Objective: To identify the anti-hemorrhoidal medicinal plants of the Department of Issia and evaluate the cytotoxic activity of the most requested species. Methods: The plants used in hemorrhoid recipes in the Departm...Objective: To identify the anti-hemorrhoidal medicinal plants of the Department of Issia and evaluate the cytotoxic activity of the most requested species. Methods: The plants used in hemorrhoid recipes in the Department of Issia (C?te d’Ivoire) were obtained using a semi-structured survey based on a questionnaire sheet. To assess the use of plants on the disease, Informant Consensus Factors (ICF) for each species were calculated. The harvested species were identified at the Centre National de Floristique (CNF) of the Félix Houphou?t Boigny University (C?te d’Ivoire). Cytotoxicity tests were performed on HFF cells with the 70% ethanolic extract, prepared from the aqueous extract of the most cited species. Results: A total of twenty four medicinal species in eighteen families were recorded. Among these taxa are ten woody and fourteen herbaceous. Only three species gave an ICF greater than 0.5. The ethanolic extract 70% of the frequently requested medicinal plant did not reveal any toxicity on HFF cells. Conclusion: These results revealed that the flora of the Department of Issia is rich in anti-hemorrhoidal medicinal plant species. Their use without side effects is revealed by the absence of toxicity in one of the most solicited plants.展开更多
VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a ra...VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a rare condition that was not reported until 2020.[2]Since then,interest among dermatologists,hematologists,and rheumatologists with published works has increased,[3]but none of them reported in the emergency setting,nor have any cases arisen following COVID-19 infection.展开更多
Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with m...Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with meningitis symptoms at a referral hospital in Mersin,Turkey,between January 2019 and January 2022.Clinical findings and laboratory results,including leukocyte count,C-reactive protein(CRP),and procalcitonin levels in blood,were examined.Logistic regression,Chi square test,and receiver operating characteristics(ROC)curve analyses assessed the predictive value of these parameters.Results:A total of 199 participants were included in the study;99 patients were diagnosed with meningitis after lumbar puncture and 100 served as controls.Patients with meningitis exhibited significantly higher leukocyte counts(median:11890×10^(3)/μL vs.7905×10^(3)/μL,P<0.001)and CRP levels(median:6.00 mg/dL vs.0.95 mg/dL,P<0.001)compared to controls.Procalcitonin levels were significantly elevated in meningitis patients(median:0.21 ng/mL vs.0.10 ng/mL,P<0.001).Logistic regression identified albumin(OR=0.16,95%CI=0.06-0.40),and CRP(OR=1.18,95%CI=1.08-1.28)as independent predictors of meningitis.ROC analysis for CRP demonstrated a sensitivity of 80.6%and specificity of 70.0%at a cut-off value of 2.23 mg/dL(AUC=0.792).Conclusions:Elevated albumin levels and CRP contents in the blood were significant predictors of meningitis in emergency service.Early identification of predictive markers may aid in timely lumbar puncture and management of atypical cases.展开更多
Phencyclidine(PCP,known as angel dust) is a nonbarbiturate,non-narcotic intravenous(IV) anesthetic with potent analgesic effects.However,its medical use was discontinued because of postoperative agitation,disorientati...Phencyclidine(PCP,known as angel dust) is a nonbarbiturate,non-narcotic intravenous(IV) anesthetic with potent analgesic effects.However,its medical use was discontinued because of postoperative agitation,disorientation,psychosis,cardiotoxicity,and hallucinogenic effects.Consequently,the PCP began to be illicitly distributed.The use methods include snorting,inhalation,IV,and subcutaneous(SC) injection.[1-5] The characteristic toxidrome of PCP includes altered mental status,tachycardia,and nystagmus.At higher doses,patients may become comatose and develop sympathomimetic effects such as tachycardia,hypertension,hypersalivation,urinary retention,and bronchospasm.In cases of intoxication,the pupillary light reflex remains intact,although the pupil size may vary.[1,3-6] PCP has a direct cardiotoxic effect and may induce arrhythmias.[2] Hyperreflexia,muscle rigidity,choreiform movements and muscle fasciculations may occur.[2,4,6] PCP-induced acute respiratory distress syndrome(ARDS) and alveolar hemorrhage(AH) are rare but potentially life-threatening complications.The main causes of non-traumatic death in patients with PCP intoxication include cardiopulmonary arrest,intracranial hemorrhage and rhabdomyolysis.[2,3,5] This case report aims to emphasize the management and potential benefits of inhaled N-acetylcysteine(NAC) and tranexamic acid(TXA)for PCP-induced ARDS and AH.展开更多
