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.Effects of methyl oxofulnonone A ameliorates hyperglucose-induced H9c2 cardiomyocyte injury
Ming-hui OUYANG ; Xiao-tong GUO ; Ting LIU ; Li-ying CHENG ; Zi-chang NIU ; Hao-ping MAO
The Chinese Journal of Clinical Pharmacology 2025;41(1):45-49
Objective To investigate the effect and mechanism of methyl oxofulnonone A(META)on high glucose(HG)-induced H9c2 cell injury.Methods H9c2 cells were divided into control group(normal culture),model group(55 mmol·L-1 glucose)and experimental-L,-M,-H groups(55 mmol·L-1 glucose+12.5,25.0,50.0 μmol·L-1 META).Cell viability was detected by cell counting kit-8;intracellular reactive oxygen species(ROS)level was detected by DCFH-DA fluorescent probe;intracellular adenosine triphosphate(ATP)content was detected by luciferase;and autophagy-related protein expression was detected by Western blotting.Results The optical density values of 72-hour cells in the control group,model group and experimental-M,-H groups were 0.91±0.03,0.61±0.01,0.69±0.02 and 0.72±0.03;the ROS levels were(40.75±1.53)%,(43.73±1.30)%,(30.87±1.27)%and(28.28±1.43)%;the ATP contents were(8.16±0.71),(4.03±0.29),(5.29±0.31)and(5.83±0.31)nmol·mg-1;the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06,1.46±0.09,0.98±0.11 and 0.89±0.09;the relative expression levels of ubiquitin-binding protein were 1.05±0.10,0.55±0.13,0.89±0.04 and 0.98±0.04;the ratios of microtubule-associated protein 1 light chain 3 11/Ⅰ protein were 1.09±0.09,1.82±0.05,1.67±0.29 and 1.09±0.15,respectively.Among the above indicators,there were statistically significant differences between the model group and the control and experimental-M,-H groups(P<0.05,P<0.01).Conclusion META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose,ameliorates oxidative stress,protects mitochondrial respiration and inhibits autophagy.
3.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.
4.Effects of methyl oxofulnonone A ameliorates hyperglucose-induced H9c2 cardiomyocyte injury
Ming-hui OUYANG ; Xiao-tong GUO ; Ting LIU ; Li-ying CHENG ; Zi-chang NIU ; Hao-ping MAO
The Chinese Journal of Clinical Pharmacology 2025;41(1):45-49
Objective To investigate the effect and mechanism of methyl oxofulnonone A(META)on high glucose(HG)-induced H9c2 cell injury.Methods H9c2 cells were divided into control group(normal culture),model group(55 mmol·L-1 glucose)and experimental-L,-M,-H groups(55 mmol·L-1 glucose+12.5,25.0,50.0 μmol·L-1 META).Cell viability was detected by cell counting kit-8;intracellular reactive oxygen species(ROS)level was detected by DCFH-DA fluorescent probe;intracellular adenosine triphosphate(ATP)content was detected by luciferase;and autophagy-related protein expression was detected by Western blotting.Results The optical density values of 72-hour cells in the control group,model group and experimental-M,-H groups were 0.91±0.03,0.61±0.01,0.69±0.02 and 0.72±0.03;the ROS levels were(40.75±1.53)%,(43.73±1.30)%,(30.87±1.27)%and(28.28±1.43)%;the ATP contents were(8.16±0.71),(4.03±0.29),(5.29±0.31)and(5.83±0.31)nmol·mg-1;the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06,1.46±0.09,0.98±0.11 and 0.89±0.09;the relative expression levels of ubiquitin-binding protein were 1.05±0.10,0.55±0.13,0.89±0.04 and 0.98±0.04;the ratios of microtubule-associated protein 1 light chain 3 11/Ⅰ protein were 1.09±0.09,1.82±0.05,1.67±0.29 and 1.09±0.15,respectively.Among the above indicators,there were statistically significant differences between the model group and the control and experimental-M,-H groups(P<0.05,P<0.01).Conclusion META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose,ameliorates oxidative stress,protects mitochondrial respiration and inhibits autophagy.
