BACKGROUND ： At present, results of a few studies demonstrate that preoperative magnetic resonance imaging （MRI） examination reveals the texture of pituitary adenoma, i.e. on the T2 -weighted image, solid pituitary...BACKGROUND ： At present, results of a few studies demonstrate that preoperative magnetic resonance imaging （MRI） examination reveals the texture of pituitary adenoma, i.e. on the T2 -weighted image, solid pituitary adenoma shows weak signal and soft one shows strong signal. Also, solid pituitary adenoma is caused by fibrosis, which is confirmed. However, some key problems are still in question and disputation, such as how to exactly quantize MRI signal intensity, which signal is used as prediction index, and the relationship of MRI signal and collagen content which reflects the texture of pituitary adenoma, and so on. OBJECTIVE： To observe the relationship of MRI signal intensity of different textures of pituitary adenoma and its collagen content, and investigate the best prediction index of the texture of pituitary adenoma. DESIGN ： Case-control observation SETTING： Department of Neurosurgery, Third Hospital Affiliated to Sun Yat-sen University; Department of Neurosurgery, Xiangya Hospital, Central South University. PARTICIPANTS ： Fifty-seven patients with pituitary adenoma, including 32 males and 25 females, aged 20 to 65 years, who received treatment in the Department of Neurosurgery, Xiangya Hospital, Central South University during June 2003 to January 2004. The involved patients were all diagnosed by MRI and confirmed by pathological resection. Informed consents were obtained from all the patients. The samples of above-mentioned patients resected by operation were fixed with 40 g/L formaldehyde for sirius red staining. METHODS ： （1） According to the texture of pituitary adenoma observed in the operation： The 57 samples of pituitary adenoma were divided into 2 groups： non-fibrosis group （n =49） and fibrosis group （n =8）. In the non-fibrosis group, the texture of pituitary adenoma was soft, Le. pituitary adenoma tissue automatically flew out, and could be aspirated by aspirater or erased by curette, and the superior part of saddle could fall in the saddle. In the fibrosis group, pituitary adenoma tissue could be difficultly erased by curette, very strong drag power existed while pituitary adenoma was taken out, and superior part of saddle could not fall in the saddle, could be resected in small pieces with the help of repeated electric coagulation or sharp instrument. （2） All the patients underwent MRI examination. The signal intensity ratio of pituitary adenoma to grey matter and white matter （pituitary adenoma/grey matter, pituitary adenoma/white matter） in T1 -weighted image （T1WI）, T2-weighted image （T2WI） and enhanced T1 -weighted image （T1^＊WI）were measured; The samples were performed sirius red staining for measuring collagen content, and analyzed by automatic image analysis system （Kontron Ibas 2.5, Germany）. Five visual fields were randomly chosen from each section to calculate the relative area occupied by collagen （%） and the mean value was obtained, ttest and linear correlation analysis were performed. MAIN OUTCOME MEASURES： （1）Signal intensity ratio of pituitary adenoma to grey matter and pituitary adenoma to white matter in T1WI, T1^＊WI and T2WI. （2） Collagen content of pituitary adenoma samples. RESULTS ： （1）Signal intensity ratio of pituitary adenoma to grey matter and pituitary adenoma to white matter in T1WI, T1^＊WI and T2WI： T2WI pituitary adenoma/grey matter and T2WI pituitary adenoma/white matter in the fibrosis group was lower than that in the non-fibrosis group, respectively （1.15±0.26 vs. 1.57±0.46; 1.48±0.39 vs. 2.10±0.61, P 〈 0.05-0.01 ）. （2） Collagen content of pituitary adenoma samples： Collagen content of pituitary adenoma in the fibrosis group was higher than that in the non-fibrosis group [（20.03±7.99）% vs. （7.87± 4.82）%, P 〈 0.01].（3） The relationship of MRI signal intensity and collagen content： The correlation coefficient of T2WI pituitary adenoma/grey matter, T2WI pituitary adenoma/white matter and the total content of collagen was -0.531 and -0.726, respectively （P 〈 0.01 ）. There were no obvious correlations between other signal intensity ratios and the total content of pituitary adenoma （r=0.124, P〉 0.05）. CONCLUSION： （1）There were obvious differences in the signal intensity ratio of T2WI pituitary adenoma and grey matter, white matter in MRI of different textures of pituitary adenoma. The difference of pituitary adenoma/white matter in T2WI was more obvious and better as predication index. When pituitary adenoma/white matter in T2WI was 〈 1.9, the texture of pituitary adenoma was solid. （2） T2WI pituitary adenoma/white matter and T2WI pituitary adenoma/grey matter in MRI of different textures of pituitary adenoma could reflect collagen content.展开更多
