Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not ...Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.展开更多
[Objectives]The effects of bag types on the appearance and internal quality of red Massh grapefruit were studied.[Methods]Outer-yellow inner-black double-layer pomelo special paper bags,white single-layer paper bags,y...[Objectives]The effects of bag types on the appearance and internal quality of red Massh grapefruit were studied.[Methods]Outer-yellow inner-black double-layer pomelo special paper bags,white single-layer paper bags,yellow plastic film bags,and red plastic film bags were used to cover the fruit of red Massh grapefruit.With the fruit free of bagging as a control,the effects of fruit bags with different materials were compared.[Results]The four kinds of fruit bag treatments effectively reduced pests and diseases,and increased the good fruit rate,and the effects of paper bag treatments were better than those of film bags.The outer-yellow inner-black double-layer pomelo special paper bags had good air permeability and were easy to operate.The bagged fruit had a smooth and beautiful surface and showed a unique uniform pink color after removing the bags.The fruit had moderate sour and sweet flavor and good overall benefits.It is worthy of popularization and application.[Conclusions]Fruit bagging has good economic benefits,and it is recommended to use the outer-yellow inner-black double-layer pomelo special paper bags.展开更多
Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography （kV-CBCT） and their dosimetric consequences for non-operative lung cancer during intensity-modul...Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography （kV-CBCT） and their dosimetric consequences for non-operative lung cancer during intensity-modulated radiotherapy （IMRT） or fractionated stereotactic radiotherapy. Methods Eighteen patients with non-operative lung cancer who received IMRT consisting of 1.8-2.2 Gy/fraction and five fractions per week or stereotactic radiotherapy with 5-8 Gy/fraction and three fractions a week were studied, kV-CBCT was performed once per week during IMRT and at every fraction during stereotactic radiotherapy. The gross tumor volume （GTV） was contoured on the kV-CBCT images, and adaptive treatment plans were created using merged kV-CBCT and primary planning computed tomogra- phy image sets. Tumor volume changes and dosimetric parameters, including the minimum dose to 95% （D95） or 1% （D1） of the planning target volume （PTV）, mean lung dose （MLD）, and volume of lung tissue that received more than 5 （Vs）, 10 （Vl0）, 20 （V20）, and 30 （V30） Gy were retrospectively analyzed. Results The average maximum change in GTV observed during IMRT or fractionated stereotactic radio- therapy was -25.85% （range, -13.09% --56.76%）. The D95 and Dr of PTV for the adaptive treatment plans in all patients were not significantly different from those for the initial or former adaptive treatment plans. In patients with tumor volume changes of 〉20% in the third or fourth week of treatment during IMRT, adap- tive treatment plans offered clinically meaningful decreases in MLD and V5, V10, V20, and V30; however, in patients with tumor volume changes of 〈 20% in the third or fourth week of treatment as well as in patients with stereotactic radiotherapy, there were no significant or clinically meaningful decreases in the dosimetric parameters. Conclusion Adaptive treatment planning for decreasing tumor volume during IMRT may be beneficial for patients who experience tumor volume changes of 〉20% in the third or fourth week of treatment.展开更多
To the Editor:Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)has replaced other high-risk invasive methods and has become the primary method of tissue collection around the gastrointestinal tract.^([1])To...To the Editor:Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)has replaced other high-risk invasive methods and has become the primary method of tissue collection around the gastrointestinal tract.^([1])To further improve the effectiveness and safety of EUS-FNA,pathologists may perform rapid on-site cytology evaluation(ROSE),but this process requires the presence of pathologists.Macroscopic on-site evaluation(MOSE)has gained attention as it resolve the shortage of pathologist resources.^([2])Endoscopists can inspect the tissue core in real time and assess the adequacy of the punctured material.In this study,we conducted a single-center and single-arm exploratory study to explore the value of MOSE in assessing specimen quality during magnifier-based EUS-FNA and to confirm the cut-off length of visible tissue core(VTC)for EUS-FNA to help endosonographers independently predict the adequacy of punctured specimens.The VTC was defined as a white or incarnadine tissue core obtained from focal lesions with a relatively complete histological structure.展开更多
