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OBJECTIVE To investigate the synergistic effect and mechanism of curcumin (CUR) combined with zerumbone (ZER) on the biological behavior of non-small cell lung cancer (NSCLC) A549 cells. METHODS CCK-8 method and Gin’s formula were used to screen the optimal concentration combination for synergistic effect after the combination of CUR and ZER. The cells were divided into blank group, CUR group, ZER group, and CUR+ZER group. Flow cytometry was used to evaluate cell apoptosis, and clone formation experiment was used to evaluate cell proliferation ability, scratch experiment and Transwell migration experiment were used to evaluate cell migration ability, and Transwell invasion experiment was used to evaluate cell invasion ability. Western blot assay was used to detect the protein expressions of phosphorylated phosphatidylinositol-3-kinase (p- PI3K), phosphorylated protein kinase B (p-Akt), and vascular endothelial growth factor A (VEGF-A). RESULTS The half inhibitory concentrations of CUR and ZER on A549 cells were approximately 16 and 12 μmol/L, respectively; the drug combination of CUR 8 μmol/L+ZER 6 μmol/L had the highest efficiency enhancement index, with the cell proliferation inhibition rate of (77.41±4.16)%, indicating the most significant synergistic effect. Compared with the CUR and ZER groups, the cell apoptosis rate in the CUR+ZER group was significantly increased (P<0.01), while the cell clone formation rate, cell migration rate, the number of migrating cells, the number of invading cells, and relative expression levels of p-PI3K, p-Akt, and VEGF-A proteins in the cells were significantly reduced (P<0.05 or P<0.01). CONCLUSIONS The combination of CUR and ZER has a synergistic effect, significantly promoting the apoptosis of NSCLC cells, and inhibiting cell proliferation, migration, and invasion. Its potential mechanism may be closely related to the inhibition of the PI3K/Akt signaling pathway, thereby down-regulating the protein expression of VEGF-A.
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As the focus of public health work in the world, diabetic foot disease has aroused high public concern. This paper introduces the application of the diabetic foot wearable monitoring equipment types, including plantar pressure monitoring, temperature monitoring, monitoring of the biomechanics and multimode monitoring, and wearable devices application status in patients with diabetes, puts forward the existing problems and prospect, in order to carry out domestic related to diabetic foot wearable monitoring equipment research to provide the reference.
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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.
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The research progress of the frailty risk prediction model for the elderly were reviewed in order to analyze its evaluation content, prediction effect and clinical application, so as to provide reference for the risk prediction model construction and application, reduce the risk of the elderly frailty.
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Tuft cells are highly specialized epithelial cells with distinct transcriptional profiles and biological functions. Recent studies have revealed that tuft cells are widely existed in a range of tissues, including digestive system, respiratory system and periodontal tissues, playing essential roles in mediating host-microbial interaction and initiating type Ⅱ immune response. Although tuft cells share many commons regarding their morphological characteristics and expression profiles, emerging evidence indicates that tuft cells possess a certain degree of heterogeneity in different tissues or loci. Of note, tuft cells consistently express a variety of taste receptors and their downstream signal transduction machineries to detect and respond a wide range of chemicals in the microenvironment or bacterial metabolites. This review discussed the molecular basis of taste signal transduction and biological functions of tuft cells in different tissues.
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Transcranial Doppler (TCD) is a method for measuring cerebral artery blood flow velocity, which has the advantages of low cost, non-invasive, high temporal resolution. Dynamic cerebral autoregulation (dCA) is to study the instantaneous change of cerebral blood flow (CBF) at the moment of arterial blood pressure or intracranial pressure change, that is, the ability to recover CBF in the face of sudden change of perfusion pressure. After the onset of acute ischemic stroke (AIS), effective dCA can maintain the stability of cerebral hemodynamics and avoid excessive or insufficient perfusion at the injured site. Therefore, it is of great significance to evaluate dCA in patients with AIS. However, at present, there is no recognized optimal evaluation method for dCA. This article mainly summarizes the advantages of TCD in evaluating dCA compared with other methods and the application of TCD combined with transfer function analysis (TFA) in evaluating dCA in AIS.
