1.Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy.
Jian ZHAO ; Xinyan LV ; Qi LU ; Kaiyuan WANG ; Lili DU ; Xiaoyuan FAN ; Fei SUN ; Fengxiang LIU ; Zhonggui HE ; Hao YE ; Jin SUN
Acta Pharmaceutica Sinica B 2025;15(7):3756-3766
Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.
2.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
3.Predictive value of serum ferritin in early gestation,pre-pregnancy body mass index and gestational age for gestational diabetes mellitus
Meimei LIN ; Hongping ZHANG ; Xiaoyuan HUANG ; Ye WANG ; Yanjun HU
China Modern Doctor 2023;61(36):18-20,24
Objective To investigate the predictive value of serum ferritin(SF)in early gestation,pre-pregnancy body mass index(BMI)and gestational age for gestational diabetes mellitus(GDM).Methods A total of 260 pregnant women who had a routine prenatal examination in Wenzhou People's Hospital were collected from January 2021 to December 2022.Fasting venous blood was collected at the first prenatal examination(within 14 weeks'gestation)for SF.According to the results of 75 grams oral glucose tolerance test(OGTT)between 24 weeks and 28 weeks,they were divided into GDM group(n=62)and normal glucose tolerance(NGT)group(n=198).The general clinical data of the two groups were compared;Multivariate Logistic regression analysis was conducted to determine the independent risk factors of GDM.Receiver operating characteristic(ROC)curve was used to further analyze the predictive value of SF in early gestation,pre-pregnancy BMI and gestational age for GDM.Results Pregnant women in GDM group had higher SF,BMI and gestational age in early pregnancy than those of NGT group(P<0.05).Pre-pregnancy BMI,gestational age and SF increased in early pregnancy were independent risk factors for GDM(P<0.05).The area under the curve(AUC)of SF in early pregnancy as well as pre-pregnancy BMI and gestational age for predicting GDM were 0.612,0.691 and 0.664.The best tangent point values were 94.045ng/ml,21.125kg/m2 and 28.500 years old,respectively.The total AUC of ROC predicted GDM by SF in early gestation,pre-pregnancy BMI and gestational age was 0.750,the sensitivity and specificity were 66.1%and 79.3%,respectively.Conclusion SF in early gestation,pre-pregnancy BMI and gestational age are important factors in the development of GDM,the combined detection of SF in early pregnancy,pre-pregnancy BMI and gestational age has a certain predictive value for GDM.
4.Association between hyperuricemia and incidence risk for cardiometabolic abnormity in children
Peiyu YE ; Xiaoyuan ZHAO ; Yinkun YAN ; Pei XIAO ; Dongqing HOU ; Zhongxin ZHU ; Zhaocang YU ; Hongjian WANG ; Aiyu GAO ; Hong CHENG ; Jie MI
Chinese Journal of Epidemiology 2021;42(3):433-439
Objective:To investigate the relationships between hyperuricemia and the incidence risk for cardiometabolic abnormity in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling at baseline survey. Follow-up investigation was conducted in 2019. Logistic regression model was used to analyze the relationships of uric acid quartiles and change in uric acid levels with incidence risks for cardiometabolic abnormity (hypertension, hyperglycemia and dyslipidemia).Results:A total of 8 807 children (4 376 boys, 4 431 girls) were included in the analysis, the average age of the children was (11.1±3.3) years at baseline survey. The adjusted odds ratios ( ORs) and 95% confidence intervals ( CIs) of incidence risk for hypertension in the third and fourth quartiles of the UA were 1.39 (1.11-1.75) and 1.56 (1.19-1.81), respectively. The ORs and 95% CIs of risk for high LDL-C in the second, third and fourth quartiles were 1.88 (1.16-3.05),1.98 (1.23-3.17) and 2.25 (1.42-3.57). The uric acid level increased by one standard deviation, the risk increased by 17% for hypertension and 27% for high LDL-C. The uric acid level increased by 10 μmol/L, the risk increased by 2.1% for hypertension and 2.9% for high LDL-C. The gender-stratified analysis showed that the similar results. The ORs and 95% CIs were 1.32 (1.09-1.60) and 1.50 (1.05-2.16) for hypertension, 1.90 (1.38-2.60) and 2.96 (1.58-5.52) for high TC, 1.78 (1.26-2.51) and 2.84 (1.60-5.03) for high LDL-C in the groups of newly diagnosed hyperuricemia and persistent hyperuricemia. Conclusions:Higher uric acid level was associated with increased incidence risks for hypertension, abnormal TC and LDL-C. Maintaining optimal uric acid level by children might contribute to the early prevention of cardiovascular diseases.
