1.Determination method of plasma concentrations of 7 anti-tumor drugs and its application
Jinxiu LYU ; Nan YAN ; Wenjun XU ; Jing ZHAO ; Hua ZHU ; Pengzhou HANG
China Pharmacy 2025;36(4):475-481
OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs (irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate) in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture (1∶ 1, V/V) containing 0.1% formic acid, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the plasma concentration, using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water (containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate) as mobile phase A and acetonitrile (containing 0.1% formic acid) as mobile phase B. The flow rate was 0.6 mL/min, and the column temperature was set at 40 ℃ . The sample size was 10 μL, and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode, and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 (irinotecan), m/z 360.1→244.1 (capecitabine), m/z 876.4→308.0 (paclitaxel), m/z 830.3→304.2 (docetaxel), m/z 372.1→129.1 (tamoxifen), m/z 284.1→242.1 (letrozole), and m/z 455.0→ 308.0 (methotrexate). A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate were 2-1 000 ng/mL (r=0.994 3), 20-10 000 ng/mL (r=0.997 5), 2-1 000 ng/mL (r=0.997 9), 1-500 ng/mL (r=0.995 8), 1-500 ng/mL (r=0.995 2), 1-500 ng/mL (r=0.996 4), 10-5 000 (r=0.997 7), respectively. The quantitative lower limits were 2, 20, 2, 1, 1, 1 and 10 ng/mL; RSDs of intra-assay precision were 0.08%-14.86% (n=6). RSDs of inter-batch precision were 1.51%-11.55% (n=3), and the accuracies were 89.17%-114.93% (n=6). The matrix effects ranged from 89.89%-119.74% (n=6). RSDs of the stability tests were 1.98%-14.88% (n=6). The results of E-mail:hangpengzhou@163.com clinical application showed, the average plasma concentrations of irinotecan, capecitabine, paclitaxel and docetaxel were 704.09, 909.40, 36.45, 150.43 ng/mL, respectively. The values of the coefficient of variation were 25.24%, 62.65%, 122.69%, and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid, and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.
2.Survey on the perception and current status of drug risk management in medical institutions
Xuelin SUN ; Mingqing XING ; Zixuan ZHANG ; Wenjing ZHAO ; Dongfang QIAN ; Yan LIANG ; Li XU ; Pengfei JIN ; Yatong ZHANG
China Pharmacy 2025;36(1):7-12
OBJECTIVE To know about the perception and current status of drug risk management among pharmacists in Chinese medical institutions, providing insights and recommendations for enhancing the drug risk management system in medical institutions. METHODS A questionnaire survey was conducted across 28 provinces, cities, and autonomous regions; stratified radom sampling was employed to study the population of medical workers and pharmaceutical professionals in medical institutions nationwide. The survey included information on the survey population, the current status of drug risk management implementation in medical institutions, the cognition, definition and process of drug risk management related concepts, and the content and mode of drug risk management work in medical institutions. Finally, suggestions were collected from various medical institutions on the system construction of drug risk management. Descriptive statistical analysis was adopted to summarize the obtained data. RESULTS A total of 446 questionnaires were collected in this survey, including 420 valid questionnaires and 26 invalid questionnaires. The questionnaire collection rate was 100%,and the effective rate was 94.17%. 51.19% of the respondents No.2020YFC2009001)。 based their understanding of drug risk management on Management Measures for Adverse Drug Reaction Reports and Monitoring, while 87.38% recognized the need for drug risk management throughout the drug use process. 63.33% of the participants stated that their medical institutions had dedicated positions related to drug risk management, with the highest proportion (72.17%) was in third-grade class A medical institutions. 66.43% reported implementing risk management across all drug use stages. Suggestions for the development of drug risk management systems in medical institutions by the research participants focused on enhancing guiding documents, clarifying concepts, establishing information-sharing mechanisms. CONCLUSIONS The overall awareness of drug risk management in China’s medical institutions is high, with practices in place across various stages in multiple forms. However, there remains a need to strengthen institutional documents, management regulations, system development, and information-sharing mechanisms to improve collaborative governance, improve drug management levels, and ensure patient safety.
