Background:There is a deficiency of bibliometric and visually represented analysis in research on the immunological related variables involved in bone tissue regeneration.Using bibliometric and visual analysis,this st...Background:There is a deficiency of bibliometric and visually represented analysis in research on the immunological related variables involved in bone tissue regeneration.Using bibliometric and visual analysis,this study sought to thoroughly examine the hotspots and future directions in the investigation of immunological important variables in bone tissue regeneration.Methods:The Web of Science Core Collection(WoSCC)database was searched and a collection of published works on the subject of immunological related factors in bone tissue regeneration between 2000 and 2021 was generated.The data chosen from the WoSCC were then subjected to a systematic bibliometric and visualized analysis using the online bibliometric analytics system,Apache ECharts,VOSviewer,Bibliographic Items Co-occurrence Matrix Builder 2.0,and Gcluto 1.0.Results:For this investigation,1,088 publications on the involvement of immune related components in bone tissue regeneration were chosen.Between 2000 and 2021,China maintained its supremacy in global research on the function of immune related components in bone tissue regeneration.Shanghai Jiao Tong University is the most productive institution.Biomaterials has published the most publications on the involvement of immune-related components in bone tissue regeneration.Xiao Y,Schmidt-Bleek K,and Ignatius A all played important roles in the study of immune-related variables in bone tissue regeneration.Research on the role of immune relevant factors in bone tissue regeneration has identified five hotspots:(1)macrophage-based immunomodulation on osteogenesis of mesenchymal stem cells(MSCs);(2)biomaterials for bone repair in bone tissue engineering;(3)osteoimmunomodulation mediated by inflammation and macrophages during bone healing;(4)osteoimmunomodulation in angiogenesis during bone regeneration;and(5)the effect of macrophage polarization regulated by bone tissue engineering on osteogenic differentiation of MSCs as bone tissue.Conclusion:This study represents the first-ever bibliometric and visualized examination of how immune factors contribute to bone tissue regeneration.The focus and forthcoming direction in bone regeneration research will be on macrophage-driven immunomodulation in the process of bone regeneration.展开更多
Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still po...Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.展开更多
Purpose:To study the effect of early restrictive fluid resuscitation(EFR)on inflammatory and immune factors in patients with severe pelvic fracture(SPF).Methods:A total of 174 SPF patients in the Department of Orthopa...Purpose:To study the effect of early restrictive fluid resuscitation(EFR)on inflammatory and immune factors in patients with severe pelvic fracture(SPF).Methods:A total of 174 SPF patients in the Department of Orthopaedics,the First Affiliated Hospital of Chengdu Medical College from July 2015 to June 2018 were involved in this study and divided into EFR group(n=87)and control group(n=87)using the random number table method.Conventional fluid resuscitation(CFR)was performed in control group,and EFR was performed in EFR group.The incidences of acute respiratory distress syndrome(ARDS)and multiple organ dysfunction syndrome(MODS)during rescue,successful rescue rate,blood transfusion volume,fluid input,and resuscitation time were compared between the two groups.The parameters including prothrombin time(PT),hematocrit(HCT),platelet(PLT)and blood lactate(BL)at the 4th hour after fluid resuscitation were recorded.The levels of inflammatory factors(TNF-α,IL-6,CRP)and immune factors(CD3^+,CD4^+,CD8^+,CD4^+/CD8^+)were compared between the two groups before treatment and 7 days after treatment.The revised acute physiologic and chronic health evaluation system and the sequential organ failure assessment scores were adopted for evaluation before treatment and 7 days after treatment.Results:The incidences of ARDS and MODS during rescue in EFR group were significantly lower than those in control group(p=0.015 and 0.010 respectively),and the successful rescue rate in EFR group was significantly higher than that in control group(p=0.011).The blood transfusion volume,fluid input,resuscitation time in EFR group were significantly lower than those in control group(p=0.016,0.002 and 0.001 respectively).At the 4th hour after fluid resuscitation,PT and BL in EFR group were significantly lower than those in control group(p=0.021 and 0.003 respectively),while HCT and PLT in EFR group were significantly higher than those in control group(p=0.016 and 0.021 