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Objective:To investigate the correlation between preterm infants with brain injury and the proportion of lymphocyte subsets, especially γδ-T cells in the postnatal peripheral blood, and to determine the predictive potential of γδ-T cells in the early peripheral blood in brain injury.Methods:It was a prospective study involving 106 preterm infants with gestational age less than 34 weeks who were delivered in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University from January 1, to June 1, 2021.Relative levels of γδ-T , CD4 + T, CD8 + T, CD3 + T and total lymphocyte subsets in peripheral blood collected within the first 24 hours after birth were measured by flow cytometry.Recruited infants were divided into brain injury group (36 cases) and non-brain injury group (70 cases) according to serial cranial ultrasound and magnetic resonance imaging(MRI) at the corrected gestational age of 36-37 weeks.Differences in general conditions and the proportion of lymphocyte subsets between groups were compared by the t-test or Chi- square test.Patients in brain injury group were further divided into intracranial hemorrhage(ICH) group(8 cases), periventricular leukomalacia (PVL) group (6 cases)and diffuse white matter damage (WMD) group(22 cases). The proportion of lymphocyte subsets among the different groups was compared by One- Way ANOVA, followed by the LSD- t test. Results:The proportion of γδ-T cells in postnatal peripheral blood of preterm infants at 24 hours after birth in brain injury group was significantly lower than that of non-brain injury group [(0.09±0.12)% vs.0.15±0.13)%, t=-2.445, P=0.016]. No significant differences in the proportion of the CD4 + and CD8 + T cell subsets were found between them.Both preterm infants in PVL group and WMD group had a significantly lower proportion of γδ-T cells at 24 hours after birth compared to that of the non-brain injury group [(0.03±0.05)%, (0.07±0.09)% and (0.15±0.13)%], respectively, ( t=-2.190, -2.659, all P<0.05). Conclusions:γδ-T cells in early postnatal peripheral blood may be involved in the development of brain injury in preterm infants and they had early predictive value for preterm infants at high risk of brain injury, especially the leukomalacia and diffuse white matter injury.
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This paper reviews the status quo of recent years’ research on autophagy and damage of chondrocytes in Kashin-Beck disease (KBD) and osteoarthritis (OA). PI3K/AKT signaling pathway and mTOR regulate the autophagy activity of chondrocytes. PI3K/AKT signaling pathway can promote the proliferation of chondrocytes and cause their damage by inhibiting their autophagy activity. This might play an important role in the occurrence and progression of bone and joint diseases such as KBD and OA, and provide scientific basis for revealing the pathogenesis and treatment plan of them.
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【Objective】 To investigate the quality changes of suspended red blood cells (SRBCs) prepared from the blood of Tibetan high Hb population, and explore the availability and safety of blood collected from Tibetan high Hb population. 【Methods】 The voluntary blood donors were grouped according to the Hb concentration at the initial screening: female blood donors from Tibet Autonomous Region (>3 500 m) with Hb≥190 g/L and male blood donors with Hb≥210 g/L were classified as plateau high hemoglobin group. A total of 13 male blood donors from Tibet Autonomous Region were recruited. And the female blood donors (n=13) with Hb(115~165) g/L and male blood donors (n=12) with Hb(120~185) g/L from Chengdu were classified as control group. Whole blood of 200 mL specification was centrifuged to remove the plasma, and MAP additive solution was added to prepare SRBCs, then SRBCs were divided into four aliquots (50 mL/bag and stored at 4℃. Parameters as blood routine, free Hb and hemolysis rate were measured aseptically at day 1, 14, 21, 35 of storage. And 10 mL SRBCs was used to extract membrane proteins for tyrosine phosphorylation detection of band 3 protein. 【Results】 The RBCs counts(×1012/L), hematocrit(%) and hemoglobin(g/L) of Tibetan high Hb group and control group were 6.76±0.95 vs 4.65±0.52, 63.3±6.8 vs 43.1±4.4 and 214.4±19.8 vs 143.2±16.9 (P<0.01). The erythrocyte deformability test on the day 1, 14, 21, 35 of storage showed that the deformability of SRBCs prepared from Tibetan high Hb group was significantly lower than that of the control group under shear stress of 3, 5.33, 9.49, 16.87, and 30 Pa, while the hemolysis rate of SRBCs prepared from the Tibetan high Hb group and the control group on the day 1, 14, 21, 35 were 0.050 2±0.040 2 vs 0.022 2±0.011 1, 0.055 4±0.043 vs 0.032 1±0.028 7, 0.061 2±0.025 9 vs 0.034 3±0.031 7 and 0.069 6±0.032 0 vs 0.044 0±0.033 3 (P<0.05). Western blotting showed that the cytoplasmic N-terminal Y21 of band 3 protein of SRBCs prepared from Tibetan high Hb group was highly phosphorylated. 【Conclusion】 The deformability of SRBCs prepared from the Tibetan high Hb group was significantly lower while the hemolysis rate of SRBCs was higher than that of the control group. The hemolysis rate of the SRBCs at the end of storage prepared from the Tibetan high Hb group meets the requirements of the national standard GB18469-2012(<0.8%). The increase of hemolysis rate of SRBCs prepared from the Tibetan high Hb group was closely related to the phosphorylation of band 3 protein.