3.Exploring the safety and the countermeasures of rational use of Psoraleae Fructus based on the evolution of efficacy/toxicity records in ancient and modern literature
Ying-jie XU ; Xiao-yan ZHAN ; Zhao-fang BAI ; Xiao-he XIAO
Acta Pharmaceutica Sinica 2025;60(2):314-322
Psoraleae Fructus is derived from the dried fruit of the
4.Exploring the mechanism and treatment principles of testicular radiation injury from the perspective of "the struggle between vital qi and pathogen" theory
Xiaoying CHEN ; An WANG ; Yifan YE ; Yan WANG ; Yuankai GAO ; Qing XU ; Shuran WANG ; Zhangdi ZHAO ; Sumin HU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):379-385
Testicular radiation injury is a structural and functional abnormality of the testes caused directly or indirectly by radiation, which disrupts spermatogenesis and compromises male fertility. The development of effective preventive and therapeutic interventions is essential because of the high prevalence of this condition in clinical settings and its profound effect on patients′ reproductive health and overall well-being. The concept of "the struggle between vital qi and pathogen" is first seen in the Treatise on Cold Pathogenic Diseases. It denotes the dynamic struggle between vital and pathogenic qi. The occurrence, development, and sequelae of all diseases reflect this ongoing conflict. In this context, this study defines the "vital qi" of the testis as its capacity to generate and preserve the essence of reproduction and to resist damage. The pathogenic qi associated with testicular radiation injury is categorized into two types: ionizing poison and retaining evil. The pathogenesis of testicular radiation damage is delineated into three stages by integrating the characteristics of vital and pathogenic qi: the injury, adhesion, and recovery phases. Based on the theoretical framework advanced by this study, the therapeutic approach for testicular radiation injury should adhere to the fundamental principle of strengthening vital qi and eliminating pathogenic factors. Although the primary focus of treatment should be on strengthening vital qi, it should also be complemented by strategies to eliminate pathogenic influences. This paper aims to provide a novel perspective and strategic approach to the traditional Chinese medicine diagnosis, prevention, and treatment of testicular radiation injury. By elucidating the process of testicular radiation injury and its corresponding treatment principles, it seeks to offer valuable insights for clinical practice.
5.Biocompatibility of poly(vinylidene fluoride)piezoelectric bionic periosteum prepared by electrospinning
Shuai ZHAO ; Dongyao LI ; Suiyan WEI ; Yijing CAO ; Yan XU ; Guoqiang XU
Chinese Journal of Tissue Engineering Research 2025;29(4):730-737
BACKGROUND:Our previous studies have found that poly(vinylidene fluoride)bionic periosteum prepared by electrospinning has good cytocompatibility,but its biocompatibility is unknown. OBJECTIVE:To evaluate the biocompatibility of poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+. METHODS:Poly(vinylidene fluoride),poly(vinylidene fluoride)bionic periosteum doped with 1%Zn2+,doped with 1%Mg2+,and doped with 1%(Zn2++Mg2+)were prepared by electrospinning to make bionic periosteum extract.SD rats were selected as the experimental subjects for hemolysis test,short-term systemic toxicity test,and heat source test.Guinea pigs were selected as the experimental subjects for skin sensitization test.The biocompatibility of bionic periosteum of four groups was tested. RESULTS AND CONCLUSION:(1)The hemolysis test results showed that the hemolysis rates of 1%Zn2+poly(vinylidene fluoride),1%Mg2+poly(vinylidene fluoride),1%Zn2++1%Mg2+poly(vinylidene fluoride)bionic periosteum and poly(vinylidene fluoride)extract were(0.130±0.013)%,(0.149±0.020)%,(0.466±0.018)%,and(0.037±0.018)%,respectively,which met the hemocompatibility standard of biomaterials.(2)The results of short-term systemic toxicity test showed that the four groups of bionic periosteal extract had no toxic signs such as body mass reduction,food intake changes,and dyspnea in SD rats,and had no toxic effects on major organs of rats.(3)Heat source test results showed that after intervention with poly(vinylidene fluoride)bionic periosteum doped with 1%Zn2+,doped with 1%Mg2+,and doped with 1%(Zn2++Mg2+),and poly(vinylidene fluoride)bionic periosteum extract,the elevated body temperature values of SD rats were(0.133±0.058),(0.100±0.010),(0.300±0.010),and(0.300±0.017)℃respectively.All were less than 0.6 ℃and the total temperature increase was less than 1.4 ℃.(4)The results of skin sensitization test showed that no erythema or edema was observed under the skin of guinea pigs after the intervention of bionic periosteum extract of four groups.(5)The results showed that poly(vinylidene fluoride)and poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+had good biocompatibility.
