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.

Risk factors for congenital nasolacrimal duct obstruction in children under two years of age

·AIM:To identify various risk factors that may play a significant role in the development of congenital nasolacrimal duct obstruction(CNLDO).·METHODS:This observational case-control study included a case group of 122 children less than two years of age with CNLDO who underwent probing and irrigation treatment at the ophthalmology department of Imam Khomeini Hospital in Ahvaz,Iran,from June 2022 to June2024.A control group of 122 age-matched children without CNLDO was also included for comparison.Data was collected from the children's medical records.·RESULTS:The study found a significant correlation between the occurrence of CNLDO and several maternal factors,such as preeclampsia,the use of levothyroxine,hypothyroidism,having more than three pregnancies(gravidity>3),natural pregnancy,and gestational diabetes mellitus.Additionally,in children,factors,such as oxygen therapy,anemia,reflux,jaundice,and a family history of CNLDO in first-degree relatives were associated with CNLDO,and maternal preeclampsia and hypothyroidism were found to significantly increase the risk of developing CNLDO in children.·CONCLUSION:Given that CNLDO affects both premature and full-term children,the present findings may potentially facilitate the early identification of children and infants at risk of nasolacrimal duct obstruction,thereby preventing the onset of chronic dacryocystitis.

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).

Association between autoimmune gastritis and gastric polyps:Clinical characteristics and risk factors

BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well understood.AIM To explore the clinical characteristics and risk factors of AIG with GPs in patients.METHODS This double center retrospective study included 530 patients diagnosed with AIG from July 2019 to July 2023.We collected clinical,biochemical,serological,and demographic data were of each patient.Logistic regression analyses,both multivariate and univariate,were conducted to pinpoint independent risk factors for GPs in patients with AIG patients.Receiver operating characteristic curves were utilized to establish the optimal cutoff values,sensitivity,and specificity of these risk factors for predicting GPs in patients with AIG.RESULTS Patients with GPs had a higher median age than those without GPs[61(52.25-69)years vs 58(47-66)years,P=0.006].The gastrin-17 levels were significantly elevated in patients with GPs compared with those without GPs[91.9(34.2-138.9)pmol/mL vs 60.9(12.6-98.4)pmol/mL,P<0.001].Additionally,the positive rate of parietal cell antibody(PCA)antibody was higher in these patients than in those without GPs(88.6%vs 73.6%,P<0.001).Multivariate and univariate analyses revealed that PCA positivity[odds ratio(OR)=2.003,P=0.017],pepsinogen II(OR=1.053,P=0.015),and enterochromaffin like cells hyperplasia(OR=3.116,P<0.001)were significant risk factors for GPs,while pepsinogen I was identified as a protective factor.CONCLUSION PCA positivity and enterochromaffin like cells hyperplasia are significant risk factor for the development of GPs in patients with AIG.Elevated gastrin-17 levels may also play a role in this process.These findings suggest potential targets for further research and therapeutic intervention in managing GPs in patients with AIG.

Social function scores and influencing factors in patients with residual depressive symptoms

BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.

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.

Brain-derived neurotrophic factor alterations and cognitive decline in schizophrenia:Implications for early intervention

This manuscript explores the recent study by Cui et al which assessed the interplay between inflammatory cytokines and brain-derived neurotrophic factor(BDNF)levels in first-episode schizophrenia patients.The study revealed that higher levels of interleukin-6 and tumor necrosis factor-αcorrelated with reduced BDNF levels and poorer cognitive performance.Schizophrenia is a severe psy-chiatric disorder impacting approximately 1%of the global population,charac-terized by positive symptoms(hallucinations and delusions),negative symptoms(diminished motivation and cognitive impairments)and disorganized thoughts and behaviors.Emerging research highlights the role of BDNF as a potential biomarker for early diagnosis and therapeutic targeting.The findings from Cui et al’s study suggest that targeting neuroinflammation and enhancing BDNF levels may improve cognitive outcomes.Effective treatment approaches involve a com-bination of pharmacological and non-pharmacological interventions tailored to individual patient needs.Hence,monitoring cognitive and neuroinflammatory markers is essential for improving patient outcomes and quality of life.Conse-quently,this manuscript highlights the need for an integrated approach to schizo-phrenia management,considering both clinical symptoms and underlying neuro-biological changes.

Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats

BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.

