Correlation of preoperative inflammatory factors and emotional disorders with postoperative delirium in patients with craniocerebral trauma

BACKGROUND Traumatic brain injury(TBI)imposes a substantial societal and familial burden due to its high disability and fatality rates,rendering it a serious public health problem.Some patients with TBI have poor treatment outcomes and are prone to postoperative delirium(POD),which affects their quality of life.Anxiety has been linked to increased POD incidence in some studies,while others have found no correlation.AIM To investigate the correlation of POD risk factors,preoperative inflammatory factors,and mood disorders in patients with TBI.METHODS We retrospectively collected data on the treatment of 80 patients with TBI from November 2021 to September 2023.Patients were grouped as POD and non-POD,according to their POD status,and the general data of the two groups were compared.Inflammatory factor levels were detected preoperatively,and the Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)were used to investigate the risk factors associated with POD in these patients.Logistic regression was used to identify the independent risk factors.RESULTS Twenty-one patients(26.25%)developed POD,including 7,10,and 4 cases of the excitatory,inhibitory,and mixed types,respectively.There were 59 cases(73.75%)in the non-POD group.Compared with the non-POD group,the POD group had a significantly higher proportion of patients with low Glasgow Coma Scale(GCS)scores before admission,unilateral mydriasis,preoperative hemorrhagic shock,intraventricular hemorrhage(IVH),and postoperative hyperglycemic hyperosmolar disease(P<0.05).In the POD group,interleukin-6(IL-6),human tumor necrosis factor-α(TNF-α),myeloperoxidase levels,HAMA,and HAMD scores were higher than those in the non-POD group(all P<0.05).Logistic multivariate analysis showed that GCS score at admission,IVH,IL-6,TNF-α,HAMA,and HAMD were independent risk factors for POD in patients with TBI(P<0.05).CONCLUSION Low GCS score at admission,IVH,elevated IL-6 and TNF-α,other inflammatory indicators,anxiety,and depression,can increase the risk of POD in patients with TBI after surgery.

Mechanistic research:Selenium regulates virulence factors,reducing adhesion ability and inflammatory damage of Helicobacter pylori

BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlation between them remains unclear.AIM To investigate how selenium acts on virulence factors and reduces their toxicity.METHODS H.pylori strains were induced by sodium selenite.The expression of cytotoxin-associated protein A(CagA)and vacuolating cytotoxin gene A(VacA)was determined by quantitative PCR and Western blotting.Transcriptomics was used to analyze CagA,CagM,CagE,Cag1,Cag3,and CagT.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction,and H.pylori colonization,inflammatory reactions,and the cell adhesion ability of H.pylori were assessed.RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H.pylori strains after sodium selenite treatment.Their expression was significantly and steadily downregulated after the 5th cycle(10 d).Transcriptome analysis revealed that sodium selenite altered the levels affect H.pylori virulence factors such as CagA,CagM,CagE,Cag1,Cag3,and CagT.Of these factors,CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite.Moreover,CagT expression was upregulated before the 3rd cycle(6 d)and significantly downregulated after the 5th cycle.Cag1 and Cag3 expression was upregulated and downregulated,respectively,but no significant change was observed by the 5th cycle.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction.The extent of H.pylori colonization in the stomach increased;however,sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H.pylori-infected mice,and the cell adhesion ability of H.pylori was significantly weakened.CONCLUSION These results demonstrate that H.pylori displayed virulence attenuation after the 10th d of sodium selenite treatment.Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H.pylori,thus mitigating the inflammatory damage to the gastric mucosa.

Assessing myocardial indices and inflammatory factors to determine anxiety and depression severity in patients with chronic heart failure