The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy(SDT).However,the limited recognition of antiautophagy agents for autophagosomes impedes the cli...The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy(SDT).However,the limited recognition of antiautophagy agents for autophagosomes impedes the clinical application of autophagy inhibition.To efficiently deliver hydroxychloroquine(HCQ),an autophagy inhibitor,to autophagosomes,we utilized a strategy based on in situ click chemistry between sulfhydryl(-SH)and maleimide(Mal)groups to trigger autophagosomes tracking and suppress tumor growth synergistically.A cascade nanoreactor was synthesized by encapsulating Mal-modified HCQ(MHCQ)into a manganese porphyrin-based metal-organic framework with sonosensitizer properties,followed by poly(ethylene glycol)ylated liposomal membrane coating.After ultrasound irradiation,SDT-induced apoptotic cells released damaged proteins with free-SH groups,which MHCQ rapidly captured in situ via a Malthiol click reaction.When autophagosomes actively wrapped damaged proteins for detoxification,they simultaneously internalized HCQ anchored on proteins.In this scenario,antiautophagy drugs could actively track intracellular autophagosomes instead of undergoing passive diffusion in the cytosol.The interaction between HCQ and autophagic vesicles was greatly enhanced,which strengthened the blocking efficiency of autophagy and resulted in complete cell death.Overall,this study with smart design provides a promising strategy for improving intracellular targeted delivery to autophagosomes,thereby enhancing antitumor therapy.展开更多
Intracranial aneurysm(IA)is characterized by defects in the middle muscular layer and pathological dilatation of cerebral arteries.The rupture of IA,resulting in aneurysmal subarachnoid hemorrhage,poses a substantial ...Intracranial aneurysm(IA)is characterized by defects in the middle muscular layer and pathological dilatation of cerebral arteries.The rupture of IA,resulting in aneurysmal subarachnoid hemorrhage,poses a substantial public health problem,especially in developed countries,due to its high mortality,morbidity,and socioeconomic burden(Bakker and Ruigrok,2021).Understanding the risk factors for IA is critical for disease prevention.Although numerous studies(Yan et al.,2015;Santiago-Sim et al.,2016;Barak et al.,2021;Liu et al.,2021)have highlighted familial aggregation of IA and identified candidate genes such as ADAMTS15,THSD1,ANK3,and PPIL4,the mechanisms underlying IA formation and rupture remain unclear.展开更多
Background This study aimed to assess whether pregnancy and puerperium were associated with the risk of brain arteriovenous malformation(bAVM)haemorrhage.Methods A retrospective review was conducted in Xiangya Hospita...Background This study aimed to assess whether pregnancy and puerperium were associated with the risk of brain arteriovenous malformation(bAVM)haemorrhage.Methods A retrospective review was conducted in Xiangya Hospital,Central South University from January 2012 to December 2021.A case-crossover design was adopted to calculate the incidence density of bAVM-related haemorrhage among female patients in risk(pregnancy and puerperium)and control(non-pregnancy and non-puerperium)periods,according to four scenarios observed in different populations scenario I:patients with haemorrhagic bAVM of all ages;scenario II:patients with haemorrhagic bAVM of all ages,with at least one previous pregnancy;scenario III:patients with haemorrhagic bAVM who are of reproductive age(15-45 years);scenario IV:patients with haemorrhagic bAVM of reproductive age(15-45 years),with at least one previous pregnancy.Next,a comprehensive literature aggregation(up to April 2022)was performed for evidence synthesis.Results Among the 311 female patients with haemorrhagic bAVM,a significant haemorrhage risk during pregnancy and puerperium was found in Scenarios I(relative risk[RR],2.08;95%CI,1.28 to 3.39),II(RR,3.21;95%CI,1.95 to 5.31)and IV(RR,2.92;95%CI,1.73 to 4.93);however,a suggestive risk was found in scenario III(RR,1.62;95%CI,0.99 to 2.67).Evidence synthesis revealed a consistent haemorrhage risk among patients of all ages(RR,3.15;95%CI,1.93 to 5.15)and those of reproductive age(RR,1.29;95%CI,0.89 to 1.86).Conclusion Compared with most previous studies,a higher but relatively moderate risk for bAVM-related haemorrhage was identified during pregnancy and puerperium.Individualised prevention and treatment strategies should be preferred when neurosurgeons make clinical decisions.展开更多
