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.Efficacy of Chevron-Akin osteotomy with cannulated compression screw and absorbable screw fixation in the treatment of moderate and severe hallux valgus
Yu ZHANG ; Yong WANG ; Wenju ZHANG ; Shanqiang XU ; Ping LI ; Kaiyuan HE ; Tingting QU
Chinese Journal of Orthopaedics 2025;45(3):151-158
Objective:To compare the clinical efficacy of Chevron-Akin osteotomy with cannulated compression screw and absorbable screw fixation in the treatment of moderate and severe hallux valgus.Methods:The data of 52 patients with moderate to severe hallux valgus treated in Sichuan Provincial Orthopaedic Hospital from January 2020 to December 2022 were retrospectively analyzed. According to the fixation method, they were divided into metal screw group and absorbable screw group. In the metal screw group, there were 25 cases (26 feet), 2 males (2 feet) and 23 females (24 feet), aged 36.7±4.9 years (range, 21-59 years), 12 feet on the left side, 14 feet on the right side, moderate 20 feet and severe 6 feet. There were 27 cases (29 feet) in the absorbable screw group, including 1 male (1 foot) and 26 female (28 feet), aged 34.1±5.5 years (range, 19-56 years), 16 feet on the left side, 13 feet on the right side, moderate 22 feet and severe 7 feet. The healing time and complications of osteotomy were recorded between the two groups, and the hallux valgus angle (HVA), first-second intermetatarsal angle (1-2 IMA), American Orthopaedic Foot and Ankle Society (AOFAS), hallux-metatarsophalangeal-interphalangeal joint score and visual analogue scale (VAS) for pain were compared before and after the operation.Results:All 52 patients were followed up. The follow-up time was 14.0±3.4 months (range, 11-27 months) in the metal screw group and 15.1±2.7 months (range, 13-24 months) in the absorbable screw group. In all patients, the incision healed in one stage, and no endovegetal rejection occurred. The osteotomy healing time was 3.8±0.8 months (range, 2-5 months) in the metal screw group and 3.4±1.1 months (range, 2.5-5 months) in the absorbable screw group, with no statistically significant difference ( t=1.014, P=0.417). In the metal screw group, there were symptoms of medial internal fixation irritation in 2 feet, medial osteophyte or thread knot irritation in 2 feet, and hallux valgus recurrence in 1 foot. The complication rate was 19%(5/26). In the absorbable screw group, medial osteophyte or thread knot stimulated one foot and hallux valgus recurred one foot, and the complication rate was 7%(2/29). The difference in complications between the two groups was statistically significant (χ 2=8.051, P=0.012). At 12 months after operation, for the metal screw group and the absorbable screw group, HVA (13.7°±2.1° and 12.9°±3.8°), 1-2 IMA (7.2°±1.5° and 7.8°±1.2°), AOFAS score (91.4±2.2 and 90.8±3.6 points) and VAS score (1.1±0.3 and 1.3±0.4 points), respectively, were significantly higher than those in the preoperative (HVA: 37.2°± 5.4° and 35.8°±4.7°, 1-2 IMA: 18.3°± 1.8° and 17.9°±1.7°, AOFAS score: 60.4±5.6 and 58.4±7.1 points, VAS: 6.4±0.6 and 6.8±0.4 points) improvement ( P<0.05), while there was no statistically significant difference between the two groups ( P>0.05). The incidence of complications in metal screw group was 19%(5/26), while in absorbable screw group it was 7%(2/29), with a statistically significant difference (χ 2=8.051, P=0.012). Conclusions:Both cannulated compression screw in Chevron-Akin osteotomy and absorbable screw fixation can have a good fixation effect in the treatment of moderate and severe hallux valgus. Absorbable screw fixation has the advantages of low complication rate, less interference with artifacts in later imaging examination and evaluation.