respectively).On day 7 after treatment,TNF-α,IL-6,CRP and CD8^+in EFR group were significantly lower than those in control group(p=0.003,0.004,0.007 and 0.003 respectively),while CD3^+,CD4^+and CD4^+/CD8^+in EFR group were significantly higher than those in control group(p=0.004,0.000,0.007 respectively).On day 7 after treatment,the revised acute physiologic and chronic health evaluation(APACHE)system and the sequential organ failure assessment(SOFA)scores in EFR group were significantly lower than those in control group.Conclusion:EFR can effectively eliminate inflammatory factors,improve immune function,maintain the stability of blood components,reduce the incidences of ARDS and MODS,and elevate the successful rescue rate in patients with SPF.展开更多
Hyperimmune sera (HIS), raised against crude giardia antigen, on in vitro interaction, caused more agglutination of Giardia lamblia trophozoites. Heat inactivated HIS possessed a comparable agglutinating activity as t...Hyperimmune sera (HIS), raised against crude giardia antigen, on in vitro interaction, caused more agglutination of Giardia lamblia trophozoites. Heat inactivated HIS possessed a comparable agglutinating activity as the non-inactivated controls. Non-inactivated normal (unimmunized) serum caused immobilization of Giardia trophozoite, which was checked on heat inactivation. Antibodies in immune sera are mainly responsible for agglutination, whereas the heat labile non-immune components control the mobility of the intestinal parasite.展开更多
In this paper,different kinds of enzymes,immune factors and regulatory factors of the immune system of crustaceans are summarized and then combed systematically and thoroughly. According to the mutual influence and ef...In this paper,different kinds of enzymes,immune factors and regulatory factors of the immune system of crustaceans are summarized and then combed systematically and thoroughly. According to the mutual influence and effects of these factors,different symbolic forms are introduced to express the effects,and ultimately the whole node graph of the system is obtained. The graph theory can be used for further researches on the immune system of crustacean.展开更多
With over 40 years of history,occult hepatitis B infection(OBI)continues to remain an important and challenging public health problem.Defined as the presence of replication-competent hepatitis B virus(HBV)DNA(i.e.,epi...With over 40 years of history,occult hepatitis B infection(OBI)continues to remain an important and challenging public health problem.Defined as the presence of replication-competent hepatitis B virus(HBV)DNA(i.e.,episomal HBV covalently closed circular DNA)in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen(HBsAg)in currently available assays,OBI is currently diagnosed using polymerase chain reaction(PCR)and real-time PCR assays.However,all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI.In recent years,significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form.These factors are mainly related to the host immune system and,to a smaller proportion,to the virus.Both innate and adaptive immune responses are important in HBV infection management,and epigenetic changes driven by host mechanisms(acetylation,methylation,and microRNA implication)are added to such actions.Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection,the mechanisms of OBI are not mainly viral mutations.展开更多
The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with...The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with an average body length (BL) of (3.04 ± 0.36) cm and body weight (BW) (0.412± 0.35) g], the large group [GL, with a BL of (4.29±0.55) cm and BW of (1.098 ±0.42) g], and the ungraded group [Gm, with a BL of (3.47±0.81) cm and BW of (0.611 ±0.79) g], were reared under the same conditions for 8 wk. Growth performance and non- specific immunity factors were measured. The results showed that BW gain, biomass gain and the specific growth rate of body length (SGRL) were significantly influenced by size grading (one-way ANOVA, P 〈 0.05). The peroxidase (POD) and antibacterial (Ua) activities of GL were lower than those of G. Superoxide dismutase (SOD) and lysozyme (U1) activities of Gm were lower than those of G. No significant difference (P = 0.121 〉 0.05) was found on phenoloxidase (PO) activity among the three size groups. Synthetically, size grading could enhance growth and rearing efficiency, and did not have a significant influence on the immunity of L. vannamei Boone. Therefore, graded fanning in L. vannamei Boone was feasible in the culture practice.展开更多
