Inadequate maintenance decisions lead to incremental overall costs. In order to minimize costs in maintenance of the multi-state repairable system, we model a preventive maintenance(PM) scheme of the multistate repair...Inadequate maintenance decisions lead to incremental overall costs. In order to minimize costs in maintenance of the multi-state repairable system, we model a preventive maintenance(PM) scheme of the multistate repairable system using non-Markov process. The periodically decreasing reliability model of the non-Markov dynamic system with dynamic transition probabilities is established to satisfy the probability change. The diesel engine system is taken as an example to illustrate the model. The reliability of the diesel engine is analyzed and its PM scheme is worked out. RENO software is used to simulate the diesel engine system. The maintenance cost of components and the optimal PM interval data of the system are obtained by using the minimal average cost as the objective function. The adaptability of PM is judged, and the optimal PM scheme is presented.展开更多
Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Amo...Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Among the factors associated with DNA repair,the MRE11-RAD50-NBS1(MRN)complex(MRE11-RAD50-XRS2 in Saccharomyces cerevisiae)plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair.Upon detecting DNA damage,the MRN complex activates signaling molecules,such as the protein kinase ataxia-telangiectasia mutated(ATM),to trigger a broad DNA damage response,including cell cycle arrest.The nuclease activity of the MRN complex is responsible for DNA end resection,which guides DNA repair to HR in the presence of sister chromatids.The MRN complex is also involved in NHEJ,and has a species-specific role in hairpin repair.This review focuses on the structure of the MRN complex and its function in DNA damage repair.展开更多
Background: Acute dislocation of the thumb carpometacarpal (CMC) joint is a rare and challenging injury, and its treatment remains controversial. The purpose of the study was to evaluate the clinical outcome after sur...Background: Acute dislocation of the thumb carpometacarpal (CMC) joint is a rare and challenging injury, and its treatment remains controversial. The purpose of the study was to evaluate the clinical outcome after surgical repair of the dorsal capsulo-ligamentous complex. Materials and methods: Eight patients with a mean age of 39.8 years (range, 23 - 56 years) treated for the thumb CMC joint were treated in our hospital between 2008 and 2018. The ruptured dorsal capsulo-ligamentous complex was repaired using suture anchors in all patients, and the joint was immobilized with a Kirschner wire pinning and splint for 3 weeks. The clinical outcome was assessed by measuring the range of motion of the thumb CMC joint and the Japanese Society for Surgery of the Hand version of the Quick Disability of the Arm, Shoulder, and Hand (Q-DASH-JSSH) score. Results: The mean radial abduction of the thumb CMC joint was 66°, and the volar abduction was 63°. The mean Q-DASH-JSSH score was 4.8 (range, 0 - 15.6). There were no cases of infection, nerve disturbance, or osteoarthritis. Anatomical reduction was observed in seven patients at the final follow-up and in a rugby football player at 6 months of follow-up;however, subluxation of the thumb CMC joint at 12 months of follow-up due to reinjury was observed. Conclusion: Surgical repair of the dorsal capsulo-ligamentous complex with suture anchors is a reliable and simple treatment for acute unstable dislocation of the thumb CMC joint.展开更多
Neuronal activity is crucial for adaptive circuit remodelling but poses an inherent risk to the stability of the genome acrossthe long lifespan of postmitotic neurons1-5. Whether neurons have acquired specialized geno...Neuronal activity is crucial for adaptive circuit remodelling but poses an inherent risk to the stability of the genome acrossthe long lifespan of postmitotic neurons1-5. Whether neurons have acquired specialized genome protection mechanisms thatenable them to withstand decades of potentially damaging stimuli during periods of heightened activity is unknown. Here weidentify an activity-dependent DNA repair mechanism in which a new form of the NuA4-TIP60 chromatin modifier assembles inactivated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex from the brain anddemonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By characterizing thelandscape of activity-induced DNA double-strand breaks in the brain, we show that NPAS4-NuA4 binds to recurrently damagedregulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound byNPAS4-NuA4 are partially protected against age-dependent accumulation of somatic mutations. Impaired NPAS4-NuA4signalling leads to a cascade of cellular defects, including dysregulated activity-dependent transcriptional responses, loss of controlover neuronal inhibition and genome instability, which all culminate to reduce organismal lifespan. In addition, mutations inseveral components of the NuA4 complex are reported to lead to neurodevelopmental and autism spectrum disorders. Together,these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation, the disruptionof which may contribute to developmental disorders, neurodegeneration and ageing.展开更多