3.Yiqi Wenyang Recipe ameliorates Excessive Mitochondrial Fission and Inflammatory Response in a Mu-rine Model of Allergic Rhinitis through Regulating SITR1
Kaiyuan HE ; Xinchen SUN ; Jiyong WU ; Daonan YAN ; Xuqing CHEN ; Yongjun WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(12):1702-1713
OBJECTIVE To explore the potential mechanism of Yiqi Wenyang Recipe in the intervention of allergic rhinitis(AR)mice.METHODS C57/BL6 mice were randomly divided into blank,model,Yiqi Wenyang Recipe and Yiqi Wenyang Recipe+EX-527[Sirtuin 1(SIRT1)inhibitor]groups.The AR model of mice was established by ovalbumin based challenge sensitization method,each group received corresponding intervention measures.Assessment of behavioral changes in mice;nasal mucosal lesions were observed by HE and toluidine blue staining;the serum levels of interleukin-4(IL-4),interferon-γ(IFN-γ),and immunoglobulin E(IgE)were measured by ELISA;the expression levels of phospho-Janus kinase 2(p-JAK2),phospho-signal transducer and activator of transcription 6(p-STAT6),phospho-dynamin-related protein 1(p-Drp1),SIRT1,peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)in nasal mucosa were determined by Western blot combined with immunofluorescence;reactive oxygen species(ROS)levels were detected by fluorescent probe method;the morphological changes of mitochondria in the microstructure of na-sal mucosa were observed by transmission electron microscopy.RESULTS Compared with the blank group,the frequency of scratch-ing and sneezing in the model group was significantly increased,and a large number of eosinophils and mast cells were found in the na-sal mucosa(P<0.05);compared with the model group,the nasal allergic symptoms and the level of nasal mucosal inflammatory reaction in the Yiqi Wenyang Recipe group were significantly improved(P<0.05);compared with the Yiqi Wenyang Recipe group,the scratch-ing and sneezing of mice in the Yiqi Wenyang Recipe+EX-527 group increased again,and the counts of eosinophils and mast cells in nasal mucosa increased significantly(P<0.05).Compared with the model group,the levels of serum IL-4 and IgE in the Yiqi Wenyang Recipe group decreased,while the level of serum IFN-γ increased(P<0.05);the serum IL-4 and IgE of mice in the Yiqi Wenyang Recipe+ex-527 group were significantly higher than those in the Yiqi Wenyang Recipe group(P<0.05).Western blot and immunofluo-rescence showed that Yiqi Wenyang Recipe could effectively inhibit the increase of p-JAK2,p-STAT6,p-Drp1(ser616)levels induced by ovalbumin sensitization,as well as the decrease of SIRT1 and PGC-1 α expression(P<0.01);however,the intervention of EX-527 significantly blunted the regulatory effect of Yiqi Wenyang Recipe on the above signaling molecules(P<0.05,P<0.01).The results of transmission electron microscopy and fluorescent probe showed that in the model group,a large number of spherical mitochondria were found in the mitochondria of nasal mucosa,and the level of ROS was significantly increased(P<0.01);;the intervention of Yiqi We-nyang recipe effectively restored the long tubular morphology of mitochondria and reduced ROS level(P<0.01);,while the intervention of EX-527 weakened the above improvement effect(P<0.01).CONCLUSION Yiqi Wenyang Recipe can regulate SIRT1 to activate PGC-1α,and then inhibit Drp1 mediated excessive mitochondrial fission to intervene AR;SIRT1 may be one of the important targets of Yiqi Wenyang Recipe in the intervention of AR.
4.Efficacy of Chevron-Akin osteotomy with cannulated compression screw and absorbable screw fixation in the treatment of moderate and severe hallux valgus
Yu ZHANG ; Yong WANG ; Wenju ZHANG ; Shanqiang XU ; Ping LI ; Kaiyuan HE ; Tingting QU
Chinese Journal of Orthopaedics 2025;45(3):151-158
Objective:To compare the clinical efficacy of Chevron-Akin osteotomy with cannulated compression screw and absorbable screw fixation in the treatment of moderate and severe hallux valgus.Methods:The data of 52 patients with moderate to severe hallux valgus treated in Sichuan Provincial Orthopaedic Hospital from January 2020 to December 2022 were retrospectively analyzed. According to the fixation method, they were divided into metal screw group and absorbable screw group. In the metal screw group, there were 25 cases (26 feet), 2 males (2 feet) and 23 females (24 feet), aged 36.7±4.9 years (range, 21-59 years), 12 feet on the left side, 14 feet on the right side, moderate 20 feet and severe 6 feet. There were 27 cases (29 feet) in the absorbable screw group, including 1 male (1 foot) and 26 female (28 feet), aged 34.1±5.5 years (range, 19-56 years), 16 feet on the left side, 13 feet on the right side, moderate 22 feet and severe 7 feet. The healing time and complications of osteotomy were recorded between the two groups, and the hallux valgus angle (HVA), first-second intermetatarsal angle (1-2 IMA), American Orthopaedic Foot and Ankle Society (AOFAS), hallux-metatarsophalangeal-interphalangeal joint score and visual analogue scale (VAS) for pain were compared before and after the operation.Results:All 52 patients were followed up. The follow-up time was 14.0±3.4 months (range, 11-27 months) in the metal screw group and 15.1±2.7 months (range, 13-24 months) in the absorbable screw group. In all patients, the incision healed in one stage, and