1.A cisplatin prodrug-based self-assembling ozone delivery nanosystem sensitizes radiotherapy in triple-negative breast cancer.
Tianyue XU ; Dan ZHENG ; Meixu CHEN ; Linlin SONG ; Zhihui LIU ; Yan CHENG ; Yujie ZHAO ; Liwen HUANG ; Yixuan LI ; Zhankun YANG ; Cong LI ; Biao DONG ; Jing JING ; Hubing SHI
Acta Pharmaceutica Sinica B 2025;15(5):2703-2722
Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.
2.Anti-CD24 antibody-nitric oxide donor conjugates bearing a self-bioorthogonal cleavable linker.
Jianbing WU ; Tianyue CHENG ; Jiajun XIE ; Ziyu QIAN ; Linhua HUANG ; Xun YUAN ; Libang ZHANG ; Shan YANG ; Yihua ZHANG ; Tonglin XU ; Juan ZHANG ; Zhangjian HUANG
Acta Pharmaceutica Sinica B 2025;15(10):5366-5386
Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.
3.Clinical efficacy of simple surgery and surgery combined with glucocorticoids in the treatment of mass type granulomatous mastitis
Tianyue CUI ; Liquan OUYANG ; Shengchu ZHANG
The Journal of Practical Medicine 2024;40(9):1268-1274
Objective To compare and analyze the clinical efficacy,recurrence rate,and breast appear-ance evaluation of simple surgery and surgery combined with glucocorticoids in the treatment of mass type granuloma-tous mastitis.Methods This study retrospectively analyzed 106 patients with nodular granulomatous mastitis who visited the Department of Breast Surgery at Yichang Central People's Hospital from January 2017 to January 2022 as the study subjects.According to the different treatment methods during the visit,patients were divided into Group A with simple surgical treatment(n = 67)and Group B with surgery combined with glucocorticoid treatment(n = 39).The general information and clinical indicators of the two groups of patients were observed and compared.Obtain patient clinical efficacy,time to clinical cure(TTCR),recurrence rate within one year,and breast appearance evaluation through follow-up.Results The prognosis of the follow-up patients after treatment showed that Group B patients had better clinical cure rate and one-year recurrence rate than the simple surgery group(P<0.05).More-over,the difference in breast appearance evaluation between the two groups was statistically significant,with Group B patients having a significantly higher rate of excellent appearance(88.06%)than Group A(92.31%).According to statistics,only 5.13%of patients in Group B experienced gastrointestinal reactions within one year after taking hormone therapy.Conclusions The combination of surgery and glucocorticoids in the treatment of mass type GM can effectively improve the overall clinical treatment effect of patients,reduce the short-term recurrence rate,and have a significant effect on ensuring the integrity of breast appearance.At the same time,low-dose oral steroid drugs have fewer adverse reactions and high safety.
4.Evaluation of GRADE Clinical Research Evidence of Chinese Patent Medicine Combined with Western Medicine in Treatment of Hypertension with Dyslipidemia
Jiaheng WANG ; Yukun LI ; Liangyu CUI ; Yilan ZHENG ; Zhiwei ZHAO ; Cong REN ; Tianyue JING ; Tong YIN ; Liying WANG ; Xuejie HAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):95-105
ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure (CNKI),Wanfang Data Knowledge Service Platform (WF),VIP,SinoMed,Embase,PubMed,Web of Science (WOS),and the Cochrane Library were searched for randomized controlled trials (RCT) of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15,2023. The literature was screened and extracted,and the risk of bias tool 2.0 (RoB2) was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment,Development and Evaluation (GRADE) was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance,Work-related Injury Insurance and Maternity Insurance (2022) and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment,and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate,Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets,Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets,Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan,Wenyading capsules combined with enalapril,and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure (SBP),diastolic blood pressure (DBP),cholesterol (TC),triglyceride (TG),low density lipoprotein cholesterol (LDL-C),and high density lipoprotein cholesterol (HDL-C). There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B,that of DBP as C,and that of total TC,TG,LDL-C,and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules,Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance,and were recommended for 7,6 and 3 times in the guidelines and consensus,respectively. ConclusionCompared with simple medicine treatment,Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid,and shows higher safety. Among them,Yindan Xinnaotong soft capsules,Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However,the quality of evidence in related clinical studies was low. In terms of trial design,large-sample,multi-center,blinded randomized controlled trials based on the consolidated standards of reporting trials (CONSORT) statement are still needed for comprehensive trial designs and reporting,to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine,so as to provide higher quality evidence-based research evidence for clinical decision-making.
5.GRADE Clinical Study Evidence Evaluation and Expert Consensus on Antihypertensive Chinese Patent Medicines Combined with Western Medicines for Treatment of Hypertension
Liangyu CUI ; Yukun LI ; Tianyue JING ; Yu WANG ; Cong REN ; Tong YIN ; Zhiwei ZHAO ; Jiaheng WANG ; Chenge SUN ; Dasheng LIU ; Zhizheng XING ; Xuejie HAN ; Liying WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):106-115
ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension, synthesize and update the evidence, form expert consensus, and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform (WanFang), Vip Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (Sinomed), National Library of Medicine (PubMed), Cochrane Library, Web of Science, and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31, 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment, Development, and Evaluation profiler (GRADEprofiler) 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included, and the results of literature quality evaluation and risk of bias showed that 70.31% (45/64) of the studies indicated some risks, and 29.69% (19/64) indicated high risks. Compared with conventional western medicines, the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure (SBP) and diastolic pressure (DBP), increase the effective rate of antihypertensive, reduce the incidence of adverse reactions, endothelin-1, and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive, and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive, without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive, and Xinmaitong capsules decreased DBP, with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally, four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension, antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety, but they are mostly weak recommendations in terms of efficacy, and more high-quality evidence is needed.
