Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that...Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.展开更多
Cerebral autoregulation(CA)is the mechanism that maintains stable cerebral blood flow(CBF)despite fluctuations in systemic blood pressure,crucial for brain homeostasis.Recent evidence highlights distinct regional vari...Cerebral autoregulation(CA)is the mechanism that maintains stable cerebral blood flow(CBF)despite fluctuations in systemic blood pressure,crucial for brain homeostasis.Recent evidence highlights distinct regional variations in CA between the anterior(carotid)and posterior(vertebrobasilar)circulations.Noninvasive neuromonitoring techniques,such as transcranial Doppler,transfer function analysis,and near-infrared spectroscopy,facilitate the dynamic assessment of CBF and autoregulation.Studies indicate a robust autoregulatory capacity in the anterior circulation,characterized by rapid adjustments in vascular resistance.On the contrary,the posterior circulation,mainly supplied by the vertebral arteries,may have a lower autoregulatory capacity.in acute brain injuries such as intracerebral and subarachnoid hemorrhage,and traumatic brain injuries,dynamic CA can be significantly altered in the posterior circulation.Proposed physiological mechanisms of impaired CA in the posterior circulation include:(1)Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity;(2)Endothelial dysfunction;(3)Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBFmetabolism(i.e.,neurovascular)uncoupling;and(4)Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances(e.g.nitric oxide,potassium,and calcium ions).Furthermore,more research is needed on the effects of collateral circulation,as well as the circle of Willis variants,such as the fetal-type posterior cerebral artery,on dynamic CA.Improving our understanding of these mechanisms is crucial to improving the diagnosis,prognosis,and management of various cerebrovascular disorders.展开更多
[SUMMARY] TTTT is a non-invasive and new investigative examination,and a most important method of clinical diagnosis for many diseases,specially for orthostatic syncope,autonomic failure,intracranial hypertension,neur...[SUMMARY] TTTT is a non-invasive and new investigative examination,and a most important method of clinical diagnosis for many diseases,specially for orthostatic syncope,autonomic failure,intracranial hypertension,neurodegenerative diseases,CVAs and so on.At the same time,TCD technique for non-invasive monitoring of CBFV has also provided a new tool for investigating CA.In clinical circumstance,we may carry on assessment of dynamic CA by TTTT,and this kind of method has been proved to be appropriate to examine patients and monitor.we can choose different tilt positions by tilt-table according to the different demands for clinical diagnosis or researches,and record the different appearances of various index signs,we can take advantage of the technique of transfer function analysis of power spectrum between spontaneous changes in CBF and other factors(such as arterial pressure) to do research on the specific mechanism of impaired CA.展开更多
Dear Editor,The primary objective of the letter is to emphasize the importance of personalized management of arterial blood pressure(ABP)in the context of off-pump coronary artery bypass grafting(CABG)surgery.Coronary...Dear Editor,The primary objective of the letter is to emphasize the importance of personalized management of arterial blood pressure(ABP)in the context of off-pump coronary artery bypass grafting(CABG)surgery.Coronary artery disease,a leading global cause of mortality,necessitates a substantial number of cardiac surgeries,with approximately 400,000 CABG operations conducted annually in the United States.Postoperative heart failure(HF)is a common occurrence after CABG surgery,with readmission rates within 30 d due to HF ranging from 12% to 16%.展开更多
基金supported by National Natural Science Foundation of China(81901006)Guangdong Basic and Applied Basic Research Foundation(2020A1515110051)+1 种基金Scientific Research Talent Cultivation Project of Stomatological Hospital,Southern Medical University(RC202005)Science Research Cultivation Program of Stomatological Hospital,Southern Medical University(PY2020002)。
文摘Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.
文摘Cerebral autoregulation(CA)is the mechanism that maintains stable cerebral blood flow(CBF)despite fluctuations in systemic blood pressure,crucial for brain homeostasis.Recent evidence highlights distinct regional variations in CA between the anterior(carotid)and posterior(vertebrobasilar)circulations.Noninvasive neuromonitoring techniques,such as transcranial Doppler,transfer function analysis,and near-infrared spectroscopy,facilitate the dynamic assessment of CBF and autoregulation.Studies indicate a robust autoregulatory capacity in the anterior circulation,characterized by rapid adjustments in vascular resistance.On the contrary,the posterior circulation,mainly supplied by the vertebral arteries,may have a lower autoregulatory capacity.in acute brain injuries such as intracerebral and subarachnoid hemorrhage,and traumatic brain injuries,dynamic CA can be significantly altered in the posterior circulation.Proposed physiological mechanisms of impaired CA in the posterior circulation include:(1)Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity;(2)Endothelial dysfunction;(3)Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBFmetabolism(i.e.,neurovascular)uncoupling;and(4)Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances(e.g.nitric oxide,potassium,and calcium ions).Furthermore,more research is needed on the effects of collateral circulation,as well as the circle of Willis variants,such as the fetal-type posterior cerebral artery,on dynamic CA.Improving our understanding of these mechanisms is crucial to improving the diagnosis,prognosis,and management of various cerebrovascular disorders.