Still common in developing countries, acute rheumatic fever (ARF) is not only a disease of children and adolescents, but can also occur in adults. At this age, the diagnosis of rheumatic flare-ups can be difficult due...Still common in developing countries, acute rheumatic fever (ARF) is not only a disease of children and adolescents, but can also occur in adults. At this age, the diagnosis of rheumatic flare-ups can be difficult due to the frequency of other types of joint diseases and the existence of degenerative and dystrophic valve disease. In adults, the initial rheumatic attack is marked by the predominance of joint damage over cardiac damage. However, it is often at this age that rheumatic valve disease is discovered. The revised Jones criteria also find their place in the diagnosis of AAR in adults. Objective: To study the demographic, clinical, and biological characteristics of acute rheumatic fever (ARF) in the General Medicine Department of the Siguiri Prefectural Hospital. Materials and Methods: This descriptive observational study examined the demographic, clinical and biological characteristics of acute rheumatic fever (ARF) at the Siguiri Prefectural Hospital, Guinea, between April 1 and September 31, 2021 according to Jones criteria. The data were collected on a form containing sociodemographic variables (age, sex, profession), rheumatological, cardiac, pulmonary and neurological clinical signs, biological variables and treatment. Results: Figure 1 shows the flow of the hospital frequency of the RAA in the General Medicine Department of the Prefectural Hospital of Siguiri. During the study period, 420 patients were hospitalized, of whom 161 patients had AAR, a frequency of 38.33%. Table 1 shows the distribution of patients diagnosed with ARB, by sociodemographic characteristics. The average age was 44.7 ± 19.78 years and the extremes of 14 and 90 years, the female sex dominated with a ratio of 0.75. The informal sector was in the majority in 45.34% of cases and most were illiterate, i.e. 53.42%. In our study, the incidence was lower during the dry season than during the rainy season, a hot season with high rainfall and humidity, the rainy period was a provider with a peak in August and September. The lifestyle was characterized by overcrowding in 87.58% of patients. The main complaint was fever, i.e. 88.82%. Rheumatological manifestations such as arthritis were 98.14%, chest pain was 37.89% (61 cases). The diagnosis was confirmed by ASLO titration in 85.71% of patients and 98.55% (136 cases) had a titration greater than 400 U/ml. Conclusion: The results obtained from our study show a high prevalence of acute rheumatic fever, which makes it a worrying health problem in the Siguiri health district. Young female adult patients, married with an informal profession and not in school residing in Siguiri were the most encountered in our study. The main functional signs mentioned by the patients were fever, cough and abdominal pain;osteoarticular pain and chest pain dominated the clinical picture. Almost all of our patients had an ASLO titer greater than 400 U/ml and a positive C-reactive protein. Our results show a high risk of spread of acute rheumatic fever within the population of Siguiri. Due to the serious complications caused by acute rheumatic fever, particular attention must be paid to it by carrying out other, much larger studies in order to identify the problem of RAA.展开更多
Propofol(2,6-di-isopropylphenol) is a short-acting,intravenous sedative drug.^([1,2]) The pharmacologic mechanism of propofol is related to its agonistic effects on the gamma-amino butyric acid receptor.^([1-3]) Propo...Propofol(2,6-di-isopropylphenol) is a short-acting,intravenous sedative drug.^([1,2]) The pharmacologic mechanism of propofol is related to its agonistic effects on the gamma-amino butyric acid receptor.^([1-3]) Propofol injection pain(PIP) is well-known in the operating room and is commonly countered by the prophylactic administration of lidocaine.In anesthesia,PIP is encountered in 28%–90% of patients.^([4,5]) However,PIPprophylaxis does not seem to be efficacious in every population.^([6,7]) Whether procedural sedation and analgesia(PSA) in the emergency department(ED) warrants lidocaine administration is unclear.展开更多