no endovegetal rejection occurred. The osteotomy healing time was 3.8±0.8 months (range, 2-5 months) in the metal screw group and 3.4±1.1 months (range, 2.5-5 months) in the absorbable screw group, with no statistically significant difference ( t=1.014, P=0.417). In the metal screw group, there were symptoms of medial internal fixation irritation in 2 feet, medial osteophyte or thread knot irritation in 2 feet, and hallux valgus recurrence in 1 foot. The complication rate was 19%(5/26). In the absorbable screw group, medial osteophyte or thread knot stimulated one foot and hallux valgus recurred one foot, and the complication rate was 7%(2/29). The difference in complications between the two groups was statistically significant (χ 2=8.051, P=0.012). At 12 months after operation, for the metal screw group and the absorbable screw group, HVA (13.7°±2.1° and 12.9°±3.8°), 1-2 IMA (7.2°±1.5° and 7.8°±1.2°), AOFAS score (91.4±2.2 and 90.8±3.6 points) and VAS score (1.1±0.3 and 1.3±0.4 points), respectively, were significantly higher than those in the preoperative (HVA: 37.2°± 5.4° and 35.8°±4.7°, 1-2 IMA: 18.3°± 1.8° and 17.9°±1.7°, AOFAS score: 60.4±5.6 and 58.4±7.1 points, VAS: 6.4±0.6 and 6.8±0.4 points) improvement ( P<0.05), while there was no statistically significant difference between the two groups ( P>0.05). The incidence of complications in metal screw group was 19%(5/26), while in absorbable screw group it was 7%(2/29), with a statistically significant difference (χ 2=8.051, P=0.012). Conclusions:Both cannulated compression screw in Chevron-Akin osteotomy and absorbable screw fixation can have a good fixation effect in the treatment of moderate and severe hallux valgus. Absorbable screw fixation has the advantages of low complication rate, less interference with artifacts in later imaging examination and evaluation.
5.Yiqi Wenyang Recipe ameliorates Excessive Mitochondrial Fission and Inflammatory Response in a Mu-rine Model of Allergic Rhinitis through Regulating SITR1
Kaiyuan HE ; Xinchen SUN ; Jiyong WU ; Daonan YAN ; Xuqing CHEN ; Yongjun WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(12):1702-1713
OBJECTIVE To explore the potential mechanism of Yiqi Wenyang Recipe in the intervention of allergic rhinitis(AR)mice.METHODS C57/BL6 mice were randomly divided into blank,model,Yiqi Wenyang Recipe and Yiqi Wenyang Recipe+EX-527[Sirtuin 1(SIRT1)inhibitor]groups.The AR model of mice was established by ovalbumin based challenge sensitization method,each group received corresponding intervention measures.Assessment of behavioral changes in mice;nasal mucosal lesions were observed by HE and toluidine blue staining;the serum levels of interleukin-4(IL-4),interferon-γ(IFN-γ),and immunoglobulin E(IgE)were measured by ELISA;the expression levels of phospho-Janus kinase 2(p-JAK2),phospho-signal transducer and activator of transcription 6(p-STAT6),phospho-dynamin-related protein 1(p-Drp1),SIRT1,peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)in nasal mucosa were determined by Western blot combined with immunofluorescence;reactive oxygen species(ROS)levels were detected by fluorescent probe method;the morphological changes of mitochondria in the microstructure of na-sal mucosa were observed by transmission electron microscopy.RESULTS Compared with the blank group,the frequency of scratch-ing and sneezing in the model group was significantly increased,and a large number of eosinophils and mast cells were found in the na-sal mucosa(P<0.05);compared with the model group,the nasal allergic symptoms and the level of nasal mucosal inflammatory reaction in the Yiqi Wenyang Recipe group were significantly improved(P<0.05);compared with the Yiqi Wenyang Recipe group,the scratch-ing and sneezing of mice in the Yiqi Wenyang Recipe+EX-527 group increased again,and the counts of eosinophils and mast cells in nasal mucosa increased significantly(P<0.05).Compared with the model group,the levels of serum IL-4 and IgE in the Yiqi Wenyang Recipe group decreased,while the level of serum IFN-γ increased(P<0.05);the serum IL-4 and IgE of mice in the Yiqi Wenyang Recipe+ex-527 group were significantly higher than those in the Yiqi Wenyang Recipe group(P<0.05).Western blot and immunofluo-rescence showed that Yiqi Wenyang Recipe could effectively inhibit the increase of p-JAK2,p-STAT6,p-Drp1(ser616)levels induced by ovalbumin sensitization,as well as the decrease of SIRT1 and PGC-1 α expression(P<0.01);however,the intervention of EX-527 significantly blunted the regulatory effect of Yiqi Wenyang Recipe on the above signaling molecules(P<0.05,P<0.01).The results of transmission electron microscopy and fluorescent probe showed that in the model group,a large number of spherical mitochondria were found in the mitochondria of nasal mucosa,and the level of ROS was significantly increased(P<0.01);;the intervention of Yiqi We-nyang recipe effectively restored the long tubular morphology of mitochondria and reduced ROS level(P<0.01);,while the intervention of EX-527 weakened the above improvement effect(P<0.01).CONCLUSION Yiqi Wenyang Recipe can regulate SIRT1 to activate PGC-1α,and then inhibit Drp1 mediated excessive mitochondrial fission to intervene AR;SIRT1 may be one of the important targets of Yiqi Wenyang Recipe in the intervention of AR.
