1.Development and dissemination of precision medicine approaches in gastric cancer management.
Zhemin LI ; Jiafu JI ; Guoxin LI ; Ziyu LI ; Zhaode BU ; Xiangyu GAO ; Di DONG ; Lei TANG ; Xiaofang XING ; Shuqin JIA ; Ting GUO ; Lianhai ZHANG ; Fei SHAN ; Xin JI ; Anqiang WANG
Journal of Peking University(Health Sciences) 2025;57(5):864-867
Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics*
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Humans
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Precision Medicine/methods*
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China
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Immunotherapy/methods*
2.Paclitaxel anti-cancer therapeutics: from discovery to clinical use.
Haizheng YU ; Fen LAN ; Yuan ZHUANG ; Qizhang LI ; Lianqing ZHANG ; Hongchang TIAN ; Xiao BU ; Ruibing CHEN ; Yingying GAO ; Zhuo WANG ; Lei ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):769-789
Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans
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Paclitaxel/pharmacology*
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Antineoplastic Agents, Phytogenic/pharmacology*
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Neoplasms/drug therapy*
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Animals
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Taxus/chemistry*
3.A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance.
Lei SUN ; Arabella H WAN ; Shijia YAN ; Ruonian LIU ; Jiarui LI ; Zhuolong ZHOU ; Ruirui WU ; Dongshi CHEN ; Xianzhang BU ; Jingxing OU ; Kai LI ; Xiongbin LU ; Guohui WAN ; Zunfu KE
Acta Pharmaceutica Sinica B 2024;14(1):223-240
Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.
4.Risk factors for parastomal hernias:a systematic review and meta-analysis
Kai-Lei WANG ; Li-Na MA ; Guang-Bo BU ; Guang-Dong ZHANG ; Hui FAN ; Fei YU ; Heng-Rui DU ; Gang MA
Chinese Journal of Current Advances in General Surgery 2024;27(6):463-470
Objective:To evaluate the risk factors for the formation of parastomal Hernias(PSH)using meta-analysis,and to provide a theoretical basis for the prevention and treatment of PSH.Methods:Case control or Cohort study of PSH risk factors were collected by searching PubMed,CNKI,Wanfang data and other databases.Extract relevant data and perform meta-analysis using RevMan 5.3.Results:The results included a total of 16 studies,with a total sample size of 2411 cases,including 670 in the PSH group and 1741 in the non PSH group.The results showed that advanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,and postoperative Hypoproteinemia could increase the risk of PSH(P<0.05);Smoking,previous ab-dominal surgery history,preoperative radiotherapy/chemotherapy etc.,were not significantly asso-ciated with the occurrence of PSH(P>0.05).Conclusion:The current evidence shows that ad-vanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,postoperative Hypoproteinemia are risk factors for PSH,and extraperitoneal stoma can reduce the occurrence of PSH.
5.Predicting the histological type of thymoma based on CT radiomics nomogram
Qingsong BU ; Haoyu ZHU ; Tao WANG ; Lei HU ; Xiang WANG ; Xiaofeng LIU ; Jiangning DONG ; Xingzhi CHEN ; Shujian WU
Journal of Practical Radiology 2024;40(10):1615-1619
Objective To investigate the value of a nomogram model based on contrast-enhanced CT radiomics in predicting the histological type of thymoma.Methods A total of 154 patients(101 in low-risk group and 53 in high-risk group)with thymoma confirmed by pathology were retrospectively selected.The cases were randomly divided into training set(n=107)and validation set(n=47)at a ratio of 7∶3.The three-dimensional volume of interest(VOI)of the whole lesion on the image from the arterial phase of contrast-enhanced CT was manually delineated,and the radiomics features were extracted.Based on the selected radiomics features,the radiomics model was constructed and the model Radiomics score(Radscore)was calculated.Clinical risk factors were screened to construct a clinical model,and a nomogram model was constructed by fusing Radscore and clinical risk factors.The receiver operating characteristic(ROC)curve,area under the curve(AUC),accuracy,sensitivity and specificity were compared to analyze the predictive efficacy and difference of different models for high-risk and low-risk thymoma.The decision curve and calibration curve were drawn to evaluate the clinical value and fitting performance of the nomogram model.Results Eleven radiomics features were selected to construct the radiomics model,and five clinical risk factors[myasthenia gravis(MG),morphology,border,surrounding tissue invasion and CT value in arterial phase]were used to construct the clinical model.In the training set,the AUC of the nomogram model(0.88)was higher than that of the radiomics model(0.80)and the clinical model(0.79),and the difference was statistically significant(Z=2.233,2.713,P=0.026,0.007,respectively).In the validation set,the AUC of the nomogram model was higher than that of the radiomics and clinical models,but the difference was not statistically significant.The calibration curve showed that the nomogram model had good fitting performance,and the decision curve showed that the nomogram model had high clinical benefit.Conclusion The nomogram model based on contrast-enhanced CT can effectively predict high-risk and low-risk thymoma,which is helpful to guide clinicians to make relevant decisions.