Introduction: Diabetic ketoacidosis (DKA) is the most common metabolic complication of diabetes. Although historically reported in children, it is increasingly observed in adults. Short-term outcomes and prognosis var...Introduction: Diabetic ketoacidosis (DKA) is the most common metabolic complication of diabetes. Although historically reported in children, it is increasingly observed in adults. Short-term outcomes and prognosis vary widely across healthcare settings. Therefore, we aimed to determine the prevalence, diagnostic characteristics, and outcomes of newly diagnosed diabetic ketoacidosis in a hospital setting in Dakar. Methodology: We conducted a descriptive and analytical cross-sectional study from January 1, 2020, to January 31, 2021, in the Endocrinology-Metabolism Department of the Pikine National Hospital Center. All diabetic patients hospitalized for newly diagnosed diabetic ketoacidosis during this period were included. Results: A total of 54 patients were enrolled in the study. The prevalence of newly diagnosed DKA in the facility was 17.1%. The mean age was 38.54 years, with a male predominance and a sex ratio of 1.16. Thirty-five patients had a family history of diabetes. Upon admission, 14.9% of patients had altered consciousness, and 92.4% exhibited cardinal symptoms, with an average duration of 14.2 days. Kussmaul breathing and gastrointestinal symptoms were observed in 13% and 33% of cases, respectively. The mean capillary blood glucose level at admission was 3.43 g/L. Infection was identified as the precipitating factor in half of the cases, while no triggering factor was found in the remaining cases. The mean BMI was 25.27 kg/m², and the average glycated hemoglobin (HbA1c) level was 12.2%. We recorded the diabetes classification for all patients. Nine had type 1 diabetes, twelve had type 1b diabetes, thirty-one had type 2 diabetes, and two had diabetes secondary to corticosteroid therapy. All patients received continuous intravenous insulin therapy via a syringe pump. The mean time to ketosis resolution was 34.6 hours. The average total dose of regular insulin administered was 442.3 IU. The mean duration of hospitalization was 7.6 days. One patient died, and fifty-one were discharged while continuing insulin therapy, with an average dose of 53 IU. Conclusion: The prevalence of newly diagnosed DKA remains high. With proper management, the prognosis is generally favorable. Diabetes classification is crucial, as it determines subsequent treatment strategies.展开更多
Toxocariasis is a helminthic zoonosis due to the presence in the human body of larvae of Toxocara sp., roundworms of the Ascaridae family. Less than 50 cases of central involvement related to toxocarasis have been rep...Toxocariasis is a helminthic zoonosis due to the presence in the human body of larvae of Toxocara sp., roundworms of the Ascaridae family. Less than 50 cases of central involvement related to toxocarasis have been reported in immunocompetent individuals. This involvement can result in epilepsy, meningoencephalitis, myelitis or encephalopathy. The standard treatment is albendazole at a dosage of 10 to 15 mg/kg/day. The duration of treatment varies greatly depending on the clinical cases reported, ranging from 5 days to several weeks in the case of severe forms. We report a case of myelitis due to Toxocara canis in a 14-year-old patient admitted for gait disorders. The laboratory assessment shows isolated hypereosinophilia at 8000 elements per mm3. Medullary magnetic resonance imaging (MRI) showed an intradural process of inflammatory and infectious appearance extended between T10 and L1 levels, hypointense in T1, hyperintense in T2, and homogeneous. Parasitological analysis of the stools noted the presence of high concentrations of Toxocara canis. Serology by ELISA (enzyme-linked immunosorbent assay) is strongly positive for toxocariasis, and western blot confirms the presence of antibodies directed against Toxocara larvae. Treatment with albendazole 400 mg × 2/day for 10 days associated with corticosteroid therapy (prednisone 50 mg/day for 5 days) allowed the disappearance of pain in 8 days, normalization of eosinophilia and improvement of walking.展开更多
The department of Tillabéri is primarily affected by climatic phenomena, impacting crop yields, growing cycles, and consequently, the economic outcomes of agricultural operations. The objective of this study is t...The department of Tillabéri is primarily affected by climatic phenomena, impacting crop yields, growing cycles, and consequently, the economic outcomes of agricultural operations. The objective of this study is to analyze these impacts of climate disruption on the economic performance of farms. The methodology adopted for this study combined documentary research with field surveys conducted on a sample of 250 randomly selected farmers. The analytical methods used mainly consisted of linear regression, profitability calculations, and linear