In higher plants, the splicing of organelle-encoded mRNA involves a complex collaboration with nuclear- encoded proteins. Pentatricopeptide repeat （PPR） proteins have been implicated in these RNA-protein interaction...In higher plants, the splicing of organelle-encoded mRNA involves a complex collaboration with nuclear- encoded proteins. Pentatricopeptide repeat （PPR） proteins have been implicated in these RNA-protein interactions. In this study, we performed the cloning and functional characterization of maize Defective kernel 35 （Dek35）. The dek35-ref mutant is a lethal-seed mutant with developmental deficiency. Dek35 was cloned through Mutator tag isolation and further confirmed by four additional independent mutant alleles. Dek35 encodes an P-type PPR protein that targets the mitochondria. The dek35 mutation causes significant reduction in the accumulation of DEK35 proteins and reduced splicing efficiency of mitochon- drial nad4 intron 1. Analysis of mitochondrial complex in dek35 immature seeds indicated severe deficiency in the complex I assembly and NADH dehydrogenase activity. Transcriptome analysis of dek35 endosperm revealed enhanced expression of genes involved in the alternative respiratory pathway and extensive differentially expressed genes related to mitochondrial function and activity. Collectively, these results indicate that Dek35 encodes an PPR protein that affects the cis-splicing of mitochondrial nad4 intron 1 and is required for mitochondrial function and seed development.展开更多
With the development of tissue engineering and regenerative medicine,it is much desired to establish bioimaging techniques to monitor the real-time regeneration efficacy in vivo in a non-invasive way.Herein,we tried m...With the development of tissue engineering and regenerative medicine,it is much desired to establish bioimaging techniques to monitor the real-time regeneration efficacy in vivo in a non-invasive way.Herein,we tried magnetic resonance imaging(MRI)to evaluate knee cartilage regeneration after implanting a biomaterial scaffold seeded with chondrocytes,namely,matrix-induced autologous chondrocyte implantation(MACI).After summary of the T2 mapping and the T1-related delayed gadolinium-enhanced MRI imaging of cartilage(dGEMRIC)in vitro and in vivo in the literature,these two MRI techniques were tried clinically.In this study,18 patients were followed up for 1 year.It was found that there was a significant difference between the regeneration site and the neighboring normal site(control),and the difference gradually diminished with regeneration time up to 1 year according to both the quantitative T1 and T2 MRI methods.We further established the correlation between the quantitative evaluation of MRI and the clinical Lysholm scores for the first time.Hence,the MRI technique was confirmed to be a feasible semiquantitative yet non-invasive way to evaluate the in vivo regeneration of knee articular cartilage.展开更多
Magnetic resonance imaging(MRI)is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracel...Magnetic resonance imaging(MRI)is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracellular matrix(ECM).To this end,in vitro experiments are performed to investigate the relationship and reveal the underlying mechanism.A series of collagen(COL)and glycosaminoglycan(GAG)solutions at different concentrations are prepared,and T_(1)and T_(2)relaxation times are measured with or without a contrast agent(Gd-DTPA2−)by MRI.Fourier transform infrared spectrometry is also used to measure the contents of biomacromolecule-bound water and other water,allowing theoretical derivation of the relationship between biomacromolecules and the resulting T_(2)values.It has been revealed that the MRI signal in the biomacromolecule aqueous systems is mainly influenced by the protons in hydrogens of biomacromolecule-bound water,which we divide into inner-bound water and outer-bound water.We have also found that COL results in higher sensitivity of bound water than GAG in T_(2)mapping.Owing to the charge effect,GAG regulates the penetration of the contrast agent during dialysis and has a more significant effect on T_(1)values than COL.Considering that COL and GAG are the most abundant biomacromolecules in the cartilage,this study is particularly useful for the real-time MRI-guided assessment of cartilage regeneration.A clinical case is reported as an in vivo demonstration,which is consistent with our in vitro results.The established quantitative relation plays a critical academic role in establishing an international standard ISO/TS24560-1:2022‘Clinical evaluation of regenerative knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage(dGEMRIC)and T_(2)mapping’drafted by us and approved by International Standard Organization.展开更多
The xenogeneic decellularized corneal matrix(DCM)was expected to be used in lamellar keratoplasty in clinic as the substitute of allogeneic cornea.After decellularization treatment,the remaining risk of xenograft reje...The xenogeneic decellularized corneal matrix(DCM)was expected to be used in lamellar keratoplasty in clinic as the substitute of allogeneic cornea.After decellularization treatment,the remaining risk of xenograft rejection needed to be assessed.The galactose-α1,3-galactose,as the most abundant and closely rejection-related xenogeneic antigen,should be one of the important factors concerned in immunological evaluation.In this study,residual αGal in the DCM was first determined by an enzyme-linked immunosorbent assay method with qualified accuracy and specificity.Then the DCM was implanted subcutaneously into the α1,3-galactosyltransferase gene-knockout(GTKO)mice,accompanied by the implantation in the wild-type C57BL/6 mice as a comparison.The total serum antibody levels,anti-Gal antibody levels,inflammatory cytokines and ratios of splenic lymphocyte subtypes were detected and the histopathological analysis of implants were performed to systematically evaluate the immune responses.The experimental result showed the fresh porcine corneal matrix samples had(9.90±1.54)×10^12 αGal epitope per mg while the content of residual aGal in the DCM was(7.90±2.00)×10^12 epitope per mg.The GTKO mice had similar potential of reaction to immune stimulation to that of wild-type C57BL/6 mice.At 4 weeks after implantation of DCM,in WT mice and GTKO mice there were both innate immunity response to the DCM characterized by macrophage infiltration.But the elevations of anti-Gal IgG level and the percentage of splenic natural killer cells were only detected in GTKO mice.These changes were thought to be pertinent to the residual αGal antigen,which could not be detected in WT mice.No further αGal antibody-mediated cellular immunity and significant changes of serum cytokine contents were found in GTKO mice,which perhaps suggested that the immune reactions to the DCM after 4 weeks of implantation were moderate and had minor effect on the survival of the corneal graft.展开更多