5.Practice and reflection of "Rain Classroom + QQ live teaching" in the teaching of obstetrics and gynecology
Yunfei YE ; Xiaoyuan WANG ; Wenxia MENG ; Bingbing PAN ; Xiangtao XIE ; Guangli CHEN ; Jinxiu HUANG
Chinese Journal of Medical Education Research 2021;20(11):1303-1307
Taking the Department of Obstetrics and Gynecology as an example, this paper expounds a series of practices of online education, in the process from pre-course training, platform selection, curriculum design, to student evaluation, etc. From that, we can provide a reference for carrying out online teaching in response to the epidemic for clinical medical colleges which have not been exposed to the online course. Furthermore, it is a new attempt to explore a way to make a change of the traditional teaching method and deepen the reform of clinical teaching in our hospital after the epidemic, not only in professional medical education, but also in the popularization of medical knowledge.
6.EIF5A2 Expression in Hepatocellular Carcinoma and Its Relation with Postoperative Survival
Qian YANG ; Dongxue YE ; Yanran MA ; Xiaoyuan HU ; Hong LI ; Xuan ZHOU ; Fenggang XIANG
Cancer Research on Prevention and Treatment 2021;48(6):617-624
Objective To detect the expression of EIF5A2 in hepatocellular carcinoma(HCC) and to explore its relation with clinicopathological characters and prognosis of HCC patients. Methods The expression of EIF5A2 mRNA and protein in 12 pairs of fresh HCC and corresponding non-tumor tissues adjacent to the cancer was examined by qRT-PCR and Western blot. The expression level of EIF5A2 in 284 pairs of HCC and adjacent non-tumor tissues was detected by IHC staining. Then we analyzed between EIF5A2 expression and clinical pathological parameters and prognosis of HCC patients. Results The relative expression levels of EIF5A2 mRNA and protein in fresh HCC tissues were significantly higher than those in the corresponding adjacent non-tumor tissues (
7.Thrombopoietin promotes megakaryopoiesis protecting bone marrow endothelial function in patients undergoing chemotherapy for hematological malignancies.
Xiaoyuan ZENG ; Yingying JIAO ; Zongpeng LI ; Yujiao ZHANG ; Jieyu YE
Journal of Southern Medical University 2020;40(8):1134-1140
OBJECTIVE:
To explore whether thrombopoietin (TPO) can rescue megakaryopoiesis by protecting bone marrowderived endothelial progenitor cells (BM-EPCs) in patients receiving chemotherapy for hematological malignancies.
METHODS:
Bone marrow samples were collected from 23 patients with hematological malignancies 30 days after chemotherapy and from 10 healthy volunteers. BM-EPCs isolated from the samples were identified by staining for CD34, CD309 and CD133, and their proliferation in response to treatment with TPO was assessed using CCK8 assay. DiL-Ac-LDL uptake and FITC-UEA-I binding assay were performed to evaluate the amount of BM-EPCs from the subjects. Tube-formation and migration experiments were used for functional assessment of the BM-EPCs. The BM-EPCs with or without TPO treatment were co-cultured with human megakaryocytes, and the proliferation of the megakaryocytes was detected with flow cytometry.
RESULTS:
Flow cytometry indicated that the TPO-treated cells had high expressions of CD34, CD133, and CD309. CCK8 assay demonstrated that TPO treatment enhanced the proliferation of the BM-EPCs, and the optimal concentration of TPO was 100 μg/L. Double immunofluorescence assay indicated that the number of BM-EPC was significantly higher in TPO-treated group than in the control group. The TPO-treated BM-EPCs exhibited stronger tube-formation and migration abilities ( < 0.05) and more significantly enhanced the proliferation of co-cultured human megakaryocytes than the control cells ( < 0.05).
CONCLUSIONS
TPO can directly stimulate megakaryopoiesis and reduce hemorrhage via protecting the function of BM-EPCs in patients following chemotherapy for hematological malignancies.
Bone Marrow
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Bone Marrow Cells
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Cells, Cultured
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Hematologic Neoplasms
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Humans
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Megakaryocytes
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Thrombopoietin
8.NUP210 and MicroRNA-22 Modulate Fasto Elicit HeLa Cell Cycle Arrest
Qiao GU ; Wenjie HOU ; Huan LIU ; Lijuan SHI ; Zonghao ZHU ; Wenfeng YE ; Xiaoyuan NI
Yonsei Medical Journal 2020;61(5):371-381
Purpose:
Cervical cancer is one of the most fatal diseases among women in under-developed countries. To improve cervical cancertreatment, discovery of new targets is needed. In this study, we investigated the expression of NUP210, miR-22, and Fas in cervicalcancer tissues and their functions in cell cycle regulation.
Materials and Methods:
We detected and compared the expression levels of NUP210, miR-22, and Fas in cervical cancer tissueswith paired normal tissues using immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction.NUP210 was knocked down in HeLa cells via lentivirus, followed by cell cycle and proliferation analysis. Using a luciferase reporterassay, we explored the link between miR-22 and NUP210. We overexpressed miR-22 in HeLa cells and analyzed cell cycle and proliferationfunction. We then overexpressed miR-22 in NUP210 knockdown cells to explore the connection between Fas and miR-22-NUP210 signaling.
