Influence of Ginkgo Biloba extract on beta-secretase in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions

BACKGROUND： Preparation of Ginkgo leaf has been widely used to improve cognitive deficits and dementia, in particular in Alzheirner＇s disease patients. However, the precise mechanism of action of Ginkgo leaf remains unclear. OBJECTIVE： To explore the effect of Ginkgo Biloba extract （Egb761）, Ginaton, on β -secretase expression in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions. DESIGN, TIME AND SETTNG： Completely by randomized, grouping study. The experiment was performed at the Laboratory of Molecular Imaging, Southeast University between August 2006 and August 2007. MATERIALS： A total of 128 Wistar rats aged 24 hours were selected, and hippocampal neurons were harvested for primary cultures. METHODS： On day 7, primary hippocampal neuronal cultures were treated with Egb761 （0, 25, 50, 100, 150, and 200μg/mL） under hypoxic/hypoglycemic or hypoglycemic culture conditions for 12, 24, and 36 hours, respectively. Hippocampal neurons cultured in primary culture medium served as control. MAIN OUTCOME MEASURES： Cell viability was assayed using 3-（4,5-Dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTT）; fluorescence detection of β -secretase activity was performed; Western Blot was used to measure β -secretase expression. RESULTS： Cell viability under hypoxic/hypoglycemic or hypoglycemic culture conditions was significantly less than control cells （P 〈 0.05）. Under hypoxic/hypoglycemic or hypoglycemic culture conditions, treatment with 25 μg/mL Egb761 did not alter cell viability. However, 〉 25 μg/mL Egb761 induced greater cell viability （P 〈 0.05）. No differences were observed between hypoxic/hypoglycemic or hypoglycemic cells （P 〉 0.05）. α -secretase activity was increased after 12 hours in hypoxic/hypoglycemic culture （P 〈 0.01）. There were no significant differences between the 12-, 24-, or 36-hour Egb761 groups and the hypoxic/hypoglycemic groups （P 〉 0.05）. β -secretase activity was greater after 12, 24, and 36 hours in hypoxic/hypoglycemic culture conditions, compared with control conditions （P 〈 0.05）. β-secretase activity was significantly decreased in neurons treated with Egb761 for 12, 24, or 36 hours, compared with the hypoxichaypoglycemic group （P 〈 0.05）. β -secretase protein expression was significantly up-regulated in neurons cultured in hypoxic/hypoglycemic conditions for 12, 24, or 36 hours, compared to control cells （P 〈 0.05）, and was decreased compared to neurons treated with Egb761 （P 〈 0.05）. CONCLUSION： β -secretase expression and activity in rat neonatal hippocampal neurons were influenced by hypoxic and hypoglycemic culture. Egb761 played a protective role in hippocampal neurons damaged by chronic hypoxic and hypoglycemic culture conditions, possibly through its effect on β -secretase expression and activity.

Brain scarring in infants:immunological insights from a neonatal hypoxic-ischemic encephalopathy model

Neonatal hypoxic-ischemic encephalopathy(HIE)is a significant cause of disability in children.Improving brain function and accelerating neurological recovery may require a combination of neuroprotective and pro-regenerative treatments at different stages of HIE.While the first hours after the neonatal insult are the most critical period for neuroprotection,the existence of secondary and tertiary mechanisms of brain injury offers the possibility of preventing delayed neurodegeneration in the subsequent days,weeks,or months(Levison et al.,2022).

Spectrum of delayed post-hypoxic leukoencephalopathy syndrome:A systematic review

BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characterized by delayed onset of neurological and cognitive deficits,DPHLS presents substantial diagnostic and therapeutic challenges.AIM To consolidate current knowledge on pathophysiology,clinical features,diagnostic approaches,and management strategies for DPHLS,providing a comprehensive overview and highlighting gaps for future research.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines,we systematically searched PubMed,ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy.Inclusion criteria were original research articles,case reports,and case series involving human subjects with detailed clinical,neuroimaging,or pathological data on DPHLS.Data were extracted on study characteristics,participant demographics,clinical features,neuroimaging findings,pathological findings,treatment,and outcomes.The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.RESULTS A total of 73 cases were reviewed.Common comorbidities included schizoaffective disorder,bipolar disorder,hypertension,and substance use disorder.The primary causes of hypoxia were benzodiazepine overdose,opioid overdose,polysubstance overdose,and carbon monoxide(CO)poisoning.Symptoms frequently include decreased level of consciousness,psychomotor agitation,cognitive decline,parkinsonism,and encephalopathy.Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter,sometimes involving the basal ganglia and the globus pallidus.Magnetic resonance spectroscopy often showed decreased N-acetylaspartate,elevated choline,choline-to-creatinine ratio,and normal or elevated lactate.Treatment is often supportive,including amantadine,an antioxidant cocktail,and steroids.Hyperbaric oxygen therapy may be beneficial in those with CO poisoning.Parkinsonism was often treated with levodopa.Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations.Early recognition and appropriate management are crucial to improving patient outcomes.Future research should focus on standardizing diagnostic criteria,using advanced imaging techniques,and exploring therapeutic interventions to improve understanding and treatment of DPHLS.Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

Pharmacological intervention for chronic phase of spinal cord injury

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery

The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.