Burden of mental disorders and risk factors in the Western Pacific region from 1990 to 2021

BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and countries.AIM To analyze the burden of MD in the WPR from 1990 to 2021,along with associated risk factors,to reveal changing trends and emerging challenges.METHODS We used data from the Global Burden of Disease 2021,analyzing prevalence,incidence,and disability-adjusted life years(DALYs)of MD from 1990 to 2021.Statistical methods included age-standardisation and uncertainty analysis to address variations in population structure and data completeness.RESULTS Between 1990 and 2021,the prevalence of MD rose from 174.40 million cases[95%uncertainty interval(UI):160.17-189.84]to 234.90 million cases(95%UI:219.04-252.50),with corresponding DALYs increasing from 22.8 million(95%UI:17.22-28.79)to 32.07 million(95%UI:24.50-40.68).During this period,the burden of MD shifted towards older age groups.Depressive and anxiety disorders were predominant,with females showing higher DALYs for depressive and anxiety disorders,and males more affected by conduct disorders,attention-deficit hyperactivity disorder,and autism spectrum disorders.Australia,New Zealand,and Malaysia reported the highest burdens,whereas Vietnam,China,and Brunei Darussalam reported the lowest.Additionally,childhood sexual abuse and bullying,and intimate partner violence emerged as significant risk factors.CONCLUSION This study highlights the significant burden of MD in the WPR,with variations by age,gender,and nation.The coronavirus disease 2019 pandemic has exacerbated the situation,emphasizing the need for a coordinated response.

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.

Heat shock transcription factors regulate thermotolerance gene networks in tomato(Solanum lycopersicum)flower buds

Tomato(Solanum lycopersicum)is an important fruit and vegetable crop in worldwide.The fertility of tomato reproductive organs can be dramatically decreased when ambient temperatures rise above 35°C,reducing tomato fruit yield.It is necessary to identify transcription factors(TFs)and target genes involved in heat stress response(HSR)signaling cascades in tomato flower buds to improve tomato plant thermotolerance.In this study,we profiled genes expressed in three developmental stages of tomato flower buds.Red and turquoise modules for heat stress(HS)were identified through gene co-expression network analysis,and the genes within these modules were enriched in HS-related pathways.By focusing on the TFs in the two modules,we identified several novel HSR-related TFs,including SlWRKY75,SlMYB117,and SlNAM.Furthermore,homology analysis illustrated a conserved signaling cascade in tomato.Lastly,we identified and experimentally validated four HSF-regulated genes,namely SlGrpE,SlERDJ3A,SlTIL,and SlPOM1,that likely modulate thermotolerance in plants.These results provide a high-resolution atlas of gene expression during tomato flower bud development under HS conditions,which is a valuable resource for uncovering potential regulatory networks associated with the HSR in tomato.

Evaluation of the prevalence and risk factors of burnout syndrome among healthcare workers:A cross-sectional study

BACKGROUND Burnout syndrome is a significant issue among healthcare professionals worldwide,marked by depersonalization,emotional exhaustion,and a reduced sense of personal achievement.This psychological and physical burden profoundly affects healthcare professionals'quality of care and overall well-being.In Somalia,where the healthcare system faces numerous challenges,the escalating demand for medical services and inadequate resources,coupled with overwhelming workloads,long hours,and high-stress levels,make healthcare providers particularly vulnerable to burnout syndrome.This,in turn,affects both the mental health of healthcare personnel and the quality of care they provide.AIM To examine the prevalence and determinants of burnout syndrome among healthcare practitioners in Mogadishu,Somalia.METHODS This cross-sectional prospective study was performed among 246 healthcare providers employed at a tertiary care hospital in Mogadishu,Somalia,who were recruited via random sampling.Data were collected using questionnaires that covered sociodemographic,psychological,work-related characteristics,and burnout syndrome.Bivariate and multivariate logistic regression analyses were performed to identify the variables that correlated with burnout syndrome.The results were presented using adjusted odds ratios(AORs),95%CIs,and P values,with a cutoff of 0.05 for identifying significant associations.RESULTS Among the participants,24%(95%CI:18.8%–29.8%)exhibited symptoms of burnout syndrome.Factors associated with burnout included female gender(AOR=6.60;95%CI:2.29-19.04),being married(AOR=3.07;95%CI:1.14-8.28),being divorced or widowed(AOR=5.84;95%CI:1.35-25.35),working more than 7 night shifts(AOR=3.19;95%CI:1.30–7.82),having less than 5 years of job experience(AOR=5.28;95%CI:1.29-21.65),experiencing poor sleep quality(AOR=5.29;95%CI:1.88-14.89),and exhibiting depressive(AOR=4.46;95%CI:1.59-12.53)and anxiety symptoms(AOR=7.34;95%CI:2.49-21.60).CONCLUSION This study found that nearly one in four healthcare professionals suffers from burnout syndrome.Improving sleep quality,monitoring,and providing mental health support could enhance their well-being and patient care.