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【Objective】 To establish the quantitative classification model of blood inventory warning for public health emergencies, so as to provide reference for practical application. 【Methods】 The classification model of blood inventory early warning for public health emergencies was constructed through literature review, fuzzy comprehensive evaluation method and analytic hierarchy process (AHP). The constructed model was used to conduct fuzzy comprehensive evaluation on the data of day 10 before, day 1/5/40 after the launch of Level I public health event response in Deyang Central Blood Station in 2020 and calculate the warning level. 【Results】 The warning levels of day 10 before, and day 1/5/40 after the response were blue, orange, red and blue, respectively, which were consistent with the actual situation of Deyang performing Level I public health event response at that time. 【Conclusion】 It is feasible to use fuzzy comprehensive evaluation method to build the blood inventory warning classification model in public health emergency, which provides theoretical reference for practical application.
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【Objective】 To investigate the application prospect of platelet-rich plasma lysate (PL) microneedles in the treatment of wound healing by optimizing the preparation process and evaluating the activity of platelet growth factor. 【Methods】 Firstly, hyaluronic acid (HA) was used as needle matrix material, and the concentration of HA was preliminarily determined by investigating the fluidity of HA solution, shape of needle, pressure change performance and puncture performance.Combined with the results of HA dissolution in PL, mechanical properties of PL microneedles and skin puncture, the preparation process of platelet-rich plasma lysis microneedles (PLMN) was optimized to investigate the growth factor activity of PLMN and evaluate the effect of PLMN on wound healing in rats. 【Results】 When the concentration of HA was 30 mg/mL, the solution had good fluidity.The HA microneedles could pierce three layers of sealing film, with the puncture rate at 70%, and the solution had good mechanical properties.When HA was dissolved in PL at a concentration of 30 mg/mL at 4℃, the solution had no crystallization and was with good fluidity.The prepared PLMN showed good needle shape and no bending under HD microscope and scanning electron microscope.In vitro transdermal simulation results showed that PLMN could penetrate 4 layers of sealing membrane, and the puncture rate of the first three layers was more than 85%.In vivo lysis experiment showed that PLMNs could be completely dissolved within 10 min after being inserted into the body.Forty minutes later, the micropores left after the insertion of the microneedle were almost closed, without redness, swelling, erythema and other adverse reactions.In vitro and in vivo transdermal experiments showed that clear blue holes were visible after PLMNs penetrated the skin stain, indicating that the microneedles could pierce the skin barrier.Growth factor detection results showed that the content of platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGFβ1) in platelet lysate were (17.67±1.23) ng/mL and (105.95±2.16) ng/mL, respectively.After PLMNs were prepared and stored at room temperature for 1 week, the content of PDGF-BB(ng/mL) and TGFβ1(ng/mL) were 15.48±2.12 and 56.26±1.53, respectively.Compared with PL(vs 17.67±1.23 and 105.95±2.16), the content of PDGF-BB and TGFβ1 decreased, but still maintained the activity of growth factors.The results of wound healing experiment in rats showed that the wound healing rate (%) of PLMN group on the third day was significantly different from that of the control group(52.51±6.15 vs 33.31±3.60, P<0.05). 【Conclusion】 The PLMN prepared in this experiment has good mechanical properties and can successfully pierce the skin cuticle.It can also maintain the activity of growth factors, and has a good effect on wound healing in rats, which provides a new idea for minimally invasive treatment in the field of tissue repair.
