1.Research progress of platelets and their derivatives based drug delivery systems
Xunyi YOU ; Kehui ZHU ; Jiaxin LIU ; Ye CAO
Chinese Journal of Blood Transfusion 2023;36(11):1068-1073
Platelets play an important role in physiological and pathological activities such as thrombosis, inflammation and tumorigenesis. At present, the application of platelets in drug delivery systems is increasingly studied. Compared with traditional drug delivery systems, new drug delivery systems based on platelets and their derivatives can effectively improve the circulation time and selective accumulation, and reduce the occurrence of related immune reactions or off-target toxic and side effects. In this paper, the types and applications of platelet and its derivatives drug delivery systems were summarized in order to provide reference for platelet-related drug delivery research.
2.The Progress of Red Blood Cells Based Drug Delivery Systems
Kehui ZHU ; Hong WANG ; Rui ZHONG ; Ye CAO ; Jiaxin LIU
Chinese Journal of Blood Transfusion 2022;35(6):672-676
Red blood cells(RBCs), as the most abundant types of blood cells in the blood, have several advantages as a drug delivery system due to their ultra-long circulation half-life, good biocompatibility, and biodegradability. To date, a variety of RBCs-based drug delivery techniques have been developed for the treatment of infection diseases, cancers, chronic diseases, and autoimmune diseases. This review summarized the progress of RBCs related drug delivery systems, and discussed the advantages and disadvantages of different loading methods and their pre-clinical application progress, promoting the research and development of drug delivery.
3.Current research status of left-sided portal hypertension after superior mesenteric-portal vein confluence pancreaticoduodenectomy
Hong ZOU ; Qiao ZHU ; Yi WEN ; Hongyin LIANG ; Mingmei ZHOU ; Kehui SHI ; Jun WU ; Lijun TANG
Journal of Clinical Hepatology 2023;39(6):1482-1487
Surgical operation is the main treatment method for pancreatic cancer, and in clinical practice, radical surgery for pancreatic cancer is often combined with superior mesenteric-portal vein confluence pancreaticoduodenectomy to achieve R0 resection. However, severe left-sided portal hypertension (LSPH) may occur after splenic vein dissection, resulting in a series of pathological changes such as congestive splenomegaly, thrombocytopenia, backflow obstruction of splenic vein, and gastrointestinal varices, and in some cases, it can lead to fatal gastrointestinal hemorrhage and hemorrhagic shock. Therefore, in order to better manage LSPH in clinical practice, this article systematically analyzes and reviews the pathogenesis, treatment regimens, and control strategies of LSPH after combined superior mesenteric-portal vein confluence pancreaticoduodenectomy and put forward corresponding suggestions based on current studies.
4.Preliminary study on polymerized human cord hemoglobin increasing the chemosensitivity of subcutaneous xenografts of breast cancer in nude mice
Yiqiu GAO ; Kehui ZHU ; Yingcan XU ; Zhengxin SUO ; Hong WANG ; Jiaxin LIU
Chinese Journal of Blood Transfusion 2022;35(5):475-479
【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) on the chemosensitivity of human breast cancer MCF-7 cell subcutaneous xenografts in nude mice and its mechanism. 【Methods】 The MCF-7 cells in exponential growth phase were collected and made into suspension cells at a density of 5×107 cells/mL.Subsequently, the cells were inoculated subcutaneously in the right limb of 18 BALB/c-nu nude mice with 0.2 mL cells per mouse to establish subcutaneous xenograft.When the tumor volume reached about 100 mm3, they were randomly divided into chemotherapy group: doxorubicin 5 mg·kg-1, once/week; chemotherapy + PolyCHb group: in addition to doxorubicin (chemotherapy group), PolyCHb 600 mg·kg-1, 3 times/week; the control group: normal saline 90 mg·kg-1, once/week; all were injected through tail vein continuously for 4 weeks.From the day of injection (d 0), the tumor volume of each group of nude mice was measured every 3 days, and the tumor growth curves were drawn accordingly.After 38 days, the tumor growth observation was completed.The tumor was removed and weighed to calculate the tumor inhibition rate.HE staining, immunohistochemistry and TUNEL method were used to observe the pathological changes of tumor tissue, detect the expression of HIF-1α, and detect tumor cell apoptosis respectively.The content of reactive oxygen species (ROS) of each group was determined by fluorescence staining. 【Results】 The tumor volume (mm3) of chemotherapy + PolyCHb group, chemotherapy group and the control group at day 38 were 196.35±103.45 vs 316.29±62.88 vs 519.42±177.33 (P<0.05), and the tumor inhibition rate (%) of chemotherapy + PolyCHb treatment group and chemotherapy group was 62.20 vs 39.11, respectively.HE staining and TUNEL detection showed that cell necrosis and apoptosis in the growth area of tumor tissue increased in chemotherapy + PolyCHb group.Immunohistochemistry and fluorescence staining showed that HIF-1α expression in chemotherapy + PolyCHb group decreased and reactive oxygen species (ROS) content increased. 【Conclusion】 PolyCHb increases the chemosensitivity of subcutaneous xenograft in nude mice with breast cancer, and its mechanism may be related to the increase of ROS in tumor tissue and the promotion of tumor cell apoptosis.
5.Preparation and in vitro evaluation of hemoglobin-paclitaxel dual loaded liposomes for improving tumor hypoxia resistance
Xunyi YOU ; Kehui ZHU ; Jing XIAO ; Jiakang WU ; Shifan ZHENG ; Along ZHANG ; Rui ZHONG ; Hong WANG ; Ye CAO ; Jiaxin LIU
Chinese Journal of Blood Transfusion 2024;37(3):297-303
【Objective】 To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. 【Methods】 LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. 【Results】 The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. 【Conclusion】 The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.
6.Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis: a prospective multicenter randomized controlled trial.
Xiaoyan TANG ; Dezheng CHEN ; Ling ZHANG ; Ping FU ; Yanxia CHEN ; Zhou XIAO ; Xiangcheng XIAO ; Weisheng PENG ; Li CHENG ; Yanmin ZHANG ; Hongbo LI ; Kehui LI ; Bizhen GOU ; Xin WU ; Qian YU ; Lijun JIAN ; Zaizhi ZHU ; Yu WEN ; Cheng LIU ; Hen XUE ; Hongyu ZHANG ; Xin HE ; Bin YAN ; Liping ZHONG ; Bin HUANG ; Mingying MAO
Journal of Zhejiang University. Science. B 2022;23(11):931-942
OBJECTIVES:
Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment.
METHODS:
Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline.
RESULTS:
A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41).
CONCLUSIONS
Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans
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Citric Acid/adverse effects*
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Prospective Studies
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Sodium Citrate
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Hemorrhage/chemically induced*
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Citrates/adverse effects*
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Anticoagulants/adverse effects*
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Renal Dialysis/adverse effects*