目的:验证应用深度学习算法的计算机辅助诊断(DL-CAD)系统检测胸部DR片肋骨骨折的应用价值。方法:回顾性收集110例因外伤拍摄胸部正位DR片的患者。DL-CAD系统及4名放射科主治医生(5~9年诊断经验)分别阅片,采用灵敏度、特异度、准确率指...目的:验证应用深度学习算法的计算机辅助诊断(DL-CAD)系统检测胸部DR片肋骨骨折的应用价值。方法:回顾性收集110例因外伤拍摄胸部正位DR片的患者。DL-CAD系统及4名放射科主治医生(5~9年诊断经验)分别阅片,采用灵敏度、特异度、准确率指标比较两者对骨折病例的筛检效能;精准度、召回率及F1值比较两种阅片模式在骨折定位诊断中的效能;采用阅片时间评价诊断效率。结果:DL-CAD系统识别患者是否存在肋骨骨折的表现与放射科医生的平均水平相比无统计学差异,ROC曲线下面积(AUC)分别为0.824 vs. 0.833(P>0.05),二者的敏感度,特异度及准确率分别为87.5%vs. 88.3%、73.9%vs. 69.6%和81.8%vs. 80.5%,差异无统计学意义(均P>0.05)。在骨折的定位诊断方面,DL-CAD系统的诊断效能逊于放射科医生,二者的精准度、召回率及F1值分别为60.6%vs. 62.1%、55.7%vs. 73.1%和0.58 vs. 0.67,差异有显著的统计学意义(均P<0.05);侧肋的诊断准确率高于后肋。DL-CAD系统每例阅片时间较医生显著缩短((2.00±0.35) s vs.(108.00±6.36) s,P<0.01)。结论:DL-CAD系统可高效的进行肋骨骨折检测,在筛检骨折病例上的效能与放射科医生相当,但其骨折定位诊断能力有待进一步提升。展开更多
Summary:Huai Qi Huang(HQH)exerts great effects in clinic,such as anti-inflammation,immune-regulation,anti-cancer,and so on.However,the mechanism by which HQH protects juvenile idiopathic arthritis(JIA)is obscure.Thus,...Summary:Huai Qi Huang(HQH)exerts great effects in clinic,such as anti-inflammation,immune-regulation,anti-cancer,and so on.However,the mechanism by which HQH protects juvenile idiopathic arthritis(JIA)is obscure.Thus,we explored deeply the protective mechanisms in juvenile collagen-induced arthritis(CIA)rat model.Pyroptosis is Gasdermin D(GSDMD)-dependent programmed cell death,involved in many diseases,such as sepsis.We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis.Juvenile Wistar rats(3-4 weeks)were injected intradermally with fully emulsified bovine typeⅡcollagen and complete Freund's adjuvant to establish CIA rat models.Later,the CIA rats received oral administration of HQH(4.16 g/kg)once a day from the day 21 of modeling,with the treatment lasting for 28 days.Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH,including hind paw swelling,arthritis scores,micro CT,and histopathological changes and the level of pro-inflammatory cytokines in the serum,including tumor necrosis factor alpha(TNF-α)and interleukin-18(IL-18).The expression of GSDMD and caspasein the joint synovial tissues was detected.The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats.The treatment of HQH ameliorated the symptoms in CIA rats,reduced levels of pro-inflammatory cytokines and hind paw swelling,down-regulated the expression of GDSMD and caspase-1.GSDMDinduced pyroptosis participated in the pathogenesis of CIA rats.The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.展开更多
Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several stud...Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that multiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.展开更多
Prolonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants.Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly...Prolonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants.Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly contribute to this risk.However,the absence of direct evidence from cohort studies and an unclear mechanism hinder intervention development based on this hypothesis.This study recruited109 young male migrants living in Xizang to investigate the microbial mechanisms underlying cognitive impairment associated with highaltitude migration.Multi-omic analysis revealed distinct microbiome and metabolome features in migrants with cognitive decline,notably a reduced abundance of Clostridium species and disrupted fecal absorption of L-valine.Mechanistic studies showed that hypobaric hypoxia significantly damaged the intestinal barrier,leading to lipopolysaccharide(LPS)leakage and an influx of inflammatory factors into the peripheral blood,which activated microglia and caused neuronal injury in the hippocampus of mice.Additionally,compromised L-valine absorption due to intestinal barrier damage correlated with lower hippocampal glutamate levels and neurotrophic factors.Intervention with Clostridium sp.effectively restored the intestinal barrier and enhanced L-valine absorption,which mitigated hypobaric hypoxiainduced inflammation and hippocampal neural damage in mice.In conclusion,cognitive impairment among young migrants at high altitude may be attributed to hypobaric hypoxia-induced gut microbiota disruption and subsequent intestinal barrier dysfunction.This study may provide a promising approach for preventing and treating high-altitude-associated cognitive impairment.展开更多
