BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However， the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder， and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently， 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory （BDI） and Beck Anxiety Inventory （BAI） were used for assessment， and decision-making behavior was evaluated using Probabilistic Reversal Learning （PRL） task. Indicators assessed included the number of trials to criterion， perseverative errors， win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group （t=3.684， P<0.01）. There were no statistically significant differences between two groups in trials to criterion， perseverative errors and win-stay rate （t=0.329， 0.132， 0.609， P>0.05）. In depression group， BDI and BAI scores were positively correlated with the win-stay rate（r=0.450， 0.398， P<0.01）. ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore， the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. ［Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University （number， 2019LZXNYDJ39］

BackgroundWith the rapid development of the networking technologies， internet addiction has increasingly become a serious mental health issue. Previous studies have revealed the link between childhood trauma and internet addiction， while the mediating role of perceived stress in this link is not yet clear. ObjectiveTo investigate the role of medical students' perceived stress in the relationship between childhood trauma and internet addiction， so as to provide references for the intervention of internet addiction. MethodsFrom February to March 2023， a random sampling technique was used to select 1 232 undergraduate students from the School of Clinical Medical Sciences of Southwest Medical University as research subjects. The Childhood Trauma Questionnaire-Short Form （CTQ-SF）， Perceived Stress Scale （PSS）， Internet Gaming Disorder Scale （IGDS）， and Bergen Social Media Addiction Scale （BSMAS） were used for assessment. Pearson's correlation coefficients were calculated. The mediation effect of perceived stress in the relationship between childhood trauma and internet addiction was tested using Model 4 in the SPSS Process 4.1， and Bootstrapping procedure involving 5 000 replicates was employed to confirm the statistical significance. ResultsA total of 1 016 （82.47%） valid completed questionnaires were gathered. The CTQ-SF scores of medical students were positively correlated with PSS scores， IGD scores， and BSMAS scores （r=0.583， 0.474， 0.465， P<0.01）. PSS scores were positively correlated with IGD scores and BSMAS scores （r=0.369， 0.479， P<0.01）. Childhood trauma in medical students was found to positively predict perceived stress （β=0.191， P<0.01）， social media addiction （β=0.160， P<0.01）， and internet gaming disorder （β=0.106， P<0.01）. Perceived stress played a significant mediating role in the relationship between childhood trauma and internet gaming disorder， indirect effect value was 0.018 （95% CI： 0.009~0.027）， accounting for 16.98%. Perceived stress also exhibited a significant mediating role in the relationship between childhood trauma and social media addiction， indirect effect value was 0.063 （95% CI： 0.048~0.079）， accounting for 39.38%. ConclusionChildhood trauma in medical students may affect internet gaming disorder and social media addiction through perceived stress. ［Funded by 2022 Annual Research Project of Sichuan Applied Psychology Research Center，（number，CSXL-22102）］

BACKGROUND: Most studies have evaluated disability-adjusted life years (DALYs) of colorectal cancer (CRC) patients based on a set of generic disability weights (DWs). This study aimed to apply local CRC-stage-specific DWs to estimate the burden of DALYs for CRC (CRC-DALYs) in populations in China and consider the influence of local screening coverage of CRC. METHODS: A prevalence-based model was constructed using data from various sources. Years lived with disability (YLDs) were estimated mainly via cumulative prevalence data (based on CRC incidence rates, population numbers, and survival rates), stage-specific proportions of CRC, and DWs of the local population. Years of life lost (YLLs) were calculated based on the CRC mortality rates and standard life expectancies. CRC incidence and mortality rates for the years 2020, 2025, and 2030 were estimated by joinpoint regression, and the corresponding DALYs were predicted. The main assumption was made for CRC screening coverage. Sensitivity analyses were used to assess the impact of population, DWs, and coverage. RESULTS: In 2017, among the Chinese population, the estimated number of CRC-DALYs was 4,303,314 (11.9% for YLDs). If CRC screening coverage rate in China (2.3%) remains unchanged, the overall DALYs in 2030 are predicted to increase by 37.2% (45.1% of those aged ≥65 years). More optimistically, the DALYs would then decrease by 0.7% in 2030 (from 5,902,454 to 5,860,200) if the coverage could be increased to 25.0%. A sensitivity analysis revealed that using local DWs would change the base-case values by 5.7%. CONCLUSIONS The estimated CRC-DALYs in China using population-specific DWs were considerably lower (with a higher percentage of YLDs) than the global burden of disease (GBD) estimates (5,865,004, of 4.6% for YLDs), suggesting the impact extent of applying local parameters. Sustainable scale-up CRC screening needs to be in place to moderate the growth trend of CRC-DALYs in China.
Humans ; Colorectal Neoplasms/diagnosis* ; China/epidemiology* ; Disability-Adjusted Life Years ; Male ; Prevalence ; Female ; Middle Aged ; Aged ; Early Detection of Cancer ; Quality-Adjusted Life Years ; Adult ; Incidence