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【Objective】 To investigate the preparation conditions of hemoglobin-based oxygen carrier (HBOC) at room temperature without oxygen isolation and the quality of poly-COHb. 【Methods】 Using human cord blood hemoglobin as raw material and glutaraldehyde as crosslinking agent, the experimental group selected hemoglobin concentration, glutaraldehyde to COHb molar ratio, reaction time and reaction temperature to do four factors and three levels of orthogonal test (n=3), to determine the best matching conditions and prepare three batches of poly-COHb, continuously.In the control, 3 batches of poly-Hb were prepared under low temperature and oxygen isolation.The contents of superlarge molecules, degree of polymerization, average molecular weight, methemoglobin and P50 of crosslinked products were compared between the two groups. 【Results】 The optimal matching conditions of poly-COHb were as follows: [Hb] 70g/L, the molar ratio of glutaraldehyde to COHb was 11∶1, the reaction time was 60 min, and the reaction temperature was 25℃.Comparison of poly-COHb and poly-Hb: The superlarge molecular content (%) was 0.67±0.51 vs 0.60±0.01 (P>0.05); degree of polymerization (%) and average molecular weight (kD) were 84.25±0.99 vs 54.16±5.12, and 235.27±13.50 vs 97.62±6.57, respectively.(P<0.05); methemohemoglobin ratio (%) was 2.40±0.66 vs 2.47±0.46 (P>0.05); P50 (mmHg) was 6.37±0.30 vs 14.20±1.09 (P<0.05). 【Conclusion】 Poly-COHb can be prepared at room temperature without oxygen isolation.Compared with poly-Hb, poly-COHb prepared under the experimental conditions can improve the polymerization degree and average molecular weight, and greatly reduce the difficulty of preparation.
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【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.
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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.
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Hemoglobin-based oxygen carriers(HBOCs) is a category of artificial blood substitute with efficient oxygen carrying and delivery functions. Due to the outstanding oxygen-carrying properties of HBOCs, the studies of expanding its clinical applications are undergoing rapidly. Studies have shown the efficacy of HBOCs in organ transplantation as machine perfusion solution in maintaining the organ metabolism or meliorating the margin donor organ quality with promising perspectives. This article aims to review the application status and prospect of HBOCs in organ transplantation in recent years.
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【Objective】 To study the red blood cell substitute preparation method of glutaraldehyde(GDA) and Bis(3, 5-dibromosalicyl) fumarate(DBBF) double polymerized, and also observe its curative effect. 【Methods】 The affecting factors of the crosslink of DBBF and human placental hemoglobin(Hb) were selected, including solution pH, inositol hexaphosphoric acid concentration, and molar ratios of DBBF/Hb. The changes of P50, Hill Co and methemoglobin(MetHb) content during the preparation process were studied and the molar ratio of GDA to DBBF-Hb were determined. The final product was obtained through the steps of ultrafiltration, filtration, and deoxygenation, etc., and the final product was subjected to a study on the curative effect of anti-hemorrhagic shock in rats. 【Results】 Under the condition of pH 8.0, the concentration of inositol hexaphosphoric acid was 10mM/L, the molar ratio of DBBF/hemoglobin was 6∶1, the content of dimer was(22.67±3.28)%, the content of tetramer was (74.64±7.05)%, and its P50 was (25.25±2.31) mmHg. As the molar ratio of DBBF/Hb increased, P50 and MetHb content would gradually increase, while the Hill Co will gradually decrease. The molar ratio of GDA and DBBF-Hb was 7∶1, the content of dimer was (8.23±0.79)%, the content of tetramer was (27.87±3.63)%, the content of super-macromolecule was (1.05±0.31)%. As the molar ratio of GDA and DBBF/Hb increased, MetHb content would increase, while the P50 and Hill Co would gradually decrease. The 24h survival rate of the product in rats with hemorrhagic shock was 83.33%(10/12), which was significantly higher than that in the negative control group[41.67%(5/12)], while similar with the positive control group [91.67%(11/12)]. 【Conclusion】 The red blood cell substitutes with GDA and DBBF double polymerized can effectively reduce the dimer content, which is more conducive to industrial production, and has a positive effect on the treatment of hemorrhagic shock.