Challenges and improvement strategies in the hospitalization of chronic multimorbid patients

BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot program.Chronic diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient outcomes.If proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid patients.AIM To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital care.METHODS The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.RESULTS The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.CONCLUSION This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary approach.The coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient complexity.The superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of care to be replicated.

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.

Sodium Sulfite as a Novel Hypoxia Revulsant Involved in Hypoxic Regulation in Escherichia coli

As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis elegans.In this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves.

Predictive value of diaphragm ultrasound for mechanical ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is often combined with respiratory failure,which increases the patient's morbidity and mortality.Diaphragm ultrasound(DUS)has developed rapidly in the field of critical care in recent years.Studies with DUS monitoring diaphragm-related rapid shallow breathing index have demonstrated important results in guiding intensive care unit patients out of the ventilator.Early prediction of the indications for withdrawal of non-invasive ventilator and early evaluation of patients to avoid or reduce disease progression are very important.AIM To explore the predictive value of DUS indexes for non-invasive ventilation outcome in patients with AECOPD.METHODS Ninety-four patients with AECOPD who received mechanical ventilation in our hospital from January 2022 to December 2023 were retrospectively analyzed,and they were divided into a successful ventilation group(68 cases)and a failed ventilation group(26 cases)according to the outcome of ventilation.The clinical data of patients with successful and failed noninvasive ventilation were compared,and the independent predictors of noninvasive ventilation outcomes in AECOPD patients were identified by multivariate logistic regression analysis.RESULTS There were no significant differences in gender,age,body mass index,complications,systolic pressure,heart rate,mean arterial pressure,respiratory rate,oxygen saturation,partial pressure of oxygen,oxygenation index,or time of inspiration between patients with successful and failed mechanical ventilation(P>0.05).The patients with successful noninvasive ventilation had shorter hospital stays and lower partial pressure of carbon dioxide(PaCO_(2))than those with failed treatment,while potential of hydrogen(pH),diaphragm thickening fraction(DTF),diaphragm activity,and diaphragm movement time were significantly higher than those with failed treatment(P<0.05).pH[odds ratio(OR)=0.005,P<0.05],PaCO_(2)(OR=0.430,P<0.05),and DTF(OR=0.570,P<0.05)were identified to be independent factors influencing the outcome of mechanical ventilation in AECOPD patients.CONCLUSION The DUS index DTF can better predict the outcome of non-invasive ventilation in AECOPD patients.

Dunbar Syndrome and Hypoxic Hepatitis: An Unusual Presentation

Hypoxic hepatitis, also known as ischemic hepatitis, is characterized by acute hepatocellular injury due to inadequate oxygen delivery to the liver. Celiac trunk stenosis can lead to hepatic ischemia and subsequent liver damage. We present the case of an 81-year-old patient with a history of hypertension, ischemic heart disease, hypothyroidism, and biliary lithiasis, who developed hypoxic hepatitis secondary to Dunbar syndrome and a stenosis of the superior mesenteric artery. The patient improved symptoms and liver function tests with conservative management, including intravenous fluids and supportive care. Long-term management involved continued antiplatelet therapy and statins, with consideration of further interventions for celiac trunk stenosis. This case underscores the importance of recognizing Dunbar syndrome as well as superior mesentery trunk stenosis as a potential cause of hypoxic hepatitis. It highlights the need for multidisciplinary management in such cases.

Palliative care for end-stage liver disease and acute on chronic liver failure:A systematic review

BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliative care(PC)is pronounced in patients grappling with ESLD and acute on chronic liver failure(ACLF).Unfortunately,the historical underutilization of PC in ESLD patients,despite their substantial needs and those of their family caregivers,underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.METHODS A systematic search in the Medline(PubMed)database was performed using a predetermined search command,encompassing studies published in English without any restrictions on the publication date.Subsequently,the retrieved studies were manually examined.Simple descriptive analyses were employed to summarize the results.RESULTS The search strategies yielded 721 references.Following the final analysis,32 fulllength references met the inclusion criteria and were consequently incorporated into the study.Meticulous data extraction from these 32 studies was undertaken,leading to the execution of a comprehensive narrative systematic review.The review found that PC provides significant benefits,reducing symptom burden,depressive symptoms,readmission rates,and hospital stays.Yet,barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization.Integrating PC early,upon the diagnosis of ESLD and ACLF,regardless of transplant eligibility and availability,improves the quality of life for these patients.CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF,where liver transplantation stands as the only curative treatment,albeit largely inaccessible,PC services have been overtly provided too late in the course of the illness.A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers,involving healthcare providers,patients,and caregivers.

