AIM: To compare the short- and long-term outcomes of vascularizing lymph node dissection (VLND) and non-vascularizing lymph node dissection (NVLND) from a single institution.METHODS: Data of 315 patients with advanced...AIM: To compare the short- and long-term outcomes of vascularizing lymph node dissection (VLND) and non-vascularizing lymph node dissection (NVLND) from a single institution.METHODS: Data of 315 patients with advanced gastric cancer who underwent standard D2 lymphadenectomy with curative intent was collected between January 1994 and December 2006. One hundred and fifty-two patients received VLND while 163 patients received NVLND. Short- and long-term clinical outcomes were compared between the two groups.RESULTS: The median followed-up time was 82 mo. The rate of postoperative complications in the VLND group was 13.2%, while that in the NVLND group was 11.7% (P = 0.686). The overall 5-year survival rate was 64% in the VLND group and 59% in the NVLND group (P = 0.047). When subgroup analyses were performed according to Bormann type, type of differentiation and lymph node status, survival benefit was demonstrated in patients with Bormann type III or IV (59% vs 50%, P = 0.032), undifferentiated type (63% vs 49%, P = 0.021) or presence of lymph node metastasis (53% vs 38%, P = 0.010) in the VLND group.CONCLUSION: D2 VLND in advanced gastric cancer treatment allows survival benefit with acceptable morbidity and mortality. VLND for patients with potentially curable advanced gastric cancer is feasible and safe when performed by a well-trained surgical team.展开更多
Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral ...Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.展开更多
BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are e...BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are exceedingly infrequent.Notwithstanding,patients with copious comorbidities should be carefully monitored for potential vascular injury.CASE SUMMARY This case report presents the management of a 75-year-old male patient with a history of diabetes mellitus and arterial hypertension who was admitted to the emergency room with a superior pubic ramus fracture.The patient experienced a significant drop in hematocrit and hemoglobin levels post-admission,necessi-tating urgent intervention.A computed tomography angiography revealed active bleeding,leading to the embolization of the medial femoral branch.The patient was stabilized hemodynamically and was discharged after 15 days,with recom-mendations for home-based follow-up care.CONCLUSION This report denotes the various challenges and strategies in managing simple fractures that are treated conservatively,but need prompt monitoring for occult vascular injuries that can be fatal.展开更多
Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a pro...Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.展开更多
AIM:To determine the risk factors and time to non-arteric ischemic optic neuropathy(NAION)occurrence among Thai type 2 diabetes mellitus(T2DM)patients.METHODS:A retrospective review of 266 newly diagnosed T2DM cases a...AIM:To determine the risk factors and time to non-arteric ischemic optic neuropathy(NAION)occurrence among Thai type 2 diabetes mellitus(T2DM)patients.METHODS:A retrospective review of 266 newly diagnosed T2DM cases at Rajavithi Hospital between 2007 and 2016 was conducted to determine time to occurrence of NAION and evaluate associated risk factors.RESULTS:Hypertension and dyslipidemia were the most common pre-existing vascular diseases and there was a significant male predominance in the NAION group.The mean age of the NAION group was significantly higher than that of the group without NAION.A higher proportion of subjects in the NAION group had hypertension,dyslipidemia,high diastolic blood pressure,smokers,and had a small cup-to-disc ratio(CDR).Higher levels of triglycerides and lowdensity lipoprotein-cholesterol in the group with NAION.Fiftyfive patients among 266 participants(20.68%)developed NAION during a mean follow-up time of 81.26±25.04mo.In a multivariable logistic regression analysis,dyslipidemia(OR=8.36,95%CI,3.447–20.273,P<0.001),high low density lipoprotein levels(OR=1.017,95%CI,1.004–1.029,P=0.009),and small CDR(OR=11.92,95%CI,4.477–31.741,P<0.001)were significant risk factors for NAION development.Smoking was the strongest predictive risk(OR=12.843,95%CI,3.959–41.659,P<0.001).Vascular complications of T2DM and aspirin were not associated with NAION.CONCLUSION:T2DM patients with dyslipidemia or a small CDR should be carefully followed up as they are at increased risk of developing NAION.展开更多
Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the J...Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.展开更多
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact...After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these me...To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.展开更多
In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause o...In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ...Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.展开更多
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its wid...Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.展开更多
Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia r...Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2500 g),normal birth weight(2500-3999 g),and macrosomia(≥4000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.展开更多
Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py ...Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.展开更多
BACKGROUND The root of mesentery dissection is one of the critical maneuvers,especially in borderline resectable pancreatic head cancer.Intra-abdominal chyle leak(CL)including chylous ascites may ensue in up to 10%of ...BACKGROUND The root of mesentery dissection is one of the critical maneuvers,especially in borderline resectable pancreatic head cancer.Intra-abdominal chyle leak(CL)including chylous ascites may ensue in up to 10%of patients after pancreatic resections.Globally recognized superior mesenteric artery(SMA)first approaches are invariably performed.The mesenteric dissection through the inferior infracolic approach has been discussed in this study emphasizing its post-operative impact on CL which is the cornerstone of this study.AIM To assess incidence,risk factors,clinical impact of CL following root of mesentery dissection,and the different treatment modalities.METHODS This is a retrospective study incorporating the patients who underwent dissection of the root of mesentery with inferior infracolic SMA first approach pancreat-oduodenectomy for the ventral body and uncinate mass of pancreas in the Department of Gastrointestinal and General Surgery of Kathmandu Medical College and Teaching Hospital from January 1,2021 to February 28,2024.Intraop-erative findings and postoperative outcomes were analyzed.RESULTS In three years,ten patients underwent root of mesentery dissection with inferior infracolic SMA first approach pancreatoduodenectomy.The mean age was 67.6 years with a male-to-female ratio of 4:5.CL was seen in four patients.With virtue of CL,Clavien-Dindo grade Ⅱ or higher morbidity was observed in four patients.Two patients had a hospital stay of more than 20 days with the former having a delayed gastric emptying and the latter with long-term total parenteral nutrition requirement.The mean operative time was 330 minutes.Curative resection was achieved in 100%of the patients.The mean duration of the intensive care unit and hospital stay were 2.55±1.45 days and 15.7±5.32 days,respectively.CONCLUSION Root of mesentery dissection with lymphadenectomy and vascular resection correlated with occurrence of CL.After complete curative resection,these were managed with total parenteral nutrition without adversely impacting outcome.展开更多
Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores th...Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.展开更多
文摘AIM: To compare the short- and long-term outcomes of vascularizing lymph node dissection (VLND) and non-vascularizing lymph node dissection (NVLND) from a single institution.METHODS: Data of 315 patients with advanced gastric cancer who underwent standard D2 lymphadenectomy with curative intent was collected between January 1994 and December 2006. One hundred and fifty-two patients received VLND while 163 patients received NVLND. Short- and long-term clinical outcomes were compared between the two groups.RESULTS: The median followed-up time was 82 mo. The rate of postoperative complications in the VLND group was 13.2%, while that in the NVLND group was 11.7% (P = 0.686). The overall 5-year survival rate was 64% in the VLND group and 59% in the NVLND group (P = 0.047). When subgroup analyses were performed according to Bormann type, type of differentiation and lymph node status, survival benefit was demonstrated in patients with Bormann type III or IV (59% vs 50%, P = 0.032), undifferentiated type (63% vs 49%, P = 0.021) or presence of lymph node metastasis (53% vs 38%, P = 0.010) in the VLND group.CONCLUSION: D2 VLND in advanced gastric cancer treatment allows survival benefit with acceptable morbidity and mortality. VLND for patients with potentially curable advanced gastric cancer is feasible and safe when performed by a well-trained surgical team.
基金supported partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
基金This work was supported by the National Natural Science Foundation of China(grant numbers 81560301 and 81160012)the Natural Science Foundation of Qinghai Province(grant number 2022-ZJ-905)‘2022 Qinghai Province Kunlun Talents High-end Innovation and Entrepreneurship Talents’Outstanding Talent Project.
文摘Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.
文摘BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are exceedingly infrequent.Notwithstanding,patients with copious comorbidities should be carefully monitored for potential vascular injury.CASE SUMMARY This case report presents the management of a 75-year-old male patient with a history of diabetes mellitus and arterial hypertension who was admitted to the emergency room with a superior pubic ramus fracture.The patient experienced a significant drop in hematocrit and hemoglobin levels post-admission,necessi-tating urgent intervention.A computed tomography angiography revealed active bleeding,leading to the embolization of the medial femoral branch.The patient was stabilized hemodynamically and was discharged after 15 days,with recom-mendations for home-based follow-up care.CONCLUSION This report denotes the various challenges and strategies in managing simple fractures that are treated conservatively,but need prompt monitoring for occult vascular injuries that can be fatal.
文摘Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.
