Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

Two-dimensional horizontal visibility graph analysis of human brain aging on gray matter

Characterizing the trajectory of the healthy aging brain and exploring age-related structural changes in the brain can help deepen our understanding of the mechanism of brain aging.Currently,most structural magnetic resonance imaging literature explores brain aging merely from the perspective of morphological features,which cannot fully utilize the grayscale values containing important intrinsic information about brain structure.In this study,we propose the construction of two-dimensional horizontal visibility graphs based on the pixel intensity values of the gray matter slices directly.Normalized network structure entropy(NNSE)is then introduced to quantify the overall heterogeneities of these graphs.The results demonstrate a decrease in the NNSEs of gray matter with age.Compared with the middle-aged and the elderly,the larger values of the NNSE in the younger group may indicate more homogeneous network structures,smaller differences in importance between nodes and thus a more powerful ability to tolerate intrusion.In addition,the hub nodes of different adult age groups are primarily located in the precuneus,cingulate gyrus,superior temporal gyrus,inferior temporal gyrus,parahippocampal gyrus,insula,precentral gyrus and postcentral gyrus.Our study can provide a new perspective for understanding and exploring the structural mechanism of brain aging.

Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

Exploring the influences of education,intelligence and income on mental disorders

Background Previous studies have shown that educational attainment(EA),intelligence and income are key factors associated with mental disorders.However,the direct effects of each factor on major mental disorders are unclear.Aims We aimed to evaluate the overall and independent causal effects of the three psychosocial factors on common mental disorders.Methods Using genome-wide association study summary datasets,we performed Mendelian randomisation(MR)and multivariable MR(MVMR)analyses to assess potential associations between the 3 factors(EA,N=766345;household income,N=392422;intelligence,N=146808)and 13 common mental disorders,with sample sizes ranging from 9907 to 807553.Inverse-variance weighting was employed as the main method in the MR analysis.Results Our MR analysis showed that(1)higher EA was a protective factor for eight mental disorders but contributed to anorexia nervosa,obsessive-compulsive disorder(OCD),bipolar disorder(BD)and autism spectrum disorder(ASD);(2)higher intelligence was a protective factor for five mental disorders but a risk factor for OCD and ASD;(3)higher household income protected against 10 mental disorders but confers risk for anorexia nervosa.Our MVMR analysis showed that(1)higher EA was a direct protective factor for attention-deficit/hyperactivity disorder(ADHD)and insomnia but a direct risk factor for schizophrenia,BD and ASD;(2)higher intelligence was a direct protective factor for schizophrenia but a direct risk factor for major depressive disorder(MDD)and ASD;(3)higher income was a direct protective factor for seven mental disorders,including schizophrenia,BD,MDD,ASD,post-traumatic stress disorder,ADHD and anxiety disorder.Conclusions Our study reveals that education,intelligence and income intertwine with each other.For each factor,its independent effects on mental disorders present a more complex picture than its overall effects.

Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating β-catenin activation and EMT pathways

Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy.To date,there is still a lack of effective drugs that target VM formation in GBM.In the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular mechanisms.Moroidin significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of moroidin.Exposure to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM cells.Moreover,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-catenin.Finally,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated EMT.Therefore,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM.

Mental health and insomnia problems in healthcare workers after the COVID-19 pandemic:A multicenter cross-sectional study

BACKGROUND Healthcare workers(HCWs)are at increased risk of contracting coronavirus disease 2019(COVID-19)as well as worsening mental health problems and insomnia.These problems can persist for a long period,even after the pandemic.However,less is known about this topic.AIM To analyze mental health,insomnia problems,and their influencing factors in HCWs after the COVID-19 pandemic.METHODS This multicenter cross-sectional,hospital-based study was conducted from June 1,2023 to June 30,2023,which was a half-year after the end of the COVID-19 emergency.Region-stratified population-based cluster sampling was applied at the provincial level for Chinese HCWs.Symptoms such as anxiety,depression,and insomnia were evaluated by the Generalized Anxiety Disorder-7,Patient Health Questionnaire-9,and Insomnia Severity Index.Factors influencing the symptoms were identified by multivariable logistic regression.RESULTS A total of 2000 participants were invited,for a response rate of 70.6%.A total of 1412 HCWs[618(43.8%)doctors,583(41.3%)nurses and 211(14.9%)nonfrontline],254(18.0%),231(16.4%),and 289(20.5%)had symptoms of anxiety,depression,and insomnia,respectively;severe symptoms were found in 58(4.1%),49(3.5%),and 111(7.9%)of the participants.Nurses,female sex,and hospitalization for COVID-19 were risk factors for anxiety,depression,and insomnia symptoms;moreover,death from family or friends was a risk factor for insomnia symptoms.During the COVID-19 outbreak,most[1086(76.9%)]of the participating HCWs received psychological interventions,while nearly all[994(70.4%)]of them had received public psychological education.Only 102(7.2%)of the HCWs received individual counseling from COVID-19.CONCLUSION Although the mental health and sleep problems of HCWs were relieved after the COVID-19 pandemic,they still faced challenges and greater risks than did the general population.Identifying risk factors would help in providing targeted interventions.In addition,although a major proportion of HCWs have received public psychological education,individual interventions are still insufficient.