Background:Treatment of tuberculosis(TB)in China is partially covered by national programs and health insurance schemes,though TB patients often face considerable medical expenditures.For some,especially those from po...Background:Treatment of tuberculosis(TB)in China is partially covered by national programs and health insurance schemes,though TB patients often face considerable medical expenditures.For some,especially those from poorer households,non-medical costs,such as transport,accommodation,and nutritional supplementation may be a substantial additional burden.In this article we aim to evaluate these non-medical costs induced by seeking TB care using data from a large scale cross-sectional survey.Methods:A total of 797 TB cases from three cities were randomly selected using a stratified cluster sampling design.Inpatient medical costs,outpatient medical costs,and direct non-medical costs related to TB treatment were collected using in-person interviews by trained interviewers.Mean and median non-medical costs for different sub-groups were calculated and compared using Kruskal-Wallis and Mann–Whitney U tests.Regression analysis was conducted to assess the influence of different patient characteristics on total non-medical cost.Results:The median non-medical cost was RMB 1429,with interquartile range RMB 424–2793.The median non-medical costs relating to inpatient treatment,outpatient treatment,and additional nutrition supplementation were RMB 540,91,and 900,respectively.Of the 797 cases,20%reported catastrophic expenditure on non-medical costs.Statistically significant differences were detected between different cities,age groups,geographical locations,inpatient/outpatient care,education levels and family income groups.Conclusions:Non-medical costs relating to TB treatment are a serious financial burden for many TB patients.Financial assistance that can limit this burden is urgently needed during the treatment period,especially for the poor.展开更多
基金the Scientific Re-search Foundation of Depart-ment of Public Healthy of Hu-nan Province, No. B2004-018
文摘BACKGROUND ： At present, results of a few studies demonstrate that preoperative magnetic resonance imaging （MRI） examination reveals the texture of pituitary adenoma, i.e. on the T2 -weighted image, solid pituitary adenoma shows weak signal and soft one shows strong signal. Also, solid pituitary adenoma is caused by fibrosis, which is confirmed. However, some key problems are still in question and disputation, such as how to exactly quantize MRI signal intensity, which signal is used as prediction index, and the relationship of MRI signal and collagen content which reflects the texture of pituitary adenoma, and so on. OBJECTIVE： To observe the relationship of MRI signal intensity of different textures of pituitary adenoma and its collagen content, and investigate the best prediction index of the texture of pituitary adenoma. DESIGN ： Case-control observation SETTING： Department of Neurosurgery, Third Hospital Affiliated to Sun Yat-sen University; Department of Neurosurgery, Xiangya Hospital, Central South University. PARTICIPANTS ： Fifty-seven patients with pituitary adenoma, including 32 males and 25 females, aged 20 to 65 years, who received treatment in the Department of Neurosurgery, Xiangya Hospital, Central South University during June 2003 to January 2004. The involved patients were all diagnosed by MRI and confirmed by pathological resection. Informed consents were obtained from all the patients. The samples of above-mentioned patients resected by operation were fixed with 40 g/L formaldehyde for sirius red staining. METHODS ： （1） According to the texture of pituitary adenoma observed in the operation： The 57 samples of pituitary adenoma were divided into 2 groups： non-fibrosis group （n =49） and fibrosis group （n =8）. In the non-fibrosis group, the texture of pituitary adenoma was soft, Le. pituitary adenoma tissue automatically flew out, and could be aspirated by aspirater or erased by curette, and the superior part of saddle could fall in the saddle. In the fibrosis group, pituitary adenoma tissue could be difficultly erased by curette, very strong drag power existed while pituitary adenoma was taken out, and superior part of saddle could not fall in the saddle, could be resected in small pieces with the help of repeated electric coagulation or