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.

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.

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.

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.

Study of tumor necrosis factor receptor in the inflammatory bowel disease

Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease:A literature review

Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells

BACKGROUND Mesenchymal stem cells(MSCs)have great potential for the treatment of various immune diseases due to their unique immunomodulatory properties.However,MSCs exposed to the harsh inflammatory environment of damaged tissue after intravenous transplantation cannot exert their biological effects,and therefore,their therapeutic efficacy is reduced.In this challenging context,an in vitro preconditioning method is necessary for the development of MSC-based therapies with increased immunomodulatory capacity and transplantation efficacy.AIM To determine whether hypoxia and inflammatory factor preconditioning increases the immunosuppressive properties of MSCs without affecting their biological characteristics.METHODS Umbilical cord MSCs(UC-MSCs)were pretreated with hypoxia(2%O_(2))exposure and inflammatory factors(interleukin-1β,tumor necrosis factor-α,interferon-γ)for 24 h.Flow cytometry,polymerase chain reaction,enzyme-linked immunosorbent assay and other experimental methods were used to evaluate the biological characteristics of pretreated UC-MSCs and to determine whether pretreatment affected the immunosuppressive ability of UC-MSCs in coculture with immune cells.RESULTS Pretreatment with hypoxia and inflammatory factors caused UC-MSCs to be elongated but did not affect their viability,proliferation or size.In addition,pretreatment significantly decreased the expression of coagulationrelated tissue factors but did not affect the expression of other surface markers.Similarly,mitochondrial function and integrity were retained.Although pretreatment promoted UC-MSC apoptosis and senescence,it increased the expression of genes and proteins related to immune regulation.Pretreatment increased peripheral blood mononuclear cell and natural killer(NK)cell proliferation rates and inhibited NK cell-induced toxicity to varying degrees.CONCLUSION In summary,hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics.

Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning

BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective preventive measures.AIM To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment.METHODS Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission.Relevant data from the initial 14 d of ICU stay,such as age,comorbidities,sedative dosage,vasopressor dosage,duration of mechanical ventilation,length of ICU stay,and rehabilitation therapy,were gathered.The relationships between these variables and ICU-AW were examined.Utilizing iterative machine learning techniques,a multilayer perceptron neural network model was developed,and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve.RESULTS Within the ICU-AW group,age,duration of mechanical ventilation,lorazepam dosage,adrenaline dosage,and length of ICU stay were significantly higher than in the non-ICU-AW group.Additionally,sepsis,multiple organ dysfunction syndrome,hypoalbuminemia,acute heart failure,respiratory failure,acute kidney injury,anemia,stress-related gastrointestinal bleeding,shock,hypertension,coronary artery disease,malignant tumors,and rehabilitation therapy ratios were significantly higher in the ICU-AW group,demonstrating statistical significance.The most influential factors contributing to ICU-AW were identified as the length of ICU stay(100.0%)and the duration of mechanical ventilation(54.9%).The neural network model predicted ICU-AW with an area under the curve of 0.941,sensitivity of 92.2%,and specificity of 82.7%.CONCLUSION The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation.A primary preventive strategy,when feasible,involves minimizing both ICU stay and mechanical ventilation duration.

Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor.Therefore,while,based on the current knowledge,the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reve rse the disease pathology per se,promoting brainderived neurotrophic factor/tro pomyosin receptor kinase B signaling still has a very high therapeutic relevance.

Transcription factor OsSPL10 interacts with OsJAmyb to regulate blast resistance in rice

Transcription factors(TFs)play essential roles in transcriptional reprogramming during activation of plant immune responses to pathogens.OsSPL10(SQUAMOSA promoter binding protein-like10)is an important TF regulating trichome development and salt tolerance in rice.Here we report that knockout of OsSPL10 reduces whereas its overexpression enhances rice resistance to blast disease.OsSPL10 positively regulates chitin-induced immune responses including reactive oxygen species(ROS)burst and callose deposition.We show that OsSPL10 physically associates with OsJAmyb,an important TF involved in jasmonic acid(JA)signaling,and positively regulates its protein stability.We then prove that OsJAmyb positively regulates resistance to blast.Our results reveal a molecular module consisting of OsSPL10 and OsJAmyb that positively regulates blast resistance.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

Biological factors driving colorectal cancer metastasis

Approximately 20%of colorectal cancer(CRC)patients present with metastasis at diagnosis.Among Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial treatment.The median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 mo.mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor development.CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations.Different genomic and nongenomic events can induce subclone diversity,which leads to cancer and metastasis.Throughout the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular functions.However,cancer cells presenting neoantigens can be recognized and eliminated by the immune system.In this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle factors.Despite remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains unclear.This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.