1.Progress in the application of microtubulin inhibitors in prostate cancer
Nan GUO ; Baokai DOU ; Jing ZHANG
China Pharmacy 2025;36(13):1683-1688
When prostate cancer (PCa) progresses to the metastatic castration-resistant stage, significant challenges arise in clinical treatment. Microtubulin inhibitors have become first-line drugs for the treatment of metastatic castration-resistant PCa due to their unique mechanism of action. Among them, taxanes (e.g. docetaxel and cabazitaxel) remain standard care with proven survival benefits, while other microtubule inhibitors (e.g. vincristine, colchicine) show limited clinical utility due to toxicity. Currently, the clinical approach primarily employs docetaxel-based triple therapy and combined with immune checkpoint inhibitors to improve the prognosis of PCa patients, reverse the immunosuppressive state of the tumor microenvironment, and enhance therapeutic efficacy. Despite the remarkable clinical efficacy of microtubule inhibitors in the treatment of PCa, the emergence of drug resistance has limited their long-term application. To address this issue, researchers have explored new solutions, including the development of novel microtubule inhibitors in combination with ATP-binding cassette subfamily B member 1 inhibitors, the concurrent use of fatty acid synthase inhibitors with microtubule inhibitors, and the development of degraders based on proteolysis-targeting chimeras technology. Future research should focus on target discovery, drug formulation optimization, and personalized approaches to overcome current therapeutic limitations.
2.Hepatitis E virus infection in liver transplant recipients
Fansheng GUO ; Qiang ZENG ; Jian DOU
Organ Transplantation 2024;15(3):352-358
Hepatitis E virus infection is a common cause of acute viral hepatitis. In recent years, the incidence of hepatitis E has shown an increasing trend, which has gradually become an important cause of acute viral hepatitis worldwide. Age, sex, intensity of immunosuppression and socio-economic factors are all risk factors for hepatitis E virus infection. Liver transplant recipients require long-term use of immunosuppressive drugs for anti rejection treatment, prone to hepatitis E virus infection and at the risk of liver fibrosis and cirrhosis due to immunosuppression status. Therefore, special attention should be paid to liver transplant recipients in clinical practice. Meantime, related risk factors should be identified to assist diagnosis and take stricter preventive measures. According to literature review, the etiological characteristics of hepatitis E virus and the epidemiological characteristics, clinical manifestations, diagnosis and treatment of hepatitis E virus infection in liver transplant recipients were reviewed, aiming to properly monitor, treat and prevent hepatitis E virus infection in liver transplant recipients in clinical practice, improving the prognosis of liver transplant recipients.
3.Role of 18F-FDG PET in the preoperative evaluation of extratemporal lobe epilepsy
Ruijie GUO ; Qijun LI ; Liri JIN ; Wanchen DOU ; Ruixue CUI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(4):207-212
Objective:To analyze the application value of 18F-FDG PET in the preoperative evaluation of patients with extratemporal lobe epilepsy (ETLE) and explore improved methods to enhance its localization accuracy. Methods:A total of 41 patients (25 males, 16 females, age (22.7±7.5) years) who underwent surgery and ultimately confirmed ETLE in Peking Union Medical College Hospital between January 2006 and November 2022 were enrolled. The accuracy of preoperative independent 18F-FDG PET imaging and the combined application of 18F-FDG PET and MRI in detecting epileptogenic foci and their impacts on treatment decisions were retrospectively analyzed by using visual and semi-quantitative methods. Fisher′s exact test was used to analyze the data. Results:In all 41 patients, 40 cases were found metabolic abnormalities in extratemporal lobe by independent 18F-FDG PET based on visual analysis. Among them, 26 showed unifocal metabolic abnormalities, which were localized as epileptogenic foci. Fourteen patients showed multifocal metabolic abnormalities, and the epileptogenic foci were further verified in 8 cases through semi-quantitative analysis. In 1 case with negative PET visual analysis, a micro-metabolism focus was found at the abnormal MRI signal area. Among 13 patients with negative independent MRI, 9 were found microstructures abnormalities in brain regions with hypometabolism. 18F-FDG PET improved clinical decision-making in 18 patients (43.9%, 18/41). There were 30 patients (73.2%, 30/41) with seizure-free postsurgery, and the prognosis was not significantly different between patients with unifocal 18F-FDG PET metabolic pattern and those with multifocal ones (73.1%(19/26) vs 10/14, P=1.000). Conclusions:18F-FDG PET can be a useful diagnostic tool for patients with ETLE. Semi-quantitative analysis helps to detect more epileptogenic foci with multifocal metabolic abnormalities. The combined evaluation of 18F-FDG PET and MRI can improve the accuracy in localizing epileptogenic foci outside the temporal lobe.