The author measured the immune function of erythrocyte in 50 cases of noninsulin dependent diabetes mellitus(NIDDM),and researched the effect of erythrocyte immune adherence adjustmeat factor on the immune function of...The author measured the immune function of erythrocyte in 50 cases of noninsulin dependent diabetes mellitus(NIDDM),and researched the effect of erythrocyte immune adherence adjustmeat factor on the immune function of erythrocyte. The results showed that in patients with NIDDM,erythrocyte C3b receptor rosette forming rate(ECRRFR)was much higher(P<0.01),erythrocyte immune adherence exciting factor(EIAEF)was much lower than that of normal controlgroup(P<0.01);erythrocyte immune complexes rosette forming rate(EICRFR)was much lower,and erythrocyte immune adherence inhibiting factor(EIAIF)was much nigher than that of normalPersons(P<0.01).The study also showed that a significant positive correlation was found betweenthe activation of erythrocyte C3b receptor and EIAEF,and a significant negative correlation wasfound between the activation of erythrocyte C3b receptor and EIAIF.展开更多
Summary Salicylic acid (SA) is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 (ICS1), whose gene transcription is controlled mai...Summary Salicylic acid (SA) is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 (ICS1), whose gene transcription is controlled mainly through two redundant transcription factors, SAR Deficient 1 (SARD0 and Calmodulin- binding protein 6o-like g (CBP60g).展开更多
Objective: To investigate whether Shen-Fu Injection(参附注射液, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes(Treg) in...Objective: To investigate whether Shen-Fu Injection(参附注射液, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes(Treg) in the spleen. Methods: After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine(EP) group, and saline(SA) group(8 in each group), which received central venous injection of SFI(1.0 m L/kg), EP(0.02 mg/kg) and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated(sham) group(n=6). After successful return of spontaneous circulation(ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the m RNA expression of forkhead/winged helix transcription factor(Foxp3) of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4(IL-4) and interferon-γ(IFN-γ) in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay(ELISA). Results: Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 m RNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group(P〈0.05 or P〈0.01). Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 m RNA expression, IFN-γ and IFN-γ/IL-4(P〈0.05). Conclusions: SFI has significant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.展开更多
文摘Background:There is a deficiency of bibliometric and visually represented analysis in research on the immunological related variables involved in bone tissue regeneration.Using bibliometric and visual analysis,this study sought to thoroughly examine the hotspots and future directions in the investigation of immunological important variables in bone tissue regeneration.Methods:The Web of Science Core Collection(WoSCC)database was searched and a collection of published works on the subject of immunological related factors in bone tissue regeneration between 2000 and 2021 was generated.The data chosen from the WoSCC were then subjected to a systematic bibliometric and visualized analysis using the online bibliometric analytics system,Apache ECharts,VOSviewer,Bibliographic Items Co-occurrence Matrix Builder 2.0,and Gcluto 1.0.Results:For this investigation,1,088 publications on the involvement of immune related components in bone tissue regeneration were chosen.Between 2000 and 2021,China maintained its supremacy in global research on the function of immune related components in bone tissue regeneration.Shanghai Jiao Tong University is the most productive institution.Biomaterials has published the most publications on the involvement of immune-related components in bone tissue regeneration.Xiao Y,Schmidt-Bleek K,and Ignatius A all played important roles in the study of immune-related variables in bone tissue regeneration.Research on the role of immune relevant factors in bone tissue regeneration has identified five hotspots:(1)macrophage-based immunomodulation on osteogenesis of mesenchymal stem cells(MSCs);(2)biomaterials for bone repair in bone tissue engineering;(3)osteoimmunomodulation mediated by inflammation and macrophages during bone healing;(4)osteoimmunomodulation in angiogenesis during bone regeneration;and(5)the effect of macrophage polarization regulated by bone tissue engineering on osteogenic differentiation of MSCs as bone tissue.Conclusion:This study represents the first-ever bibliometric and visualized examination of how immune factors contribute to bone tissue regeneration.The focus and forthcoming direction in bone regeneration research will be on macrophage-driven immunomodulation in the process of bone regeneration.
