1.Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin α v β 3-positive tumors: A first-in-human study.
Huimin SUI ; Feng GUO ; Hongfei LIU ; Rongxi WANG ; Linlin LI ; Jiarou WANG ; Chenhao JIA ; Jialin XIANG ; Yingkui LIANG ; Xiaohong CHEN ; Zhaohui ZHU ; Fan WANG
Acta Pharmaceutica Sinica B 2025;15(2):669-680
Integrin α v β 3 is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2, a novel integrin α v β 3-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α v β 3-avid tumors were recruited to accept 177Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. 177Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of 177Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α v β 3-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.
2.AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing.
Kaiyi WANG ; Xinhai CHEN ; Nan LI ; Huimin FENG ; Xiaoyi LIU ; Yifei WANG ; Yanfei WU ; Yufeng GUO ; Shuoshuo XU ; Lu YAO ; Zhaohua ZHANG ; Jun JIA ; Zhishu TANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2025;15(8):4193-4209
The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.
3.The characteristics of intestinal flora and its correlation with peripheral blood microinflammatory factors in patients with pulmonary tuberculosis complicated with diabetes mellitus
Manjiao FU ; Jia LIU ; Huimin LIU ; Yi KANG ; An ZHAI ; Hongmei CHEN ; Liang CHEN ; Yuexi YUAN
International Journal of Laboratory Medicine 2025;46(14):1736-1741
Objective To investigate the characteristics of intestinal flora and its correlation with peripheral blood microinflammatory factors in patients with pulmonary tuberculosis complicated with diabetes mellitus(PTB-DM).Methods A total of 162 patients with PTB-DM admitted to the hospital from September 2022 to September 2024 were selected as the PTB-DM group,and another 150 healthy subjects who underwent physi-cal examinations during the same period in the hospital were selected as the control group.The clinical data of all research subjects was collected.The composition of intestinal flora of the research subjects was analyzed by using 16S rRNA gene sequencing technology.The levels of peripheral blood microinflammatory factors[inter-feron-γ(IFN-γ),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)]in all research subjects were detected.The clinical data,composition of intestinal flora and levels of microinflammatory factors of the PTB-DM group were compared with those of the control group.Spearman correlation analysis was used to analyze the correlation between the relative abundance of intestinal flora and the levels of peripheral blood microin-flammatory factors in patients with PTB-DM.Results The relative abundances of Bacteroidales and Clostridi-ales in the PTB-DM group were significantly lower than those in the control group,while the relative abun-dances of Enterobacterales and Actinobacteriales were significantly higher than those in the control group,and the differences were statistically significant(P<0.05).The levels of IFN-γ,IL-6 and TNF-α in the PTB-DM group were significantly higher than those in the control group,and the differences were statistically signifi-cant(P<0.05).The relative abundances of Bacteroidales and Clostridiales in the PTB-DM group were nega-tively correlated with the levels of IFN-γ,IL-6 and TNF-α.The relative abundances of Enterobacterales and Actinobacteriales were positively correlated with the levels of IFN-γ,IL-6 and TNF-α(all P<0.05).Conclu-sion There is a significant imbalance of intestinal flora in patients with PTB-DM,and the levels of microin-flammatory factors IFN-γ,IL-6 and TNF-α in peripheral blood are significantly increased,and are closely re-lated to the relative abundance of specific flora.
4.Diagnosis and treatment of the portal vein complications for children undergoing spilt liver transplantation
Kaining ZENG ; Qing YANG ; Jia YAO ; Hui TANG ; Binsheng FU ; Xiao FENG ; Haijin LYU ; Huimin YI ; Shuhong YI ; Yang YANG
Organ Transplantation 2024;15(1):63-69
Objective To investigate the diagnosis and treatment strategy of the portal vein complications in children undergoing split liver transplantation. Methods The clinical data of 88 pediatric recipients who underwent split liver transplantation were retrospectively analyzed. Intraoperative anastomosis at the bifurcating site of the portal vein or donor iliac vein bypass anastomosis was performed depending on the internal diameter and development of the recipient's portal vein. A normalized portal venous blood stream monitoring was performed during the perioperative stage. After operation, heparin sodium was used to bridge warfarin for anticoagulation therapy. After portal vein stenosis or thrombosis was identified with enhanced CT or portography, managements including embolectomy, systemic anticoagulation, interventional thrombus removal, balloon dilatation and/or stenting were performed. Results Among the 88 recipients, a total of 10 children were diagnosed with portal vein complications, of which 4 cases were diagnosed with portal vein stenosis at 1 d, 2 months, 8 months, and 11 months after surgery, and 6 cases were diagnosed with portal vein thrombosis at intraoperative, 2 d, 3 d (n=2), 6 d, and 11 months after surgery, respectively. One patient with portal vein stenosis and one patient with portal vein thrombosis died perioperatively. The fatality related to portal vein complications was 2% (2/88). Of the remaining 8 patients, 1 underwent systemic anticoagulation, 2 underwent portal venous embolectomy, 1 underwent interventional balloon dilatation, and 4 underwent interventional balloon dilatation plus stenting. No portal venous related symptoms were detected during postoperative long term follow up, and the retested portal venous blood stream parameters were normal. Conclusions The normalized intra- and post-operative portal venous blood stream monitoring is a useful tool for the early detection of portal vein complications, the early utilization of useful managements such as intraoperative portal venous embolectomy, interventional balloon dilatation and stenting may effectively treat the portal vein complications, thus minimizing the portal vein complication related graft loss and recipient death.