Base excision repair （BER） is an evolutionarily conserved process for maintaining genomic integrity by eliminating several dozen damaged （oxidized or aikylated） or inappropriate bases that are generated endogenous...Base excision repair （BER） is an evolutionarily conserved process for maintaining genomic integrity by eliminating several dozen damaged （oxidized or aikylated） or inappropriate bases that are generated endogenously or induced by genotoxicants, predominantly, reactive oxygen species （ROS）. BER involves 4-5 steps starting with base excision by a DNA glycosylase, followed by a common pathway usually involving an AP-endonuclease （APE） to generate 3＇ OH terminus at the damage site, followed by repair synthesis with a DNA polymerase and nick sealing by a DNA iigase. This pathway is also responsible for repairing DNA single-strand breaks with blocked termini directly generated by ROS. Nearly all glycosylases, far fewer than their substrate lesions particularly for oxidized bases, have broad and overlapping substrate range, and could serve as back-up enzymes in vivo. In contrast, mammalian cells encode only one APE, APEI, unlike two APEs in lower organisms. In spite of overall similarity, BER with distinct subpathways in the mammals is more complex than in E. coli. The glycosylases form complexes with downstream proteins to carry out efficient repair via distinct subpathways one of which, responsible for repair of strand breaks with 3＇ phosphate termini generated by the NEIL family glycosylases or by ROS, requires the phosphatase activity of polynucleotide kinase instead of APE1. Different complexes may utilize distinct DNA polymerases and iigases. Mammalian glycosylases have nonconserved extensions at one of the termini, dispensable for enzymatic activity but needed for interaction with other BER and non-BER proteins for complex formation and organeile targeting. The mammalian enzymes are sometimes covalently modified which may affect activity and complex formation. The focus of this review is on the early steps in mammalian BER for oxidized damage.展开更多
BACKGROUND Surgical repair of complex abdominal aortic aneurysm is associated with a higher perioperative mortality and morbidity.The advent of endovascular aortic repair(EVAR)has reduced perioperative complications,a...BACKGROUND Surgical repair of complex abdominal aortic aneurysm is associated with a higher perioperative mortality and morbidity.The advent of endovascular aortic repair(EVAR)has reduced perioperative complications,although the utilization of such techniques is limited by lesion characteristics,such as involvement of the visceral or renal arteries(RA)and/or presence of a sealing zone.CASE SUMMARY A 60-year-old male presented with a Crawford type IV complex thoracoabdominal aortic aneurysm(CAAA)starting directly distal to the diaphragm extending to both common iliac arteries(CIAs).The CAAA consist of a proximal and distal aneurysmal sac separated by a 1 cm-healthy zone in the infrarenal level.Due to the poor performance of the patient and the expansive disease,we planned a stepwise-combined surgery and EVAR to minimize invasiveness.A branched graft was implanted after surgical debranching of the visceral and RA.Since the patient had renal and liver injury after surgery,the second stage EVAR was performed 10 mo later.The stent graft was implanted from the distal portion of surgical branched graft to both CIAs during EVAR.The patient has been uneventful for 5-years after discharge and is being followed in the outpatient clinic.CONCLUSION The current case demonstrates that the surgical graft can provide a landing zone for second stage EVAR to avoid aggressive surgery in patients with poor performance with a long hostile CAAA.展开更多
基金the National Natural Science Foundation of China(Nos.61164009 and 61463021)the Science Foundation of Education Commission of Jiangxi Province(No.GJJ14420)+1 种基金the Young Scientists Object Program of Jiangxi Province(No.20144BCB23037)the Natural Science Foundation of Jiangxi Province(No.20132BAB206026)
文摘Inadequate maintenance decisions lead to incremental overall costs. In order to minimize costs in maintenance of the multi-state repairable system, we model a preventive maintenance(PM) scheme of the multistate repairable system using non-Markov process. The periodically decreasing reliability model of the non-Markov dynamic system with dynamic transition probabilities is established to satisfy the probability change. The diesel engine system is taken as an example to illustrate the model. The reliability of the diesel engine is analyzed and its PM scheme is worked out. RENO software is used to simulate the diesel engine system. The maintenance cost of components and the optimal PM interval data of the system are obtained by using the minimal average cost as the objective function. The adaptability of PM is judged, and the optimal PM scheme is presented.