programming. The findings indicate that all productions across different crops have experienced a decrease over the past 30 years. For instance, the production of millet, sorghum, and cowpea, which were respectively 812 kg/ha, 260 kg/ha, and 100 kg/ha between the last 30 and 20 years, has now dropped to 412 kg/ha, 106 kg/ha, and 46 kg/ha respectively. A negative and significant effect on agricultural net margin was observed due to variables such as flooding, drought, pest invasion in rice fields, and temperature changes. Smallholder farms show a relatively low margin (46%) to cover their fixed costs, which may indicate a risk if fixed expenses are high. Furthermore, the analysis results from linear programming reveal that farmers could achieve an additional net profit per hectare of 116,861 FCFA, 217201.5 FCFA, and 291988.2 FCFA respectively for small, medium, and large producers by managing variable costs and health-related expenses for households.展开更多
BACKGROUND:Rapid and accurate identification of high-risk patients in the emergency departments(EDs)is crucial for optimizing resource allocation and improving patient outcomes.This study aimed to develop an early pre...BACKGROUND:Rapid and accurate identification of high-risk patients in the emergency departments(EDs)is crucial for optimizing resource allocation and improving patient outcomes.This study aimed to develop an early prediction model for identifying high-risk patients in EDs using initial vital sign measurements.METHODS:This retrospective cohort study analyzed initial vital signs from the Chinese Emergency Triage,Assessment,and Treatment(CETAT)database,which was collected between January 1^(st),2020,and June 25^(th),2023.The primary outcome was the identification of high-risk patients needing immediate treatment.Various machine learning methods,including a deep-learningbased multilayer perceptron(MLP)classifier were evaluated.Model performance was assessed using the area under the receiver operating characteristic curve(AUC-ROC).AUC-ROC values were reported for three scenarios:a default case,a scenario requiring sensitivity greater than 0.8(Scenario I),and a scenario requiring specificity greater than 0.8(Scenario II).SHAP values were calculated to determine the importance of each predictor within the MLP model.RESULTS:A total of 38,797 patients were analyzed,of whom 18.2%were identified as high-risk.Comparative analysis of the predictive models for high-risk patients showed AUC-ROC values ranging from 0.717 to 0.738,with the MLP model outperforming logistic regression(LR),Gaussian Naive Bayes(GNB),and the National Early Warning Score(NEWS).SHAP value analysis identified coma state,peripheral capillary oxygen saturation(SpO_(2)),and systolic blood pressure as the top three predictive factors in the MLP model,with coma state exerting the most contribution.CONCLUSION:Compared with other methods,the MLP model with initial vital signs demonstrated optimal prediction accuracy,highlighting its potential to enhance clinical decision-making in triage in the EDs.展开更多
The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit...Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.展开更多
Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells...Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.展开更多
Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxid...Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.展开更多
The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role i...The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.展开更多
Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
The term“gut microbiota”primarily refers to the ecological community of various microorganisms in the gut,which constitutes the largest microbial community in the human body.Although adequate bowel preparation can i...The term“gut microbiota”primarily refers to the ecological community of various microorganisms in the gut,which constitutes the largest microbial community in the human body.Although adequate bowel preparation can improve the results of colonoscopy,it may interfere with the gut microbiota.Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota,potentially affecting an individual’s health,especially in vulnerable populations,such as patients with inflammatory bowel disease.However,measures such as oral pro-biotics may ameliorate these adverse effects.We focused on the bowel prepa-ration-induced changes in the gut microbiota and host health status,hypothesized the factors influencing these changes,and attempted to identify measures that may reduce dysbiosis,thereby providing more information for individualized bowel preparation for colonoscopy in the future.展开更多
Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory resp...Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.展开更多
Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect...Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.展开更多
Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
文摘Objective: To identify the anti-hemorrhoidal medicinal plants of the Department of Issia and evaluate the cytotoxic activity of the most requested species. Methods: The plants used in hemorrhoid recipes in the Department of Issia (C?te d’Ivoire) were obtained using a semi-structured survey based on a questionnaire sheet. To assess the use of plants on the disease, Informant Consensus Factors (ICF) for each species were calculated. The harvested species were identified at the Centre National de Floristique (CNF) of the Félix Houphou?t Boigny University (C?te d’Ivoire). Cytotoxicity tests were performed on HFF cells with the 70% ethanolic extract, prepared from the aqueous extract of the most cited species. Results: A total of twenty four medicinal species in eighteen families were recorded. Among these taxa are ten woody and fourteen herbaceous. Only three species gave an ICF greater than 0.5. The ethanolic extract 70% of the frequently requested medicinal plant did not reveal any toxicity on HFF cells. Conclusion: These results revealed that the flora of the Department of Issia is rich in anti-hemorrhoidal medicinal plant species. Their use without side effects is revealed by the absence of toxicity in one of the most solicited plants.
基金National High Level Hospital Clinical Research Funding(Scientific Research Seed Fund of Peking University First Hospital).
文摘VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a rare condition that was not reported until 2020.[2]Since then,interest among dermatologists,hematologists,and rheumatologists with published works has increased,[3]but none of them reported in the emergency setting,nor have any cases arisen following COVID-19 infection.
文摘Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with meningitis symptoms at a referral hospital in Mersin,Turkey,between January 2019 and January 2022.Clinical findings and laboratory results,including leukocyte count,C-reactive protein(CRP),and procalcitonin levels in blood,were examined.Logistic regression,Chi square test,and receiver operating characteristics(ROC)curve analyses assessed the predictive value of these parameters.Results:A total of 199 participants were included in the study;99 patients were diagnosed with meningitis after lumbar puncture and 100 served as controls.Patients with meningitis exhibited significantly higher leukocyte counts(median:11890×10^(3)/μL vs.7905×10^(3)/μL,P<0.001)and CRP levels(median:6.00 mg/dL vs.0.95 mg/dL,P<0.001)compared to controls.Procalcitonin levels were significantly elevated in meningitis patients(median:0.21 ng/mL vs.0.10 ng/mL,P<0.001).Logistic regression identified albumin(OR=0.16,95%CI=0.06-0.40),and CRP(OR=1.18,95%CI=1.08-1.28)as independent predictors of meningitis.ROC analysis for CRP demonstrated a sensitivity of 80.6%and specificity of 70.0%at a cut-off value of 2.23 mg/dL(AUC=0.792).Conclusions:Elevated albumin levels and CRP contents in the blood were significant predictors of meningitis in emergency service.Early identification of predictive markers may aid in timely lumbar puncture and management of atypical cases.
文摘Phencyclidine(PCP,known as angel dust) is a nonbarbiturate,non-narcotic intravenous(IV) anesthetic with potent analgesic effects.However,its medical use was discontinued because of postoperative agitation,disorientation,psychosis,cardiotoxicity,and hallucinogenic effects.Consequently,the PCP began to be illicitly distributed.The use methods include snorting,inhalation,IV,and subcutaneous(SC) injection.[1-5] The characteristic toxidrome of PCP includes altered mental status,tachycardia,and nystagmus.At higher doses,patients may become comatose and develop sympathomimetic effects such as tachycardia,hypertension,hypersalivation,urinary retention,and bronchospasm.In cases of intoxication,the pupillary light reflex remains intact,although the pupil size may vary.[1,3-6] PCP has a direct cardiotoxic effect and may induce arrhythmias.[2] Hyperreflexia,muscle rigidity,choreiform movements and muscle fasciculations may occur.[2,4,6] PCP-induced acute respiratory distress syndrome(ARDS) and alveolar hemorrhage(AH) are rare but potentially life-threatening complications.The main causes of non-traumatic death in patients with PCP intoxication include cardiopulmonary arrest,intracranial hemorrhage and rhabdomyolysis.[2,3,5] This case report aims to emphasize the management and potential benefits of inhaled N-acetylcysteine(NAC) and tranexamic acid(TXA)for PCP-induced ARDS and AH.
