BACKGROUND C3 glomerulopathies(C3G)are a rare cause of kidney failure resulting from complement dysregulation.Small studies demonstrate a high rate of recurrence and poor outcomes in kidney transplantation.Treatment e...BACKGROUND C3 glomerulopathies(C3G)are a rare cause of kidney failure resulting from complement dysregulation.Small studies demonstrate a high rate of recurrence and poor outcomes in kidney transplantation.Treatment efficacy in this setting with eculizumab,a terminal complement inhibitor,is largely unknown.AIM To determine the outcomes of kidney transplantation in patients with C3G and the potential impact of eculizumab.METHODS We retrospectively studied kidney transplant recipients who underwent a post-transplant biopsy confirming C3G between January 1,1993 and December 31,2023 at a single center.Only the first episode of kidney transplant was reviewed.The electronic medical records were reviewed for post-transplant allograft function,indication for biopsy,time to biopsy from transplant,time to allograft failure from transplantation,post-C3G treatment,complement laboratory testing,and concurrent malignancy/infection.Reports,and when available slides and immunofluorescence/electron microscopic images,were re-reviewed by a renal pathologist.RESULTS A total of fifteen patients were included in this study.Fourteen patients had suspected recurrent disease,with a pre-transplant native kidney report of C3G.One patient developed de novo C3G.Median post kidney transplant clinical follow up time was 91 months.Median time to recurrence was 7 months with median graft survival of 48 months post kidney transplantation.The most common index biopsy pattern of injury was endocapillary prolif-erative glomerulonephritis(often with exudative features)with or without mesangial hypercellularity(56%)followed by membranoproliferative glomerulonephritis(25%).Most patients developed membranoproliferative glomerulonephritis pattern of injury on follow up biopsies(63%).Seven patients with recurrent disease received treatment with eculizumab with a median graft survival of 73 months,with five functioning grafts by the end of the study period.Seven patients with recurrent disease did not receive therapy,and all lost their graft with a median graft survival of 22 months(P=0.003).CONCLUSION C3G following kidney transplantation is mostly a recurrent disorder with a poor prognosis in untreated patients.Untreated recurrence has a poor prognosis with median allograft survival<2 years.Early treatment with eculizumab may improve transplant outcomes in patients with recurrent C3G.展开更多
BACKGROUND Esophageal cancer is a common malignancy with high mortality.Radiotherapy is an important treatment.Sarcopenia affects patients'physical function and prog-nosis.However,the relationship between sarcopen...BACKGROUND Esophageal cancer is a common malignancy with high mortality.Radiotherapy is an important treatment.Sarcopenia affects patients'physical function and prog-nosis.However,the relationship between sarcopenia diagnosed by Chun-Hou Chen method for sarcopenia measurement and index(C3SMI)criteria and eso-phageal cancer prognosis after radiotherapy is unclear.AIM To explore the correlation between sarcopenia(SA)diagnosed based on C3SMI criteria and the prognosis of patients with esophageal cancer following radiothe-rapy.METHODS A retrospective analysis was conducted on the general clinical data of 131 eso-phageal cancer patients who received radiotherapy in the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University from March 2021 to July 2024.Based on the presence of SA,the patients were assigned into two groups-the SA group and the non-SA group.Logistic regression analysis was used for investi-gating the risk factors influencing SA in esophageal cancer patients.Additionally,the patients were followed up,with their prognosis recorded.As per their prognostic outcomes,the patients were allocated into a good prognosis group and a poor prognosis group.The data of the two groups were compared.Using logistic regression analysis,the risk factors that may influence the prognosis of these patients were analyzed.SPSS 26.0 statistical software was introduced for analyzing the study data.Comparisons were made between groups using t-tests or χ_(2) tests based on the data type.RESULTS As revealed through logistic regression analysis,age[odds ratio(OR)=2.898,P=0.038],body mass index(OR=5.983,P=0.006),prealbumin(OR=6.253,P=0.003),and Karnofsky performance status score(OR=3.854,P=0.010)were independent risk factors impacting SA for esophageal cancer patients(P<0.05).Logistic regression analysis also found that age(OR=3.823,P=0.030),differentiation degree(OR=4.802,P=0.028),American Joint Committee on Cancer clinical staging(OR=3.732,P=0.013),alpha-fetoprotein level(OR=3.508,P=0.018),thrombospondin-1 level(OR=5.749,P=0.006),carcinoembryonic antigen level(OR=3.873,P=0.030),and SA(OR=3.593,P=0.017)were independent risk factors that may influence esophageal cancer patients'prognosis(P<0.05).CONCLUSION The presence of SA has a significant relation to the poor prognosis of esophageal cancer patients,which highlights the importance of assessing and intervening in SA in clinical management so as to improve patient prognosis.展开更多
Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigati...Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.展开更多
BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous pop...BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous populations like Saudi Arabia.CASE SUMMARY This report presents a Saudi pediatric patient diagnosed with PCD who exhibited persistent neonatal tachypnea,chronic productive cough,and recurrent otitis media.Whole-exome sequencing revealed a novel homozygous nonsense variant in the C3orf67 gene(NM_198463.2:c.508C>T),resulting in a truncated,nonfunctional protein.This mutation likely impairs ciliary motility due to the production of a truncated,non-functional protein.The clinical findings were supported by multiple positive sputum cultures and a significant family history of similar symptoms,suggesting a genetic etiology consistent with autosomal recessive inheritance.CONCLUSION This case highlights the importance of genetic studies in diagnosing PCD,particularly in communities with a high rate of consanguinity.The identification of a novel homozygous variant in the C3orf67 gene expands the known genetic landscape of the disease.Further research is essential to clarify the functional role of C3orf67 in ciliary biology and its contribution to PCD pathogenesis.展开更多