6.Research advances of noninvasive diagnosis of fibrotic non-alcoholic steatohepatitis
Gong FENG ; Rongyao KONG ; Jiaxue WANG ; Tianyue WU ; Xiaohui WU ; Juning WANG ; Qinqin YAN ; Man MI
Journal of Clinical Hepatology 2024;40(11):2293-2299
A subset of patients with non-alcoholic fatty liver disease(NAFLD)can progress to nonalcoholic steatohepatitis(NASH).When NASH reaches a fibrosis degree of F≥2 and a NAS score of≥4,this stage of NASH is referred to as fibrotic NASH,which is a key focus in clinical drug trials.Currently,liver biopsy is the gold standard for assessing the histological changes of the liver,but its clinical application is limited by its invasiveness,and therefore,it is of particular importance to develop noninvasive detection methods for fibrotic NASH.This article summarizes the recent research achievements in novel noninvasive diagnostic methods for fibrotic NASH and elaborates on these new diagnostic methods for predicting fibrotic NASH in terms of current status,challenges faced,and prospects for future development.
7.Research progresses of 68Ga-FAPI PET/CT and PET/MR for diagnosing malignant tumors
Tianyue LI ; Tuo MA ; Xinming ZHAO ; Zhaoqi ZHANG ; Jianfang WANG ; Meng DAI ; Xiujuan ZHAO ; Jingmian ZHANG
Chinese Journal of Medical Imaging Technology 2024;40(11):1794-1797
Fibroblast activation protein inhibitors(FAPI)can specifically bind to fibroblast activation protein,which is highly expressed in tumor stroma,and 68Ga-FAPI do not get involved into the procedure of glucose metabolism in tumor cells.68Ga-FAPI PET/CT and PET/MR can be used for displaying malignant tumors at various sites and play a unique role for diagnosis and differential diagnosis.The research progresses of 68 Ga-FAPI-based PET/CT and PET/MR for diagnosing malignant tumors were reviewed in this article.
8.Multidisciplinary treatment of advanced ALK-positive squamous cell lung carcinoma
Wu TIANYUE ; Guo YAOYANG ; Pan ZHANYU ; Jiang ZHANSHENG
Chinese Journal of Clinical Oncology 2024;51(12):616-621
Anaplastic lymphoma kinase(ALK)fusion is commonly observed in lung adenocarcinoma,with an incidence rate of 5%-7%.Due to the tumor heterogeneity in advanced non-small cell lung cancer,ALK fusion can also occur in lung squamous cell carcinoma.A mul-tidisciplinary team(MDT)combines various professional opinions and evidence-based medical principles to provide personalized treatment recommendations,particularly for complex cases.This study presents the MDT diagnostic and treatment approach for a patient with lung squamous cell carcinoma with an ALK mutation.Following initial diagnosis at stage ⅢB,the patient exhibited rapid disease progression with liver and brain metastases after sequence chemoradiotherapy.After genetic testing revealed ALK fusion,the patient was treated with the ALK inhibitor,lorlatinib,which resulted in tumor regression and a persistent partial response.
9.Structural Design and Analysis of Portable Intelligent Wheelchair for Knee Rehabilitation
Dongmei MA ; Jingyan WANG ; Liming PAN ; Jinshi CHEN ; Tianyue CHU ; Lei HUANG ; Baoyue YIN ; Xin XU
Chinese Journal of Medical Instrumentation 2024;48(4):445-450
Objective In order to address the issues of inconvenience,high medical costs,and lack of universality associated with traditional knee rehabilitation equipment,a portable intelligent wheelchair for knee rehabilitation was designed in this study.Methods Based on the analysis of the knee joint's structure and rehabilitation mechanisms,an electric pushrod-driven rehabilitation institution was developed.A multi-functional module was designed with a modular approach,and the control of the wheelchair body and each functional module was implemented using an STM32 single-chip microcomputer.A three-dimensional model was established using SolidWorks software.In conjunction with Adams and Ansys simulation software,kinematic and static analyses were conducted on the knee joint rehabilitation institution and its core components.A prototype was constructed to verify the equipment's actual performance.Results According to the prototype testing,the actual range of motion for the knee joint swing rod is 15.1°~88.9°,the angular speed of the swing rod ranges from-7.9 to 8.1°/s,the angular acceleration of the swing rod varies from-4.2 to 1.6°/s2,the thrust range of the electric pushrod is-82.6 to 153.1 N,and the maximum displacement of the load pedal is approximately 1.7 mm,with the leg support exhibiting a maximum deformation of about 1.5 mm.Conclusion The intelligent knee joint rehabilitation wheelchair meets the designed functions and its actual performance aligns with the design criteria,thus validating the rationality and feasibility of the structural design.
10.Advances in oxidative stress-related pathways with diagnostic and predictive value in schizophrenia
Tianyue YU ; Qian GUO ; Hao HU ; Yujing SU ; Jianhua CHEN
The Journal of Practical Medicine 2024;40(20):2935-2940
Schizophrenia is a severe mental illness with a significant disease burden.The interaction between oxidative stress and pro-inflammatory factors promotes chronic neuroinflammation and immune damage,leads to dysregulation of dopaminergic and glutamatergic pathways and occurrence of psychotic symptoms and is believed to be closely related to the pathogenesis of schizophrenia.In this paper,we aim to identify biomarkers within the tryptophan kynurenine metabolic pathway,the WNT/β-Catenin pathway and the NF-κB pathway,and dopamine metabolism.These pathways have been extensively studied and are known to be involved in the interac-tion between inflammation and oxidative stress.We will also explore the potential application of related antioxidants in the diagnosis and treatment of schizophrenia,summarizing their current research progress.

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