BACKGROUND Acute pancreatitis(AP)is an emergency gastrointestinal disease that requires immediate diagnosis and urgent clinical treatment.An accurate assessment and precise staging of severity are essential in initial...BACKGROUND Acute pancreatitis(AP)is an emergency gastrointestinal disease that requires immediate diagnosis and urgent clinical treatment.An accurate assessment and precise staging of severity are essential in initial intensive therapy.AIM To explore the prognostic value of inflammatory markers and several scoring systems[Acute Physiology and Chronic Health Evaluation II,the bedside index of severity in AP(BISAP),Ranson’s score,the computed tomography severity index(CTSI)and sequential organ failure assessment]in severity stratification of earlyphase AP.METHODS A total of 463 patients with AP admitted to our hospital between 1 January 2021 and 30 June 2024 were retrospectively enrolled in this study.Inflammation marker and scoring system levels were calculated and compared between different severity groups.Relationships between severity and several predictors were evaluated using univariate and multivariate logistic regression models.Predictive ability was estimated using receiver operating characteristic curves.RESULTS Of the 463 patients,50(10.80%)were classified as having severe AP(SAP).The results revealed that the white cell count significantly increased,whereas the prognostic nutritional index measured within 48 hours(PNI48)and calcium(Ca^(2+))were decreased as the severity of AP increased(P<0.001).According to multivariate logistic regression,C-reactive protein measured within 48 hours(CRP_(48)),Ca^(2+)levels,and PNI48 were independent risk factors for predicting SAP.The area under the curve(AUC)values for the CRP_(48),Ca^(2+),PNI48,Acute Physiology and Chronic Health Evaluation II,sequential organ failure assessment,BISAP,CTSI,and Ranson scores for the prediction of SAP were 0.802,0.736,0.871,0.799,0.783,0.895,0.931 and 0.914,respectively.The AUC for the combined CRP_(48)+Ca^(2+)+PNI48 model was 0.892.The combination of PNI48 and Ranson achieved an AUC of 0.936.CONCLUSION Independent risk factors for developing SAP include CRP_(48),Ca^(2+),and PNI48.CTSI,BISAP,and the combination of PNI48 and the Ranson score can act as reliable predictors of SAP.展开更多
BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyro...BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.展开更多
Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe CO...Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe COVID-19.But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.Methods:We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 pa-tients upon admission and one-month after their discharge,comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.Results:Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients.These altered microbial metabolites included tryptophan,bile acids,fatty acids,amino acids,vitamins and those containing benzene.A total of 13 distinct microbial metabolites were identi-fied in COVID-19 patients compared to healthy controls.Notably,correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19.Furthermore,these metabolites did not restore to the normal levels one month after discharge.Importantly,two mi-crobial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.Conclusions:The microbial metabolites were altered in the acute and recovery stage,correlating with dis-ease severity of COVID-19.These results indicated the important role of gut microbiota in the progression of COVID-19,and facilitated the potential therapeutic microbial target for severe COVID-19 patients.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for...BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for assessing this risk.In Gabon,early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19.This study hypothesizes that elevated Ddimer levels are linked to increased COVID-19 severity.AIM To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions.METHODS This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023.The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission.Data on demographics,clinical outcomes,D-dimer levels,and healthcare costs were collected.COVID-19 severity was classified as non-severe(outpatients)or severe(inpatients).A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity,with adjusted odds ratios(OR)and 95%CI.RESULTS A total of 3004 patients were included,with a mean age of 50.17 years,and the majority were female(53.43%).Elevated D-dimer levels were found in 65.81%of patients,and 57.21%of these experienced severe COVID-19.Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19(OR=3.33,95%CI:2.84-3.92,P<0.001),and this association remained significant in the multivariable analysis,adjusted for age,sex,and year of collection.The financial analysis revealed a substantial burden,particularly for uninsured patients.CONCLUSION D-dimer predicts COVID-19 severity and guides treatment,but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.展开更多