4.Application of 8-ring traction-assisted endoscopic submucosal dissection for gastric lesions
Dandan ZHU ; Xiaotan DOU ; Huimin GUO ; Min CHEN ; Lei WANG ; Chenggong YU
Chinese Journal of Digestive Endoscopy 2024;41(1):65-67
To evaluate the effectiveness and safety of 8-ring assisted traction in endoscopic submucosal dissection (ESD), a total of 13 patients with 15 gastric lesions who underwent 8-ring traction-assisted ESD in Nanjing Drum Tower Hospital from July 2021 to January 2022 were included in the retrospective cohort study. All patients successfully completed the operation. The median procedure time was 56 min, and the dissected area per unit time was 0.20±0.02 cm 2/min. The en bloc resection rate, the complete resection rate and the curative resection rate were 93.3% (14/15), 80.0% (12/15) and 80.0% (12/15), respectively. There were no ESD-related complications, such as delayed bleeding or intraperative and postoperative perforation. No deaths occurred. As a novel internal traction technology, 8-ring traction method is simple to operate, providing a good field of vision during ESD to improve the dissection efficiency and reduce complications, which is worthy of further clinical research and promotion.
5.Efficacy and safety of endoscopic submucosal dissection for circular superficial esophageal cancer
Xiaotan DOU ; Jianhai WU ; Ting ZHOU ; Huimin GUO ; Min CHEN ; Tian YANG ; Tingsheng LING ; Xiaoqi ZHANG ; Ying LYU ; Lei WANG ; Xiaoping ZOU
Chinese Journal of Digestive Endoscopy 2024;41(2):117-120
Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for circular superficial esophageal cancer.Methods:A retrospective analysis was conducted on 74 consecutive cases of circular superficial esophageal squamous cell carcinoma treated with ESD at Nanjing Drum Tower Hospital from January 2015 to December 2019. The success rate of ESD, curative resection rate, incidence of complications, and additional treatment were mainly observed.Results:One case was transferred to surgery, and the remaining 73 cases successfully completed ESD treatment. The success rate of ESD was 98.6%. Postoperative pathology of ESD revealed that 39 cases achieved curative resection, with a curative resection rate of 53.4% (39/73). Intraoperative muscle layer injury occurred in 15 cases (20.5%), and intraoperative perforation occurred in 1 case (1.4%). Two cases (2.7%) experienced delayed bleeding, and one case (1.4%) experienced delayed perforation. Eleven cases were lost to follow-up, and the remaining 62 cases received follow-up for 36.4±19.0 months. Among the follow-up cases, 12 underwent additional surgery and 5 cases additional chemotherapy and radiotherapy. Among the 57 patients with follow-up data who did not underwent surgery, 49 developed esophageal stenosis after ESD, with an incidence rate of 86.0%.Conclusion:ESD for circular superficial esophageal cancer is generally safe, but it is prone to muscle layer injury during the operation, with a low curative resection rate, a high incidence of postoperative esophageal stenosis, and a high proportion of additional surgical procedures.
6.Perioperative outcomes of single-lumen versus double-lumen endotracheal tubes in totally thoracoscopic cardiac surgery: A retrospective cohort study
Zhenzhong WANG ; Shuo XIAO ; Dou FANG ; Yuxin LI ; Jinfeng WEI ; Yingxian YE ; Jianjun ZHANG ; Xiaogang GUO ; Qingshi ZENG ; Huanlei HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(11):1606-1612
Objective To investigate the relationship between two-lung ventilation (TLV) with single-lumen endotracheal tube (SLT), one-lung ventilation (OLV) with double-lumen endotracheal tube (DLT) and postoperative pulmonary complications (PPCs) after total thoracoscopic cardiac surgery. Methods The clinical data of patients who underwent totally thoracoscopic cardiac surgeries in the Guangdong Provincial People’s Hospital from October 2019 to October 2021 were retrospectively analyzed. The patients were divided into 2 group according to the type of endotracheal tube, including a SLT group and a DLT group. Baseline data, surgical variables and PPCs were compared. The influencing factors of PPCs in the two groups were analyzed by binary logistic regression analysis. Results Finally 349 patients were enrolled, including 180 males and 169 females with an average age of (50.0±14.8) years. There were 219 patients in the SLT group and 130 patients in the DLT group. There was no statistical difference in baseline data, surgical variables or PPCs between the two groups (P>0.05). Binary logistic regression analysis showed that PPCs were related to body mass index in the SLT group (OR=0.778, 95%CI 0.637 to 0.951, P=0.014) and preoperative smoking history in the DLT group (OR=0.058, 95%CI 0.004 to 0.903, P=0.042). Conclusion For the patients who undergo totally thoracoscopic cardiac surgery, TLV with SLT and OLV with DLT show no significant association with PPCs. At the same time, PPCs are associated with body mass index in the SLT group, while associated with preoperative smoking history in the DLT group.