文摘Still common in developing countries, acute rheumatic fever (ARF) is not only a disease of children and adolescents, but can also occur in adults. At this age, the diagnosis of rheumatic flare-ups can be difficult due to the frequency of other types of joint diseases and the existence of degenerative and dystrophic valve disease. In adults, the initial rheumatic attack is marked by the predominance of joint damage over cardiac damage. However, it is often at this age that rheumatic valve disease is discovered. The revised Jones criteria also find their place in the diagnosis of AAR in adults. Objective: To study the demographic, clinical, and biological characteristics of acute rheumatic fever (ARF) in the General Medicine Department of the Siguiri Prefectural Hospital. Materials and Methods: This descriptive observational study examined the demographic, clinical and biological characteristics of acute rheumatic fever (ARF) at the Siguiri Prefectural Hospital, Guinea, between April 1 and September 31, 2021 according to Jones criteria. The data were collected on a form containing sociodemographic variables (age, sex, profession), rheumatological, cardiac, pulmonary and neurological clinical signs, biological variables and treatment. Results: Figure 1 shows the flow of the hospital frequency of the RAA in the General Medicine Department of the Prefectural Hospital of Siguiri. During the study period, 420 patients were hospitalized, of whom 161 patients had AAR, a frequency of 38.33%. Table 1 shows the distribution of patients diagnosed with ARB, by sociodemographic characteristics. The average age was 44.7 ± 19.78 years and the extremes of 14 and 90 years, the female sex dominated with a ratio of 0.75. The informal sector was in the majority in 45.34% of cases and most were illiterate, i.e. 53.42%. In our study, the incidence was lower during the dry season than during the rainy season, a hot season with high rainfall and humidity, the rainy period was a provider with a peak in August and September. The lifestyle was characterized by overcrowding in 87.58% of patients. The main complaint was fever, i.e. 88.82%. Rheumatological manifestations such as arthritis were 98.14%, chest pain was 37.89% (61 cases). The diagnosis was confirmed by ASLO titration in 85.71% of patients and 98.55% (136 cases) had a titration greater than 400 U/ml. Conclusion: The results obtained from our study show a high prevalence of acute rheumatic fever, which makes it a worrying health problem in the Siguiri health district. Young female adult patients, married with an informal profession and not in school residing in Siguiri were the most encountered in our study. The main functional signs mentioned by the patients were fever, cough and abdominal pain;osteoarticular pain and chest pain dominated the clinical picture. Almost all of our patients had an ASLO titer greater than 400 U/ml and a positive C-reactive protein. Our results show a high risk of spread of acute rheumatic fever within the population of Siguiri. Due to the serious complications caused by acute rheumatic fever, particular attention must be paid to it by carrying out other, much larger studies in order to identify the problem of RAA.
文摘Propofol(2,6-di-isopropylphenol) is a short-acting,intravenous sedative drug.^([1,2]) The pharmacologic mechanism of propofol is related to its agonistic effects on the gamma-amino butyric acid receptor.^([1-3]) Propofol injection pain(PIP) is well-known in the operating room and is commonly countered by the prophylactic administration of lidocaine.In anesthesia,PIP is encountered in 28%–90% of patients.^([4,5]) However,PIPprophylaxis does not seem to be efficacious in every population.^([6,7]) Whether procedural sedation and analgesia(PSA) in the emergency department(ED) warrants lidocaine administration is unclear.