BACKGROUND Patients with chronic heart failure(CHF)have a progressive disease that is associated with poor quality of life and high mortality.Many patients experience anxiety and depression(A&D)symptoms,which can further accelerate disease progression.We hypothesized that indicators of myocardial function and inflammatory stress may reflect the severity of A&D symptoms in patients with CHF.Changes in these biomarkers could potentially predict whether A&D symptoms will deteriorate further in these individuals.AIM To measure changes in cardiac and inflammatory markers in patients with CHF to determine A&D severity and predict outcomes.METHODS We retrospectively analyzed 233 patients with CHF treated at the Jingzhou Hospital,Yangtze University between 2018-2022 and grouped them according to Self-Rating Anxiety Scale(SAS)and Self-Rating Depression Scale(SDS)scores.We compared clinical data in the no-A&D,mild-A&D,moderate-A&D,and severe-A&D groups,the SAS and SDS scores with the New York Heart Association(NYHA)functional classification,and cardiac markers and inflammatory factors between the no/mild-A&D and moderate/severe-A&D groups.Regression analysis was performed on the markers with P<0.05 to determine their ability to predict A&D severity in patients and the area under the receiver operating characteristic curve(AUROC)was used to evaluate their accuracy.RESULTS In the inter-group comparison,the following variables had an effect on A&D severity in patients with CHF:NYHA class,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-6(IL-6),and tumor necrosis factor-alpha(P<0.05).Other variables did not differ significantly between the A&D groups(P>0.05).In addition,we found that higher NYHA classes were associated with higher the SAS and SDS scores(P<0.05).Regression analysis showed that LVEF,NTproBNP,and IL-6 were independent risk factors for A&D severity(P<0.05).Among them,NT-proBNP had the best predictive ability as a single indicator(AUROC=0.781).Furthermore,the combination of these three indicators exhibited a good predictive effect toward discriminating the extent of A&D severity among patients(AUROC=0.875).CONCLUSION Cardiac and inflammatory biomarkers,such as LVEF,NT-proBNP,and IL-6,are correlated with A&D severity in patients with CHF and have predictive value.

Relationship between postoperative rehabilitation style, gastrointestinal function, and inflammatory factor levels in children with intussusception

BACKGROUND Intussusception occurs in children and progresses rapidly.If not treated in time,it may lead to secondary complications such as intestinal perforation,which affect the quality of life and health of children.Surgery is the most common clinical treatment and has a good effect.However,the postoperative prognosis of children with intussusception has a correlation with the postoperative rehabilitation method.Therefore,in this study,we explored the relationship between postopera-tive rehabilitation,gastrointestinal function,and the expression of inflammatory factors in children with intussusception.The medical records of 18 children who were admitted to our hospital for intussusception surgery between October 2022 and May 2024 were retrospectively reviewed.The patients were divided into the routine nursing group(n=6)and rehabilitation training group(n=12)according to the postoperative rehabilitation method.The general data,gastrointestinal function,and inflammatory factor levels of the two groups were statistically analyzed.Pearson correlation analysis of gastrointestinal function,inflammatory factors,and postoperative rehabil-itation was performed.RESULTS We found no significant intergroup differences in sex,age,or disease course(P>0.05).The times to first defecation,bowel sound recovery,and anal exhaust were shorter and inflammatory factor levels were lower in the rehabilitation training group than in the routine nursing group(P<0.05).Pearson correlation analysis showed that gastrin and motilin levels were positively correlated with postoperative rehabilitation(P<0.05).Interleukin(IL)-2,IL-4,IL-6,IL-10,high-sensitivity C-reactive protein,and tumor necrosis factor-αlevels were negatively correlated with postoperative rehabilitation(P<0.05).Gastrointestinal function was positively correlated(P<0.05),and levels of inflammatory factors were negatively correlated with postoperative recovery time(P<0.05).CONCLUSION We found a positive correlation between gastrointestinal function and postoperative rehabilitation training,and a negative correlation between inflammatory factor levels and rehabilitation training in children with intussus-ception.

Effects of serum inflammatory factors,health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep disorders.METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study.The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes.The serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were measured.Disease activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were assessed.The health index was obtained through the Short Form-36 questionnaire.RESULTS The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep disorders.Positive correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional impairment.Conversely,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of life.Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and prognostication.CONCLUSION The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep disorders.The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors,health index and disease activity scores as prognostic markers in this patient population.

Mendelian Randomization Study of Causal Relationship between Inflammatory Factors and Vascular Dementia and Chinese Herbal Medicines Screening for Prevention and Treatment

