3.Development of oral preparations of poorly soluble drugs based on polymer supersaturated self-nanoemulsifying drug delivery technology.
Xu-Long CHEN ; Jiang-Wen SHEN ; Wei-Wei ZHA ; Jian-Yun YI ; Lin LI ; Zhang-Ting LAI ; Zheng-Gen LIAO ; Ye ZHU ; Yue-Er CHENG ; Cheng LI
China Journal of Chinese Materia Medica 2025;50(16):4471-4482
Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility
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Administration, Oral
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Polymers/chemistry*
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Drug Delivery Systems/methods*
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Humans
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Emulsions/chemistry*
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Biological Availability
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Animals
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Pharmaceutical Preparations/administration & dosage*
4.Clinical guidelines for the diagnosis and treatment of lung cancer complicated with tuberculosis in China (2025 edition)
Chang CHEN ; Yayi HE ; Ying HU ; Jie ZHANG ; Shanhao CHEN ; Wenwen SUN ; Shaohua MA ; Gen LIN ; Feng LI ; Liang LI ; Lunxu LIU ; Xiuyi ZHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1521-1539
China is facing the double burden of high incidence of lung cancer and tuberculosis epidemic. Lung cancer combined with tuberculosis has a high incidence and complexity in clinical practice. High-risk groups include immunocompromised people, long-term smokers and people with a history of tuberculosis. The coexistence of the two diseases not only increases the difficulty of diagnosis and treatment decision-making, but also increases the risk of treatment-related adverse reactions and drug interactions. The guideline was developed by Committee of Integrated Rehabilitation for Lung Cancer, Chinese Anti-Cancer Association; Chinese and Western Integrated Lung Cancer Committee of Chinese Anti-Cancer Association; Society of Tuberculosis, Chinese Medical Association, aiming to standardize the diagnosis and treatment of lung cancer complicated with pulmonary tuberculosis. The guideline emphasizes the core position of combined diagnosis of multimodal imaging, etiology and pathology. It is proposed that anti-tuberculosis and anti-tumor treatment should be coordinated under the framework of multidisciplinary team, and drug interactions and timing optimization should be paid attention to. For surgical treatment, minimally invasive resection combined with systematic lymph node dissection is recommended after infection control. Systemic therapy requires individualized risk stratification and dynamic monitoring of efficacy and adverse reactions. Based on evidence-based medicine and Chinese clinical practice, combined with the accessibility of drugs and technologies, this guideline proposes a whole-process management pathway covering screening, diagnosis, treatment and follow-up, in order to improve the prognosis and quality of life of patients.
5.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
6.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.
7.Multi-omics prognostic modeling of locoregional recurrence after radiotherapy for patients with locoregionally advanced hypopharyngeal squamous cell carcinoma
Nan ZHANG ; Gen YANG ; Qijian LU ; Hongjia LIU ; Dan ZHAO ; Chen LIN ; Tian LI ; Yibao ZHANG
Chinese Journal of Radiological Medicine and Protection 2025;45(9):876-883
Objective:To explore the value of an integrated modeling approach combining radiomics, dosiomics, and clinical factors in the prediction of the locoregional recurrence (LRR) risk after radiotherapy for patients with locoregionally advanced hypopharyngeal squamous cell carcinoma (HPSCC), in order to provide supplementary clinical evidence and decision-making basis for personalized treatment for this rare disease characterized by low incidence and poor prognosis.Methods:The clinical images and pathological data were retrospectively enrolled from 76 HPSCC patients treated at the Peking University Cancer Hospital from October 2011 to July 2020. The planning gross tumor volumes (PGTVs) were taken as the volumes of interest (VOIs). A total of 1 316 radiomic and dosiomic features were extracted from the planning CT and dose distribution images. After stability testing, feature dimensionality reduction was achieved using least absolute shrinkage and selection operator (LASSO) regression and principal component analysis (PCA), with radiomic principal components (RPCs) and dosiomic principal components (DPCs) obtained, respectively. Using various combinations of RPCs, DPCs, and clinical variables as predictors, multivariate Cox regression models were developed after 5-fold cross-validation 100 times. The model performance was evaluated based on the Akaike information criterion (AIC) and concordance index (C-index).Results:Using two RPCs and three DPCs selected, dosiomics and radiomic Cox proportional hazards models were constructed, with C-index values of 0.781 and 0.778 and AIC values of 94.44 and 92.27, respectively. The result indicated that one RPC and three DPCs showed significant associations in Cox regression ( P < 0.05). Other prediction models were established by integrating the clinical data of patients with radiomic features, dosiomic features, or both. The prediction result demonstrated that compared to models based on individual factors or dual components, the multi-omics model yielded the highest prediction accuracy (C-index: 0.823, AIC: 84.94). Conclusions:Integrated models that combine radiomic features, dosiomic features, and clinical factors demonstrate great potential for enhancing the accuracy of LRR risk prediction. These models are expected to provide decision-making support for devising personalized treatment strategies and ultimately improve the prognosis of HPSCC patients.