6.Mechanism of Quanduzhong Capsules in treating knee osteoarthritis from perspective of spatial heterogeneity.
Zhao-Chen MA ; Zi-Qing XIAO ; Chu ZHANG ; Yu-Dong LIU ; Ming-Zhu XU ; Xiao-Feng LI ; Zhi-Ping WU ; Wei-Jie LI ; Yi-Xin YANG ; Na LIN ; Yan-Qiong ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2209-2216
This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals
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Osteoarthritis, Knee/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Rats, Sprague-Dawley
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Rats
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Male
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Humans
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Capsules
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Female
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Disease Models, Animal
7.A new amide alkaloid from Cannabis Fructus.
Rui-Wen XU ; Yong-Zhuo ZHAO ; Yu-Guo MA ; Hui LIU ; Yan-Jun SUN ; Wei-Sheng FENG ; Hui CHEN
China Journal of Chinese Materia Medica 2025;50(11):3043-3048
Eight amide alkaloids(1-8) were isolated from the 70% ethanol extract of Cannabis Fructus using silica gel column chromatography, MCI column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). Their structures were identified as hempspiramide A(1), N-[(4-hydroxyphenyl)ethyl]formamide(2), N-acetyltyramide(3), N-trans-p-coumaroyltyramine(4), N-trans-caffeoyltyramine(5), N-trans-feruloyltyramine(6), N-cis-p-coumaroyltyramine(7), N-cis-feruloyltyramine(8) by using spectroscopic methods such as NMR and MS. Among these compounds, compound 1 was a new amide alkaloid, while compounds 2 and 3 were isolated from Cannabis Fructus for the first time. Some of the isolates were assayed for their α-glucosidase inhibitory activity. Compounds 5-7 displayed significant inhibitory activity against α-glucosidase with IC_(50) values ranging from 1.07 to 4.63 μmol·L~(-1).
Cannabis/chemistry*
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Alkaloids/pharmacology*
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Amides/isolation & purification*
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Drugs, Chinese Herbal/isolation & purification*
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Fruit/chemistry*
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Molecular Structure
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alpha-Glucosidases/chemistry*
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Chromatography, High Pressure Liquid
8.Rapid characterization and identification of non-volatile components in Rhododendron tomentosum by UHPLC-Q-TOF-MS method.
Su-Ping XIAO ; Long-Mei LI ; Bin XIE ; Hong LIANG ; Qiong YIN ; Jian-Hui LI ; Jie DU ; Ji-Yong WANG ; Run-Huai ZHAO ; Yan-Qin XU ; Yun-Bo SUN ; Zong-Yuan LU ; Peng-Fei TU
China Journal of Chinese Materia Medica 2025;50(11):3054-3069
This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Drugs, Chinese Herbal/chemistry*
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Mass Spectrometry/methods*
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Plant Leaves/chemistry*
9.Bacteroi des fragilis-derived succinic acid promotes the degradation of uric acid by inhibiting hepatic AMPD2: Insight into how plant-based berberine ameliorates hyperuricemia.
Libin PAN ; Ru FENG ; Jiachun HU ; Hang YU ; Qian TONG ; Xinyu YANG ; Jianye SONG ; Hui XU ; Mengliang YE ; Zhengwei ZHANG ; Jie FU ; Haojian ZHANG ; Jinyue LU ; Zhao ZHAI ; Jingyue WANG ; Yi ZHAO ; Hengtong ZUO ; Xiang HUI ; Jiandong JIANG ; Yan WANG
Acta Pharmaceutica Sinica B 2025;15(10):5244-5260
In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.
10.Predicting Postoperative Progression of Ossification of the Posterior Longitudinal Ligament in the Cervical Spine Using Interpretable Radiomics Models
Siyuan QIN ; Ruomu QU ; Ke LIU ; Ruixin YAN ; Weili ZHAO ; Jun XU ; Enlong ZHANG ; Feifei ZHOU ; Ning LANG
Neurospine 2025;22(1):144-156
Objective:
This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery.
Methods:
This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression.
Results:
Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability.
Conclusion
Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.


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