Multimodal medical imaging of human pathological tissues provides comprehensive information to assist in clinical diagnosis.However,due to the high cost of imaging,physiological incompatibility,and the harmfulness of ...Multimodal medical imaging of human pathological tissues provides comprehensive information to assist in clinical diagnosis.However,due to the high cost of imaging,physiological incompatibility,and the harmfulness of radioactive tracers,multimodal medical image data remains scarce.Currently,cross-modal medical synthesis methods can generate desired modal images from existing modal images.However,most existing methods are limited to specific domains.This paper proposes an Adaptive Domain Medical Image Synthesis Method based on Generative Adversarial Networks(ADGAN)to address this issue.ADGAN achieves multidirectional medical image synthesis and ensures pathological consistency by constructing a single generator to learn the latent shared representation of multiple domains.The generator employs dense connections in shallow layers to preserve edge details and incorporates auxiliary information in deep layers to retain pathological features.Additionally,spectral normalization is introduced into the discriminator to control discriminative performance and indirectly enhance the image synthesis ability of the generator.Theoretically,it can be proved that the proposed method can be trained quickly,and spectral normalization contributes to adaptive and multidirectional synthesis.In practice,comparing with recent state-of-the-art methods,ADGAN achieves average increments of 4.7%SSIM,6.7%MSIM,7.3%PSNR,and 9.2%VIF.展开更多
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2219-195 and No.BJ-2023-090).
文摘Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.
基金2015 Guangxi Higher Institutions Scientific Research Project(KY2015YB428)Professional(Academic)Leaders and Young and Middle-aged Backbone Teachers(GNZY[2016]33).
文摘[Objectives]The effects of bag types on the appearance and internal quality of red Massh grapefruit were studied.[Methods]Outer-yellow inner-black double-layer pomelo special paper bags,white single-layer paper bags,yellow plastic film bags,and red plastic film bags were used to cover the fruit of red Massh grapefruit.With the fruit free of bagging as a control,the effects of fruit bags with different materials were compared.[Results]The four kinds of fruit bag treatments effectively reduced pests and diseases,and increased the good fruit rate,and the effects of paper bag treatments were better than those of film bags.The outer-yellow inner-black double-layer pomelo special paper bags had good air permeability and were easy to operate.The bagged fruit had a smooth and beautiful surface and showed a unique uniform pink color after removing the bags.The fruit had moderate sour and sweet flavor and good overall benefits.It is worthy of popularization and application.[Conclusions]Fruit bagging has good economic benefits,and it is recommended to use the outer-yellow inner-black double-layer pomelo special paper bags.
文摘Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography （kV-CBCT） and their dosimetric consequences for non-operative lung cancer during intensity-modulated radiotherapy （IMRT） or fractionated stereotactic radiotherapy. Methods Eighteen patients with non-operative lung cancer who received IMRT consisting of 1.8-2.2 Gy/fraction and five fractions per week or stereotactic radiotherapy with 5-8 Gy/fraction and three fractions a week were studied, kV-CBCT was performed once per week during IMRT and at every fraction during stereotactic radiotherapy. The gross tumor volume （GTV） was contoured on the kV-CBCT images, and adaptive treatment plans were created using merged kV-CBCT and primary planning computed tomogra- phy image sets. Tumor volume changes and dosimetric parameters, including the minimum dose to 95% （D95） or 1% （D1） of the planning target volume （PTV）, mean lung dose （MLD）, and volume of lung tissue that received more than 5 （Vs）, 10 （Vl0）, 20 （V20）, and 30 （V30） Gy were retrospectively analyzed. Results The average maximum change in GTV observed during IMRT or fractionated stereotactic radio- therapy was -25.85% （range, -13.09% --56.76%）. The D95 and Dr of PTV for the adaptive treatment plans in all patients were not significantly different from those for the initial or former adaptive treatment plans. In patients with tumor volume changes of 〉20% in the third or fourth week of treatment during IMRT, adap- tive treatment plans offered clinically meaningful decreases in MLD and V5, V10, V20, and V30; however, in patients with tumor volume changes of 〈 20% in the third or fourth week of treatment as well as in patients with stereotactic radiotherapy, there were no significant or clinically meaningful decreases in the dosimetric parameters. Conclusion Adaptive treatment planning for decreasing tumor volume during IMRT may be beneficial for patients who experience tumor volume changes of 〉20% in the third or fourth week of treatment.