6.Biological characteristics of triple negative breast cancer with low expression of HER2
Jing LIAN ; Ruoqi LI ; Lei YAN ; Peng BU ; Huiwen WANG ; Yanfeng XI
Chinese Journal of Pathology 2024;53(9):898-904
Objective:To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low).Methods:A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups.Results:Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different ( P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group ( P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions:There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.
7.Setup error analysis during proton and heavy ion therapy for head and head neck tumor patients with fixation by thermoplastic film combined with styrofoam
Zhu-Lei LIU ; Rui-Rui BU ; Dan ZHOU ; Yao LI ; Ling-Min WU ; Dong-Peng ZHANG ; Jiang-Bing ZHANG ; Dan YOU
Chinese Medical Equipment Journal 2024;45(7):56-61
Objective To analyze the setup errors during proton and heavy ion therapy for head and head neck tumor patients fixed by thermoplastic film combined with styrofoam.Methods Totally 20 patients undergoing proton and heavy ion therapy at some hospital from January to December 2018 were selected retrospectively,of whom 10 ones had head tumors with clinical targets located in the head and the other 10 cases had head and neck tumors with clinical targets distributed in the head and neck.All the 20 patients were fixed with thermoplastic film combined with styrofoam.The head and neck images of the patients acquired after image guidance were aligned with the CT localization-based digitally reconstructed radiograph images,and the setup errors at six-dimensional directions(left-right translation,head-foot translation,forward-backward translation,isocentric rotation,pitch rotation and transverse-roll rotation)were recorded in the first five and the last five times of radiotherapy treatment.The data were processed by using the SPSS 23.0 statistical software and EXCEL.Results There were no significant differences between the head tumor patients in the setup errors at the six directions during the first and last five times of radiotherapy(P>0.05).The head and neck tumor patients did not have obvious differences in the setup errors at the the directions of left-right translation,forward-backward translation,isocentric rotation and transverse-roll rotation(P>0.05),while did at the directions of head-foot translation and pitch rotation(P<0.05).The head and head neck tumor patients with the fixation by thermoplastic film combined with styrofoam had their setup errors at the six directions meet clinical requirements after calibration by the six-dimensional treatment table.Conclusion The fixation mode by thermoplastic film and styrofoam behaves well to enhance the setup repeatability for head tumor patients at the six-dimensional directions,while not so well for head neck tumor patients at the directions of head-foot translation and pitch rotation.Proper measures have to be taken to decrease the setup errors during proton and heavy ion therapy for head and head neck tumor patients.[Chinese Medical Equipment Journal,2024,45(7):56-61]
8.Effects of acupuncture medication combined on facial function and mimetic muscle strength and motor conduction in patients with peripheral facial palsy
Xiuhuan BU ; Lei WANG ; Tian WANG ; Fuqing ZHANG
Journal of Acupuncture and Tuina Science 2024;22(4):311-319
Objective:To observe the improvement of facial weakness in patients with peripheral facial palsy treated with needling the muscle regions of meridians plus Da Qin Jiao Tang[decoction of Qin Jiao(Radix Gentianae Macrophyllae)],and the effects on facial paralysis injury function and mimetic muscle atrophy and motor conduction. Methods:A total of 120 patients with peripheral facial palsy were randomized into a Chinese medication group and an acupuncture medication combined group by the random number table method,with 60 cases in each group.The Chinese medication group was treated with Da Qin Jiao Tang,and the acupuncture medication combined group was treated with needling the muscle regions of meridians based on oral Da Qin Jiao Tang.After treatment,the clinical efficacy was compared between the two groups.The changes in the facial symptom score,facial muscle thickness,facial muscle strength,facial nerve function,and facial disability index were observed. Results:The total effective rate in the acupuncture medication combined group was 98.3%,which was higher than 85.0%in the Chinese medication group(P<0.05).Each facial symptom score in the acupuncture medication combined group was lower than that in the Chinese medication group(P<0.05).The muscle thickness of the depressor anguli oris,frontalis,and depressor labii inferioris in the acupuncture medication combined group was thicker than that in the Chinese medication group(P<0.05).The scores of physical function and social/behavioral function in the acupuncture medication combined group were lower than those in the Chinese medication group(P<0.05),while the scores of manual muscle test(MMT)and Sunnybrook facial nerve were higher than those in the Chinese medication group(P<0.05).The facial nerve motor latency of the upper lip quadrate muscle,frontalis,and orbicularis oculi in the acupuncture medication combined group was lower than that in the Chinese medication group(P<0.05),while the M-wave amplitude was higher than that in the Chinese medication group(P<0.05). Conclusion:Needling the muscle regions of meridians plus Da Qin Jiao Tang can improve facial muscle strength,mimetic muscle atrophy,facial paralysis function injury,and facial nerve motor conduction in the treatment of peripheral facial palsy and enhance clinical efficacy.