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective:To investigate the clinicopathological features, molecular pathology characteristics, and prognosis of non-small cell lung carcinoma (NSCLC) exhibiting co-expression of p40 and thyroid transcription factor1 (TTF1).Methods:Clinical and pathological data of six NSCLC cases with co-expression of p40 and TTF1 diagnosed at the First People′s Hospital of Xiaoshan District, Hangzhou, China from January 2016 to December 2023 were collected. Relevant literature was also reviewed.Results:NSCLC with co-expression of p40 and TTF1 commonly occurred in male smokers and had been in stage Ⅲ-Ⅳ when diagnosis. Microscopic examination revealed that the tumor cells were arranged in solid nests and sheets with marked atypia and visible mitotic figures. There was no prominent evidence of keratinization or glandular formation. The tumor cells diffusely co-expressed p40 and TTF1, exhibiting a dual immunophenotype characteristic of both squamous cell carcinoma and adenocarcinoma. Molecular testing of four NSCLC co-expressing p40 and TTF1 revealed the presence of common EGFR mutations, as well as mutations of NRAS (mutation rate of 2.09%), EML4-ALK (mutation rate of 24.77%), and PIK3CA (exon 10 c.1658 G>C p.S553T, mutation rate of 4.32%). All six tumors were poorly differentiated, highly invasive, and associated with poor prognosis. Four of the six patients experienced widespread metastasis and died within 7 to 30 months after the diagnosis or initial treatment.Conclusions:NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.

Objective To investigate the expression of Bone morphogenetic protein 4(BMP4)in human endometrial stromal cells(hESCs)of patients with recurrent spontaneous abortion(RSA)and the regulation of Forkhead transcription factor 1(FOXO1)by BMP4.Methods The decidua tissues of RSA patients and Healthy control(HC)patients in People's Hospital of Wuhan University were collected,and the expression of BMP4 was analyzed by immunohistochemistry and RT-qPCR.hESC was used in vitro cell experiments,lentivirus was transfected to knock down the expression of BMP4 and establish the cell model of RSA.After decidualization,CCK-8 as-say,inverted microscope,and Western blot assay were used to detect the cell proliferation,morphology,and expression levels of decidual-ization marker genes.To verify whether BMP4 knockdown affects FOXO1 expression,a FOXO1 inhibitor(AS1842856)was used to per-form a response experiment,and the upstream and downstream relationship between FOXO1 and BMP4 was analyzed by CCK-8 experi-ment,inverted microscope,and Western blot.In animal experiments,intraperitoneal injection of LPS-induced abortion in pregnant mice,and the expression of BMP4 in decidua were detected to explore the relationship between BMP4 and abortion in mice.Results Compared with the HC group,the expression of BMP4 in the deciduous tissues of RSA patients was significantly decreased.After BMP4 was knocked down,the decidualization was significantly abnormal,which showed that the proliferation rate increased,the cell morphologi-cal transformation was not obvious,and the expression of decidualization marker genes was down-regulated.FOXO1 was the downstream regulatory molecule of BMP4,knocking down BMP4 could inhibit the expression of FOXO1,and BMP4 could regulate the decidualization of hESC through FOXO1.In animal models,the expression of BMP4 in decidua and placental weight of aborted pregnant mice were signif-icantly reduced.Conclusion The expression of BMP4 was significantly down-regulated in decidual tissues of RSA patients and aborted mice.In cell experiments,BMP4 can promote decidualization of hESC by regulating the expression of FOXO1.Abnormally low expression of BMP4 may be one of the reasons for decidualization defects in RSA patients.

AIM:To investigate the interaction mechanisms of estrogen receptor β(ERβ),nuclear factor-κB(NF-κB)and activator protein-1(AP-1)in colorectal cancer by analyzing the transcriptome data after tumor necrosis fac-tor α(TNF-α)treatment and combining it with NF-κB/p65 and ERβ cistrome data in colon cancer cell lines HT29 and SW480.METHODS:The TNF-α transcriptome was integrated with p65 and ERβ cistrome data.Protein interaction net-works of TNF-α,NF-κB/p65 and ERβ were constructed in colon cancer cell lines HT29 and SW480 using R.RE-SULTS:TNF-α regulated genes through p65 DNA binding,which were mainly enriched in the NF-κB and mitogen-acti-vated protein kinase(MAPK)pathways.Components of the NF-κB/p65 and MAPK pathways had potential interactions with AP-1 family proteins.ERβ overexpression did not significantly affect TNF-α-mediated gene regulation but may regu-late AP-1 activity through the MAPK and phosphatidylinositol 3-kinase(PI3K)/Akt pathways.Furthermore,ERβ de-creased p65 DNA binding sites in HT29 but increased p65 binding sites in SW480,suggesting cell line-specific regulation of NF-κB by ERβ.CONCLUSION:In colorectal cancer,NF-κB,ERβ and AP-1 have potential interactions:TNF-α can regulate AP-1 through NF-κB,while ERβ overexpression can alter NF-κB-mediated regulation,and the influence of ERβ on NF-κB may be gender-related.

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.

BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.