1.Construction of Saikosaponin D Multifunctional Liposomes and Evaluation of Its Anti-liver Cancer Efficacy and Targeting
Kun YU ; Guochun YANG ; Yaliang JIANG ; Yunting XIAO ; Congxian WANG ; Qionge SUN ; Ziyue LI ; Yikun SHANG ; Yu MAO ; Xin CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):205-216
ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol(Chol) in conventional liposomes with saikosaponin D(SSD) and modifying with poloxamer 407(P407) for co-delivery of curcumin(Cur). The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes, and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes(P407-DiR-Chol-LPs, PDCL) and novel SSD-based liposomes(P407-DiR-SSD-LPs, PDSL) were prepared by the optimized formulation process, and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups, including blank group, model group, free doxorubicin(DOX) group(2 mg·kg-1), free Cur group(8 mg·kg-1), free SSD group(10 mg·kg-1), P407-Cur-Chol-LPs(PCCL) group, P407-SSD-LPs(PSL) group, and P407-Cur-SSD-Lps(PCSL) group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change, organ indices, tumor volume and mass, relative tumor proliferation rate(T/C), and tumor growth inhibition rate(TGI). Histopathological analysis of liver, kidney, and tumor tissues was performed using hematoxylin-eosin(HE) staining. Serum levels of aspartate aminotransferase(AST), alanine aminotransferase (ALT), blood urea nitrogen(BUN), and creatinine(Crea)in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur, SSD, and P407 to soybean phosphatidylcholine(SPC) as 1∶25, 1∶20, and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm, a Zeta potential of -47.25 mV, and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics, demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group(P<0.05, P<0.01). Among the treatment groups, PCSL group showed superior efficacy over free Cur group, free SSD group, PCCL group, and PSL group, with TGI>40% and T/C<60%, indicating pronounced anti-hepatocellular carcinoma effects(P<0.05, P<0.01). Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy, achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma, providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.
2.Functional mechanism of Xihuang pill drug containing serum in intervention of breast cancer cells based on miR21-5p targeting FAM13A gene
Juling CHENG ; Jie MAO ; Hui HE ; Jiaqi PENG ; Yingqian XU ; Huanzi PENG ; Jinquan WANG ; Yunhao LI ; Xiaobing XIE
International Journal of Laboratory Medicine 2025;46(19):2339-2346
Objective To explore the related functional mechanism of Xihuang pill containing serum inter-vention in breast cancer cells based on microRNA(miR)21-5p targeting FAM13A gene.Methods Bioinfor-matics websites was used to predict potential miRNAs of FAM13A gene,double luciferase reporter experi-ments were conducted to verify the binding site relationship between FAM13A and predicted miRNAs.The Xihuang pill containing serum was prepared,and human breast cancer MDA-MB-231 cells were cultured.The proliferation of MDA-MB-231 cells was interfered by the Xihuang pill containing serum with different dilution ratios by CCK-8 test,and the best dilution ratio concentration of Xihuang pill containing serum to inhibit the proliferation of breast cancer cells was selected.Real time fluorescence quantitative PCR(RT-qPCR)was ap-plied to detect the relative expression levels of FAM13A mRNA,as well as the relative expression levels of miR21-5p,in MDA-MB-231 cells after intervention with Xihuang pill containing serum.Cell proliferation(Edu)assay and cell apoptosis detection(TUNEL)assay were used to detect the effects of Xihuang pill con-taining serum intervention on cell proliferation and apoptosis function in MDA-MB-231 cells.The siRNA lentiviral transfection on MDA-MB-231 cells was performed to knock down the FAM13A gene,and Edu assay and TUNEL assay were used to detect changes in proliferation and apoptosis ability of MDA-MB-231 cells af-ter lentiviral transfection.The expression level of miR21-5p in MDA-MB-231 cells after FAM13A gene knock-out was detected by RT-qPCR technology.Results Target Scan online website predicted the potential miR-21-5p binding sequence in the 3'UTR of FAM13A mRNA,and dual luciferase reporter assay confirmed the in-teraction between miR-21-5p and FAM13A.After intervention of MDA-MB-231 cells with Xihuang pill drug containing serum,RT-qPCR results showed that compared with the control group(NC group),the Xihuang pill drug containing serum group(XHW group)downregulated the expression levels of FAM13A mRNA(P<0.05),and upregulated the expression level of miR21-5p(P<0.05).Compared with the NC group,the XWH group showed reduced cell proliferation ability and promoted cell apoptosis.(P<0.05).After silencing the FAM13A gene in MDA-MB-231 cells,compared with the control group(shCtrl group),the shFAM13A group showed a significant decrease in cell proliferation ability and promoted cell apoptosis.The RT-qPCR re-sults showed that compared with the shCtrl group,the expression level of miR21-5p was significantly upregu-lated in the shFAM13A group(P<0.05).Conclusion Xihuang pill could participate in the anti-tumor treat-ment of breast cancer by regulating miR21-5p to affect the expression level of FAM13A gene.