文摘AIM:To determine the risk factors and time to non-arteric ischemic optic neuropathy(NAION)occurrence among Thai type 2 diabetes mellitus(T2DM)patients.METHODS:A retrospective review of 266 newly diagnosed T2DM cases at Rajavithi Hospital between 2007 and 2016 was conducted to determine time to occurrence of NAION and evaluate associated risk factors.RESULTS:Hypertension and dyslipidemia were the most common pre-existing vascular diseases and there was a significant male predominance in the NAION group.The mean age of the NAION group was significantly higher than that of the group without NAION.A higher proportion of subjects in the NAION group had hypertension,dyslipidemia,high diastolic blood pressure,smokers,and had a small cup-to-disc ratio(CDR).Higher levels of triglycerides and lowdensity lipoprotein-cholesterol in the group with NAION.Fiftyfive patients among 266 participants(20.68%)developed NAION during a mean follow-up time of 81.26±25.04mo.In a multivariable logistic regression analysis,dyslipidemia(OR=8.36,95%CI,3.447–20.273,P<0.001),high low density lipoprotein levels(OR=1.017,95%CI,1.004–1.029,P=0.009),and small CDR(OR=11.92,95%CI,4.477–31.741,P<0.001)were significant risk factors for NAION development.Smoking was the strongest predictive risk(OR=12.843,95%CI,3.959–41.659,P<0.001).Vascular complications of T2DM and aspirin were not associated with NAION.CONCLUSION:T2DM patients with dyslipidemia or a small CDR should be carefully followed up as they are at increased risk of developing NAION.
文摘Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.
基金supported by European Regional Development Funds RE0022527 ZEBRATOX(EU-Région Réunion-French State national counterpart,to Nicolas Diotel and Jean-Loup Bascands).
文摘After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by University of Macao,China,Nos.MYRG2022-00054-FHS and MYRG-GRG2023-00038-FHS-UMDF(to ZY)the Macao Science and Technology Development Fund,China,Nos.FDCT0048/2021/AGJ and FDCT0020/2019/AMJ and FDCT 0011/2018/A1(to ZY)Natural Science Foundation of Guangdong Province of China,No.EF017/FHS-YZ/2021/GDSTC(to ZY)。
文摘To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.
文摘In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
基金supported by the Lorenz B?hler Fonds,#2/19 (obtained by the Neuroregeneration Group,Ludwig Boltzmann Institute for Traumatology)the City of Vienna project ImmunTissue,MA23#30-11 (obtained by the Department Life Science Engineering,University of Applied Sciences Technikum Wien)。
文摘Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.
基金supported by grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
基金supported by the National Natural Science Foundation of China(82072675,82273197,82173933)Fundamental Research Funds for the Central Universities(020814380160).
文摘Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.
文摘Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2500 g),normal birth weight(2500-3999 g),and macrosomia(≥4000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.
基金Supported by the National Natural Science Foundation of China(82371373,W2412120)the Shanghai Natural Science Foundation(21ZR1436100).
文摘Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.
文摘BACKGROUND The root of mesentery dissection is one of the critical maneuvers,especially in borderline resectable pancreatic head cancer.Intra-abdominal chyle leak(CL)including chylous ascites may ensue in up to 10%of patients after pancreatic resections.Globally recognized superior mesenteric artery(SMA)first approaches are invariably performed.The mesenteric dissection through the inferior infracolic approach has been discussed in this study emphasizing its post-operative impact on CL which is the cornerstone of this study.AIM To assess incidence,risk factors,clinical impact of CL following root of mesentery dissection,and the different treatment modalities.METHODS This is a retrospective study incorporating the patients who underwent dissection of the root of mesentery with inferior infracolic SMA first approach pancreat-oduodenectomy for the ventral body and uncinate mass of pancreas in the Department of Gastrointestinal and General Surgery of Kathmandu Medical College and Teaching Hospital from January 1,2021 to February 28,2024.Intraop-erative findings and postoperative outcomes were analyzed.RESULTS In three years,ten patients underwent root of mesentery dissection with inferior infracolic SMA first approach pancreatoduodenectomy.The mean age was 67.6 years with a male-to-female ratio of 4:5.CL was seen in four patients.With virtue of CL,Clavien-Dindo grade Ⅱ or higher morbidity was observed in four patients.Two patients had a hospital stay of more than 20 days with the former having a delayed gastric emptying and the latter with long-term total parenteral nutrition requirement.The mean operative time was 330 minutes.Curative resection was achieved in 100%of the patients.The mean duration of the intensive care unit and hospital stay were 2.55±1.45 days and 15.7±5.32 days,respectively.CONCLUSION Root of mesentery dissection with lymphadenectomy and vascular resection correlated with occurrence of CL.After complete curative resection,these were managed with total parenteral nutrition without adversely impacting outcome.
文摘Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.