基金supported by the Program for GUSU medicine talents(No.GSWS2020026)Program for Suzhou Science and Technology Project(No.SKY2021044)the State Key Laboratory of Radiology Medicine and Radiation Protection(No.GZK1202214)
文摘To the Editor:Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)has replaced other high-risk invasive methods and has become the primary method of tissue collection around the gastrointestinal tract.^([1])To further improve the effectiveness and safety of EUS-FNA,pathologists may perform rapid on-site cytology evaluation(ROSE),but this process requires the presence of pathologists.Macroscopic on-site evaluation(MOSE)has gained attention as it resolve the shortage of pathologist resources.^([2])Endoscopists can inspect the tissue core in real time and assess the adequacy of the punctured material.In this study,we conducted a single-center and single-arm exploratory study to explore the value of MOSE in assessing specimen quality during magnifier-based EUS-FNA and to confirm the cut-off length of visible tissue core(VTC)for EUS-FNA to help endosonographers independently predict the adequacy of punctured specimens.The VTC was defined as a white or incarnadine tissue core obtained from focal lesions with a relatively complete histological structure.
文摘In higher plants, the splicing of organelle-encoded mRNA involves a complex collaboration with nuclear- encoded proteins. Pentatricopeptide repeat （PPR） proteins have been implicated in these RNA-protein interactions. In this study, we performed the cloning and functional characterization of maize Defective kernel 35 （Dek35）. The dek35-ref mutant is a lethal-seed mutant with developmental deficiency. Dek35 was cloned through Mutator tag isolation and further confirmed by four additional independent mutant alleles. Dek35 encodes an P-type PPR protein that targets the mitochondria. The dek35 mutation causes significant reduction in the accumulation of DEK35 proteins and reduced splicing efficiency of mitochon- drial nad4 intron 1. Analysis of mitochondrial complex in dek35 immature seeds indicated severe deficiency in the complex I assembly and NADH dehydrogenase activity. Transcriptome analysis of dek35 endosperm revealed enhanced expression of genes involved in the alternative respiratory pathway and extensive differentially expressed genes related to mitochondrial function and activity. Collectively, these results indicate that Dek35 encodes an PPR protein that affects the cis-splicing of mitochondrial nad4 intron 1 and is required for mitochondrial function and seed development.
基金supported by National Key Research and Development Program of China(grant no.2018YFC1105900,2016YFC1100300 and 2016YFC1103203)National Natural Science Foundation of China(grant no.21961160721).
文摘With the development of tissue engineering and regenerative medicine,it is much desired to establish bioimaging techniques to monitor the real-time regeneration efficacy in vivo in a non-invasive way.Herein,we tried magnetic resonance imaging(MRI)to evaluate knee cartilage regeneration after implanting a biomaterial scaffold seeded with chondrocytes,namely,matrix-induced autologous chondrocyte implantation(MACI).After summary of the T2 mapping and the T1-related delayed gadolinium-enhanced MRI imaging of cartilage(dGEMRIC)in vitro and in vivo in the literature,these two MRI techniques were tried clinically.In this study,18 patients were followed up for 1 year.It was found that there was a significant difference between the regeneration site and the neighboring normal site(control),and the difference gradually diminished with regeneration time up to 1 year according to both the quantitative T1 and T2 MRI methods.We further established the correlation between the quantitative evaluation of MRI and the clinical Lysholm scores for the first time.Hence,the MRI technique was confirmed to be a feasible semiquantitative yet non-invasive way to evaluate the in vivo regeneration of knee articular cartilage.