3.A preclinical and first-in-human study of superstable homogeneous radiolipiodol for revolutionizing interventional diagnosis and treatment of hepatocellular carcinoma.
Hu CHEN ; Yongfu XIONG ; Minglei TENG ; Yesen LI ; Deliang ZHANG ; Yongjun REN ; Zheng LI ; Hui LIU ; Xiaofei WEN ; Zhenjie LI ; Yang ZHANG ; Syed Faheem ASKARI RIZVI ; Rongqiang ZHUANG ; Jinxiong HUANG ; Suping LI ; Jingsong MAO ; Hongwei CHENG ; Gang LIU
Acta Pharmaceutica Sinica B 2025;15(10):5022-5035
Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as 131I,177Lu, or 18F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, 18F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).
4.HAN Mingxiang's Experience in Staged and Syndrome-Based Treatment of Chronic Obstructive Pulmonary Disease
Jian DING ; Hui TAO ; Gang CHENG ; Weizhen GUO ; Zegeng LI ; Ya MAO ;
Journal of Traditional Chinese Medicine 2025;66(8):780-785
This paper summarizes Professor HAN Mingxiang's clinical experience in treating chronic obstructive pulmonary disease (COPD). He believes that the key pathomechanism of COPD in the acute exacerbation stage is the invasion of external pathogens triggering latent illness, while lung qi deficiency is the primary mechanism in the stable stage. The core pathological factors throughout disease progression are deficiency, phlegm, and blood stasis. Treatment emphasizes a staged and syndrome-based approach. During the acute exacerbation stage, for wind-cold invading the lung syndrome, the self-formulated Sanzi Wenfei Decoction (三子温肺汤) is used to relieve the exterior, dispel cold, warm the lung, and resolve phlegm. For phlegm-dampness obstructing the lung syndrome, Huatan Jiangqi Fomulation (化痰降气方) is prescribed to warm the lung, transform phlegm, descend qi, and calm wheezing. For phlegm-heat obstructing the lung syndrome, Qingfei Huatan Fomulation (清肺化痰方) is applied to clear heat, resolve phlegm, moisten the lung, and stop coughing. For phlegm and blood stasis interlocking syndrome, Qibai Pingfei Fomulation (芪白平肺方) is used to tonify qi, resolve phlegm, and activate blood circulation to remove stasis. During the stable stage, for lung qi deficiency syndrome, Shenqi Wenfei Decoction (参芪温肺汤) is employed to warm the lung, tonify qi, resolve phlegm, and eliminate turbidity. For lung-spleen qi deficiency syndrome, Shenqi Buzhong Decoction (参芪补中汤) is utilized to strengthen the spleen, tonify qi, and reinforce metal (lung) from earth (spleen). For lung-kidney deficiency syndrome, Shenqi Tiaoshen Fomulation (参芪调肾方) is prescribed to tonify the lung, warm yang, and regulate kidney function to calm wheezing. These strategies provide insights into the traditional Chinese medicine treatment of COPD.