8.Efficacy of modified pelvic floor reconstruction in non-nerve-sparing robot-assisted radical prostatectomy
Xuexing FAN ; Gen LI ; Jincheng LI ; Jiasong LI ; Yuhao YU ; Pugui LI ; Xiaopeng CHEN ; Zhiguo LU ; Geng ZHANG ; Yong WANG
Journal of Modern Urology 2025;30(12):1038-1042,1063
Objective To evaluate the efficacy and safety of modified pelvic floor reconstruction in non-nerve-sparing robot-assisted radical prostatectomy (NNS RARP) for improving postoperative urinary control. Methods A retrospective analysis was conducted on the clinical data of 79 prostate cancer patients who underwent NNS RARP at Tangdu Hospital during Jan.2020 and Dec.2023, including 29 in the reconstruction group, and 50 in the non-reconstruction group. The baseline characteristics including age, body mass index, prostate-specific antigen (PSA) level, clinical stage, prostate volume, and biopsy Gleason score, and perioperative indexes including operation time, intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins were compared between the two groups. Additionally, urinary continence function was assessed before operation and 1,3,6, and 12 months after operation using the international consultation on incontinence questionnaire-short form (ICIQ-SF) and the incontinence quality of life questionnaire score (I-QoL). Results No statistically significant differences were observed in the baseline characteristics between the two groups (P>0.05). The operation time was significantly longer in the reconstruction group than in the non-reconstruction group [ (110.24±15.08) min vs. (101.80±9.89) min, P=0.010]. There were no significant differences in intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins between the two groups (P>0.05). The reconstruction group demonstrated significantly lower ICIQ-SF scores at 1 month [ (10.17±2.16) vs. (11.56±1.66), P=0.002],3 months [ (7.62±1.29) vs. (9.52±1.80), P<0.001], and 6 months postoperatively [ (4.93±1.22) vs. (6.18± 1.67), P=0.001]compared to the non-reconstruction group (adjusted P<0.0125). Conversely, the I-QoL scores were significantly higher in the reconstruction group at 1 month [ (73.32±10.30) vs. (63.88±9.55), P<0.001]and 3 months postoperatively [ (78.91±4.82) vs. (75.66±5.17), P=0.007] (adjusted P<0.0125). However, no significant differences were found in ICIQ-SF or I-QoL scores between the two groups preoperatively and 12 months postoperatively (adjusted P>0.0125). Conclusion The application of modified pelvic floor reconstruction technique in NNS RARP is safe and feasible. Although it slightly prolongs the operation time, it does not increase surgical risks; instead, it effectively promotes early recovery of postoperative urinary continence, thereby significantly enhancing patients'quality of life.
9.Predicting the surgical difficulty,complications and prognosis of kidney tumors based on anatomical features:advances in renal tumor scoring systems
Gen LI ; Yuhao YU ; Xuexing FAN ; Jincheng LI ; Jiasong LI ; Pugui LI ; Xiaopen CHEN ; He WANG ; Geng ZHANG ; Yong WANG
Journal of Modern Urology 2025;30(4):355-363
Renal tumor scoring systems can describe the anatomical characteristics of renal tumors. It is an important standard to evaluate the surgical complexity and to evaluate the surgical complexity and feasibility of partial nephrectomy. Scholars at home and abroad have established various scoring systems based on different anatomical parameters,such as R.E.N.A.L.,PADUA,C-Index,which are used to guide the clinical selection of surgical modalities,and predict perioperative complications and prognosis. In this paper,various scoring systems are grouped into three major categories according to their functions:prediction of surgical complexity,prediction of complications,and prediction of prognosis. The contents,characteristics and clinical application value of various renal tumor scoring systems are introduced in detail to guide urologists,enhance their surgical decision-making ability,and improve the clinical outcomes.

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