History of chronic gastritis:How our perceptions have changed

Currently,the diagnostic strategy for chronic gastritis(CG)is aimed not just at fixing the presence of gastric mucosal inflammation,but also at gastric cancer(GC)risk stratification in a particular patient.Modern classification approach with the definition of the stage of gastritis determines the need,activities and frequency of dynamic monitoring of a patient.However,this attitude to the patient suffering from CG was far from always.The present publication is a literature review describing the key milestones in the history of CG research,from the description of the first observations of inflammation of the gastric mucosa,assessment of gastritis as a predominantly functional disease,to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy,assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy,intestinal metaplasia,dysplasia and GC.

Meta-analysis of the association between chronic periodontitis and chronic kidney disease

BACKGROUND Many scholars have performed several clinical studies have investigated the association between chronic periodontitis(CP)and chronic kidney disease(CKD).However,there are still differences between these research results,and there is no unified conclusion.Therefore,a systematic review is required to understand this issue fully.AIM To explore the correlation between CP and CKD.METHODS Literature on the correlation between CP and CKD,as well as the clinical attachment level(CAL)and pocket probing depth(PPD)of CKD and non-CKD,were retrieved from PubMed,Embase,the Cochrane Library,and Web of Science repositories until January 2024.After the effective data were extracted,data processing and statistics were performed using Stata 12.0.RESULTS Of the 22 studies,13 were related to CP and CKD,and 9 reported CAL and PPD in patients with CKD and healthy controls.Meta-analysis of the correlation between CP and CKD revealed that CKD probability in people with CP was 1.54 times that of healthy individuals[relative risk=1.54,95%confidence interval(CI):1.40-1.70],and CP incidence in patients with CKD was 1.98 times that of healthy individuals[overall risk(OR)=1.98,95%CI:1.53-2.57].Meta-analysis of CAL and PPD evaluations between CKD patients and healthy individuals showed that CAL and PPD levels were higher in CKD patients[standard mean difference(SMD)of CAL=0.65,95%CI:0.29-1.01;SMD of PPD=0.33,95%CI:0.02-0.63].CONCLUSION A bidirectional association exists between CP and CKD.CKD risk is increased in CP patients and vice versa.Periodontal tissue or tooth loss risks increase over time in CKD patients.

Association of physical activity with risk of chronic kidney disease in China:A population-based cohort study

Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in China

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.

Regenerative medicine strategies for chronic complete spinal cord injury

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis

BACKGROUND Helicobacter pylori(H.pylori)infection is a major risk factor for chronic gastritis,affecting approximately half of the global population.H.pylori eradication is a popular treatment method for H.pylori-positive chronic gastritis,but its mecha-nism remains unclear.Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment.However,no clinical study has been conducted on urinary metabolomics of chronic gastritis.AIM To elucidate the urinary metabolic profiles during H.pylori eradication in patients with chronic gastritis.METHODS We applied LC–MS-based metabolomics and network pharmacology to in-vestigate the relationships between urinary metabolites and H.pylori-positive chronic gastritis via a clinical follow-up study.RESULTS Our study revealed the different urinary metabolic profiles of H.pylori-positive chronic gastritis before and after H.pylori eradication.The metabolites regulated by H.pylori eradication therapy include cis-aconitic acid,isocitric acid,citric acid,L-tyrosine,L-phenylalanine,L-tryptophan,and hippuric acid,which were involved in four metabolic pathways:(1)Phenylalanine metabolism;(2)phenylalanine,tyrosine,and tryptophan biosynthesis;(3)citrate cycle;and(4)glyoxylate and dicarboxylate metabolism.Integrated metabolomics and network pharmacology revealed that MPO,COMT,TPO,TH,EPX,CMA1,DDC,TPH1,and LPO were the key proteins involved in the biological progress of H.pylori eradication in chronic gastritis.CONCLUSION Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H.pylori-positive chronic gastritis patients.

Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery:A case report

BACKGROUND With the popularization of various cerebrovascular imaging methods and increased attention to the field,more cerebrovascular diseases are being detected in asymptomatic patients.Different cerebrovascular diseases are typically isolated but occasionally occur simultaneously,causing difficulties in diagnosis and treatment.Morphological changes in the collateral circulation of blood vessels in chronic cerebral artery occlusion patients are slow and dynamic,intercepting morphological development at a specific moment.Excessive reliance on single imaging tests such as digital subtraction cerebral angiography(DSA)can lead to misdiagnosis.CASE SUMMARY We report a 52-year-old male who was admitted to our department for treatment of an unruptured aneurysm during a follow-up examination for brain trauma after 1 mo.Computed tomography(CT)scan was negative,but CT angiography(CTA)revealed a sac-like bulge at the bifurcation of the left middle cerebral artery.DSA revealed an unruptured aneurysm with unique scapular morphology.The stump of a middle cerebral artery occlusion was observed during exposure during aneurysm clipping surgery,and the diagnosis of chronic cerebral artery occlusion was confirmed intraoperatively.This case was confusing because of the peculiar morphology of the arterial stump and compensatory angiogenesis due to multiple cerebral artery stenoses observed on preoperative CTA and DSA.The surgery did not cause secondary damage to the patient,and medical treatment for risk factors was continued postoperatively.CONCLUSION Multiple cerebral arterial stenoses can occur in conjunction with aneurysms or arteriovenous malformations,and their unique morphology can lead to misdiagnosis.