6.Visual analysis of acupuncture and moxibustion treatment for cognitive impairment after stroke based on CiteSpace
Shujin HE ; Yan LI ; Dandan CHENG ; Yiwen LI ; Yan CHEN ; Yuanhong LIU ; Qianru CHEN ; Huiwen MAO
Chinese Journal of General Practitioners 2025;24(7):840-851
Objective:To identify the characteristics of research on scalp acupuncture in the treatment of post-stroke cognitive impairment (PSCI).Methods:This was a bibliometric analysis. We selected relevant studies from both Chinese databases (China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and WanFang Data Knowledge Service Platform) and English databases (Web of Science, PubMed, and Scopus) from their inception to December 2023. The CiteSpace software was used to perform visual-based analyses of publication trends, collaborative networks among countries and institutions, author collaboration networks, and research hotspots.Results:We included 730 Chinese studies and 112 English-language studies. From 2004 to 2023, the number of publications on scalp acupuncture for PSCI showed an increasing trend. All Chinese studies were published in China, mainly by universities, and the institutional collaboration density was low (0.002 9). For English-language studies, China had the most publications (103), followed by the USA (7) and Germany (3). Chinese universities were the main publishing institutions, and the density of inter-institutional collaboration (0.183 3) was higher than that for Chinese literature. The density of the author collaboration network was 0.005 0 for Chinese studies and 0.023 8 for English-language studies. In Chinese studies, the most frequent keywords with a centrality greater than 0.1 were cognitive impairment (248 times), stroke (240 times), needling (162 times), cerebral infarction (82 times), and electroacupuncture (80 times). In English-language studies, these were stroke (40 times), cognitive impairment (32 times), acupuncture (15 times), dementia (15 times), ischemic stroke (10 times), and mechanism (7 times). For Chinese studies, the top 3 clusters focused on clinical studies of the effects of scalp acupuncture on PSCI. In English-language studies, the top 4 clusters mainly involved research on the effects and assessment methods of scalp acupuncture for PSCI. The timeline map of keywords in Chinese studies showed that before 2015, the high-frequency keywords were stroke, cognitive impairment, needling, electroacupuncture, scalp acupuncture, body acupuncture, rehabilitation, moxibustion, and clinical research. From 2015 onwards, keywords such as rat, apoptosis, inflammatory factors, mechanism research, signaling pathways, mice, and animal experiments appeared. The timeline map of keywords in English-language studies showed that before 2013, there were few accumulated keywords. After 2013, high-frequency keywords included "multi-infarction rat""computer-based cognitive training""apoptosis""electroacupuncture""mild cognitive impairment""randomized controlled trial""scalp acupuncture""post-stroke cognitive impairment""stroke rehabilitation""systematic review" and "hippocampal CA1 region". In Chinese studies, keywords with high burst intensity included cerebral infarction, acupuncture therapy, vascular, baihui (GV-20), review, learning and memory, and scalp acupuncture. In English-language studies, these included "multi-infarction rat""mild cognitive impairment""electroacupuncture""post-stroke cognitive impairment"and"systematic review".Conclusions:Research in this field has grown rapidly in recent years. Chinese studies focus mainly on the clinical effects of scalp acupuncture for PSCI, while English-language studies focus more on related mechanisms. Furthermore, both Chinese and English-language studies show good consistency in the focus of experimental research, which mainly focuses on the mechanisms of electroacupuncture in the treatment of PSCI.
7.Research progress of liquid biopsy based on exosomes in tumor diagnosis and treatment
Li MAO ; Yao CHENG ; Qiuqian LIU
International Journal of Laboratory Medicine 2025;46(3):329-334
Exosome-based liquid biopsy technology,with its unique advantages,has demonstrated signifi-cant application potential in the field of tumor diagnosis and treatment.This article aims to outline the basic characteristics of exosomes,their extraction and identification techniques,and focuses on the latest research progress of exosomes in the field of tumor diagnosis and treatment.Current studies indicate that the quantity,size of exosomes,and the biomarkers they carry are of great clinical value in achieving personalized medicine,improving the accuracy of early diagnosis,monitoring treatment effects,and assessing prognosis.These aspects hold profound significance for advancing the development of precision medicine in tumors.Although there are still certain challenges in the standardization of exosome isolation and purification,and the diversity of sample processing,with ongoing research and continuous technological development,exosomes are expected to play an even more important role in the field of tumor diagnosis and treatment.