5.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.
6.Effect of subanesthetic dose of esketamine on decreasing nausea and vomiting of carboprost during CESA for caesarean section
Tenghuan WANG ; Dan CHENG ; Yuanyuan MAO ; Huixin LI ; Yuning FAN ; Na XING
The Journal of Practical Medicine 2025;41(1):90-94
Objective To evaluate the efficacy and safety of a subanesthetic dose of esketamine in prevent-ing postoperative nausea and vomiting following carboprost administration during cesarean section.Methods One hundred thirty-five full-term singleton parturients,ASAⅠ-Ⅱ,aged 20-40 years,scheduled for elective cesarean section,were recruited.They were randomly assigned to three groups(n=45):the normal saline group(Group C),the palonosetron group(Group P),and the esketamine group(Group E).All parturients received combined spinal-epidural anesthesia,achieving a sensory level of T5-7.Following umbilical cord clamping,carboprost tromethamine was injected into the uterine body.Concurrently,Group C received intravenous normal saline,Group P received palonosetron,and Group E received esketamine.The incidence of nausea,vomiting,and chest discomfort was recorded from the time of carboprost administration until the parturients left the operating theater.Additionally,mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),and Ramsay sedation scores were mea-sured at six time points:upon entering the room(T0),1 minute before intervention(T1),2 minutes(T2),5 min-utes(T3),15 minutes(T4),and 30 minutes(T5)post-intervention.Maternal satisfaction was evaluated as the parturients left the operating room.Results Compared with group C,the incidence of nausea,vomiting,and chest discomfort in group E was significantly lower(all P<0.05).Additionally,group E showed a significantly lower incidence of nausea and chest discomfort compared to group P(all P<0.05).In terms of maternal satisfaction,group E reported significantly higher levels than both group C(P<0.05)and group P(P<0.05).No significant differences were observed in the incidence of nausea,vomiting,chest discomfort,or satisfaction between the other groups(P>0.05).Conclusion The administration of subanesthetic doses of esketamine significantly decreases the incidence of adverse effects such as nausea,vomiting,and chest tightness that are commonly associated with carboprost tromethamine use during cesarean sections,thereby enhancing patient satisfaction in the perioperative period.
7.Feasibility and exploration of optimal communication models for robot-assisted urological telesurgery: a multicenter, single-arm, retrospective study
Ye WANG ; Taoping SHI ; Sheng TAI ; Sunyi YE ; Yubai ZHANG ; Bingzhang QIAO ; Chenfeng WANG ; Gen CHENG ; Zhi LI ; Qing AI ; Qingbo HUANG ; Baojun WANG ; Qing YUAN ; Junnan XU ; Guojun LIU ; Yu CHEN ; Wuyi ZHAO ; Jianle MAO ; Shiwei LI ; Shuo WANG ; Dan XIA ; Wanhai XU ; Chaozhao LIANG ; Hongzhao LI ; Xin MA ; Xu ZHANG
Chinese Journal of Urology 2025;46(5):331-336
Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter,single-arm,retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients,47 were male(79.7%)and 12 were female(20.3%),with a median age of 63.0(56.0,68.0)years and a body mass index of(24.7 ± 3.0)kg/m 2. Surgical procedures included 32 radical prostatectomies,24 partial nephrectomies,one radical nephrectomy,one adrenalectomy,and one ureteral reconstruction. The perioperative indicators,pathological results and postoperative complications were analyzed. The network monitoring data were collected,and the perioperative data of patients,remote system monitoring data and costs were compared between the two communication modes of optical transport network(OTN)and cloud-connect network(CCN). Results:All 59 remote surgeries were successfully completed,with a mean operative time of(138.0 ± 54.0)minutes,median intraoperative blood loss of 50.0(30.0,100.0)ml and a postoperative hospital stay of 5.0(4.0,6.0)days. No cases required reoperation,Clavien-Dindo grade ≥3 complications,or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing:the shortest latency time(Hefei-Hangzhou,450 km)was(16.59 ± 0.80)ms,while the longest(Harbin-Hangzhou,2 200 km)latency time was(53.31 ± 0.31)ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time[(130.7 ± 70.5)minutes vs.(142.1 ± 42.9)minutes, P = 0.442],postoperative hospitalization[6.0(4.0,8.0)d vs. 5.0(4.0,6.0)d, P = 0.581],or readmission rates(0 vs. 0). However,CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode,with its cost-effectiveness,excellent usability,and multi-point interconnection flexibility,is currently the preferred communication model for telesurgical applications.