7.Hypercalcaemia crisis: A retrospective series of 143 cases
Yang LIU ; Xianling WANG ; Qinghua GUO ; Jin DU ; Yu PEI ; Jianming BA ; Weijun GU ; Jingtao DOU ; Zhaohui LYU ; Yiming MU
Chinese Journal of Endocrinology and Metabolism 2024;40(2):115-120
Objective:The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis.Methods:The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis.Results:A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143).Conclusion:Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.
8.Design and Effect Evaluation of in Vitro Diagnostic Reagents for Beijing Hospital Based on Performance Management of the Whole Process Closed-loop Management
Jingchen SONG ; Zhixuan GUO ; Jingjing DOU ; Lei LIU ; Suowei WU ; Chuanbao LI
Journal of Modern Laboratory Medicine 2024;39(4):197-202
Objective To establish in vitro diagnostic(IVD)reagents closed-loop management scheme for the whole process and implement,and optimize the IVD management.Methods Based on the status quo of IVD management in Beijing Hospital,the closed-loop management scheme of the whole IVD process was designed,such as IVD application,IVD selection,IVD subscription,IVD purchase,IVD receipt,IVD inbound and outbound,and IVD use.Key indicators were selected to establish an evaluation framework.Management data,procurement data and testing data before(2020)and after(2023)implementation of the program were collected and counted by means of interviews and consulting relevant information systems,and then process management,quality management and cost management were evaluated.Results The management process was optimized,the IVD purchase time was shortened by about 60%on average,the IVD purchase did not need manual processing,the order was split in real time and sent to the corresponding supplier,and the IVD collection time was shortened by about 75%on average.IVD and test quality management were satisfactory,supplier qualification perfection reached 100%,full marks were obtained in the inter-room quality assessment,and no IVD-related adverse events were observed.The cost management was effective,and the IVD procurement cost was reduced by about 15%.IVD cost fine management models were established for four items,namely,human immunodeficiency virus antibody assay,hepatitis C antibody assay,treponemal antibody assay and hepatitis B surface antigen quantitative assay.The average value of IVD loss was 0.07%~1.21%,and the standard deviation was 0.07%~0.66%.Conclusion The IVD whole process closed-loop management scheme is feasible,which can improve the efficiency of IVD management,ensure the quality of IVD and detection,reduce the cost of IVD,and refine the cost management work.
9.Mechanism of glioma stem cells with high expression of PTPRZ1 inducing TAMs polarization to M2 immunosuppressive phenotype
Lele AN ; Ying YANG ; Qing LIU ; Feiyue DOU ; Lujing WANG ; Yue CHENG ; Chao WANG ; Qianying RUAN ; Lei ZHOU ; Haitao GUO ; Weikai KONG ; Xuegang LI ; Chuan LAN ; Fei LI ; Yu SHI
Journal of Army Medical University 2024;46(8):796-803
Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.
10.Research on the deep learning model based on the combination of intratumoral and peritumoral dynamic contrast-enhanced MRI for predicting axillary lymph node metastasis in breast cancer
Yijun GUO ; Rui YIN ; Junqi HAN ; Zhaoxiang DOU ; Jingjing CHEN ; Peifang LIU ; Hong LU ; Wenjuan MA
Journal of Practical Radiology 2024;40(6):907-912
Objective To explore the value of deep learning models in predicting axillary lymph node(ALN)metastasis of breast cancer based on intratumoral and peritumoral dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods A retrospective analysis was conducted on cases from Tianjin Medical University Cancer Hospital and Laoshan Branch of Affiliated Hospital of Qingdao University,involving a total of 850 lesions in 850 patients.The region of interest within the tumor was delineated at the largest area of the lesion on the first enhancement images and automatically expanded by 3 mm and 6 mm in a conformal fashion.Deep learning prediction models based on ResNet50 were developed via intratumoral,peritumoral,and intratumoral combined peritumoral models,respectively,and a comprehensive prediction model was developed by integrating semantic features of imaging reports.Cases from Tianjin Medical University Cancer Hospital were randomly divided into training and test cohorts in a 7∶3 ratio,while cases from Laoshan Branch of Affiliated Hospital of Qingdao University served as the external validation cohort.The area under the curve(AUC),accuracy,sensitivity,specificity,F1-score,and Brier-score were calculated,respectively.Results The model incorporating intratumoral,peritumoral(3 mm),and semantic features demonstrated the highest performance,with AUC of 0.801[95%confidence interval(CI)0.765-0.845],0.781(95%CI 0.745-0.817),and 0.752(95%CI 0.700-0.793)in the training cohort,test cohort,and external validation cohort,respectively,and there was no significant difference in AUC between combined model and intratumoral/peritumoral model,respectively,but it demonstrated the higher sensitivity and F1-score,and the lower Brier-score.Conclusion Incorporating peritumoral images into the conventional model based on intratumoral images enhanced the predictive ability of ALN metastasis in breast cancer.

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