8.Pathways to regional coordination of medical insurance catalogs:The case of Zhejiang and Shanghai
Rui HUANG ; Li LUO ; Tian-tian ZHANG ; Cheng MAO
Chinese Journal of Health Policy 2025;18(10):19-23
Objective:Under the framework of regional coordinated development,this study aims to construct a generalizable pathway for the coordination of medical insurance catalogs,providing methodological support for dynamic adjustment and fund impact estimation,thereby promoting convergence among regional catalogs.Methods:The medical insurance catalogs of the insured and treatment regions were systematically compared to identify discrepant items.Based on the National Healthcare Security Administration(NHSA)service coding system,a"treatment region-national-insured region"mapping process was established to standardize item correspondence and accurately calculate interregional service volumes.A static scenario simulation was then conducted,using the number of interregional hospitalizations as the core indicator to design multi-threshold inclusion schemes and estimate the resulting impacts on insurance fund expenditures.Results:Using Zhejiang and Shanghai as a case study,344 discrepant items were identified,with therapeutic services being predominant.When the inclusion threshold for interregional hospitalizations increased from 0 to 500 cases,the number of included items decreased from 244 to 36,while the additional insurance expenditure declined from 892 million to 322 million CNY.Conclusion:The proposed coordination pathway demonstrates both scientific rigor and operational feasibility.It is recommended that regions establish a demand-oriented dynamic adjustment mechanism,prioritize the inclusion of high-frequency and high-demand therapeutic items,and improve multi-tier insurance systems to systematically advance the integration of regional medical insurance.
9.Capping versus non-capping decannulation strategy in adult tracheostomized patients:a systematic review
Yiqing GU ; Shupeng CHENG ; Yongqiang LI ; Erli MAO ; Jian'an LI
Chinese Journal of Rehabilitation Theory and Practice 2025;31(6):666-673
Objective To systematically review the advantages and disadvantages of capping and non-capping decannulation strate-gies in adult tracheostomized patients.Methods The PICO framework was developed.Literatures on decannulation measures in adult tracheostomized patients were searched in PubMed,EMbase,Cochrane Library,CNKI,Wanfang Database and SinoMed from establish-ment to February 1st,2025.The non-capping group included patients who underwent decannulation after passing the assessment,without≥24 hours of tube capping.The capping group included patients who underwent≥24 hours of tube occlusion before decannulation.Study types included randomized controlled trial(RCT),cohort studies,and case-control studies.The Newcastle-Ottawa Scale(NOS)was used to evaluate the quality of non-ran-domized studies,while the Cochrane Risk of Bias Tool was applied to assess RCTs.The GRADE was used to evaluate the evidence quality of outcome measures.Relevant information was extracted from the included studies for systematic review.Results A total of six studies were ultimately included,published between 2003 and 2020,originating from Spain,Chi-na,Nepal,and Israel,involving 745 patients.Non-RCT studies scored six to eight points on NOS.Among RCT,one study had a low risk of bias,while another had a moderate risk based on the Cochrane Risk of Bias Tool.Capping strategies included complete capping for 24 to 48 hours before decannulation,stepwise tube downsizing followed by capping,and progressive capping prior to decannulation.Non-capping strategies involved immediate decannulation after passing the assessment or following endoscopic evaluation.Compared with the capping strat-egy,non-capping decannulation significantly reduced decannulation time and incidence of adverse events.No sig-nificant differences were observed in decannulation success rates or pulmonary infection rates between the two strategies.However,findings on pulmonary infections and adverse events were inconsistent across studies.Ac-cording to the GRADE assessment,the strength of evidence was rated as low for decannulation success rate and decannulation time,and very low for incidence of pulmonary infection and adverse events.Conclusion For adult tracheostomized patients,non-capping decannulation strategy appears superior to capping strategy,demonstrating shorter decannulation time and reduced adverse events.No significant difference were observed in decannulation success rates and pulmonary infection rates between the two strategies.
10.Mechanism of tight junctional function injury of testicular Sertoli cells induced by high-fat diet based on NF-κB/NLRP3 signaling pathway
Run-min MAO ; Hai-xia ZHAO ; Hai-li DUAN ; Zi-hui GAO ; Ya-nan QU ; Guo-qing FU ; Jian-min MAO ; Jian-ming SUN ; Chang-cheng ZHANG
Chinese Pharmacological Bulletin 2025;41(11):2134-2142
Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

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