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This paper briefly reviewed blood substitutes, focusing on the background, history of research and development(R&D), types, functions, characteristics, the indications that will be mainly targeted in clinical, and their special status and role in the future, especially in the rescue of war/trauma patients using hemoglobin-based oxygen carriers(HBOCs). Additionally, the authors put forward unique insights and suggestions on some key concepts and R&D bottlenecks in the development of HBOCs through combining the authors′ own R&D experience for decades with efforts and lessons given by many scholars in this field at home and abroad, hoping to provide some new inspirations and ideas for colleagues to innovate and develop blood substitutes to benefit the clinical as soon as possible.
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【Objective】 To observe the effect of glutaraldehyde polymerized bovine hemoglobin injection (code: HSRP1) oxygen-carrying fluid on early perfusion of severe hemorrhagic anemia in rabbits. 【Methods】 The rabbit model of controlled severe hemorrhagic anemia was established. Twelve modeled rabbits were divided into glutaraldehyde polymerized bovine hemoglobin injection (code: HSRP1) group and sodium lactate ringer′s injection (LR) group, with 6 rabbits in each group(half male and half female). HSPR1 group and LR group were treated with HSRP1 and LR, respectively. The survival rate of experimental rabbits was observed, and the indexes of hemodynamics, venous blood gas, plasma hemoglobin, base surplus, lactic acid and bicarbonate were measured before and after blood loss, as well as each point within 24 h after infusion. 【Results】 The survival rate of HSRP1 group was significantly different from that of LR group (P<0.05); After exsanguination, the mean arterial pressure of each group was significantly different from that before exsanguination (P<0.05), but there was no significant difference between HSPR1 group and LR group after infusion; In the second stage of perfusion, the blood lactate concentration and base excess in the HSRP1 group were significantly different from those in the LR group at each time point (P<0.05), at 2 h after perfusion, the respiratory rate started to differ significantly from that of the LR group (P<0.05), heart rate was significantly different from LR group at 4 h after perfusion(P<0.05); There were no significant differences between HSRP1 group and LR group in plasma venous oxygen partial pressure, venous oxygen saturation and plasma hemoglobin at all time points. 【Conclusion】 HSPR1 is used for severe traumatic hemorrhagic shock in rabbits, and can improve the survival rate of experimental rabbits by providing oxygen to hypoxic tissues and correcting anaerobic metabolism. As a new oxygen-carrying fluid, HSPR1 can correct the oxygen supply balance of patients with severe hemorrhagicanemia in early stage.
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Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.
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High-quality donor organs is of significance for the success of organ transplantation. However, standard donors fail to meet the requirements of kidney transplantation due to the increasing quantity of patients with kidney failure. Marginal donor kidneys have been widely applied in clinical practice, which also poses challenges to the existing preservation methods of donor kidneys. Ischemia-reperfusion injury (IRI) is one of the critical factors affecting the early graft function after kidney transplantation. In addition, it exerts harmful effect upon the long-term survival of the graft. Current studies have demonstrated that hemoglobin-based oxygen carrier (HBOC) may reduce the IRI during kidney transplantation, effectively improve the preservation quality and prolong the preservation time of donor kidney. In this article, the research progress on HBOC in kidney transplantation was reviewed, aiming to provide reference for modifying the preservation method of donor kidney, improve the quality of donor kidney and enhance clinical prognosis of the recipients.