1.Advances in the application of physiologically-based pharmacokinetic model in EGFR-TKI precision therapy
Yingying YANG ; Jiaqi SHAO ; Qiulin XIANG ; Guoxing LI ; Xian YU
China Pharmacy 2025;36(8):1013-1018
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) represent a class of small-molecule targeted therapeutics for oncology treatment, and serve as first-line therapy for advanced non-small cell lung cancer (NSCLC) with EGFR- sensitive mutations, with representative agents including gefitinib, dacomitinib, and osimertinib. In clinical practice, dose adjustment of EGFR-TKI may be required for cancer patients under special circumstances such as drug combinations or hepatic/ renal impairment. Physiologically-based pharmacokinetic (PBPK) model, capable of predicting pharmacokinetic (PK) processes in humans, has emerged as a vital tool for clinical dose optimization. This article sorts the modeling methodologies, workflows, and commonly used software tools for PBPK model, and summarizes the current applications of PBPK model in EGFR-TKI precision therapy as of June 30, 2024. Findings demonstrate that PBPK modeling methods commonly employ the “bottom-up” approach and the middle-out approach. The process typically involves four steps: parameter collection, compartment selection, model validation, and model application. Commonly used software for modeling includes Simcyp, GastroPlus, and open-source software such as PK- Sim. PBPK model can be utilized for predicting drug-drug interactions of EGFR-TKI co-administered with metabolic enzyme inducers or inhibitors, acid-suppressive drugs, or traditional Chinese and Western medicines. It can also adjust dosages in conjunction with genomics, predict PK processes in special populations (such as patients with liver or kidney dysfunction, pediatric patients), evaluate the efficacy and safety of drugs, and extrapolate PK predictions from animal models to humans.
2.Comparison of the value of three different methods for diagnosing TBSRTC Ⅲ-Ⅴ thyroid nodules individually and in combination
Chunhui SHAO ; Junzhi ZHAO ; Ran XIANG
Chinese Journal of Primary Medicine and Pharmacy 2024;31(6):811-816
Objective:To investigate the value of the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS), real-time ultrasound elastography (RTE), and contrast-enhanced ultrasound (CEUS), individually and in combination, in the diagnosis of TBSRTC Ⅲ-Ⅴ thyroid nodules.Methods:A retrospective analysis was performed on 106 patients with TBSRTC Ⅲ-Ⅴ thyroid nodules who were pathologically diagnosed by fine needle aspiration cytology at Bao Ji People's Hospital between February 2022 and December 2023. All patients were assessed using ACR TI-RADS grading, RTE, and CEUS, with postoperative pathological diagnosis serving as the gold standard. The diagnostic effectiveness of ACR TI-RADS, RTE, and CEUS, individually and in combination, for TBSRTC Ⅲ-Ⅴ thyroid nodules was analyzed using the receiver operating characteristic (ROC) curve.Results:There were statistically significant differences in nodule size, blood supply, and proportion of TBSRTC Ⅲ-Ⅴ nodule between the two groups ( χ2 = 4.67, 42.56, 26.09, all P < 0.05), while there was no statistical significance in other general data (all P > 0.05). Of the 106 patients with TBSRTC Ⅲ-Ⅴ nodules, 69 patients were diagnosed with malignant nodules and 37 with benign nodules. The area under the curve (95% CI) of ACR-TIRADS, RTE, and CEUS in