Acute pancreatitis(AP)is a complex and potentially life-threatening inflammatory condition with a highly variable clinical course,ranging from mild,selflimiting episodes to severe necrotizing forms.Among its common co...Acute pancreatitis(AP)is a complex and potentially life-threatening inflammatory condition with a highly variable clinical course,ranging from mild,selflimiting episodes to severe necrotizing forms.Among its common complications ascites has traditionally been viewed as a passive byproduct of peritoneal inflammation and enzymatic leakage with limited diagnostic or prognostic utility.However,growing evidence challenges this perspective,suggesting that ascitic fluid in AP represents a dynamic and clinically meaningful component of disease progression.In this editorial we reflected on the findings presented by Rao et al,who highlighted the diagnostic,prognostic,and therapeutic significance of ascitic fluid in AP.Easily accessible markers such as lactate dehydrogenase may provide early prognostic insight while emerging molecular biomarkers and cytokine pro-files offer promise for more precise risk stratification and individualized therapy.We argue that the systematic evaluation of ascitic fluid should be integrated into the clinical management of moderate to severe AP.Incorporating ascites analysis into standard diagnostic protocols may enhance early risk assessment,inform therapeutic decisions,and ultimately improve patient outcomes.Ascitic fluid should be recognized as a clinically valuable marker and an important source of information in the evolving landscape of AP care.展开更多
Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneu...Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneumonia who were diagnosed and treated in the hospital from May 2024 to May 2025.The expression level of IL-17D in the serum of all patients was recorded.Patients were divided into severe and mild groups based on their disease severity.Gender,age,disease duration,presence of fever,atelectasis,pneumothorax,interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),and interleukin-17D were selected as independent variables.Statistical software SPSS 22.00 was used for univariate analysis,and variables with statistical significance in the univariate analysis were included in a multivariate logistic regression analysis to determine the correlation between IL-17D and the severity of severe pneumonia.Results:The results of this study showed that the level of IL-17D in patients with severe pneumonia was significantly higher than the normal threshold.Univariate analysis indicated that atelectasis,IL-2,IL-6,and IL-17D were statistically significant(P<0.05)and could be considered as influencing factors for the severity of severe pneumonia.Multivariate logistic regression analysis revealed that atelectasis(OR=2.141,95%CI:1.684–2.391),IL-2(OR=2.884,95%CI:2.240–3.614),IL-6(OR=2.571,95%CI:2.190–2.943),and IL-17D(OR=2.416,95%CI:2.093–2.735)were positively correlated with the severity of severe pneumonia.Conclusion:The expression level of IL-17D in the serum of patients with severe pneumonia is higher than the normal threshold and is positively correlated with disease severity.展开更多
BACKGROUND Depression,anxiety,and insomnia were found out that were significant relevance to the mental health impact of the coronavirus disease 2019(COVID-19)lock-down.AIM To examine the interrelationships among perc...BACKGROUND Depression,anxiety,and insomnia were found out that were significant relevance to the mental health impact of the coronavirus disease 2019(COVID-19)lock-down.AIM To examine the interrelationships among perceived severity,anxiety,depression,insomnia,and sense of security in Chinese community residents during the COVID-19 lockdown period.METHODS Participants were selected using simple random sampling from four large gated communities in Chengdu,China.All participants were invited to complete a survey that included the Perceived Severity Questionnaire,Security Question-naire,Patient Health Questionnaire-9,Generalized Anxiety Disorder 7-item,and Insomnia Severity Index-7.In total,568 valid questionnaires were gathered.Co-rrelation analysis and structural equation models were used to explore the rela-RESULTS The observed prevalence rates of anxiety,depression,and insomnia among residents during lockdown were 27.5%,17.6%,and 16.0%,respectively.Correlation analysis showed that both perceived severity and sense of security were positively correlated with anxiety,depression,and insomnia[Pearson’s r was perceived