基金financially supported by the Key Project of Zhejiang Provincial Natural Science Foundation of China(LZ22C200003)the National Natural Science Foundation of China(32072290)。
文摘Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.
文摘Purpose:To study the effect of early restrictive fluid resuscitation(EFR)on inflammatory and immune factors in patients with severe pelvic fracture(SPF).Methods:A total of 174 SPF patients in the Department of Orthopaedics,the First Affiliated Hospital of Chengdu Medical College from July 2015 to June 2018 were involved in this study and divided into EFR group(n=87)and control group(n=87)using the random number table method.Conventional fluid resuscitation(CFR)was performed in control group,and EFR was performed in EFR group.The incidences of acute respiratory distress syndrome(ARDS)and multiple organ dysfunction syndrome(MODS)during rescue,successful rescue rate,blood transfusion volume,fluid input,and resuscitation time were compared between the two groups.The parameters including prothrombin time(PT),hematocrit(HCT),platelet(PLT)and blood lactate(BL)at the 4th hour after fluid resuscitation were recorded.The levels of inflammatory factors(TNF-α,IL-6,CRP)and immune factors(CD3^+,CD4^+,CD8^+,CD4^+/CD8^+)were compared between the two groups before treatment and 7 days after treatment.The revised acute physiologic and chronic health evaluation system and the sequential organ failure assessment scores were adopted for evaluation before treatment and 7 days after treatment.Results:The incidences of ARDS and MODS during rescue in EFR group were significantly lower than those in control group(p=0.015 and 0.010 respectively),and the successful rescue rate in EFR group was significantly higher than that in control group(p=0.011).The blood transfusion volume,fluid input,resuscitation time in EFR group were significantly lower than those in control group(p=0.016,0.002 and 0.001 respectively).At the 4th hour after fluid resuscitation,PT and BL in EFR group were significantly lower than those in control group(p=0.021 and 0.003 respectively),while HCT and PLT in EFR group were significantly higher than those in control group(p=0.016 and 0.021 respectively).On day 7 after treatment,TNF-α,IL-6,CRP and CD8^+in EFR group were significantly lower than those in control group(p=0.003,0.004,0.007 and 0.003 respectively),while CD3^+,CD4^+and CD4^+/CD8^+in EFR group were significantly higher than those in control group(p=0.004,0.000,0.007 respectively).On day 7 after treatment,the revised acute physiologic and chronic health evaluation(APACHE)system and the sequential organ failure assessment(SOFA)scores in EFR group were significantly lower than those in control group.Conclusion:EFR can effectively eliminate inflammatory factors,improve immune function,maintain the stability of blood components,reduce the incidences of ARDS and MODS,and elevate the successful rescue rate in patients with SPF.
文摘Hyperimmune sera (HIS), raised against crude giardia antigen, on in vitro interaction, caused more agglutination of Giardia lamblia trophozoites. Heat inactivated HIS possessed a comparable agglutinating activity as the non-inactivated controls. Non-inactivated normal (unimmunized) serum caused immobilization of Giardia trophozoite, which was checked on heat inactivation. Antibodies in immune sera are mainly responsible for agglutination, whereas the heat labile non-immune components control the mobility of the intestinal parasite.
文摘In this paper,different kinds of enzymes,immune factors and regulatory factors of the immune system of crustaceans are summarized and then combed systematically and thoroughly. According to the mutual influence and effects of these factors,different symbolic forms are introduced to express the effects,and ultimately the whole node graph of the system is obtained. The graph theory can be used for further researches on the immune system of crustacean.