基金supported by the National Key Research and Development Program of China(No.2018YFC2000100)the National Natural Science Foundation of China(Nos.31730021,31971220,and 31961160725)+1 种基金the Fok Ying Tung Education Foundationthe China’s Fundamental Research Funds for the Central Universities。
文摘Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Among the factors associated with DNA repair,the MRE11-RAD50-NBS1(MRN)complex(MRE11-RAD50-XRS2 in Saccharomyces cerevisiae)plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair.Upon detecting DNA damage,the MRN complex activates signaling molecules,such as the protein kinase ataxia-telangiectasia mutated(ATM),to trigger a broad DNA damage response,including cell cycle arrest.The nuclease activity of the MRN complex is responsible for DNA end resection,which guides DNA repair to HR in the presence of sister chromatids.The MRN complex is also involved in NHEJ,and has a species-specific role in hairpin repair.This review focuses on the structure of the MRN complex and its function in DNA damage repair.
文摘Background: Acute dislocation of the thumb carpometacarpal (CMC) joint is a rare and challenging injury, and its treatment remains controversial. The purpose of the study was to evaluate the clinical outcome after surgical repair of the dorsal capsulo-ligamentous complex. Materials and methods: Eight patients with a mean age of 39.8 years (range, 23 - 56 years) treated for the thumb CMC joint were treated in our hospital between 2008 and 2018. The ruptured dorsal capsulo-ligamentous complex was repaired using suture anchors in all patients, and the joint was immobilized with a Kirschner wire pinning and splint for 3 weeks. The clinical outcome was assessed by measuring the range of motion of the thumb CMC joint and the Japanese Society for Surgery of the Hand version of the Quick Disability of the Arm, Shoulder, and Hand (Q-DASH-JSSH) score. Results: The mean radial abduction of the thumb CMC joint was 66°, and the volar abduction was 63°. The mean Q-DASH-JSSH score was 4.8 (range, 0 - 15.6). There were no cases of infection, nerve disturbance, or osteoarthritis. Anatomical reduction was observed in seven patients at the final follow-up and in a rugby football player at 6 months of follow-up;however, subluxation of the thumb CMC joint at 12 months of follow-up due to reinjury was observed. Conclusion: Surgical repair of the dorsal capsulo-ligamentous complex with suture anchors is a reliable and simple treatment for acute unstable dislocation of the thumb CMC joint.
文摘Neuronal activity is crucial for adaptive circuit remodelling but poses an inherent risk to the stability of the genome acrossthe long lifespan of postmitotic neurons1-5. Whether neurons have acquired specialized genome protection mechanisms thatenable them to withstand decades of potentially damaging stimuli during periods of heightened activity is unknown. Here weidentify an activity-dependent DNA repair mechanism in which a new form of the NuA4-TIP60 chromatin modifier assembles inactivated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex from the brain anddemonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By characterizing thelandscape of activity-induced DNA double-strand breaks in the brain, we show that NPAS4-NuA4 binds to recurrently damagedregulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound byNPAS4-NuA4 are partially protected against age-dependent accumulation of somatic mutations. Impaired NPAS4-NuA4signalling leads to a cascade of cellular defects, including dysregulated activity-dependent transcriptional responses, loss of controlover neuronal inhibition and genome instability, which all culminate to reduce organismal lifespan. In addition, mutations inseveral components of the NuA4 complex are reported to lead to neurodevelopmental and autism spectrum disorders. Together,these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation, the disruptionof which may contribute to developmental disorders, neurodegeneration and ageing.