文摘Introduction: Diabetic ketoacidosis (DKA) is the most common metabolic complication of diabetes. Although historically reported in children, it is increasingly observed in adults. Short-term outcomes and prognosis vary widely across healthcare settings. Therefore, we aimed to determine the prevalence, diagnostic characteristics, and outcomes of newly diagnosed diabetic ketoacidosis in a hospital setting in Dakar. Methodology: We conducted a descriptive and analytical cross-sectional study from January 1, 2020, to January 31, 2021, in the Endocrinology-Metabolism Department of the Pikine National Hospital Center. All diabetic patients hospitalized for newly diagnosed diabetic ketoacidosis during this period were included. Results: A total of 54 patients were enrolled in the study. The prevalence of newly diagnosed DKA in the facility was 17.1%. The mean age was 38.54 years, with a male predominance and a sex ratio of 1.16. Thirty-five patients had a family history of diabetes. Upon admission, 14.9% of patients had altered consciousness, and 92.4% exhibited cardinal symptoms, with an average duration of 14.2 days. Kussmaul breathing and gastrointestinal symptoms were observed in 13% and 33% of cases, respectively. The mean capillary blood glucose level at admission was 3.43 g/L. Infection was identified as the precipitating factor in half of the cases, while no triggering factor was found in the remaining cases. The mean BMI was 25.27 kg/m², and the average glycated hemoglobin (HbA1c) level was 12.2%. We recorded the diabetes classification for all patients. Nine had type 1 diabetes, twelve had type 1b diabetes, thirty-one had type 2 diabetes, and two had diabetes secondary to corticosteroid therapy. All patients received continuous intravenous insulin therapy via a syringe pump. The mean time to ketosis resolution was 34.6 hours. The average total dose of regular insulin administered was 442.3 IU. The mean duration of hospitalization was 7.6 days. One patient died, and fifty-one were discharged while continuing insulin therapy, with an average dose of 53 IU. Conclusion: The prevalence of newly diagnosed DKA remains high. With proper management, the prognosis is generally favorable. Diabetes classification is crucial, as it determines subsequent treatment strategies.
文摘Toxocariasis is a helminthic zoonosis due to the presence in the human body of larvae of Toxocara sp., roundworms of the Ascaridae family. Less than 50 cases of central involvement related to toxocarasis have been reported in immunocompetent individuals. This involvement can result in epilepsy, meningoencephalitis, myelitis or encephalopathy. The standard treatment is albendazole at a dosage of 10 to 15 mg/kg/day. The duration of treatment varies greatly depending on the clinical cases reported, ranging from 5 days to several weeks in the case of severe forms. We report a case of myelitis due to Toxocara canis in a 14-year-old patient admitted for gait disorders. The laboratory assessment shows isolated hypereosinophilia at 8000 elements per mm3. Medullary magnetic resonance imaging (MRI) showed an intradural process of inflammatory and infectious appearance extended between T10 and L1 levels, hypointense in T1, hyperintense in T2, and homogeneous. Parasitological analysis of the stools noted the presence of high concentrations of Toxocara canis. Serology by ELISA (enzyme-linked immunosorbent assay) is strongly positive for toxocariasis, and western blot confirms the presence of antibodies directed against Toxocara larvae. Treatment with albendazole 400 mg × 2/day for 10 days associated with corticosteroid therapy (prednisone 50 mg/day for 5 days) allowed the disappearance of pain in 8 days, normalization of eosinophilia and improvement of walking.
文摘The department of Tillabéri is primarily affected by climatic phenomena, impacting crop yields, growing cycles, and consequently, the economic outcomes of agricultural operations. The objective of this study is to analyze these impacts of climate disruption on the economic performance of farms. The methodology adopted for this study combined documentary research with field surveys conducted on a sample of 250 randomly selected farmers. The analytical methods used mainly consisted of linear regression, profitability calculations, and linear programming. The findings indicate that all productions across different crops have experienced a decrease over the past 30 years. For instance, the production of millet, sorghum, and cowpea, which were respectively 812 kg/ha, 260 kg/ha, and 100 kg/ha between the last 30 and 20 years, has now dropped to 412 kg/ha, 106 kg/ha, and 46 kg/ha respectively. A negative and significant effect on agricultural net margin was observed due to variables such as flooding, drought, pest invasion in rice fields, and temperature changes. Smallholder farms show a relatively low margin (46%) to cover their fixed costs, which may indicate a risk if fixed expenses are high. Furthermore, the analysis results from linear programming reveal that farmers could achieve an additional net profit per hectare of 116,861 FCFA, 217201.5 FCFA, and 291988.2 FCFA respectively for small, medium, and large producers by managing variable costs and health-related expenses for households.