5.Discussion on the Scientific Connotation of Fortifying Spleen, Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein
Lianqun JIA ; Qige WANG ; Guoyuan SUI ; Nan SONG ; Huimin CAO ; Liang KONG ; Meijun LV ; Yuan CAO ; Ning YU ; Siyuan DING ; Guanlin YANG
Journal of Traditional Chinese Medicine 2024;65(2):128-133
The key pathogenesis of coronary heart disease (CHD) is spleen deficiency and phlegm stasis, and dysfunctional high-density lipoprotein (dys-HDL) may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein (HDL), it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL; and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways, namely, mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells, thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency, and spleen deficiency makes foundation for the production of dys-HDL; dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen, resolving phlegm, and dispelling stasis, is proposed as an important principle in the treatment of CHD by traditional Chinese medicine, which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL, thus revealing the scientific connotation of this method, and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.
6.Effects of intraoperative blood glucose fluctuation and postoperative insulin resistance on cognitive dyfunction in elderly patients after thoracoscopic radical resection of lung cancer under general anesthesia
Huimin CHEN ; Hongfeng JIA ; Tingting JIANG ; Yaohui JIA
Tianjin Medical Journal 2024;52(2):201-205
Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance(IR)on postoperative cognitive dyfunction(POCD)in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia.Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group(n=84)and the non-POCD group(n=268).The covariates between the two groups were balanced by propensity score matching method(PSM).Eighty-four cases in each group were successfully matched.The data between the two groups before and after PSM were compared.After PSM,receiver operating characteristic(ROC)curve of blood glucose fluctuation amplitude for predicting POCD was drawn,and patients were divided into the low-level blood glucose fluctuation group(n=97)and the high-level blood glucose fluctuation group(n=71)according to the cut-off value.According to the existence of postoperative IR,patients were divided into the IR group(n=53)and the non-IR group(n=115).Then,incidences of POCD between groups were compared.Logistic regression was used to analyze the influencing factors of POCD.Results Before PSM,the POCD group had older age,higher blood glucose fluctuation amplitude,IR ratio,operation time,anesthesia time,propofol dosage,remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group(P<0.05).The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM(P<0.05).After PSM,the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group(P<0.05).Logistic regression analysis showed that higher intraoperative blood glucose fluctuation(OR=9.140,95%CI:4.338-19.257)and postoperative IR(OR=4.034,95%CI:1.163-13.991)were risk factors of POCD.Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.
7.Prospects for the application of blood-based biomarkers in Alzheimer′s disease
Chinese Journal of Laboratory Medicine 2024;47(2):116-121
The early diagnosis of Alzheimer′s disease (AD) has long been a challenge in the field of medicine. In recent years, research on blood biomarkers of AD has flourished, which holds significant promise for advancing the early diagnosis, monitoring, and early intervention of AD. With the new generation of ultra-sensitive detection techniques, a series of studies have successfully validated core biomarkers, non-specific biomarkers, and other relevant biomarkers of AD in blood. However, the use of blood-based biomarkers for the diagnosis and prediction of AD still faces some challenges related to accuracy and robustness. This article compiles and analyzes the advances, strengths, and limitations of each type of biomarkers, and provides several potential strategies to address these challenges.
8.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.
9.Exploration and practice of building a disciplinary inspection management platform in public hospitals
Jianchun YU ; Huimin LV ; Jin YAN ; Jia ZHANG
Modern Hospital 2024;24(10):1515-1517
The second plenary session of the 20th Central Commission for Discipline Inspection proposed the"develop-ment of a five-year plan for information technology construction to establish a digital disciplinary inspection and supervision system that covers the entire process and all elements."This provides guidance and momentum for disciplinary inspection agencies at all levels to implement the strategic deployment of the Party's 20th National Congress regarding comprehensive and strict governance of the Party.In this context,utilizing information technology to enhance the efficiency of supervision,discipline enforcement,and accountability while ensuring the high-quality development of public hospitals has become a key task for their disciplinary inspec-tion departments.The Disciplinary Inspection Commission of a public hospital has explored the establishment of a disciplinary in-spection management platform to achieve modular management of inspection tasks.By utilizing functions such as task allocation,statistical analysis,data migration,and early warning reminders,the platform aims to improve the efficiency of disciplinary in-spection work.This approach helps address the challenges of heavy workloads and limited inspection resources in hospitals,enab-ling real-time supervision,early warning correction,and time-bound oversight,thereby providing strong support for the construc-tion of integrity in the hospital.
10.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Result Analysis
Print
Save
E-mail