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

Lithium carbonate-induced giant goiter and subclinical hyperthyroidism in a patient with schizophrenia:A case report and review of literature

BACKGROUND Lithium carbonate is used to manage various mood disorders,but it can cause thyroid abnormalities,including goiter,hypothyroidism,and hyperthyroidism.In rare cases,it can lead to giant goiter and subclinical hyperthyroidism,which may require surgical intervention in severe cases.CASE SUMMARY This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment.The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve,which led to respiratory distress,hoarseness,and dysphagia.The immediate danger of suffocation required urgent surgical intervention.In this report,we describe the case of a 41-year-old Chinese woman.This sheds light on the etiology and challenges associated with managing a giant goiter.The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion.Prior to the procedure,the patient was given iodine to prepare.Concurrently,changes were made to the psychiatric medication regimen.Following surgery,the patient's respiratory function and vocal cord functionality improved significantly,and her mental state remained stable.CONCLUSION It is essential to monitor thyroid function,test thyroid antibody levels,and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment.This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.

Necrolytic migratory erythema caused by pancreatic hyperglycemia with emphasis on therapeutic and prognosis:A case report

BACKGROUNDWith the incidence of pancreatic diseases increasing year by year,pancreatichyperglycemia,as one of the common complications,is gradually gaining attentionfor its impact on the skin health of patients.CASE SUMMARYThis was the case of an elderly female with clinical manifestations of necrolyticmigratory erythema,“three more and one less,”diabetes mellitus,hypertension,anemia,hypoproteinemia,and other syndromes,which had been misdiagnosedas eczema.Abdominal computed tomography showed a pancreatic caudal spaceoccupyinglesion,and the magnetic resonance scanning of the epigastric regionwith dynamic enhancement and diffusion-weighted imaging suggested a tumorof the pancreatic tail,which was considered to be a neuroendocrine tumor orcystadenoma.The patient was referred to a more equipped hospital for laparoscopicpancreatic tail resection.Post-surgery diagnosis revealed a neuroendocrinetumor in the tail of the pancreas.To date,the patient’s general condition is good,and she is still under close follow-up.CONCLUSIONNecrolytic migratory erythema can be induced by endocrine system tumors orendocrine metabolic abnormalities,with complex clinical manifestations,difficultdiagnosis,and easy misdiagnosis by dermatologists.The initial treatment principlesin dermatology include symptomatic supportive therapy and effectivedrugs to relieve skin lesions.After clarifying the etiology of glucagonoma,comprehensive treatment in collaboration with endocrinologists,generalsurgeons,and oncologists can help provide individualized treatment for patientsand improve their prognosis.

Neurosyphilis complicated by anti-γ-aminobutyric acid-B receptor encephalitis: A case report

BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing encephalitis.Few cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secondary to neurosyphilis have been reported.We report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor(GABABR)AE.CASE SUMMARY A young man in his 30s who presented with acute epileptic status was admitted to a local hospital.He was diagnosed with neurosyphilis,according to serum and cerebrospinal fluid(CSF)tests for syphilis.After 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin,epilepsy was controlled but serious cognitive impairment,behavioral,and serious psychiatric symptoms were observed.He was then transferred to our hospital.The Mini-Mental State Examination(MMSE)crude test results showed only 2 points.Cranial magnetic resonance imaging revealed significant cerebral atrophy and multiple fluidattenuated inversion recovery high signals in the white matter surrounding both lateral ventricles,left amygdala and bilateral thalami.Anti-GABABR antibodies were discovered in CSF(1:3.2)and serum(1:100).The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE,and received methylprednisolone and penicillin.Following treatment,his mental symptoms were alleviated.Cognitive impairment was significantly improved,with a MMSE of 8 points.Serum anti-GABABR antibody titer decreased to 1:32.The patient received methylprednisolone and penicillin after discharge.Three months later,the patient’s condition was stable,but the serum anti-GABABR antibody titer was 1:100.CONCLUSION This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.