文摘With over 40 years of history,occult hepatitis B infection(OBI)continues to remain an important and challenging public health problem.Defined as the presence of replication-competent hepatitis B virus(HBV)DNA(i.e.,episomal HBV covalently closed circular DNA)in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen(HBsAg)in currently available assays,OBI is currently diagnosed using polymerase chain reaction(PCR)and real-time PCR assays.However,all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI.In recent years,significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form.These factors are mainly related to the host immune system and,to a smaller proportion,to the virus.Both innate and adaptive immune responses are important in HBV infection management,and epigenetic changes driven by host mechanisms(acetylation,methylation,and microRNA implication)are added to such actions.Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection,the mechanisms of OBI are not mainly viral mutations.
基金supported by the National High-TechR&D Program of China (2004BA526B02)the Natural Science Foundation of Qingdao Agricultural Univesity,China (610804)the High Level Talents Fund of Qingdao Agricultural University, China (630628)
文摘The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with an average body length (BL) of (3.04 ± 0.36) cm and body weight (BW) (0.412± 0.35) g], the large group [GL, with a BL of (4.29±0.55) cm and BW of (1.098 ±0.42) g], and the ungraded group [Gm, with a BL of (3.47±0.81) cm and BW of (0.611 ±0.79) g], were reared under the same conditions for 8 wk. Growth performance and non- specific immunity factors were measured. The results showed that BW gain, biomass gain and the specific growth rate of body length (SGRL) were significantly influenced by size grading (one-way ANOVA, P 〈 0.05). The peroxidase (POD) and antibacterial (Ua) activities of GL were lower than those of G. Superoxide dismutase (SOD) and lysozyme (U1) activities of Gm were lower than those of G. No significant difference (P = 0.121 〉 0.05) was found on phenoloxidase (PO) activity among the three size groups. Synthetically, size grading could enhance growth and rearing efficiency, and did not have a significant influence on the immunity of L. vannamei Boone. Therefore, graded fanning in L. vannamei Boone was feasible in the culture practice.
文摘The author measured the immune function of erythrocyte in 50 cases of noninsulin dependent diabetes mellitus(NIDDM),and researched the effect of erythrocyte immune adherence adjustmeat factor on the immune function of erythrocyte. The results showed that in patients with NIDDM,erythrocyte C3b receptor rosette forming rate(ECRRFR)was much higher(P<0.01),erythrocyte immune adherence exciting factor(EIAEF)was much lower than that of normal controlgroup(P<0.01);erythrocyte immune complexes rosette forming rate(EICRFR)was much lower,and erythrocyte immune adherence inhibiting factor(EIAIF)was much nigher than that of normalPersons(P<0.01).The study also showed that a significant positive correlation was found betweenthe activation of erythrocyte C3b receptor and EIAEF,and a significant negative correlation wasfound between the activation of erythrocyte C3b receptor and EIAIF.
基金supported by grants from the Natural Sciences and Engineering Research Council of Canada(NSERC)Discovery programthe Dewar Cooper Memorial Fund from the University of British Columbia(UBC)+1 种基金partially supported by a 4YF scholarship from UBCpartially supported by a Chinese Scholarship Council(CSC)fellowship
文摘Summary Salicylic acid (SA) is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 (ICS1), whose gene transcription is controlled mainly through two redundant transcription factors, SAR Deficient 1 (SARD0 and Calmodulin- binding protein 6o-like g (CBP60g).
基金Supported by the National Natural Science Foundation of China(No.81372025)Basic and Clinical Research Cooperation Project of Capital Medical University(No.15JL42)Beijing Municipal Administration of Hospitals Incubating Program(No.Px2016022)
文摘Objective: To investigate whether Shen-Fu Injection(参附注射液, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes(Treg) in the spleen. Methods: After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine(EP) group, and saline(SA) group(8 in each group), which received central venous injection of SFI(1.0 m L/kg), EP(0.02 mg/kg) and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated(sham) group(n=6). After successful return of spontaneous circulation(ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the m RNA expression of forkhead/winged helix transcription factor(Foxp3) of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4(IL-4) and interferon-γ(IFN-γ) in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay(ELISA). Results: Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 m RNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group(P〈0.05 or P〈0.01). Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 m RNA expression, IFN-γ and IFN-γ/IL-4(P〈0.05). Conclusions: SFI has significant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.