Objective: This study aims to examine the causal relationship between inflammatory factors and the probability of developing vascular dementia (VD) using Mendelian Randomization (MR) and Chinese herbal medicine prediction method, and to screen potential Chinese herbal medicines for the prevention and treatment of VD. Methods: Single nucleotide polymorphisms (SNPs) that exhibit a strong association with vascular dementia (VD) were identified as instrumental variables from the summary statistics of genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighting (IVW), while auxiliary analyses included the MR-Egger method, weighted median method, simple model, and weighted model. A two-way Mendelian randomization analysis was conducted to assess the causal relationship between inflammatory factors and the risk of VD, thereby identifying the key inflammatory factors involved. The MR-Egger intercept test and Cochran’s Q test were employed to assess the horizontal polymorphism and heterogeneity of instrumental variables. A sensitivity analysis was conducted by excluding one method at a time. Ultimately, based on key inflammatory factors, predictions for the prevention and treatment using traditional Chinese medicine were made, along with the screening of homologous herbal remedies. Results: Based on the results of the forward MR, the probability of developing VD was elevated when the inflammatory factors CXCL10 and CXCL5 were expressed at higher levels, whereas the probability of developing VD decreased as the expression levels of IL-13 and IL-20RA increased. These findings were supported by the assessment of pleiotropy, heterogeneity, and sensitivity. The results of the reverse MR analysis showed that there was no causal relationship between VD, as an exposure dataset, and these four inflammatory factors. According to the key inflammatory factors, 37 Chinese herbal medicines such as Siraitia grosvenorii were selected. Their characteristics including four natures, five flavors, channel tropism and treatment efficiency were cold, warm, neutral, pungent, sweet, bitter, lung meridian, spleen meridian, liver meridian, kidney meridian and clearing heat. Among them, Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi were all medicine and food homologous Chinese herbal medicines. Conclusions: The increase of CXCL10 and CXCL5 expression levels can increase the risk of VD, and the increase of IL-13 and IL-20 RA expression levels can reduce the risk of VD. Siraitia grosvenorii and other Chinese herbal medicines might be potential sources of therapeutic drugs for the treatment of VD. Medicine and food homologous Chinese herbal medicines, such as Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi, may help the elderly population with corresponding Traditional Chinese Medicine (TCM) constitutions to prevent VD.

Clinical effects of nonconvulsive electrotherapy combined with mindfulness-based stress reduction and changes of serum inflammatory factors in depression

BACKGROUND Depression is a common and serious psychological condition,which seriously affects individual well-being and functional ability.Traditional treatment methods include drug therapy and psychological counseling;however,these methods have different degrees of side effects and limitations.In recent years,nonconvulsive electrotherapy(NET)has attracted increasing attention as a noninvasive treatment method.However,the clinical efficacy and potential mechanism of NET on depression are still unclear.We hypothesized that NET has a positive clinical effect in the treatment of depression,and may have a regulatory effect on serum inflammatory factors during treatment.AIM To assess the effects of NET on depression and analyze changes in serum inflammatory factors.METHODS This retrospective study enrolled 140 patients undergoing treatment for depression between May 2017 and June 2022,the observation group that received a combination of mindfulness-based stress reduction(MBSR)and NET treatment(n=70)and the control group that only received MBSR therapy(n=70).The clinical effectiveness of the treatment was evaluated by assessing various factors,including the Hamilton Depression Scale(HAMD)-17,self-rating idea of suicide scale(SSIOS),Pittsburgh Sleep Quality Index(PSQI),and levels of serum inflammatory factors before and after 8 wk of treatment.The quality of life scores between the two groups were compared.Comparisons were made using t and χ^(2) tests.RESULTS After 8 wk of treatment,the observation group exhibited a 91.43%overall effectiveness rate which was higher than that of the control group which was 74.29%(64 vs 52,χ^(2)=7.241;P<0.05).The HAMD,SSIOS,and PSQI scores showed a significant decrease in both groups.Moreover,the observation group had lower scores than the control group(10.37±2.04 vs 14.02±2.16,t=10.280;1.67±0.28 vs 0.87±0.12,t=21.970;5.29±1.33 vs 7.94±1.35,t=11.700;P both<0.001).Additionally,there was a notable decrease in the IL-2,IL-1β,and IL-6 in both groups after treatment.Furthermore,the observation group exhibited superior serum inflammatory factors compared to the control group(70.12±10.32 vs 102.24±20.21,t=11.840;19.35±2.46 vs 22.27±2.13,t=7.508;32.25±4.6 vs 39.42±4.23,t=9.565;P both<0.001).Moreover,the observation group exhibited significantly improved quality of life scores compared to the control group(Social function:19.25±2.76 vs 16.23±2.34;Emotions:18.54±2.83 vs 12.28±2.16;Environment:18.49±2.48 vs 16.56±3.44;Physical health:19.53±2.39 vs 16.62±3.46;P both<0.001)after treatment.CONCLUSION MBSR combined with NET effectively alleviates depression,lowers inflammation(IL-2,IL-1β,and IL-6),reduces suicidal thoughts,enhances sleep,and improves the quality of life of individuals with depression.