severity and anxiety r=0.44(P<0.01);with depression r=0.48(P<0.01);with insomnia r=0.43(P<0.01);security with anxiety r=-0.65(P<0.01);with depression r=-0.65(P<0.01);with insomnia r=-0.53(P<0.01)].Structural equation modeling and bootstrap tests revealed that sense of security acted as a significant mediator in the relationship between perceived severity and emotional and sleep disorders(anxiety,depression,and insomnia).CONCLUSION This study demonstrates that sense of security is a significant predictor of emotional and sleep disorders(namely,depression,anxiety,and insomnia)among residents during the COVID-19 lockdown,with sense of security acting as a mediating factor.These findings suggest that mental health interventions for Chinese community residents during lockdowns may benefit from developing community-based educational programs to reduce perceived severity and ensuring the stable supply of essential resources and promoting social support networks to enhance the sense of security.展开更多
Objective:To assess whether there is a correlation between CT scan severity score and pulmonary function in Interstitial Lung Disease,and provide a more reliable basis for clinical diagnosis and treatment.Materials an...Objective:To assess whether there is a correlation between CT scan severity score and pulmonary function in Interstitial Lung Disease,and provide a more reliable basis for clinical diagnosis and treatment.Materials and Methods:Sixty patients with clinical diagnosis of Interstitial Lung Disease(ILD)were collected,and chest CT and pulmonary function tests were performed at the same time.Here DLCO%and FEV1%were used as the pulmonary function indexes.The severity of the patients was assessed by CT scores as mild(range,1~10),moderate(range 11~20),and severe(range 21~30).Correlation analysis was carried out between CT score and pulmonary function index,and the lung function parameters of patients at three grades were compared between groups and pairwise among the means.Results:As per the CT severity classification,there were 13 mild cases,31 moderate cases,and 16 severe cases.CT score was negatively correlated with DLCO%and FEV1%.R value was-0.814 and-0.797,respectively;The comparison of the mean value of DLCO%and FEV1%among the three groups and the pairings of the mean value of DLCO%and FEV1%were statistically significant.Conclusion:There was good correlation between CT score of ILD and the pulmonary function index.The pulmonary function index of patients with different CT severity grading was statistically significant,which can provide a new basis for the clinical evaluation and diagnosis of the disease.展开更多
A recent single-center retrospective study proposed novel combinations of hematological parameters and scoring systems for predicting severe acute pancre-atitis.While these combinations showed promising predictive per...A recent single-center retrospective study proposed novel combinations of hematological parameters and scoring systems for predicting severe acute pancre-atitis.While these combinations showed promising predictive performance,several limitations warrant consideration,including the lack of calibration,the absence of key inflammatory markers such as procalcitonin,and practical challenges in integrating these models into routine clinical workflows.To improve predictive accuracy and clinical applicability,prospective validation and the inclusion of additional variables are recommended.展开更多
Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019(COVID19).In older individuals,a dysregulated immune response to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2...Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019(COVID19).In older individuals,a dysregulated immune response to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection contributes to disease severity;however,the underlying mechanism remains elusive.In this study,we established an aging mouse model of COVID-19,successfully replicating the development of a relatively severe disease in older adults.Further single-cell transcriptome analysis revealed a distinct immune cell landscape in the infected lungs,accompanied by an over-activated inflammatory response,especially in aging mice.Compared to young mice,aging mice showed extensive neutrophil activation,NETosis,and a dramatic decrease in the number of alveolar macrophages(AMs).Moreover,as important executors of efferocytosis,AMs exhibited a low efferocytotic gene signature and downregulation of multiple efferocytosis receptors in aged mice.Further analysis indicated that the efferocytosis of neutrophils,whether undergoing apoptosis or NETosis,was compromised after SARS-CoV-2 infection.Since efferocytosis is a key process in inflammatory resolution,impaired efferocytosis may contribute to hyperinflammation in aging lungs.Our study reveals the characteristics and role of efferocytosis in aging mice after SARS-CoV-2 infection and provides valuable insights for the potential treatment of COVID-19.展开更多