Results:
We found that NUP210 was overexpressed in cervical cancer patients. Knocking down NUP210 restored cell apoptosisand proliferation. We confirmed miR-22 as a regulator of NUP210 and verified that miR-22 was inhibited in cervical cancer development.We also found that restoring miR-22 expression could induce cell apoptosis. Finally, we found that miR-22-regulated expressionof NUP210 could alter Fas expression and, in turn, elicit cell cycle arrest and proliferation.
Conclusion
miR-22 in cervical cancer is downregulated, resulting in NUP210 overexpression and inhibition of Fas-induced cellapoptosis.
9.Effects of Hymagic-4D on sensitive skin: a randomized, parallel, self-controlled clinical study
Xiangyue ZHANG ; Congxiu YE ; Yufang LIU ; Haiyan CHEN ; Xiaoyuan XIE ; Wei LAI ; Yue ZHENG
Chinese Journal of Medical Aesthetics and Cosmetology 2020;26(4):325-329
Objective:To evaluate the efficacy and safety of Hymagic-4D multi-essence (miniHA, acetylated sodium hyaluronate, sodium hyaluronate, sodium hyaluronate cross-linked polymer) on sensitive skin.Methods:The clinical trial was conducted from April 2, 2019 to April 30, 2019 in the Cosmetic Dermatology Laboratory of the Third Affiliated Hospital of Sun Yat-Sen University. A total of 33 subjects (average age of 43±9.5) completed the trial. Subjects diagnosed as sensitive skin according to the criteria were enrolled. Hymagic-4D were randomly applied on one side of the face while macromolecular hyaluronic acid was applied on opposite side for 28 days. Skin biophysical properties, lactic test, clinical efficacy and safety were evaluated by the investigators at day 0, day 7, day 14 and day 28. Skin water content, TEWL and a*value were measured at the same time.Results:Dates showed that at day 7, day 14 and day 28, the a* values on Hymagy-4D using side were 8.54±3.08, 8.87 ±3.21 and 8.39±3.21, lower than that on the side of control 9.48±3.09, 9.51±3.30 and 9.03±2.95 ( P<0.01); skin roughness score, dryness score and erythema score on hymagy-4d using side were significantly lower than before ( P<0.01), and significantly lower than that on the control side ( P<0.01). Hydration, TEWL, pH value, L value and total score of lactic acid tingling test which were significantly improved on both facial skin compared to the baseline ( P<0.05) showed no statistical difference between two facial sides ( P>0.05) during 28-day treatment. Conclusions:This study demonstrates that Hymagic-4D has more effective in repairing skin barrier and inhibiting skin inflammation than single component hyaluronic acid on sensitive skin persons.
10.Significance of expression of Myc-induced nuclear antigen 53 in hepatocellular carcinoma and its relationship with patient prognosis
Dongxue YE ; Xuan ZHOU ; Qian YANG ; Xiaoyuan HU ; Hong LI ; Fenggang XIANG
Chinese Journal of Hepatology 2020;28(3):259-265
Objective:To detect the expression of Myc-induced nuclear antigen 53 (Mina53) and liver tissue >5 cm from the edge of the tumor (LTM5), and analyze its relationship with tumorigenesis, clinicopathological characteristics, and patient survival and prognosis in hepatocellular carcinoma (HCC).Methods:The expression levels of Mina53 mRNA and protein in 18 pairs of fresh HCC and LTM5 were assessed by qRT-PCR and Western blot, respectively. The expression of Mina53 in 284 pairs of HCC and LTM5 sample was determined by immunohistochemistry. Paired-sample t-test was used for the comparison of measurement data among groups, and heterogeneity of variance was tested using Wilcoxon rank-sum test. χ2 test was used for the comparison of measurement data among groups. Kaplan-Meier method and log-rank test were used for survival analysis. Cox regression model was used for single factor and multi factor analysis. Results:The relative expression levels of Mina53 mRNA and protein in 18 fresh HCC tissues were significantly higher than those in LTM5 tissues (mRNA: -4.41 ± 1.48 and -5.93 ± 1.65, t = 3.100, P = 0.007; protein: 1.12 ± 0.29 and 0.46 ± 0.21, t = 10.616, P < 0.001). The relative expression level of Mina53 in 284 HCC tissues was higher than that of LTM5 ( z = -18.739, P < 0.001). The expression level of Mina53 was associated with tumor size ( χ2 = 5.474, P = 0.019), vascular invasion ( χ2 = 8.965, P = 0.003), pathological grade ( χ2 = 12.006, P = 0.002), and TNM stage ( χ2 = 16.686, P < 0.001). The overall postoperative survival time and disease-free survival time of patients with high expression of Mina53 (28.5 months and 22.7 months, respectively) were shorter than those with low expression (33.0 months and 31.8 months, respectively) ( P < 0.05) in HCC. Cox multivariate regression analysis showed that Mina53 and multiple tumors were independent prognostic factors affecting the overall postoperative survival time and disease-free survival time of HCC patients ( P < 0.05). Conclusion:Mina53 may play an important role in the occurrence of HCC and participate in the process of tumor growth as well as invasion and metastasis. The high expression of Mina53 signifies that the patient has a poor prognosis and thus can be used as a potential marker for judging the prognosis of HCC patients.

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