Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore th...Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.Methods: Diabetic db/db mice received Risa-inhibition adeno-associated virus(AAV) via tail vein injection, and intraperitoneal injection of lithium chloride(LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells(MPCs) were cultured and treated with Risa-inhibition lentivirus(LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy,Periodic Acid-Schiff staining, and immunofluorescence staining.Results: Risa and activated GSK3β were overexpressed, but Sirt1 was downregulated in DN mice and high glucosetreated MPCs(P<0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1(P<0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527(P<0.001, db/db+Risa-AAV vs. db/db, HG+Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3β-mediated autophagy of podocytes(P<0.001, db/db+LiCl vs. db/db, HG+LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy.Conclusions: Risa could inhibit autophagy by regulating the Sirt1/GSK3β axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.展开更多
Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor(EGFR)signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy.In this phase 3 study(Clin...Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor(EGFR)signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy.In this phase 3 study(ClinicalTrial.gov:NCT04028778),315 patients with treatment-naïve,EGFR-mutated,advanced non-small cell lung cancer(NSCLC)were randomized(1:1)to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle.At the prespecified final analysis of progression-free survival(PFS),a significant improvement in PFS was observed for the anlotinib arm over the placebo arm(hazards ratio[HR]=0.64,95%CI,0.48–0.80,P=0.003).Particularly,patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib.The incidence of grade 3 or higher treatment-emergent adverse events was 49.7%of the patients receiving gefitinib plus anlotinib versus 31.0%of the patients receiving gefitinib plus placebo.Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve,EGFR-mutated,advanced NSCLC,with a manageable safety profile.展开更多
Importance:Pediatric palliative care(PPC)is an interdisciplinary collaboration that focuses on the prevention and relief of patient suffering.PPC has emerged as a critical field of medical expertise and practice.Howev...Importance:Pediatric palliative care(PPC)is an interdisciplinary collaboration that focuses on the prevention and relief of patient suffering.PPC has emerged as a critical field of medical expertise and practice.However,no information is available regarding the progress of PPC in the Chinese mainland.Objective:This study investigated the geographic distribution,team structure,and services of PPC teams in the Chinese mainland.It also investigated the level of understanding and implementation among pediatric oncologists regarding PPC.Methods:The PPC subspecialty group of the Pediatrics Society of the Chinese Medical Association included 45 PPC teams.The team structure and services were investigated using questionnaires mailed to the team leader of each PPC team.In addition,we sent questionnaires regarding the level of PPC understanding and implementation of PPC practices to 170 pediatric oncologists in 11 hospitals.Results:The geographical distribution of PPC teams is uneven in China.Most PPC teams are concentrated in the eastern provincial capital of China.Most PPC teams had limited staff and services.The level of PPC understanding was considerably limited across all demographics;most pediatric oncologists reported“some understanding”(n=71,41.8%)or“poor understanding”(n=50,29.4%).Only 62.9%of pediatric oncologists had experience providing advice to family members regarding PPC matters.Interpretation:China is currently experiencing a critical shortage of PPC resources.Most pediatric oncologists had a limited understanding of PPC and reported limited practical implementation of PPC,which leads to underutilization of PPC resources.展开更多
To the Editor:Hearing loss is the most common sensory disorder in humans.There is one case of congenital deafness among every 1000 newborns,and in 50%of cases,the deafness is hereditary.Deafness exhibits high genetic ...To the Editor:Hearing loss is the most common sensory disorder in humans.There is one case of congenital deafness among every 1000 newborns,and in 50%of cases,the deafness is hereditary.Deafness exhibits high genetic heterogeneity.To date,over 110 non-syndromic deafness genes have been identified(https://hereditaryhearingloss.org/).Lots of those genes can cause both autosomaldominant hearing loss(ADNSHL)and autosomal-recessive non-syndromic hearing loss(ARNSHL)andTMC1(encoding the transmembrane channel-like 1)is one of them.TMC1(OMIM:606706)is a member of the TMC family located at 9q21.13.The protein contains 760 amino acids and has six transmembrane regions.TMC1 is expressed in the inner and outer hair cells of the cochlea.A TMC1 mutation was first shown to cause deafness in 2002.[1]The prevalence of TMC1 variants ranged from 3.4%(19/557)among Pakistani ARNSHL families to 8.1%(7/86)in Turkish families.To date,around 20 hearing loss families associated withTMC1 variants have been reported in China.展开更多
基金supported by grants from the Joint construction project of Henan Province(SB201901015)the General Program of the National Natural Science Foundation of China General Project(81970633)+2 种基金the Major public welfare special projects in Henan Province(201300310600)the National Natural Science Young Scientists Foundation of China(81800648)the Excellent Young Scientists Fund Program of the Natural Science Foundation of Henan Province(202300410363)。
文摘Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.Methods: Diabetic db/db mice received Risa-inhibition adeno-associated virus(AAV) via tail vein injection, and intraperitoneal injection of lithium chloride(LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells(MPCs) were cultured and treated with Risa-inhibition lentivirus(LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy,Periodic Acid-Schiff staining, and immunofluorescence staining.Results: Risa and activated GSK3β were overexpressed, but Sirt1 was downregulated in DN mice and high glucosetreated MPCs(P<0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1(P<0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527(P<0.001, db/db+Risa-AAV vs. db/db, HG+Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3β-mediated autophagy of podocytes(P<0.001, db/db+LiCl vs. db/db, HG+LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy.Conclusions: Risa could inhibit autophagy by regulating the Sirt1/GSK3β axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.