6.New progress in immunotherapy of solid tumors targeting B7-H3
Wu SHUO ; He WEI ; Hu PENGWU ; Hui KAIYUAN ; Jiang YANTING ; Jiang XIAODONG
Chinese Journal of Clinical Oncology 2024;51(24):1291-1295
B7-H3,a member of the B7 family within the immunoglobulin superfamily,is aberrantly expressed in tumor tissues and can be in-duced by immune cells,but is minimally expressed or not expressed in normal tissues.B7-H3 has gained attention for its ability to induce malignant behaviors in tumors and promote cancer progression through various complex pathways.Immunotherapy targeting B7-H3 has shown significant efficacy in clinical trials by modulating the immune system to enhance anti-tumor immune responses.We comprehens-ively summarize the abnormal expression and impact of B7-H3 in various human tumor types,and its role in immunotherapy,highlighting recent advances in clinical research targeting B7-H3.These findings suggest that B7-H3 holds great value as a future target for cancer dia-gnosis and treatment.
7.Study on the Thematic Characteristics of Sleep Disorders Disease Description Texts in Online Health Communities
Panxing PANG ; Cairong HE ; Lei ZHANG ; Jingxin CHEN ; Rongli SHI ; Zhongyue XU ; Kaiyuan WENG
Journal of Medical Informatics 2024;45(10):59-64
Purpose/Significance Disease description texts are analyzed to reach a deeper understanding of the current status of on-line consultations for sleep disorders and the thematic characteristics of users with sleep disorders.Method/Process Data about sleep dis-orders from"haodf.com"website is collected by using a web crawler.Furthermore,the main themes about patients'description are i-dentified by the latent Dirichlet allocation(LDA)model.Result/Conclusion The departments of sleep disorders are more dispersed,and the main treatment is drug therapy.Online consultations could improve 83.2%of patients'condition.The themes of patients's disease descriptions include medication and consultation,external environment,description of symptoms,surrogate questions and causes.It is suggested that the platform and doctors should pay attention to the prognosis of patients'medication and mental health status,and pay at-tention to the popularization of comorbidities.
8.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
9.New progress in immunotherapy of solid tumors targeting B7-H3
Wu SHUO ; He WEI ; Hu PENGWU ; Hui KAIYUAN ; Jiang YANTING ; Jiang XIAODONG
Chinese Journal of Clinical Oncology 2024;51(24):1291-1295
B7-H3,a member of the B7 family within the immunoglobulin superfamily,is aberrantly expressed in tumor tissues and can be in-duced by immune cells,but is minimally expressed or not expressed in normal tissues.B7-H3 has gained attention for its ability to induce malignant behaviors in tumors and promote cancer progression through various complex pathways.Immunotherapy targeting B7-H3 has shown significant efficacy in clinical trials by modulating the immune system to enhance anti-tumor immune responses.We comprehens-ively summarize the abnormal expression and impact of B7-H3 in various human tumor types,and its role in immunotherapy,highlighting recent advances in clinical research targeting B7-H3.These findings suggest that B7-H3 holds great value as a future target for cancer dia-gnosis and treatment.
10.Modern Pharmacological Effect of Zhishi Xiebai Guizhitang: A Review
Zhanzhan HE ; Zhen YANG ; Yujie QI ; Xiangyun CHEN ; Ying GENG ; Zhenhong LIU ; Xuguang TAO ; Jing YU ; Kaiyuan ZHANG ; Ce CHU ; Yulu YUAN ; Wenlai WANG ; Hongxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):254-259
Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine (First Batch), with the effect of activating Yang, dissipating mass, moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain, or even chest pain radiating to the back, wheezing, coughing, shortness of breath, and Qi reversal from the hypochondrium. In modern traditional Chinese medicine, Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system, digestive system, respiratory system and other diseases, among which coronary heart disease, unstable angina pectoris, myocardial infarction, sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent, with the pharmacological effects of improving intravascular environment, myocardial ischemia, myocardial ischemia-reperfusion injury, and myocardial hypoxia, anti-inflammation, plaque stabilisation, etc., and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels, mainly including thromboxane B2 (TXB2), prostacyclin I2(PGI2) and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathways, and ATP-sensitive potassium channels. In addition, the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 (TRPA1) has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases, which is worth of further study.

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