文摘Base excision repair （BER） is an evolutionarily conserved process for maintaining genomic integrity by eliminating several dozen damaged （oxidized or aikylated） or inappropriate bases that are generated endogenously or induced by genotoxicants, predominantly, reactive oxygen species （ROS）. BER involves 4-5 steps starting with base excision by a DNA glycosylase, followed by a common pathway usually involving an AP-endonuclease （APE） to generate 3＇ OH terminus at the damage site, followed by repair synthesis with a DNA polymerase and nick sealing by a DNA iigase. This pathway is also responsible for repairing DNA single-strand breaks with blocked termini directly generated by ROS. Nearly all glycosylases, far fewer than their substrate lesions particularly for oxidized bases, have broad and overlapping substrate range, and could serve as back-up enzymes in vivo. In contrast, mammalian cells encode only one APE, APEI, unlike two APEs in lower organisms. In spite of overall similarity, BER with distinct subpathways in the mammals is more complex than in E. coli. The glycosylases form complexes with downstream proteins to carry out efficient repair via distinct subpathways one of which, responsible for repair of strand breaks with 3＇ phosphate termini generated by the NEIL family glycosylases or by ROS, requires the phosphatase activity of polynucleotide kinase instead of APE1. Different complexes may utilize distinct DNA polymerases and iigases. Mammalian glycosylases have nonconserved extensions at one of the termini, dispensable for enzymatic activity but needed for interaction with other BER and non-BER proteins for complex formation and organeile targeting. The mammalian enzymes are sometimes covalently modified which may affect activity and complex formation. The focus of this review is on the early steps in mammalian BER for oxidized damage.
文摘BACKGROUND Surgical repair of complex abdominal aortic aneurysm is associated with a higher perioperative mortality and morbidity.The advent of endovascular aortic repair(EVAR)has reduced perioperative complications,although the utilization of such techniques is limited by lesion characteristics,such as involvement of the visceral or renal arteries(RA)and/or presence of a sealing zone.CASE SUMMARY A 60-year-old male presented with a Crawford type IV complex thoracoabdominal aortic aneurysm(CAAA)starting directly distal to the diaphragm extending to both common iliac arteries(CIAs).The CAAA consist of a proximal and distal aneurysmal sac separated by a 1 cm-healthy zone in the infrarenal level.Due to the poor performance of the patient and the expansive disease,we planned a stepwise-combined surgery and EVAR to minimize invasiveness.A branched graft was implanted after surgical debranching of the visceral and RA.Since the patient had renal and liver injury after surgery,the second stage EVAR was performed 10 mo later.The stent graft was implanted from the distal portion of surgical branched graft to both CIAs during EVAR.The patient has been uneventful for 5-years after discharge and is being followed in the outpatient clinic.CONCLUSION The current case demonstrates that the surgical graft can provide a landing zone for second stage EVAR to avoid aggressive surgery in patients with poor performance with a long hostile CAAA.
文摘目的探讨3D打印个性化导板辅助腕关节镜下修复PalmerⅠB型三角纤维软骨复合体(triangular fibrocartilage complex,TFCC)损伤的疗效。方法回顾分析2023年1月—2024年3月收治且符合选择标准的20例PalmerⅠB型TFCC损伤患者临床资料。其中男13例,女7例;年龄23~35岁,平均30.3岁。均有外伤史,摔伤12例、扭伤8例。“琴键征”阳性,MRI示TFCC尺侧端深层撕裂,经保守治疗6周临床疗效不佳或无效。受伤至手术时间2~9个月,平均5.0个月。行3D打印个性化导板辅助腕关节镜下修复术。手术前后采用疼痛视觉模拟评分(VAS)、改良Mayo腕关节评分、腕关节掌屈-背伸、尺偏-桡偏、旋前-旋后活动度(range of motion,ROM)评价功能恢复情况;末次随访时复查MRI评估TFCC修复愈合程度。结果20例患者均顺利完成手术,未发生血管神经损伤、骨折、切口感染及关节僵硬等并发症。所有患者均获随访,随访时间9~18个月,平均12.4个月。末次随访时,患者VAS评分、改良Mayo腕关节评分、掌屈-背伸ROM、尺偏-桡偏ROM、旋前-旋后ROM均较术前显著改善,差异有统计学意义(P<0.05)。末次随访时,MRI示TFCC连续性均存在,愈合良好,固定牢靠。结论3D打印个性化导板辅助腕关节镜下修复术治疗PalmerⅠB型TFCC损伤疗效满意,可提供高质量缝合,有利于解剖修复,明显改善腕关节功能。