Effects of Wuwei Xiaodu Decoction on Uterine Energy Metabolism and Serum Inflammatory Factors in Rats with Acute Pelvic Inflammatory Disease

[Objectives]To observe the effects of Wuwei Xiaodu Decoction on uterine energy metabolism and serum inflammatory factors in the acute pelvic inflammatory disease(APID)model.[Methods]75 Wistar rats(females)were randomly divided into control group,model group and Wuwei Xiaodu Decoction low,medium and high dose groups(n=15).Except for the control group,the rat APID model was established by right uterine inoculation.On the fifth day after inoculation,the low,medium and high dose groups of Wuwei Xiaodu Decoction were administered at 4,8 and 16 g/kg,and the control group and model group received normal saline.Rats were killed 12 h after nondose administration,blood was collected from the abdominal aorta and measured by ELISA for serum interleukin-6(interleukin-6,IL-6),IL-8,and C-reactive proteins(CRP);the right uterus of rats was tested for high-energy phosphate adenosine phosphate(AMP),adenosine diphosphate(ADP),adenosine triphosphate(ATP)and total adenine nucleotides(TAN)level to evaluate the uterine energy metabolism.[Results]AMP,ADP,ATP and TAN were significantly higher in the Wuwei Xiaodu Decoction of low,medium and high dose than the model group,while the serum IL-6,IL-8 and CRP were significantly lower than the model group,and the difference between the low,medium and high doses(P<0.05).[Conclusions]The Wuwei Xiaodu Decoction can dose-dependent promote uterine energy metabolism and inhibit inflammatory response in APID model rats.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

Functions of nuclear factor Y in nervous system development,function and health

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently regeneration.However,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive.In this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.

The effects of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents:a meta-analysis

Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the Pub Med, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using Review Manager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference(MD;before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants(60 children and 471 adolescents, 10.9–16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I^(2) test provided by Review Manager software. The meta-analysis showed that there was no heterogeneity among the studies(P = 0.67, I^(2) = 0.00%). The combined effect of the interventions was significant(MD = 2.88, 95% CI: 1.53–4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This metaanalysis was registered at PROSPERO(registration ID: CRD42023439408).

The effect of Huanglian Jiedu Decoction on inflammatory factors and oxidative stress in patients with acute ischemic stroke

Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recruited as the study subjects and randomly divided into a control group and a treatment group using a random number table method.The control group consisted of 26 patients and the treatment group consisted of 27 patients.The control group received conventional Western medicine treatment.The control group received routine Western medicine treatment,while the treatment group received Huanglian Jiedu decoction based on the control group,with 14 days as a course of treatment.The effects of Huanglian Jiedu decoction on neurological function and activities of daily living were evaluated using the National Institute of Health stroke scale(NIHSS)and activities of daily living(ADL)scores.The effects of Huanglian Jiedu decoction on inflammatory reactions and oxidative stress were evaluated by detecting interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factorβ(TGF-β),total antioxidative capacity(T-AOC),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)levels.Results:After treatment with Huanglian Jiedu Decoction,the ALD scores of AIS patients in both groups increased,while the NISHH scores decreased,suggesting that Huanglian Jiedu Decoction has therapeutic effects on AIS patients.It also reduces the levels of serum IL-6,TNF-α,MDA in AIS patients and increases the levels of IL-4,TGF-β,CAT,SOD,T-AOC,suggesting that Huanglian Jiedu decoction can improve the anti-inflammatory and antioxidant abilities of AIS patients.Conclusion:Huanglian Jiedu decoction can help AIS patients recover their neurological function,increase their capacity for self-care in daily life,and strengthen the body’s anti-inflammatory and antioxidant defenses.