文摘BACKGROUND C3 glomerulopathies(C3G)are a rare cause of kidney failure resulting from complement dysregulation.Small studies demonstrate a high rate of recurrence and poor outcomes in kidney transplantation.Treatment efficacy in this setting with eculizumab,a terminal complement inhibitor,is largely unknown.AIM To determine the outcomes of kidney transplantation in patients with C3G and the potential impact of eculizumab.METHODS We retrospectively studied kidney transplant recipients who underwent a post-transplant biopsy confirming C3G between January 1,1993 and December 31,2023 at a single center.Only the first episode of kidney transplant was reviewed.The electronic medical records were reviewed for post-transplant allograft function,indication for biopsy,time to biopsy from transplant,time to allograft failure from transplantation,post-C3G treatment,complement laboratory testing,and concurrent malignancy/infection.Reports,and when available slides and immunofluorescence/electron microscopic images,were re-reviewed by a renal pathologist.RESULTS A total of fifteen patients were included in this study.Fourteen patients had suspected recurrent disease,with a pre-transplant native kidney report of C3G.One patient developed de novo C3G.Median post kidney transplant clinical follow up time was 91 months.Median time to recurrence was 7 months with median graft survival of 48 months post kidney transplantation.The most common index biopsy pattern of injury was endocapillary prolif-erative glomerulonephritis(often with exudative features)with or without mesangial hypercellularity(56%)followed by membranoproliferative glomerulonephritis(25%).Most patients developed membranoproliferative glomerulonephritis pattern of injury on follow up biopsies(63%).Seven patients with recurrent disease received treatment with eculizumab with a median graft survival of 73 months,with five functioning grafts by the end of the study period.Seven patients with recurrent disease did not receive therapy,and all lost their graft with a median graft survival of 22 months(P=0.003).CONCLUSION C3G following kidney transplantation is mostly a recurrent disorder with a poor prognosis in untreated patients.Untreated recurrence has a poor prognosis with median allograft survival<2 years.Early treatment with eculizumab may improve transplant outcomes in patients with recurrent C3G.
文摘BACKGROUND Esophageal cancer is a common malignancy with high mortality.Radiotherapy is an important treatment.Sarcopenia affects patients'physical function and prog-nosis.However,the relationship between sarcopenia diagnosed by Chun-Hou Chen method for sarcopenia measurement and index(C3SMI)criteria and eso-phageal cancer prognosis after radiotherapy is unclear.AIM To explore the correlation between sarcopenia(SA)diagnosed based on C3SMI criteria and the prognosis of patients with esophageal cancer following radiothe-rapy.METHODS A retrospective analysis was conducted on the general clinical data of 131 eso-phageal cancer patients who received radiotherapy in the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University from March 2021 to July 2024.Based on the presence of SA,the patients were assigned into two groups-the SA group and the non-SA group.Logistic regression analysis was used for investi-gating the risk factors influencing SA in esophageal cancer patients.Additionally,the patients were followed up,with their prognosis recorded.As per their prognostic outcomes,the patients were allocated into a good prognosis group and a poor prognosis group.The data of the two groups were compared.Using logistic regression analysis,the risk factors that may influence the prognosis of these patients were analyzed.SPSS 26.0 statistical software was introduced for analyzing the study data.Comparisons were made between groups using t-tests or χ_(2) tests based on the data type.RESULTS As revealed through logistic regression analysis,age[odds ratio(OR)=2.898,P=0.038],body mass index(OR=5.983,P=0.006),prealbumin(OR=6.253,P=0.003),and Karnofsky performance status score(OR=3.854,P=0.010)were independent risk factors impacting SA for esophageal cancer patients(P<0.05).Logistic regression analysis also found that age(OR=3.823,P=0.030),differentiation degree(OR=4.802,P=0.028),American Joint Committee on Cancer clinical staging(OR=3.732,P=0.013),alpha-fetoprotein level(OR=3.508,P=0.018),thrombospondin-1 level(OR=5.749,P=0.006),carcinoembryonic antigen level(OR=3.873,P=0.030),and SA(OR=3.593,P=0.017)were independent risk factors that may influence esophageal cancer patients'prognosis(P<0.05).CONCLUSION The presence of SA has a significant relation to the poor prognosis of esophageal cancer patients,which highlights the importance of assessing and intervening in SA in clinical management so as to improve patient prognosis.
基金National Research Fund of South Africa(grant number:137792).
文摘Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.
文摘BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous populations like Saudi Arabia.CASE SUMMARY This report presents a Saudi pediatric patient diagnosed with PCD who exhibited persistent neonatal tachypnea,chronic productive cough,and recurrent otitis media.Whole-exome sequencing revealed a novel homozygous nonsense variant in the C3orf67 gene(NM_198463.2:c.508C>T),resulting in a truncated,nonfunctional protein.This mutation likely impairs ciliary motility due to the production of a truncated,non-functional protein.The clinical findings were supported by multiple positive sputum cultures and a significant family history of similar symptoms,suggesting a genetic etiology consistent with autosomal recessive inheritance.CONCLUSION This case highlights the importance of genetic studies in diagnosing PCD,particularly in communities with a high rate of consanguinity.The identification of a novel homozygous variant in the C3orf67 gene expands the known genetic landscape of the disease.Further research is essential to clarify the functional role of C3orf67 in ciliary biology and its contribution to PCD pathogenesis.