Risk factors,monitoring,and treatment strategies for early recurrence after rectal cancer surgery

Early recurrence(ER)following surgery for rectal cancer is a significant factor impacting patient survival rates.Tsai et al identified age,preoperative neoadjuvant therapy,length of hospital stay,tumour location,and pathological stage as factors influencing the risk of ER.Postoperative monitoring for ER should encompass a thorough medical history review,physical examination,tumour marker testing,and imaging studies.Additionally,noninvasive circulating tumour cell DNA testing can be utilized to predict ER.Treatment strategies may involve radical surgery,radiation therapy,chemotherapy,and immunotherapy.Through a comprehensive analysis of risk factors,the optimization of monitoring methods,and the development of personalized treatment strategies,it is anticipated that both the efficacy of treatment and the quality of life for rectal cancer patients with postoperative recurrence can be significantly improved.

Prognosis in stage II colon cancer:Expanding the horizons of risk factors

we critically review the authors’perspective and analyze the relevance of the results obtained in the original article of clinical research by Liu et al.We consider that additional factors associated with colon cancer progression have recently been described in extensive clinical research,and should be included in this analysis to achieve a more accurate prognosis.These factors include inflammation,gut microbiota composition,immune status and nutritional balance,as they influence the post-surgical survival profile of patients with stage II colorectal cancer.We also address the clinical implementation and limitations of these analyses.Evaluation of the patient´s entire context is essential for selection of the most appropriate therapy.

Parameter changes and influencing factors in sixty patients with interventional surgery for liver cancer diagnoses

BACKGROUND The development of hepatocellular carcinoma(HCC)is influenced by multiple factors.Interventional therapy offers an effective treatment option for patients with unresectable intermediate-to-advanced HCC.Interventional therapy can induce electrocardiographic(ECG)abnormalities that may be associated with liver dysfunction,electrolyte disorders,and cardiac injury.AIM To explore the ECG alterations and determinants following interventional therapy in patients with HCC.METHODS Sixty patients undergoing interventional treatment for liver cancer were selected as study participants.According to the results of the dynamic ECG examination 1 day after surgery,the patients were divided into an abnormal group(n=21)and a nonabnormal group(n=39).With the help of dynamic ECG examination,the ECG parameters were compared and the baseline data of patients was recorded in the two groups.RESULTS The 24 hours QT interval variability,24 hours normal atrial polarization to ventricular polarization(R-R)interval(standard deviation),24 hours consecutive 5 minutes normal R-R interval,and 24 hours continuous 5 minutes normal R-R interval(standard deviation mean)were lower than patients in the nonabnormal group(P<0.05).The logistic analysis showed that age>60 years,liver function grade B,and postoperative body temperature 38°C were risk factors for abnormal dynamic electrocardiogram in patients with liver cancer intervention(P<0.05).CONCLUSION Interventional therapy for HCC can lead to ECG abnormalities,underscoring the clinical need for enhanced cardiac monitoring to mitigate myocardial complications.

Classification and identification of risk factors for type 2 diabetes

The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors,which are categorized in this paper into five categories:Social determinants,lifestyle,checkable/testable risk factors,history of illness and medication,and other factors,which are discussed in a narrative review.Meanwhile,this paper points out the problems of the current research,helps to improve the systematic categorisation and practicality of T2DM risk factors,and provides a professional research basis for clinical practice and industry decision-making.

Spatial Pattern and Influencing Factors of China’s Digital Trade Resilience under the Impact of Trade Frictions

In the era of the digital economy,digital trade has demonstrated strong vitality,becoming a crucial driving force for the highquality development of national and regional economies.However,understanding the resilience of digital trade in the face of external crises is an important topic.Taking the backdrop of Sino-US trade friction,this paper constructs a resilience index system for digital trade.It utilizes entropy method,kernel density estimation,and ArcGIS mapping to calculate and visually analyze the resilience of China’s digital trade from 2017 to 2021.Additionally,a Tobit model is constructed to explore the main influencing factors of digital trade resilience patterns.The research findings indicate:1)temporally,during the period of Sino-US trade friction,China’s digital trade resilience shows an overall upward trend,but there are regional differences in resilience levels across the country,with a severe polarization phenomenon.2)Spatially,high resilience is observed in the eastern and central regions of China,while the western and northeastern regions exhibit low resilience.3)From a dimensional perspective,the resistance of digital trade resilience displays a spatial distribution of high values in the east and low values in the west.The recovery force is aggregated along coastal areas,and the renewal force tends to aggregate along the eastern coastline.4)Factors such as economic scale,industrial structure,urbanization rate,government fiscal expenditure,and technological talents significantly promote the enhancement of digital trade resilience.This study reveals the dynamic characteristics and influencing factors of digital trade resilience in responding to external shocks,providing theoretical basis and policy suggestions for enhancing digital trade resilience,and promoting high-quality economic development in China.

Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric

BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.