Vitamin D deficiency and increased inflammatory factor intercellular cell adhesion molecule-1 indicate severe leukoaraiosis in northern China

Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Leukoaraiosis(LA)is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses.This study aimed to investigate the impact of vitamin D on the severity of LA.Methods:Patients with LA were categorized based on 3.0 T brain MRI findings into mild(N=43),moderate(N=40),or severe groups(N=29)using the Fazekas scale(scoring 1-6).A control group consisting of 41 healthy individuals was included.Serum fibrinogen C,homocysteine,plasma 25-hydroxyvitamin D,and intercellular cell adhesion molecule-1(ICAM-1)levels were measured using ELISA.Results:All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group,with a more pronounced decrease observed as LA severity increased.Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA(P<0.05)according to Multiple logistic regression analysis.Additionally,a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1.Conclusions:Disease severity positively correlated with levels of the inflammatory marker ICAM-1,worsening as plasma 25-hydroxyvitamin D concentration decreased.Low 25-hydroxyvitamin D emerged as an independent risk factor for LA,potentially exacerbating the inflammatory response.These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

Efficacy and Impact on Inflammatory Factors and Lung Function in Pediatric Bronchial Asthma Treated with Modified Dingchuan Decoction

Objective:To study the efficacy of treating pediatric bronchial asthma with a modified Dingchuan Decoction and its effect on inflammatory factors and lung function levels.Methods:Sixty cases of bronchial asthma admitted to the hospital between January and December 2023 were divided into two groups using a computerized randomization method.One group of 30 cases received basic treatment with a salmeterol ticarcoson powder inhaler(control group),while the observation group received the same treatment plus a modified Dingchuan Decoction.The disappearance time of symptoms,levels of inflammatory factors,lung function indexes,and clinical efficacy were compared between the two groups.Results:The disappearance time of symptoms in the observation group was shorter than that in the control group.The levels of inflammatory factors after treatment were lower,and lung function indexes were higher in the observation group compared to the control group.Additionally,the total effective rate of treatment in the observation group was higher than that in the control group(P<0.05).Conclusion:In the clinical treatment of pediatric bronchial asthma,supplementing conventional Western medicine with a modified Dingchuan Decoction is effective,as it actively reduces inflammatory factor levels and improves lung function.

The effect of Jiangan Xiaozhi Formula on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease

Objective:To investigate the effects of Jiangan Xiaozhi Formula(JGXZ)on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease(NAFLD).Methods:Between September 2022 and December 2023,our hospital admitted a total of 58 patients with NAFLD.These patients were split into two groups at random:one for experimentation and the other for control.There were 27 patients in the experimental group at the end,compared to 26 in the control group,reasonable exercise,weight management,lipid regulation,and oral polyene phosphatidylcholine capsules(PPC).The experimental group received JGXZ in addition to the above treatments for 12 consecutive weeks.Changes in Traditional Chinese Medicine(TCM)syndrome scores,blood lipids,liver function indicators,the levels of oxidative stress markers,such as malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and superoxide dismutase(SOD),as well as serum inflammatory factors,such as interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α),were measured both before and after treatment.Results:After treatment,both groups showed significant reductions in TCM syndrome scores(P<0.05)and improvements in blood lipids,liver function indicators,inflammatory factors,and oxidative stress markers(P<0.05).Improvements were noticeably better in the experimental group than in the control group.(P<0.05).Conclusion:JGXZ can significantly improve clinical symptoms,regulate blood lipids,and protect liver function in patients with NAFLD.Its mechanism may be related to inhibiting inflammatory responses and regulating the balance of the oxidation-antioxidation system.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Lipopolysaccharide-induced cerebral inflammatory damage and the therapeutic effect of platelet activating factor receptor antoganist

Objective To investigate lipopolysaccharide （LPS） induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B （BN52021）. Methods Thirty Sprague-Dawley rats were randomly divided into 3 groups （n = 10 for each group）： Control group, Model group and Treatment group （treated with BN52021）. LPS were injected into the fourth ventricle of rat to make a neuroinflammatory murine model. Morris water maze was used to detect the learning and memory ability of rats; changes of synapse number and subcellular ultrastructures were observed under a transmission electron microscope; OX-42 positive microglia in the brain was detected by immunohistochemical method. Results The average escape latency in the Treatment group were significantly shortened than that in the Model group; and the percentage of swimming distance traveled in platform quadrant accounting for total distance increased markedly. The rough endoplasmic reticulum and polyribosomes in the Treatment group were more than that in the Model group, but the number of synapses seemed to have no obvious change. The number of OX-42 positive microglia in the Treatment group decreased markedly than that in the Model group, and the grey density of OX-42-positive cells increased significantly. Conclusion LPS can induce inflammatory damages to the brain, but the damage could be antagonized by BN52021. Platelet activating factor receptor antagonist may offer an effective therapy for neurodegeneration diseases.