9.Relationship between lower limb muscle strength and walk speed in community dwelling older adults: the chain mediating role of flexibility and dynamic balance
Xiaohuan TAN ; Guiping JIANG ; Xinyi HUANG ; Dandan WANG ; Lei ZHANG ; Qingguo BU ; Xueping WU
Chinese Journal of Rehabilitation Theory and Practice 2023;29(6):646-653
ObjectiveTo investigate the relationship between lower limb muscle strength and walking speed in older adults, and to analyze the mediating role of flexibility and dynamic balance. MethodsFrom November to December, 2021, a total of 155 older adults at the Shanghai Senior Sports and Health Home were included. Their basic health information was collected, and the lower limb muscle strength, flexibility, dynamic balance and walking speed were tested. A mediated effects analysis was conducted. ResultsThere was a pairwise correlation among lower limb muscle strength, flexibility, dynamic balance and walking speed in older adults (r > 0.210, P < 0.01). In the mediated effects model, after controlling for age and gender, lower limb muscle strength did not directly predict walking speed in older adults (β = 0.029, P = 0.699), however, lower limb muscle strength could influence walking speed through the partial mediation of dynamic balance (effect = 0.0130, 95% CI 0.0073~0.0197) and the chain mediation of lower flexibility and dynamic balance (effect = 0.0019, 95% CI 0.0003~0.0043). ConclusionLower limb muscle strength can indirectly affect walking speed in older adults through the mediators of flexibility and dynamic balance, or the dynamic balance alone.
10.Determination of multi-index components and quality evaluation of Dilong formula granules
Lei LI ; Chengzhong ZHANG ; Hanming ZHANG ; Qitao BU ; Lei ZHANG
Journal of Pharmaceutical Practice 2023;41(9):547-551
Objective To establish the method for the simultaneous determination of hypoxanthine, inosine, guanosine and adenosine in Dilong formula granules by HPLC and compare the fingerprints of Dilong formula granules from different manufacturers by HPLC chromatogram. Methods The contents of hypoxanthine, inosine, guanosine and adenosine were determined by Thermo AcclaimTM120C18 column (4.6 mm×250 mm 5 μm). The mobile phase was acetonitrile-water. Gradient elution with flow rate of 0.6 ml/min was used. Column temperature was 25 ℃. Detection wavelength was 254 nm. 10 batches of samples were tested. The HPLC chromatogram were compared and analyzed by using the similarity Evaluation system of chromatographic fingerprint of traditional Chinese Medicine (version 2012.130723). Results The linear ranges for the detection of hypoxanthine, inosine, guanosine and adenosine showed good linear relationships within their own ranges (r≥0.999 9). The average recoveries were 99.20%~102.98% with RSD of 0.26 %~0.71%. The contents of 4 components in 10 batches of samples were 0.740 0~4.457 4 mg/g, 2.132 3~7.805 0 mg/g, 0.325 4~1.596 1 mg/g, 0.537 2~2.222 9 mg/g respectively. The similarity between HPLC chromatogram and control fingerprints of Dilong formula granules from different manufacturers was greater than 0.91. Conclusion The method could be used to determine the contents of hypoxanthine, inosine, guanosine and adenosine in Dilong formula granule. HPLC fingerprints could be used to evaluation the quality in Dilong formula granule. The similarity of HPLC fingerprints from different manufacturer production of Dilong formula granule is high, but 4 contents in composition are difference.

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