基金funded by the Chinese National Natural Science Foundation Project(Grant No.82173101,82373262,82241232,82272789,82102864)Guangzhou Basic and Applied Basic Research Foundation(2024A04J4082)partly funded by the 308 Clinical Research Foundation of Sun Yat-sen University Cancer Center.
文摘Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor(EGFR)signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy.In this phase 3 study(ClinicalTrial.gov:NCT04028778),315 patients with treatment-naïve,EGFR-mutated,advanced non-small cell lung cancer(NSCLC)were randomized(1:1)to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle.At the prespecified final analysis of progression-free survival(PFS),a significant improvement in PFS was observed for the anlotinib arm over the placebo arm(hazards ratio[HR]=0.64,95%CI,0.48–0.80,P=0.003).Particularly,patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib.The incidence of grade 3 or higher treatment-emergent adverse events was 49.7%of the patients receiving gefitinib plus anlotinib versus 31.0%of the patients receiving gefitinib plus placebo.Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve,EGFR-mutated,advanced NSCLC,with a manageable safety profile.
基金The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals(No.XTCX201812)Management Research Project of Beijing Children’s Hospital,Capital Medical University(No.YGLQ202001)。
文摘Importance:Pediatric palliative care(PPC)is an interdisciplinary collaboration that focuses on the prevention and relief of patient suffering.PPC has emerged as a critical field of medical expertise and practice.However,no information is available regarding the progress of PPC in the Chinese mainland.Objective:This study investigated the geographic distribution,team structure,and services of PPC teams in the Chinese mainland.It also investigated the level of understanding and implementation among pediatric oncologists regarding PPC.Methods:The PPC subspecialty group of the Pediatrics Society of the Chinese Medical Association included 45 PPC teams.The team structure and services were investigated using questionnaires mailed to the team leader of each PPC team.In addition,we sent questionnaires regarding the level of PPC understanding and implementation of PPC practices to 170 pediatric oncologists in 11 hospitals.Results:The geographical distribution of PPC teams is uneven in China.Most PPC teams are concentrated in the eastern provincial capital of China.Most PPC teams had limited staff and services.The level of PPC understanding was considerably limited across all demographics;most pediatric oncologists reported“some understanding”(n=71,41.8%)or“poor understanding”(n=50,29.4%).Only 62.9%of pediatric oncologists had experience providing advice to family members regarding PPC matters.Interpretation:China is currently experiencing a critical shortage of PPC resources.Most pediatric oncologists had a limited understanding of PPC and reported limited practical implementation of PPC,which leads to underutilization of PPC resources.
基金Collaborative Innovation Project of Zhengzhou (Zhengzhou University)(No. 18XTZX12004)
文摘To the Editor:Hearing loss is the most common sensory disorder in humans.There is one case of congenital deafness among every 1000 newborns,and in 50%of cases,the deafness is hereditary.Deafness exhibits high genetic heterogeneity.To date,over 110 non-syndromic deafness genes have been identified(https://hereditaryhearingloss.org/).Lots of those genes can cause both autosomaldominant hearing loss(ADNSHL)and autosomal-recessive non-syndromic hearing loss(ARNSHL)andTMC1(encoding the transmembrane channel-like 1)is one of them.TMC1(OMIM:606706)is a member of the TMC family located at 9q21.13.The protein contains 760 amino acids and has six transmembrane regions.TMC1 is expressed in the inner and outer hair cells of the cochlea.A TMC1 mutation was first shown to cause deafness in 2002.[1]The prevalence of TMC1 variants ranged from 3.4%(19/557)among Pakistani ARNSHL families to 8.1%(7/86)in Turkish families.To date,around 20 hearing loss families associated withTMC1 variants have been reported in China.