Myocardial injury is a common disease in the plateau,especially in the lowlanders who have migrated to the plateau,in which the pathogenesis is not well understood.Here,we established a cohort of lowlanders comprising...Myocardial injury is a common disease in the plateau,especially in the lowlanders who have migrated to the plateau,in which the pathogenesis is not well understood.Here,we established a cohort of lowlanders comprising individuals from both low-altitude and high-altitude areas and conducted plasma proteomic profiling.Proteomic data showed that there was a significant shift in energy metabolism and inflammatory response in individuals with myocardial abnormalities at high altitude.Notably,integrin alpha-Ⅱb(ITGA2B)emerged as a potential key player in this context.Functional studies demonstrated that ITGA2B upregulated the transcription and secretion of interleukin-6(IL-6)through the integrin-linked kinase(ILK)/nuclear factor-κB(NF-κB)signaling axis under hypoxic conditions.Moreover,ITGA2B disrupted mitochondrial structure and function,increased glycolytic capacity,and aggravated energy reprogramming from oxidative phosphorylation to glycolysis.Leveraging the therapeutic potential of traditional Chinese medicine in cardiac diseases,we discovered that tanshinoneⅡA(TanⅡA)effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice,thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.展开更多
Background:Incision and drainage(I&D)for perianal abscesses is associated with high rates of fistula formation.Our study aimed to evaluate the effectiveness of a novel technique,trans-intersphincteric double seton...Background:Incision and drainage(I&D)for perianal abscesses is associated with high rates of fistula formation.Our study aimed to evaluate the effectiveness of a novel technique,trans-intersphincteric double seton(TRISDS),designed to preserve anal sphincter integrity and improve clinical outcomes compared to I&D.Methods:This prospective,randomized,non-blinded controlled study included adult patients with perianal abscesses located below the levator ani muscle with an internal opening.Patients were randomly assigned to either the TRISDS group(n=55)or the I&D group(n=51).The TRISDS technique involved two incisions:intersphincteric and drainage incisions with the placement of two loose setons.One seton was positioned to preserve the internal anal sphincter and facilitate drainage through the intersphincteric space,while the other seton aimed to protect the external anal sphincter to ensure comprehensive drainage.The I&D group underwent conventional I&D without damaging the anal sphincter complex.The primary outcome was the cure rate of perianal abscesses,which was defined as complete epithelialization of wounds without fistula or exudate and no recurrence within 12 months after surgery.Results:The TRISDS group achieved a significantly higher cure rate of 78.2%(43/55)compared to 41.2%(21/51)in the I&D group(P<0.05).There were no significant differences in anal function at 2 months postoperatively between the groups(median Wexner score,IQR:1.0[0.0-1.0]vs 1.0[0.0-1.0],P>0.05).Conclusions:The study highlighted the effectiveness of TRISDS in improving cure rate without compromising anal function.The TRISDS technique represents a promising strategy for the treatment of perianal abscesses.Further multicenter studies are recommended to validate these findings and expand the application of TRISDS in diverse patient populations.展开更多
文摘目的:验证应用深度学习算法的计算机辅助诊断(DL-CAD)系统检测胸部DR片肋骨骨折的应用价值。方法:回顾性收集110例因外伤拍摄胸部正位DR片的患者。DL-CAD系统及4名放射科主治医生(5~9年诊断经验)分别阅片,采用灵敏度、特异度、准确率指标比较两者对骨折病例的筛检效能;精准度、召回率及F1值比较两种阅片模式在骨折定位诊断中的效能;采用阅片时间评价诊断效率。结果:DL-CAD系统识别患者是否存在肋骨骨折的表现与放射科医生的平均水平相比无统计学差异,ROC曲线下面积(AUC)分别为0.824 vs. 0.833(P>0.05),二者的敏感度,特异度及准确率分别为87.5%vs. 88.3%、73.9%vs. 69.6%和81.8%vs. 80.5%,差异无统计学意义(均P>0.05)。在骨折的定位诊断方面,DL-CAD系统的诊断效能逊于放射科医生,二者的精准度、召回率及F1值分别为60.6%vs. 62.1%、55.7%vs. 73.1%和0.58 vs. 0.67,差异有显著的统计学意义(均P<0.05);侧肋的诊断准确率高于后肋。DL-CAD系统每例阅片时间较医生显著缩短((2.00±0.35) s vs.(108.00±6.36) s,P<0.01)。结论:DL-CAD系统可高效的进行肋骨骨折检测,在筛检骨折病例上的效能与放射科医生相当,但其骨折定位诊断能力有待进一步提升。
基金This study was supported by the National Natural Science Foundation of China(No.81270949).
文摘Summary:Huai Qi Huang(HQH)exerts great effects in clinic,such as anti-inflammation,immune-regulation,anti-cancer,and so on.However,the mechanism by which HQH protects juvenile idiopathic arthritis(JIA)is obscure.Thus,we explored deeply the protective mechanisms in juvenile collagen-induced arthritis(CIA)rat model.Pyroptosis is Gasdermin D(GSDMD)-dependent programmed cell death,involved in many diseases,such as sepsis.We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis.Juvenile Wistar rats(3-4 weeks)were injected intradermally with fully emulsified bovine typeⅡcollagen and complete Freund's adjuvant to establish CIA rat models.Later,the CIA rats received oral administration of HQH(4.16 g/kg)once a day from the day 21 of modeling,with the treatment lasting for 28 days.Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH,including hind paw swelling,arthritis scores,micro CT,and histopathological changes and the level of pro-inflammatory cytokines in the serum,including tumor necrosis factor alpha(TNF-α)and interleukin-18(IL-18).The expression of GSDMD and caspasein the joint synovial tissues was detected.The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats.The treatment of HQH ameliorated the symptoms in CIA rats,reduced levels of pro-inflammatory cytokines and hind paw swelling,down-regulated the expression of GDSMD and caspase-1.GSDMDinduced pyroptosis participated in the pathogenesis of CIA rats.The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82192910,82192911)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202207).