基金supported by National Natural Science Foundation of China(grant no.52130302).W。
文摘Magnetic resonance imaging(MRI)is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracellular matrix(ECM).To this end,in vitro experiments are performed to investigate the relationship and reveal the underlying mechanism.A series of collagen(COL)and glycosaminoglycan(GAG)solutions at different concentrations are prepared,and T_(1)and T_(2)relaxation times are measured with or without a contrast agent(Gd-DTPA2−)by MRI.Fourier transform infrared spectrometry is also used to measure the contents of biomacromolecule-bound water and other water,allowing theoretical derivation of the relationship between biomacromolecules and the resulting T_(2)values.It has been revealed that the MRI signal in the biomacromolecule aqueous systems is mainly influenced by the protons in hydrogens of biomacromolecule-bound water,which we divide into inner-bound water and outer-bound water.We have also found that COL results in higher sensitivity of bound water than GAG in T_(2)mapping.Owing to the charge effect,GAG regulates the penetration of the contrast agent during dialysis and has a more significant effect on T_(1)values than COL.Considering that COL and GAG are the most abundant biomacromolecules in the cartilage,this study is particularly useful for the real-time MRI-guided assessment of cartilage regeneration.A clinical case is reported as an in vivo demonstration,which is consistent with our in vitro results.The established quantitative relation plays a critical academic role in establishing an international standard ISO/TS24560-1:2022‘Clinical evaluation of regenerative knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage(dGEMRIC)and T_(2)mapping’drafted by us and approved by International Standard Organization.
基金supported by the funds from National Key Research and Development Program of Ministry of science and technology of China(2016YFC1103200 and 2016YFC1103203).
文摘The xenogeneic decellularized corneal matrix(DCM)was expected to be used in lamellar keratoplasty in clinic as the substitute of allogeneic cornea.After decellularization treatment,the remaining risk of xenograft rejection needed to be assessed.The galactose-α1,3-galactose,as the most abundant and closely rejection-related xenogeneic antigen,should be one of the important factors concerned in immunological evaluation.In this study,residual αGal in the DCM was first determined by an enzyme-linked immunosorbent assay method with qualified accuracy and specificity.Then the DCM was implanted subcutaneously into the α1,3-galactosyltransferase gene-knockout(GTKO)mice,accompanied by the implantation in the wild-type C57BL/6 mice as a comparison.The total serum antibody levels,anti-Gal antibody levels,inflammatory cytokines and ratios of splenic lymphocyte subtypes were detected and the histopathological analysis of implants were performed to systematically evaluate the immune responses.The experimental result showed the fresh porcine corneal matrix samples had(9.90±1.54)×10^12 αGal epitope per mg while the content of residual aGal in the DCM was(7.90±2.00)×10^12 epitope per mg.The GTKO mice had similar potential of reaction to immune stimulation to that of wild-type C57BL/6 mice.At 4 weeks after implantation of DCM,in WT mice and GTKO mice there were both innate immunity response to the DCM characterized by macrophage infiltration.But the elevations of anti-Gal IgG level and the percentage of splenic natural killer cells were only detected in GTKO mice.These changes were thought to be pertinent to the residual αGal antigen,which could not be detected in WT mice.No further αGal antibody-mediated cellular immunity and significant changes of serum cytokine contents were found in GTKO mice,which perhaps suggested that the immune reactions to the DCM after 4 weeks of implantation were moderate and had minor effect on the survival of the corneal graft.
基金supported by the National Natural Science Foundation of China(Nos.62176217 and 62206224)the Innovation Team Funds of China West Normal University(No.KCXTD2022-3)+2 种基金the Postdoctoral Science Foundation of China(No.2023M732428)the Natural Science Foundation of Sichuan Province(No.2022NSFSC0866)the Doctoral Research Innovation Project(No.21E025).
文摘Multimodal medical imaging of human pathological tissues provides comprehensive information to assist in clinical diagnosis.However,due to the high cost of imaging,physiological incompatibility,and the harmfulness of radioactive tracers,multimodal medical image data remains scarce.Currently,cross-modal medical synthesis methods can generate desired modal images from existing modal images.However,most existing methods are limited to specific domains.This paper proposes an Adaptive Domain Medical Image Synthesis Method based on Generative Adversarial Networks(ADGAN)to address this issue.ADGAN achieves multidirectional medical image synthesis and ensures pathological consistency by constructing a single generator to learn the latent shared representation of multiple domains.The generator employs dense connections in shallow layers to preserve edge details and incorporates auxiliary information in deep layers to retain pathological features.Additionally,spectral normalization is introduced into the discriminator to control discriminative performance and indirectly enhance the image synthesis ability of the generator.Theoretically,it can be proved that the proposed method can be trained quickly,and spectral normalization contributes to adaptive and multidirectional synthesis.In practice,comparing with recent state-of-the-art methods,ADGAN achieves average increments of 4.7%SSIM,6.7%MSIM,7.3%PSNR,and 9.2%VIF.