Soil liquefaction,a seismic-induced phenomenon,is of significant concern in geotechnical engineering due to its potential to cause severe structural damage and ground instability during earthquakes.This study explores...Soil liquefaction,a seismic-induced phenomenon,is of significant concern in geotechnical engineering due to its potential to cause severe structural damage and ground instability during earthquakes.This study explores the prediction of the Liquefaction Severity Index(LSI)by integrating extensive borehole investigation data with seismic records from the Kahramanmara?(M_(w)7.8)and Hatay(M_(w)6.4)earthquakes that occurred in 2023.Nine machine learning models,Random Forest(RF),M5P,REPTree,IBk,Random Tree(RT),Gaussian Processes(GP),SMOreg,Locally Weighted Learning(LWL),and Linear Regression(LR),were employed with 10-fold cross-validation to ensure reliable predictions.Twelve geotechnical and seismic parameters,groundwater level,earthquake magnitude,peak ground acceleration,V_(s30),dominant frequency,dominant period,longitudinal wave velocity,dynamic modulus of elasticity,dynamic shear modulus,modulus of incompressibility,standard penetration test(SPT)values,and cyclic stress ratio(CSR)values,were utilized as inputs.The analysis results were evaluated with respect to RMSE,MAE,R2,RAE,P/M,error category limits,Taylor diagram,and relative importance of input parameters.Among the models,Random Forest outperformed with an R2 of 0.94,MAE of 2.35,with minimal prediction errors,followed by M5P and REPTree.Error analysis indicated that 80%of Random Forest and REPTree predictions fell within±7,while M5P showed slightly higher variability.Model-based feature ranking demonstrated that Cyclic Stress Ratio(CSR),Ground Water Level(GWL),and Standard Penetration Test(SPT)value emerged as dominant predictors.These findings highlight the study’s contribution to developing a reliable,datadriven framework for LSI prediction,offering a robust basis for improving site-specific liquefaction risk assessment and informed geotechnical decisionmaking in future seismic events.展开更多
This study examines the interaction between emotional states(anxiety and depression)and tinnitus severity in individuals undergoing a four-month sound therapy intervention.43 participants(28 males and 15 females)of a ...This study examines the interaction between emotional states(anxiety and depression)and tinnitus severity in individuals undergoing a four-month sound therapy intervention.43 participants(28 males and 15 females)of a study on four-month sound therapy of tinnitus were recruited and their tinnitus severity(Tinnitus Handicap Inventory,THI,and Tinnitus Functional Index,TFI)and emotional state(Hospitalary Anxiety and Depression Scale,HADS)were assessed before and after finishing the treatment.The participants,predominantly with moderate tinnitus,showed a significant reduction in tinnitus-related distress,with a mean reduction of approximately 30 points on both the THI and the TFI.Analysis revealed significant gender differences,with women experiencing higher baseline tinnitus distress but higher response to sound therapy.Emotional state assessments revealed moderate levels of anxiety and depression at baseline,which decreased significantly after therapy,particularly in women.Correlational analyses revealed a strong relationship between changes in emotional state and tinnitus severity,with reductions in anxiety and depression associated with improved tinnitus outcomes.The results highlight the complex relationship between emotional well-being and tinnitus severity and underline the potential of sound therapy to alleviate both emotional distress and tinnitus symptoms.展开更多
BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as ...BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.展开更多
In this editorial,we critically evaluate the recent article by Niu et al,which ex-plores the potential of phospholipase D2(PLD2)as a biomarker for stratifying disease severity in acute pancreatitis(AP).AP is a clinica...In this editorial,we critically evaluate the recent article by Niu et al,which ex-plores the potential of phospholipase D2(PLD2)as a biomarker for stratifying disease severity in acute pancreatitis(AP).AP is a clinically heterogeneous inflam-matory condition that requires reliable biomarkers for early and accurate classi-fication of disease severity.PLD2,an essential regulator of neutrophil migration and inflammatory responses,has emerged as a promising candidate.Although current biomarkers such as C-reactive protein and procalcitonin provide general indications