基金Applicable Funding Source University of Science and Technology of China(to YLL)National Natural Science Foundation of China(12126604)(to MPZ)+1 种基金R&D project of Pazhou Lab(Huangpu)(2023K0609)(to MPZ)Anhui Provincial Natural Science(grant number 2208085MH235)(to KJ)。
文摘BACKGROUND:Rapid and accurate identification of high-risk patients in the emergency departments(EDs)is crucial for optimizing resource allocation and improving patient outcomes.This study aimed to develop an early prediction model for identifying high-risk patients in EDs using initial vital sign measurements.METHODS:This retrospective cohort study analyzed initial vital signs from the Chinese Emergency Triage,Assessment,and Treatment(CETAT)database,which was collected between January 1^(st),2020,and June 25^(th),2023.The primary outcome was the identification of high-risk patients needing immediate treatment.Various machine learning methods,including a deep-learningbased multilayer perceptron(MLP)classifier were evaluated.Model performance was assessed using the area under the receiver operating characteristic curve(AUC-ROC).AUC-ROC values were reported for three scenarios:a default case,a scenario requiring sensitivity greater than 0.8(Scenario I),and a scenario requiring specificity greater than 0.8(Scenario II).SHAP values were calculated to determine the importance of each predictor within the MLP model.RESULTS:A total of 38,797 patients were analyzed,of whom 18.2%were identified as high-risk.Comparative analysis of the predictive models for high-risk patients showed AUC-ROC values ranging from 0.717 to 0.738,with the MLP model outperforming logistic regression(LR),Gaussian Naive Bayes(GNB),and the National Early Warning Score(NEWS).SHAP value analysis identified coma state,peripheral capillary oxygen saturation(SpO_(2)),and systolic blood pressure as the top three predictive factors in the MLP model,with coma state exerting the most contribution.CONCLUSION:Compared with other methods,the MLP model with initial vital signs demonstrated optimal prediction accuracy,highlighting its potential to enhance clinical decision-making in triage in the EDs.
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of China,No.82201460(to YH)Nanjing Medical University Science and Technology Development Fund,No.NMUB20210202(to YH).
文摘Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2022MH124the Youth Science Foundation of Shandong First Medical University,No.202201–105(both to YX)。
文摘Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China,No.82071442 (to LS)a grant from the Jilin Provincial Department of Finance,No.JLSWSRCZX2021-004 (to LS)。
文摘Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,Nos.92049120 and 81870897STI2030-Major Projects,No.2021ZD0204001+6 种基金Guangdong Key Project for Development of New Tools for the Diagnosis and Treatment of Autism,No.2018B030335001the Natural Science Foundation of Jiangsu Province,No.BK20181436the National Major Scientific and Technological Special Project for Significant New Drug Development,No.2019ZX09301102the Discipline Construction Program of the Second Affiliated Hospital of Soochow University,No.XKTJ-TD202003Sino-German Cooperation Mobility Programme,No.M-0679the Science and Technology Project of Suzhou,No.SKY2022161Research Project of Neurological Diseases of the Second Affiliated Hospital of Soochow University Medical Center,No.ND2023A01(all to QHM)。
文摘The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
文摘The term“gut microbiota”primarily refers to the ecological community of various microorganisms in the gut,which constitutes the largest microbial community in the human body.Although adequate bowel preparation can improve the results of colonoscopy,it may interfere with the gut microbiota.Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota,potentially affecting an individual’s health,especially in vulnerable populations,such as patients with inflammatory bowel disease.However,measures such as oral pro-biotics may ameliorate these adverse effects.We focused on the bowel prepa-ration-induced changes in the gut microbiota and host health status,hypothesized the factors influencing these changes,and attempted to identify measures that may reduce dysbiosis,thereby providing more information for individualized bowel preparation for colonoscopy in the future.
文摘Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.
基金supported by the Science and Technology(S&T)Program of Hebei Province,No.22377798D(to YZ).
文摘Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.