8.Multi-system involvement characteristics and influencing factors of disease progression in Kennedy′s disease
Yifan LI ; Fei YANG ; Hongfen WANG ; Zhaohui CHEN ; Li LING ; Hongmei CHENG ; Xusheng HUANG ; Mao LI
Chinese Journal of Internal Medicine 2025;64(9):845-853
Objective:To investigate multi-system involvement in Kennedy′s disease and its association with disease progression.Methods:We retrospectively reviewed the clinical, laboratory, and electrophysiological data from 48 genetically confirmed patients with Kennedy′s disease at the Department of Neurology, First Medical Center of the Chinese PLA General Hospital, between February 2016 and February 2024. The disease progression rate was calculated based on the functional scores at baseline and follow-up. Correlation analyses and multiple linear regression models were employed to assess the relationships among clinical variables and to identify potential predictors of disease progression.Results:The age of muscle weakness onset ranged from 16 to 66 years (mean 42±11 years), with a diagnostic delay of 5.0 (3.0, 9.8) years. Lower limb weakness was the most common initial symptom in 72.9% (35/48) of patients, and 37.5% (18/48) exhibited non-motor manifestations prior to the onset of weakness. Core motor manifestations included bulbar weakness (89.6%, 43/48) and symmetric proximal limb weakness (83.3%, 40/48), frequently accompanied by gynecomastia (74.2%, 23/31) and sexual dysfunction (64.6%, 31/48). The median CAG repeat length was 43 (42, 46), which showed a significant negative correlation with the age at onset ( r=-0.406, P=0.004). Patients with CAG repeats > 43 had a higher prevalence of sexual dysfunction. Elevated serum muscle enzymes were observed in 97.9% (47/48), and abnormal sex hormone levels were detected in 81.2% (39/48). Sensory neuropathy was present in 68.1% (32/47), with CAG repeat length inversely correlating with compound muscle action potential (CMAP) amplitudes in the median ( β=-0.29; t=-2.27, P=0.029) and ulnar ( β=-0.22; t=-2.23, P=0.031) nerves. Low-frequency repetitive nerve stimulation (RNS) revealed a decrement in 43.3% (13/30) of patients, most commonly affecting the axillary and spinal accessory nerves. The disease progression rate was 1.3±0.3 (range: 0.5-2.0). Furthermore, serum creatine kinase-MB (CK-MB) levels were negatively correlated with disease progression rate ( r=-0.303, P=0.036). Conclusions:Kennedy′s disease presents with diverse initial manifestations and frequent multi-system involvement. Non-motor manifestations may precede muscle weakness, serving as valuable clues for early diagnosis. Widespread sex hormone abnormalities (particularly testosterone/luteinizing hormone dysregulation) support the role of androgen insensitivity in disease pathogenesis. Sensory neuropathies are frequent and not length-dependent. The presence of decremental responses on low-frequency RNS suggests neuromuscular junction dysfunction, which may underlie motor impairment in patients with Kennedy′s disease. Finally, serum CK-MB may serve as a potential biomarker for disease progression.
9.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).
10.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.

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