of inflammation,they lack specificity regarding the molecular mechanisms underlying AP progression.Recent studies,including the research conducted by Niu et al,suggest an inverse correlation between PLD2 expression and AP severity,offering both diagnostic insights and mechanistic understanding.This editorial critically evaluates the role of PLD2 as a biomarker in the broader context of AP research.Evidence indicates that decreased levels of PLD2 are associated with increased neutrophil chemotaxis and cytokine release,con-tributing to pancreatic and systemic inflammation.However,several challenges remain,including the need for large-scale validation and functional studies to establish causation,and standardization of measurement protocols.Additionally,further investigation into the temporal dynamics of PLD2 expression and its variability across diverse populations is warranted.Looking ahead,PLD2 holds the potential to revolutionize AP management by integrating molecular diagnostics with precision medicine.The utilization of large-scale multi-omics approaches and advancements in diagnostic platforms could position PLD2 as a fundamental biomarker for early diagnosis,prognosis,and potentially therapeutic targeting.While promising,it is crucial to conduct critical evaluations and rigorous validations of PLD2’s role to ensure its efficacy in improving patient outcomes.展开更多
Objective:To investigate the value of dynamic monitoring of serum interleukin(IL)-33 and tumor necrosis factor(TNF)-αlevels in the early diagnosis,severity assessment and prognosis of acute pancreatitis(AP)combined w...Objective:To investigate the value of dynamic monitoring of serum interleukin(IL)-33 and tumor necrosis factor(TNF)-αlevels in the early diagnosis,severity assessment and prognosis of acute pancreatitis(AP)combined with abdominal CT radiomics and intestinal microbiota data.Methods:A total of 170 AP patients were admitted immediately after the onset of the disease and divided into MAP group(85 cases)and SAP group(85 cases).The levels of serum IL-33,TNF-α,IL-6,and HMGB1,as well as the expression of miRNA-155 in extracellular vesicles(EVs),were dynamically monitored at multiple time points(0 h,6 h,12 h,24 h,3 d,5 d,7 d,14 d)after admission.Abdominal CT radiomics analyzed the texture characteristics of pancreatic necrosis,and stool samples collected at admission were metagenomic sequencing of the gut microbiome.The Acute Pancreatitis Severity Bedside Index(BISAP)score is calculated within 48 hours of admission.Multivariate regression analysis assessed the independent effects of various factors on the prognosis of mortality groups.Results:Serum IL-33 and TNF-αlevels in SAP patients were significantly higher than those in MAP patients(p<0.05)at all time points,peaked on day 3,and decreased with treatment.The levels of these cytokines in patients with SIRS were also higher than in patients without SIRS(p<0.05).The serum IL-33,TNF-αlevels and BISAP scores in the mortality group were higher than those in the survival group(p<0.05).Multivariate regression analysis showed that serum IL-33(OR=3.21,95%CI:1.12–9.23,p=0.03),TNF-α(OR=4.05,95%CI:1.37–11.96,p=0.01),and BISAP score(OR=5.67,95%CI:1.83–17.54,p<0.01)were independent prognostic risk factors.Spearman correlation analysis showed that serum IL-33 and TNF-αlevels were positively correlated with BISAP scores(r=0.68,p<0.01;r=0.73,p<0.01).Conclusion:Dynamic monitoring of serum IL-33 and TNF-αlevels combined with BISAP score has important clinical value for early diagnosis,severity assessment,treatment guidance and prognosis evaluation of AP,and provides a basis for accurate diagnosis and treatment.展开更多
Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic ce...Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic cells in disc degeneration has been reported,yet their nature and origin remain elusive.In this study,we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.We found that disc degeneration severity is associated with an enrichment of fibrocyte phenotype,characterized by CD45 and collagen I dual positivity,and expression of myofibroblast markerα-smooth muscle actin.Refined clustering and classification distinguished the fibrocyte-like populations as subtypes in the NP cells-and immunocytes-clusters,expressing disc degeneration markers HTRA1 and ANGPTL4 and genes related to response to TGF-β.In injury-induced mouse disc degeneration model,fibrocytes were found recruited into the NP undergoing fibrosis and adopted a myofibroblast phenotype.Depleting the fibrocytes in CD11b-DTR mice in which myeloid-derived lineages were ablated by diphtheria toxin could markedly attenuate fibrous modeling and myofibroblast formation in the NP of the degenerative discs,and prevent disc height loss and histomorphological abnormalities.Marker analysis supports that disc degeneration progression is dependent on a function of CD45^(+)COL1A1^(+)andαSMA^(+)cells.Our findings reveal that myeloid-derived fibrocytes play a pivotal role in NP fibrosis and may therefore be a target for modifying disc degeneration and promoting its repair.展开更多