文摘[SUMMARY] TTTT is a non-invasive and new investigative examination,and a most important method of clinical diagnosis for many diseases,specially for orthostatic syncope,autonomic failure,intracranial hypertension,neurodegenerative diseases,CVAs and so on.At the same time,TCD technique for non-invasive monitoring of CBFV has also provided a new tool for investigating CA.In clinical circumstance,we may carry on assessment of dynamic CA by TTTT,and this kind of method has been proved to be appropriate to examine patients and monitor.we can choose different tilt positions by tilt-table according to the different demands for clinical diagnosis or researches,and record the different appearances of various index signs,we can take advantage of the technique of transfer function analysis of power spectrum between spontaneous changes in CBF and other factors(such as arterial pressure) to do research on the specific mechanism of impaired CA.
基金supported by the National Key Technologies Research and Development Program(2021YFF1200602)the National Science Fund for Excellent Overseas Scholars(0401260011)+1 种基金the National Defense Science and Technology Innovation Fund of Chinese Academy of Sciences(c02022088)Tianjin Science and Technology Program(20JCZDJC00810).
文摘Dear Editor,The primary objective of the letter is to emphasize the importance of personalized management of arterial blood pressure(ABP)in the context of off-pump coronary artery bypass grafting(CABG)surgery.Coronary artery disease,a leading global cause of mortality,necessitates a substantial number of cardiac surgeries,with approximately 400,000 CABG operations conducted annually in the United States.Postoperative heart failure(HF)is a common occurrence after CABG surgery,with readmission rates within 30 d due to HF ranging from 12% to 16%.
文摘目的:探讨颈动脉支架成形术(carotid artery stenting,CAS)后强化双重抗血小板治疗(dual antiplatelet therapy,DAPT)对脑血流自动调节功能重建的影响。方法:回顾性分析2023年2月至2024年6月郑州市中医院收治的70例CAS患者,按照治疗方法分为对照组(常规DAPT:阿司匹林+氯吡格雷,35例)和观察组(强化DAPT:阿司匹林+替格瑞洛,35例)。通过经颅多普勒(transcranial doppler,TCD)和动态脑自动调节指数(autoregulation index,ARI)评估术前、术后7 d及1个月的脑血流自动调节功能(屏气指数(breath holding index,BHI)、ARI、CO_(2)反应性指数),并比较血小板功能、炎症标志物及临床结局指标。结果:术后7 d及1个月,观察组BHI(0.91±0.19 vs 0.82±0.17,P<0.05;1.17±0.23 vs 0.96±0.21,P<0.001)、ARI(5.85±1.21 vs 5.18±1.18,P<0.05;6.92±1.17 vs 6.04±1.13,P<0.05)及CO_(2)反应性指数(2.12±0.38 vs 1.87±0.35,P<0.05;2.67±0.41 vs 2.23±0.37,P<0.001)均优于对照组。术后7 d,观察组ADP诱导血小板聚集率(31.25%±6.83%vs 42.37%±7.51%,P<0.001)、胶原诱导血小板聚集率(34.62%±7.19%vs.45.93%±7.81%,P<0.001)及炎症标志物[高敏C反应蛋白:(8.27±2.31)mg/L vs(12.59±3.05)mg/L,P<0.001;白细胞介素-6:(9.37±2.67)pg/mL vs(14.82±3.45)pg/mL,P<0.001]更低。观察组缺血事件发生率(2.86%vs 22.86%,P<0.05)和支架内再狭窄率(0.00%vs 17.14%,P<0.05)显著降低,两组出血并发症无统计学差异(8.57%vs 5.71%,P>0.05)。结论:强化DAPT可更有效改善CAS术后脑血流自动调节功能,减少缺血事件及支架内再狭窄,且不增加出血风险。