identifying malignant nodules were 0.860 [95% CI (0.779-0.920)], 0.712 [95% CI (0.616-0.796)], and 0.788 [95% CI (0.698-0.862)], respectively, with sensitivities of 85.51%, 66.67%, and 73.91%, respectively and specificities of 86.49%, 75.68%, and 83.78%, respectively. The Youden indices were 0.719, 0.423, and 0.577, respectively. Among the three diagnostic methods, ACR TI-RADS had the highest diagnostic efficiency, while RTE had the lowest. Pairwise comparisons in ROC analysis revealed statistically significant differences between ACR TI-RADS and RTE, ACR TI-RADS and CEUS, as well as RTE and CEUS ( Z = 4.22, 3.02, 2.78, all P < 0.05). The ACR TI-RADS + RTE + CEUS combination had the highest sensitivity, specificity, Youden index, and AUC (95% CI) values: 94.20%, 89.19%, 0.834, and 0.917 (95% CI: 0.847-0.962). The RTE + CEUS combination had the lowest values: 76.81%, 78.38%, 0.552, and 0.776 (95% CI: 0.685-0.851). The pairwise comparison results in the ROC curve revealed that significant differences were observed between ACR TI-RADS + RTE and RTE + CEUS, ACR TI-RADS + RTE and ACR TI-RADS + RTE + CEUS, ACR TI-RADS + CEUS and ACR TI-RADS + RTE + CEUS, RTE + CEUS and ACR TI-RADS + RTE + CEUS, and ACR TI-RADS + CEUS and RTE + CEUS ( Z = 3.13, 2.40, 2.16, 4.07, 3.32, all P < 0.05). However, there was no significant difference between ACR TI-RADS + RTE and ACR TI-RADS + CEUS in ROC analysis ( Z = 0.06, P > 0.05). Conclusion:The combined utilization of ACR TI-RADS, RTE, and CEUS offers enhanced information on thyroid nodules, encompassing malignant risk stratification, nodular elasticity, and contrast agent perfusion, thereby aiding in improving the diagnostic precision of TBSRTC Ⅲ-Ⅴ malignant nodules.
3.Influencing factors of bone nonunion after intramedullary needle operation for tibial fracture
Shao-Wei CHEN ; Wen-Bo LI ; Jie SHI ; Wei-Duo YANG ; Yu-Xiang ZHANG ; Fu-Hui WANG ; Qiu-Ming GAO
Journal of Regional Anatomy and Operative Surgery 2024;33(10):927-930
Intramedullary needle(IMN)has the advantages of high healing rate and low incidence of complications in treatment of tibial fracture,and has become one of the most commonly used fixation methods for the treatment of tibial fracture.However,due to the patient's own factors,fracture location and fracture type,infection and surgical treatment,bone nonunion after IMN still occurs in clinic.Bone nonunion leads to the increase of medical cost and prolonged the hospitalization time of patients,which causes great pain to patients,and also brings great challenges to the treatment of orthopedic surgeons.Therefore,this paper reviews the influencing factors of bone nonunion after IMN for tibial fracture,in order to provide reference for clinical treatment.
4.Investigation of tick species and potential pathogenic ricks in certain areas of Wuwei City,Gansu Province
Rui-Shan LI ; Zhen HE ; Xiang YUAN ; Shi-Wei SUN ; Yi-Wen LIU ; Wen-Kai ZHANG ; Lin ZHANG ; Yu-Hua WANG ; Zhen-Hua LU ; Zhao-Hua JI ; Zhong-Jun SHAO
Chinese Journal of Zoonoses 2024;40(4):328-333
To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.
5.Clinical characteristics of myeloid tumors combined with the proliferation of large granular lymphocytes
Chenxiao DU ; Guangpeng XIANG ; Lan PENG ; Xiangyao XIAO ; Guangshuai TENG ; Yuhui ZHANG ; Yan WANG ; Yifan DUAN ; Zonghong SHAO ; Jie BAI
Chinese Journal of Hematology 2024;45(4):396-400
Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.