sharp instrument. （2） All the patients underwent MRI examination. The signal intensity ratio of pituitary adenoma to grey matter and white matter （pituitary adenoma/grey matter, pituitary adenoma/white matter） in T1 -weighted image （T1WI）, T2-weighted image （T2WI） and enhanced T1 -weighted image （T1^＊WI）were measured; The samples were performed sirius red staining for measuring collagen content, and analyzed by automatic image analysis system （Kontron Ibas 2.5, Germany）. Five visual fields were randomly chosen from each section to calculate the relative area occupied by collagen （%） and the mean value was obtained, ttest and linear correlation analysis were performed. MAIN OUTCOME MEASURES： （1）Signal intensity ratio of pituitary adenoma to grey matter and pituitary adenoma to white matter in T1WI, T1^＊WI and T2WI. （2） Collagen content of pituitary adenoma samples. RESULTS ： （1）Signal intensity ratio of pituitary adenoma to grey matter and pituitary adenoma to white matter in T1WI, T1^＊WI and T2WI： T2WI pituitary adenoma/grey matter and T2WI pituitary adenoma/white matter in the fibrosis group was lower than that in the non-fibrosis group, respectively （1.15±0.26 vs. 1.57±0.46; 1.48±0.39 vs. 2.10±0.61, P 〈 0.05-0.01 ）. （2） Collagen content of pituitary adenoma samples： Collagen content of pituitary adenoma in the fibrosis group was higher than that in the non-fibrosis group [（20.03±7.99）% vs. （7.87± 4.82）%, P 〈 0.01].（3） The relationship of MRI signal intensity and collagen content： The correlation coefficient of T2WI pituitary adenoma/grey matter, T2WI pituitary adenoma/white matter and the total content of collagen was -0.531 and -0.726, respectively （P 〈 0.01 ）. There were no obvious correlations between other signal intensity ratios and the total content of pituitary adenoma （r=0.124, P〉 0.05）. CONCLUSION： （1）There were obvious differences in the signal intensity ratio of T2WI pituitary adenoma and grey matter, white matter in MRI of different textures of pituitary adenoma. The difference of pituitary adenoma/white matter in T2WI was more obvious and better as predication index. When pituitary adenoma/white matter in T2WI was 〈 1.9, the texture of pituitary adenoma was solid. （2） T2WI pituitary adenoma/white matter and T2WI pituitary adenoma/grey matter in MRI of different textures of pituitary adenoma could reflect collagen content.
基金China Postdoctoral Science Foundation,Grant/Award Numbers:2022TQ0396,2023MD744153National Natural Science Foundation of China,Grant/Award Numbers:82302218,82171946+2 种基金CQMU Program for Youth Innovation in Future Medicine,Grant/Award Number:W0026Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University,Grant/Award Number:KR2023Y044Chongqing Science and Health Joint Medical Research Project-Young and Middle-Aged High-Level Talent Project,Grant/Award Number:2020GDRC011。
文摘The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy(SDT).However,the limited recognition of antiautophagy agents for autophagosomes impedes the clinical application of autophagy inhibition.To efficiently deliver hydroxychloroquine(HCQ),an autophagy inhibitor,to autophagosomes,we utilized a strategy based on in situ click chemistry between sulfhydryl(-SH)and maleimide(Mal)groups to trigger autophagosomes tracking and suppress tumor growth synergistically.A cascade nanoreactor was synthesized by encapsulating Mal-modified HCQ(MHCQ)into a manganese porphyrin-based metal-organic framework with sonosensitizer properties,followed by poly(ethylene glycol)ylated liposomal membrane coating.After ultrasound irradiation,SDT-induced apoptotic cells released damaged proteins with free-SH groups,which MHCQ rapidly captured in situ via a Malthiol click reaction.When autophagosomes actively wrapped damaged proteins for detoxification,they simultaneously internalized HCQ anchored on proteins.In this scenario,antiautophagy drugs could actively track intracellular autophagosomes instead of undergoing passive diffusion in the cytosol.The interaction between HCQ and autophagic vesicles was greatly enhanced,which strengthened the blocking efficiency of autophagy and resulted in complete cell death.Overall,this study with smart design provides a promising strategy for improving intracellular targeted delivery to autophagosomes,thereby enhancing antitumor therapy.
基金supported by the National Natural Science Foundation of China(32222028)Natural Science Foundation of Chongqing,China(CSTB2023NSCQ-MSX0505)+1 种基金Financial Science and Technology Project of Hunan Province,China(422000008)Hunan Province Nature Science Foundation,China(2021JJ30911).