Efficacy and safety of Nafamostat mesylate in patients with endstage renal failure

BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fiber activity.AIM To evaluate the efficacy and safety of Nafamostat mesylate in patients with end-stage renal failure.METHODS Seventy-five patients with end-stage renal failure who received hemodialysis at our hospital between January 2020 and August 2021 were selected and divided into the observation group(Nafamostat mesylate for injection,n=33)and control group(heparin sodium injection,n=32).General patient data,indicators of clinical efficacy,dialyzer hemocoagulation parameters,coagulation function indices,and hemoglobin concentration and platelet count before and after treatment,and the occurrence of adverse reactions after treatment were compared between the two groups.RESULTS The two groups showed no significant differences in general patient data(P>0.05).The post-treatment effectiveness rate in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the number of patients in grade I(P>0.05),while the number of patients in grade 0 was lower in the control group,and the number of patients in grades II and III was higher in the control group(P<0.05).The post-treatment prothrombin time,activated partial thromboplastin time,thrombin time,and international normalized ratio values in the control group were higher than those in the observation group,while the fibrinogen level in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the platelet count and hemoglobin level before and after treatment(P>0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(P<0.05).CONCLUSION Treatment of patients showing end-stage renal failure with Nafamostat mesylate can significantly improve therapeutic efficacy and has high safety and clinical value.

Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

Cognitive dysfunction in schizophrenia patients caused by downregulation of γ-aminobutyric acid receptor subunits

BACKGROUND The expression pattern of gamma aminobutyric acid(GABA)receptor subunits are commonly altered in patients with schizophrenia,which may lead to nerve excitation/inhibition problems,affecting cognition,emotion,and behavior.AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period.The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy.The recognized cognitive battery tool,the MATRICS Consensus Cognitive Battery,was used to evaluate the scores for various dimensions of cognitive function.The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed.RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups(P<0.05).A significant difference was also found between the case and control groups in terms of cognitive function measures,including attention/alertness and learning ability(P<0.05).Specifically,as the expression levels of GABRA1(α1 subunit gene),GABRB2(β2 subunit gene),GABRD(δsubunit),and GABRE(εsubunit)decreased,the severity of the patients’condition increased gradually,indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia(P<0.05).However,the expression levels of GABRA5(α5 subunit gene)and GABRA6(α6 subunit gene)showed no significant correlation with schizophrenia(P>0.05).CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia.In other words,when GABA receptor subunits are downregulated in patients,cognitive impairment becomes more severe.

Exploration of cardiac rehabilitation nursing for elderly patients with myocardial infarction based on individualized cardiac rehabilitation

BACKGROUND Myocardial infarction is a high-risk condition prevalent among the elderly population,often leading to adverse clinical manifestations such as reduced cardiopulmonary function,anxiety,and depression post-surgery.Consequently,cardiac rehabilitation holds immense importance in mitigating these complications.AIM To evaluate the effect of individualized cardiac rehabilitation on blood pressure variability(BPV)and baroreflex sensitivity(BRS)in elderly patients with myocardial infarction.METHODS A cohort of 74 elderly patients diagnosed with myocardial infarction and admitted to our hospital between January 2021 and January 2022 were subjected to random selection.Subsequently,all patients were divided into two groups,namely the research group(n=37)and the control group(n=37),utilizing the number table method.The control group received conventional drug treatment and nursing guidance intervention,while the study group underwent individualized cardiac rehabilitation in addition to the interventions received by the control group.All patients were continuously intervened for 12 wk,and the BPV of these two groups in the 1st wk(T0),the 4th wk(T1)and the 12th wk(T2)were compared,BRS,changes in cardiopulmonary function measures,and adverse cardiovascular events.RESULTS Of 24 h diastolic BPV,24 h systolic BPV,carbon dioxide ventilation equivalent slope of the research group were lower than those of the control group at T1 and T2,BRS,peak heart rate and systolic blood pressure product,1 min heart rate recovery were higher than those of the control group,and the incidence of adverse events in the research group was lower than that of the control group,the difference was statistically significant(P<0.05).CONCLUSION In this study,we found that after individualized cardiac rehabilitation in elderly patients with myocardial infarction,BPV and BRS can be effectively improved,cardiac function is significantly enhanced,and a better prognosis is obtained.