6.Compliance of residents with repeated screening for colorectal cancer in Jiading District, Shanghai
Dan CHEN ; Yawei WANG ; Fang HUANG ; Yifan XU ; Fang XIANG ; Yiying ZHANG ; Na WANG ; Yueqin SHAO
Shanghai Journal of Preventive Medicine 2024;36(7):706-711
ObjectiveTo explore the compliance related factors of repeated screening for colorectal cancer in Jiading District, and to provide a scientific basis for the prevention and control of colorectal cancer. MethodsBased on the natural population cohort in Jiading District, and the screening situation in 2017‒2019 and 2020‒2022, the study subjects were divided into the groups of never participating in screening and participating in screening. Subjects in the participating group were further divided into participating in one round of screening or having repeated screening. SPSS 21.0 software was used to analyze the demographic characteristics of each group. χ2 test or Fisher precise probability test were used to conduct univariate analysis of the factors such as gender, age, education level, marital status, retirement status, and type of medical insurance. Factors with the significant difference (P<0.05) were selected for inclusion in multivariate analysis, and factors related to compliance with repeated screening were analyzed by multivariate logistic regression. ResultsA total of 8 179 subjects were included in the study, including 3 323 males (40.6%) and 4 856 females (59.4%). The average age of the subjects was (61.26±6.06) years old. A total of2 652 (32.4%) had educated in primary school or below, 4 242 (51.9%) in secondary school, and 1 285 (15.7%) in higher secondary school. Mostly, 7 579 (92.7%) were married. Among the participants, 4 062 people had never participated in screening, 4 117 people had participated in screening, and 1 485 of them had repeated screening, with a repeated screening rate of 18.2%. Multivariate logistic regression analysis showed that women had better compliance with repeated screening than men (OR=1.31, 95%CI: 1.14‒1.50). Compared with the population aged 50 to 54 years, the population aged 55‒59 years (OR=1.57, 95%CI: 1.19‒2.08), 60-64 years (OR=2.77, 95%CI: 2.13‒3.61), and 65-69 years (OR=3.31, 95%CI: 2.51‒4.36) had higher compliance with repeated screening. Compared with employees' medical insurance, residents' medical insurance group had worse compliance with repeated screening (OR=0.76, 95%CI: 0.66‒0.87). People with a history of intestinal polyps were more likely to undergo repeat screening than those without (OR=2.07, 95%CI: 1.50‒2.87). ConclusionCompliance with repeated screening for colorectal cancer still needs to be improved, and there are differences in compliance with repeated screening for different populations with different characteristics. Identifying groups that are unlikely to adhere to community-based colorectal cancer screening and taking targeted interventions can help improve the continued compliance of residents with colorectal cancer screening.
7.Genomic analysis and biomarker discovery of thymic cancer based on whole exome sequencing: A retrospective cohort study
Run XIANG ; Shaohua XIE ; Qiong LIAO ; Qiang LI ; Weikang SHAO ; Juan LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):288-303
Objective To examined gene mutations in thymic carcinoma (TC) patients and to explore prognostic correlates and potential targets for therapy. Methods We retrospectively included TC patients in Sichuan Cancer Hospital between January 2015 and Febuary 2021.Whole-exome sequencing was performed on tumor tissues from TC patients and their control peripheral blood samples, and the raw data were subjected to bioinformatics analysis and statistical analysis. Results We finally included 24 TC patients with 16 males and 8 females at a median age of 55 (42-74) years. The highest frequency of single nucleotide mutations in this cohort were in the TTN gene (42%), HSPG2 (29%), and OBSCN (29%). Higher frequency of copy number variations occurred in ZNF276 gene (54%, loss), BEND3 (50%, loss), DHODH (50%, loss), and VAC14 (50%, loss). Microsatellite instability (MSI) phenotype was found in 25% of the patients, and the mean tumor mutation burden (TMB) was 9.86. Conclusion This study is the first comprehensive analysis of the mutation profile of thymic carcinoma in China to date. The mutation frequencies of TTN, OBSCN, and ZNF276 genes were high. The biomarker analysis suggests that patients may benefit from immunotherapy and have a long effective survival.
8.Research progress in micro/nanobubbles for ultrasound diagnosis or treatment
Qing-qing AN ; Chen-xi LI ; Shao-kun YANG ; Xiao-ming HE ; Yue-heng WANG ; Chao-xing HE ; Bai XIANG
Acta Pharmaceutica Sinica 2024;59(3):581-590
In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.
9.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
10.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

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