文摘Intracranial aneurysm(IA)is characterized by defects in the middle muscular layer and pathological dilatation of cerebral arteries.The rupture of IA,resulting in aneurysmal subarachnoid hemorrhage,poses a substantial public health problem,especially in developed countries,due to its high mortality,morbidity,and socioeconomic burden(Bakker and Ruigrok,2021).Understanding the risk factors for IA is critical for disease prevention.Although numerous studies(Yan et al.,2015;Santiago-Sim et al.,2016;Barak et al.,2021;Liu et al.,2021)have highlighted familial aggregation of IA and identified candidate genes such as ADAMTS15,THSD1,ANK3,and PPIL4,the mechanisms underlying IA formation and rupture remain unclear.
基金supported by the grants from the Hunan Province Nature Science Foundation,China(2021JJ30911,2021JJ31077,2021JJ31121)Financial Science and Technology Project of Hunan Province,China(422000008)Central South University Case Database Construction Project for Graduate Students,China(2020ALK24).
文摘Background This study aimed to assess whether pregnancy and puerperium were associated with the risk of brain arteriovenous malformation(bAVM)haemorrhage.Methods A retrospective review was conducted in Xiangya Hospital,Central South University from January 2012 to December 2021.A case-crossover design was adopted to calculate the incidence density of bAVM-related haemorrhage among female patients in risk(pregnancy and puerperium)and control(non-pregnancy and non-puerperium)periods,according to four scenarios observed in different populations scenario I:patients with haemorrhagic bAVM of all ages;scenario II:patients with haemorrhagic bAVM of all ages,with at least one previous pregnancy;scenario III:patients with haemorrhagic bAVM who are of reproductive age(15-45 years);scenario IV:patients with haemorrhagic bAVM of reproductive age(15-45 years),with at least one previous pregnancy.Next,a comprehensive literature aggregation(up to April 2022)was performed for evidence synthesis.Results Among the 311 female patients with haemorrhagic bAVM,a significant haemorrhage risk during pregnancy and puerperium was found in Scenarios I(relative risk[RR],2.08;95%CI,1.28 to 3.39),II(RR,3.21;95%CI,1.95 to 5.31)and IV(RR,2.92;95%CI,1.73 to 4.93);however,a suggestive risk was found in scenario III(RR,1.62;95%CI,0.99 to 2.67).Evidence synthesis revealed a consistent haemorrhage risk among patients of all ages(RR,3.15;95%CI,1.93 to 5.15)and those of reproductive age(RR,1.29;95%CI,0.89 to 1.86).Conclusion Compared with most previous studies,a higher but relatively moderate risk for bAVM-related haemorrhage was identified during pregnancy and puerperium.Individualised prevention and treatment strategies should be preferred when neurosurgeons make clinical decisions.
基金The study upon which this paper was written is part of the large program entitled“China National Health and Family Planning Commission and the Gates Foundation TB Project”-a collaboration between the Government of China and the Bill and Melinda Gates Foundation(Grant No.51914)implemented by the China Center of Disease Control and Prevention(CDC).
文摘Background:Treatment of tuberculosis(TB)in China is partially covered by national programs and health insurance schemes,though TB patients often face considerable medical expenditures.For some,especially those from poorer households,non-medical costs,such as transport,accommodation,and nutritional supplementation may be a substantial additional burden.In this article we aim to evaluate these non-medical costs induced by seeking TB care using data from a large scale cross-sectional survey.Methods:A total of 797 TB cases from three cities were randomly selected using a stratified cluster sampling design.Inpatient medical costs,outpatient medical costs,and direct non-medical costs related to TB treatment were collected using in-person interviews by trained interviewers.Mean and median non-medical costs for different sub-groups were calculated and compared using Kruskal-Wallis and Mann–Whitney U tests.Regression analysis was conducted to assess the influence of different patient characteristics on total non-medical cost.Results:The median non-medical cost was RMB 1429,with interquartile range RMB 424–2793.The median non-medical costs relating to inpatient treatment,outpatient treatment,and additional nutrition supplementation were RMB 540,91,and 900,respectively.Of the 797 cases,20%reported catastrophic expenditure on non-medical costs.Statistically significant differences were detected between different cities,age groups,geographical locations,inpatient/outpatient care,education levels and family income groups.Conclusions:Non-medical costs relating to TB treatment are a serious financial burden for many TB patients.Financial assistance that can limit this burden is urgently needed during the treatment period,especially for the poor.