Distinguishing the severity of burned skin from structural optical coherence tomography(OCT)intensity maps remains a challenging task,and functional imaging from an elastic perspective can improve the accuracy of burn...Distinguishing the severity of burned skin from structural optical coherence tomography(OCT)intensity maps remains a challenging task,and functional imaging from an elastic perspective can improve the accuracy of burned skin examination.As a functional extension of OCT,optical coherence elastography(OCE)can reveal the mechanical properties of samples while inheriting the imaging advantages of OCT.In this study,we used OCE to reveal the shear modulus and anisotropy parameters of burned skin before and after burning.A porcine skin burn model was constructed at a series of burned time durations and tested by elastic anisotropy imaging.Normal skin after hydration maintains good consistency in shear modulus.Interestingly,the shear modulus and longitudinal modulus of the burned skin show a tendency to stepwise increase with increasing burned times.A dataset was constructed by sampling the modulus parameters of burned skin maps through a scratch window,and its category was automatically identi¯ed by Kmeans and density peak clustering(DPC)algorithms with good agreement.The elastic anisotropy-based skin burn assessment method shows a prospect to be supplemented into the nondestructive means of burned skin examination.展开更多
BACKGROUND: Although pneumonia severity index(PSI) is widely used to evaluate the severity of community-acquired pneumonia(CAP), the calculation of PSI is very complicated. The present study aimed to evaluate the role...BACKGROUND: Although pneumonia severity index(PSI) is widely used to evaluate the severity of community-acquired pneumonia(CAP), the calculation of PSI is very complicated. The present study aimed to evaluate the role of B-type natriuretic peptide(BNP) in predicting the severity of CAP.METHODS: For 202 patients with CAP admitted to the emergency department, BNP levels, cardiac load indexes, inf lammatory indexes including C-reactive protein(CRP), white blood cell count(WBC), and PSI were detected. The correlation between the indexes and PSI was investigated. BNP levels for survivor and non-survivor groups were compared, and a receiver operating characteristic(ROC) curve analysis was performed on the BNP levels versus PSI.RESULTS: The BNP levels increased with CAP severity(r=0.782, P<0.001). The BNP levels of the high-risk group(PSI classes IV and V) were signifi cantly higher than those of the low-risk group(PSI classes I–III)(P<0.001). The BNP levels were signifi cantly higher in the non-survivor group than in the survivor group(P<0.001). In addition, there were positive correlations between BNP levels and PSI scores(r=0.782, P<0.001). The BNP level was highly accurate in predicting the severity of CAP(AUC=0.952). The optimal cut-off point of BNP level for distinguishing high-risk patients from low-risk ones was 125.0 pg/m L, with a sensitivity of 0.891 and a specifi city of 0.946. Moreover, BNP level was accurate in predicting mortality(AUC=0.823). Its optimal cut-off point for predicting death was 299.0 pg/m L, with a sensitivity of 0.675 and a specifi city of 0.816. Its negative predictive cut-off value was 0.926, and the positive predictive cut-off value was 0.426.CONCLUSION: BNP level is positively correlated with the severity of CAP, and may be used as a biomarker for evaluating the severity of CAP.展开更多
BACKGROUND Acute pancreatitis(AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and...BACKGROUND Acute pancreatitis(AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and death. However, scoring systems are complicated and time consuming, and the predictive values for the clinical course are vague.AIM To determine whether the dynamic changes in presepsin levels can be used to evaluate the severity of disease and outcome of AP.METHODS In this multicentric cohort study, 133 patients with AP were included. Clinical severity was dynamically evaluated using the 2012 revised Atlanta Classification. Blood presepsin levels were measured at days 1, 3, 5 and 7 after admission by chemiluminescent enzyme immunoassay.RESULTS The median concentration of presepsin increased and the clearance rate of presepsin decreased with disease severity and organ failure in AP patients. The presepsin levels on days 3, 5 and 7 were independent predictors of moderately severe and severe AP with time-specific area under the curve(AUC) values of 0.827, 0.848 and 0.867, respectively. The presepsin levels positively correlated with bedside index of severity in AP, Ranson, acute physiology and chronic health evaluation II, computed tomography severity index and Marshall scores. Presepsin levels on days 3, 5 and 7 were independent predictors of 28-d mortality of AP patients with AUC values of 0.781, 0.846 and 0.843, respectively.CONCLUSION Blood presepsin levels within 7 d of admission were associated with and may be useful to dynamically predict the severity of disease course and 28-d mortality in AP patients.展开更多