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.

MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder

Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses.Finally,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale scores.Additionally,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice.Notably,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice.Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice.Mechanistically,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine plasticity.Conclusions Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.

Intermittent melena and refractory anemia due to jejunal cavernous lymphangioma:A case report

BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and intussusception.Here,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult.CASE SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months prior.Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding.Conservative management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after surgery.Ultimately,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active bleeding.After singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical resection.No complications or recurrences were observed postoperatively.CONCLUSION Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding.Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis.Surgical resection is an effective management method.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Dissecting the association between gut microbiota,body mass index and specific depressive symptoms:a mediation Mendelian randomisation study

Background Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking.Aims We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index(BMI).Methods We performed a two-sample Mendelian randomisation(MR)analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies.The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.Results MR evidence suggested the Bifidobacterium genus(β=0.03;95%CI-0.05 to-0.02;p<0.001 andβ=0.03;95%CI-0.05 to-0.02;p<0.001)and Actinobacteria phylum(β=-0.04;95%CI-0.06 to-0.02;p<0.001 andβ=-0.03;95%CI-0.05 to-0.03;p=0.001)had protective effects on both anhedonia and depressed mood.The Actinobacteria phylum also had protective effects on appetite changes(β=-0.04;95%CI-0.06 to-0.01;p=0.005),while the FamilyⅪhad an antiprotective effect(β=0.03;95%CI 0.01 to 0.04;p<0.001).The Bifidobacteriaceae family(β=-0.01;95%CI-0.02 to-0.01;p=0.001)and Actinobacteria phylum(β=-0.02;95%CI-0.03 to-0.01;p=0.001)showed protective effects against suicidality.The two-step MR analysis revealed that BMl also acted as a mediating moderator between the Actinobacteria phylum and appetite changes(mediated proportion,34.42%)and that BMI partially mediated the effect of the Bifidobacterium genus(14.14%and 8.05%)and Actinobacteria phylum(13.10%and 8.31%)on both anhedonia and depressed mood.Conclusions These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity.Further studies are required to translate these findings into clinical practice.

Research Progress of PTCH1 Gene in Lung Cancer

Background: The PTCH1 gene, also known as Patched 1, is located on the long arm of human chromosome 9 (9q22.3). It encodes the PTCH1 protein, which is a critical transmembrane receptor within the Hedgehog signaling pathway (Hh), playing a pivotal role in cellular communication and developmental processes. Recent studies have highlighted the significance of mutations in PTCH1 in the pathogenesis of lung cancer, positioning it as a crucial molecule for investigation in oncology. Purpose: This review aims to elucidate the role of the PTCH1 and the Hedgehog pathway in the initiation, progression, and potential treatment of lung cancer, thereby providing a theoretical foundation for personalized and precise therapeutic strategies. Method: To ensure a comprehensive review, this study systematically searched for literature related to the PTCH1, lung cancer, and the Hedgehog pathway across multiple databases including PubMed, Web of Science, and CNKI (China National Knowledge Infrastructure). The search strategy involved using specific keywords and advanced filtering options to include the most relevant and recent studies. Initial screening excluded irrelevant articles, followed by a detailed evaluation of the selected studies based on their scientific quality and relevance. Results: This review indicated that specific mutations in the PTCH1 gene are closely associated with the onset and progression of lung cancer. These mutations impede normal Hedgehog signaling, leading to unregulated cell proliferation and tumor growth. Targeting PTCH1, including vismodegib, have shown efficacy in clinical cases, particularly in SCCL with specific PTCH1 mutations, leading to complete remissions. Furthermore, the interaction between PTCH1 and microRNA-212 suggests potential therapeutic approaches by targeting miRNA to regulate PTCH1 expression. In addition, the investigation of traditional Chinese medicines such as Ginsenosides and Cordyceps sinensis extracts has shown their potential to modulate the Hedgehog pathway and reverse drug resistance. Conclusions: An in-depth understanding of the precise mechanisms by which PTCH1 mutations promote lung cancer could facilitate the development of targeted therapies. This study highlights the potential of PTCH1 as a biomarker for diagnosis and a target for precision medicine in lung cancer treatment, advocating for further research into its molecular pathways and therapeutic applications.