of human bronchial epithelial cells(HBECs).Methods CCK-8 assay was used to evaluate the cell viability in HBECs after treated with 0%,1%,2.5%,5%,7.5%and 10%CSE and/or 0,10,100,250 and 500 ng/mL rhCC16.β-galactosidase staining was used to observe the activity of the enzyme in control,CSE,and CSE+rhCC16 treated HBECs.The mRNA levels of P16 and P21 in above cell groups were detected by real-time fluorescence quantitative PCR(qPCR),and the protein levels of P16,P21,p-P53,P38,p-P38,ERK1/2 and p-ERK1/2 were detected with Western blot in control group,CSE and CSE+rhCC16 groups.Results Compared with the control group,5%CSE stimulation for 72 h or the treatment of 500 ng/mL or lower dose of rhCC16 had no significant effect on cell viability of HBECs.Stimulation 5%CSE for 72 h resulted in significantly higher positive rate to β-galactosidase staining(P<0.05),elevated mRNA and protein levels of P16 and P21(P<0.05),and enhanced protein levels of p-P53,p-P38 and p-ERK1/2(P<0.05)when compared with the control group.Compared with the simple CSE stimulation,250 ng/mL 1hCC16 treatment decreased positive rate to β-galactosidase staining(P<0.05),reduced mRNA and protein levels of P16 and P21(P<0.05)and protein levels of p-P53,p-P38 and p-ERK1/2(P<0.05).Conclusion rhCC16 inhibits CSE-induced cellular senescence of HBECs,which may due to its suppression in P38 MAPK and ERK1/2 signaling pathway.
8.Effectiveness of ultrasound assessing risk of gastric content aspiration in patients undergoing emergency abdominal surgery
Lei ZHANG ; Xue GAO ; Long JIANG ; Hailong JIN ; Fushan XUE
Chinese Journal of Anesthesiology 2024;44(10):1190-1194
Objective:To evaluate the effectiveness of ultrasound assessing the risk of gastric content aspiration in patients undergoing emergency abdominal surgery.Methods:This was a prospective self-control study. Seventy-three American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged >18 yr, who underwent emergency abdominal surgery in Beijing Daxing District People′s Hospital from June 2022 to December 2023, were selected. Time method assessment: The time and category of fasting and no-drinking were inquired, the patient′s gastric emptying status and risk of gastric content aspiration were assessed based on the time of fasting and no-drinking, and a preliminary anesthesia plan was formulated. Ultrasound method assessment: The properties of gastric contents were determined, the cross-sectional area of the gastric antrum was measured, the volume of gastric fluid was estimated, the Perlas grading of the gastric antrum was performed to assess the risk of gastric content aspiration, and a final anesthesia plan for implementation was formulated.Results:The number of patients with a high-risk of gastric content aspiration determined by the time method and ultrasound method was 2 cases (3%) and 11 cases (15%), respectively, with a statistically significant difference between the two methods ( P<0.05). The risk class of gastric content aspiration changed after ultrasound examination in 11 patients. One patient with a high risk determined by the time method was identified as having a low risk by the ultrasound method, and the other 10 patients with a low risk determined by the time method were identified as having a high risk by the ultrasound method. There was a statistically significant difference in the anesthesia induction plans formulated based on two methods ( P<0.05), while there was no statistically significant difference in the airway maintenance plans between the two methods ( P>0.05). Regurgitation of gastric contents occurred only in one case (1.4%), and no gastric content aspiration was found in any case. Conclusions:Preoperative gastric ultrasound examination can be used to assess the risk of gastric content aspiration and guide the formulation of anesthesia plans for the patients undergoing emergency abdominal surgery.
9.ANKRD49 promoted epithelial-mesenchymal transition by increasing ex-pression of Snail/Slug/ZEB1 in NCI-H1299 cells
Rui GAO ; Chaofeng LIU ; Jinrui HU ; Gang LIANG ; Rong FU ; Wei WANG ; Hailong WANG ; Min PANG
Chinese Journal of Pathophysiology 2024;40(7):1190-1196
AIM:To investigate the effect of ankyrin repeat domain 49(ANKRD49)on epithelial-mesenchy-mal transition(EMT)in NCI-H1299 cells,and to explore its mechanism.METHODS:The ANKRD49 was over-ex-pressed in NCI-H1299 cells.The morphological changes of ANKRD49-overpressing NCI-H1299 cells were observed under microscope.The mRNA and protein expression levels of EMT-related markers[E-cadherin,transforming growth factor-β1(TGF-β1),vimentin and α-smooth muscle actin(α-SMA)]and EMT-related transcription factors(Snail1,Slug,Twist and ZEB1)were detected by RT-qPCR Western blot.Immunofluorescence staining was performed to observe the localiza-tion and expression of E-cadherin and vimentin in ANKRD49-overexpressing cells or control cells.Immunohistochemical method was performed to examine the levels of E-cadherin,α-SMA,Snail,Slug and ZEB1 in lung tissues of nude mice in-oculated with ANKRD49-overexpressing H1299 cells or control cells.RESULTS:Compared with the control group,the ANKRD49 overexpressing cells showed mesenchymal cell morphology(fusiform and less tight connections).RT-qPCR and Western blot results showed that the mRNA and protein levels of mesenchymal markers vimentin and α-SMA in ANKRD49 overexpressing cells were significantly higher than those in cells of control group,while the mRNA and protein levels of epithelial marker E-cadherin were lower than those in cells of control group.Compared with control group,the im-munofluorescence intensity of E-cadherin of H1299 cells decreased in after ANKRD49 overexpression,while that of vimen-tin increased significantly.Snail,Slug and ZEB1 expression were significantly elevated in ANKRD49 overexpressing cells compared with control group.The levels of E-cadherin in lung tissues of nude mice inoculated with ANKRD49-overexpressing H1299 cells declined,while the levels of α-SMA,Snail,Slug and ZEB1 increased compared with those in control mice.CONCLUSION:ANKRD49 promoted EMT of NCI-H1299 cells by increasing the expression of Snail1,Slug and ZEB1 and consequent downreguation of E-cadherin and upregulation of vimentin and α-SMA.
10.Research progress on the application of artificial intelligence in the early diagnosis and treatment of burn diseases
Hailong SI ; Shutian GAO ; Yundou WANG
Chinese Critical Care Medicine 2024;36(8):887-891
Artificial intelligence (AI) technology is advancing rapidly, constantly presenting its application value and broad prospects in the medical field. Especially in the early intervention of burn diseases, the new developments, applications, and challenges of AI technology have a significant impact on the clinical outcomes of burn patients. Based on this, this article reviews the concept, classification, learning style, and application of AI in the early diagnosis and treatment of burn diseases, with a focus on discussing the challenges and suggestions of the application of AI technology in the medical field, in order to provide reference and suggestions for the better application of AI in the early diagnosis and treatment of burn diseases.

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