A spatial analysis of drought characteristics in the Limpopo basin is undertaken to evaluate its regional implications to water management challenges. In this study, drought duration, frequency and severity are invest...A spatial analysis of drought characteristics in the Limpopo basin is undertaken to evaluate its regional implications to water management challenges. In this study, drought duration, frequency and severity are investigated. In addition drought Severity-Area-Frequency (SAF) curves were constructed. The entire Limpopo River Basin is subdivided into four homogeneous regions based on topographic and climate variations in the basin, which was constructed with the K-Means Clustering algorithm. Using the medium range time series of the Standardized Precipitation Index (SPI) as an indicator of drought for each homogeneous region, monthly and annual SAF curves and maps of probability of drought occurrence were produced. The results indicated localized severe droughts in higher frequencies compared to moderate to severe low frequency droughts spread over wider areas in the basin. The approach can be used to develop improved drought indicators to assess the relationship between drought hazard and vulnerability and to enhance the performance of methods currently used for drought forecasting. In general, this preliminary investigation reveals that the western part of the basin will face a higher risk of drought when compared to other regions of the Limpopo Basin in terms of the medium-term drought patterns. The Limpopo Basin is water stressed and livelihood challenges remain high, thus impacts of droughts and related resilience options should be taken into account in the formulation of regional sustainable water resources development strategies.展开更多
文摘BACKGROUND Acute pancreatitis(AP)is an emergency gastrointestinal disease that requires immediate diagnosis and urgent clinical treatment.An accurate assessment and precise staging of severity are essential in initial intensive therapy.AIM To explore the prognostic value of inflammatory markers and several scoring systems[Acute Physiology and Chronic Health Evaluation II,the bedside index of severity in AP(BISAP),Ranson’s score,the computed tomography severity index(CTSI)and sequential organ failure assessment]in severity stratification of earlyphase AP.METHODS A total of 463 patients with AP admitted to our hospital between 1 January 2021 and 30 June 2024 were retrospectively enrolled in this study.Inflammation marker and scoring system levels were calculated and compared between different severity groups.Relationships between severity and several predictors were evaluated using univariate and multivariate logistic regression models.Predictive ability was estimated using receiver operating characteristic curves.RESULTS Of the 463 patients,50(10.80%)were classified as having severe AP(SAP).The results revealed that the white cell count significantly increased,whereas the prognostic nutritional index measured within 48 hours(PNI48)and calcium(Ca^(2+))were decreased as the severity of AP increased(P<0.001).According to multivariate logistic regression,C-reactive protein measured within 48 hours(CRP_(48)),Ca^(2+)levels,and PNI48 were independent risk factors for predicting SAP.The area under the curve(AUC)values for the CRP_(48),Ca^(2+),PNI48,Acute Physiology and Chronic Health Evaluation II,sequential organ failure assessment,BISAP,CTSI,and Ranson scores for the prediction of SAP were 0.802,0.736,0.871,0.799,0.783,0.895,0.931 and 0.914,respectively.The AUC for the combined CRP_(48)+Ca^(2+)+PNI48 model was 0.892.The combination of PNI48 and Ranson achieved an AUC of 0.936.CONCLUSION Independent risk factors for developing SAP include CRP_(48),Ca^(2+),and PNI48.CTSI,BISAP,and the combination of PNI48 and the Ranson score can act as reliable predictors of SAP.
文摘BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.
基金supported by grants from the National Key R&D Program of China(2021YFA1301001)the Natural Science Founda-tion of China(82170668)+1 种基金the Sino-German Center for Research Promotion(GZ1546)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-045).