文摘Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that multiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.
基金supported by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207,Y.G.)the Young Elite Scientists Sponsorship Program by CAST(2021-QNRC1-03,W.Z.)。
文摘Prolonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants.Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly contribute to this risk.However,the absence of direct evidence from cohort studies and an unclear mechanism hinder intervention development based on this hypothesis.This study recruited109 young male migrants living in Xizang to investigate the microbial mechanisms underlying cognitive impairment associated with highaltitude migration.Multi-omic analysis revealed distinct microbiome and metabolome features in migrants with cognitive decline,notably a reduced abundance of Clostridium species and disrupted fecal absorption of L-valine.Mechanistic studies showed that hypobaric hypoxia significantly damaged the intestinal barrier,leading to lipopolysaccharide(LPS)leakage and an influx of inflammatory factors into the peripheral blood,which activated microglia and caused neuronal injury in the hippocampus of mice.Additionally,compromised L-valine absorption due to intestinal barrier damage correlated with lower hippocampal glutamate levels and neurotrophic factors.Intervention with Clostridium sp.effectively restored the intestinal barrier and enhanced L-valine absorption,which mitigated hypobaric hypoxiainduced inflammation and hippocampal neural damage in mice.In conclusion,cognitive impairment among young migrants at high altitude may be attributed to hypobaric hypoxia-induced gut microbiota disruption and subsequent intestinal barrier dysfunction.This study may provide a promising approach for preventing and treating high-altitude-associated cognitive impairment.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.ZYYCXTD-D-202207)the National Natural Science Foundation of China(Grant No.82204774).
文摘Myocardial injury is a common disease in the plateau,especially in the lowlanders who have migrated to the plateau,in which the pathogenesis is not well understood.Here,we established a cohort of lowlanders comprising individuals from both low-altitude and high-altitude areas and conducted plasma proteomic profiling.Proteomic data showed that there was a significant shift in energy metabolism and inflammatory response in individuals with myocardial abnormalities at high altitude.Notably,integrin alpha-Ⅱb(ITGA2B)emerged as a potential key player in this context.Functional studies demonstrated that ITGA2B upregulated the transcription and secretion of interleukin-6(IL-6)through the integrin-linked kinase(ILK)/nuclear factor-κB(NF-κB)signaling axis under hypoxic conditions.Moreover,ITGA2B disrupted mitochondrial structure and function,increased glycolytic capacity,and aggravated energy reprogramming from oxidative phosphorylation to glycolysis.Leveraging the therapeutic potential of traditional Chinese medicine in cardiac diseases,we discovered that tanshinoneⅡA(TanⅡA)effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice,thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.
基金the Chinese Clinical Trial Registry(ChiCTR2000032941)the Medical Ethics Committee of the Affiliated Hospital of Jiangxi University of Chinese Medicine(JZFYKYLL20200420007).
文摘Background:Incision and drainage(I&D)for perianal abscesses is associated with high rates of fistula formation.Our study aimed to evaluate the effectiveness of a novel technique,trans-intersphincteric double seton(TRISDS),designed to preserve anal sphincter integrity and improve clinical outcomes compared to I&D.Methods:This prospective,randomized,non-blinded controlled study included adult patients with perianal abscesses located below the levator ani muscle with an internal opening.Patients were randomly assigned to either the TRISDS group(n=55)or the I&D group(n=51).The TRISDS technique involved two incisions:intersphincteric and drainage incisions with the placement of two loose setons.One seton was positioned to preserve the internal anal sphincter and facilitate drainage through the intersphincteric space,while the other seton aimed to protect the external anal sphincter to ensure comprehensive drainage.The I&D group underwent conventional I&D without damaging the anal sphincter complex.The primary outcome was the cure rate of perianal abscesses,which was defined as complete epithelialization of wounds without fistula or exudate and no recurrence within 12 months after surgery.Results:The TRISDS group achieved a significantly higher cure rate of 78.2%(43/55)compared to 41.2%(21/51)in the I&D group(P<0.05).There were no significant differences in anal function at 2 months postoperatively between the groups(median Wexner score,IQR:1.0[0.0-1.0]vs 1.0[0.0-1.0],P>0.05).Conclusions:The study highlighted the effectiveness of TRISDS in improving cure rate without compromising anal function.The TRISDS technique represents a promising strategy for the treatment of perianal abscesses.Further multicenter studies are recommended to validate these findings and expand the application of TRISDS in diverse patient populations.