文摘Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe COVID-19.But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.Methods:We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 pa-tients upon admission and one-month after their discharge,comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.Results:Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients.These altered microbial metabolites included tryptophan,bile acids,fatty acids,amino acids,vitamins and those containing benzene.A total of 13 distinct microbial metabolites were identi-fied in COVID-19 patients compared to healthy controls.Notably,correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19.Furthermore,these metabolites did not restore to the normal levels one month after discharge.Importantly,two mi-crobial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.Conclusions:The microbial metabolites were altered in the acute and recovery stage,correlating with dis-ease severity of COVID-19.These results indicated the important role of gut microbiota in the progression of COVID-19,and facilitated the potential therapeutic microbial target for severe COVID-19 patients.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for assessing this risk.In Gabon,early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19.This study hypothesizes that elevated Ddimer levels are linked to increased COVID-19 severity.AIM To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions.METHODS This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023.The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission.Data on demographics,clinical outcomes,D-dimer levels,and healthcare costs were collected.COVID-19 severity was classified as non-severe(outpatients)or severe(inpatients).A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity,with adjusted odds ratios(OR)and 95%CI.RESULTS A total of 3004 patients were included,with a mean age of 50.17 years,and the majority were female(53.43%).Elevated D-dimer levels were found in 65.81%of patients,and 57.21%of these experienced severe COVID-19.Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19(OR=3.33,95%CI:2.84-3.92,P<0.001),and this association remained significant in the multivariable analysis,adjusted for age,sex,and year of collection.The financial analysis revealed a substantial burden,particularly for uninsured patients.CONCLUSION D-dimer predicts COVID-19 severity and guides treatment,but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.
文摘Acute pancreatitis(AP)is a complex and potentially life-threatening inflammatory condition with a highly variable clinical course,ranging from mild,selflimiting episodes to severe necrotizing forms.Among its common complications ascites has traditionally been viewed as a passive byproduct of peritoneal inflammation and enzymatic leakage with limited diagnostic or prognostic utility.However,growing evidence challenges this perspective,suggesting that ascitic fluid in AP represents a dynamic and clinically meaningful component of disease progression.In this editorial we reflected on the findings presented by Rao et al,who highlighted the diagnostic,prognostic,and therapeutic significance of ascitic fluid in AP.Easily accessible markers such as lactate dehydrogenase may provide early prognostic insight while emerging molecular biomarkers and cytokine pro-files offer promise for more precise risk stratification and individualized therapy.We argue that the systematic evaluation of ascitic fluid should be integrated into the clinical management of moderate to severe AP.Incorporating ascites analysis into standard diagnostic protocols may enhance early risk assessment,inform therapeutic decisions,and ultimately improve patient outcomes.Ascitic fluid should be recognized as a clinically valuable marker and an important source of information in the evolving landscape of AP care.
基金Chongqing Shapingba District Technology Innovation Project(Project No.:2024046)。
文摘Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneumonia who were diagnosed and treated in the hospital from May 2024 to May 2025.The expression level of IL-17D in the serum of all patients was recorded.Patients were divided into severe and mild groups based on their disease severity.Gender,age,disease duration,presence of fever,atelectasis,pneumothorax,interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),and interleukin-17D were selected as independent variables.Statistical software SPSS 22.00 was used for univariate analysis,and variables with statistical significance in the univariate analysis were included in a multivariate logistic regression analysis to determine the correlation between IL-17D and the severity of severe pneumonia.Results:The results of this study showed that the level of IL-17D in patients with severe pneumonia was significantly higher than the normal threshold.Univariate analysis indicated that atelectasis,IL-2,IL-6,and IL-17D were statistically significant(P<0.05)and could be considered as influencing factors for the severity of severe pneumonia.Multivariate logistic regression analysis revealed that atelectasis(OR=2.141,95%CI:1.684–2.391),IL-2(OR=2.884,95%CI:2.240–3.614),IL-6(OR=2.571,95%CI:2.190–2.943),and IL-17D(OR=2.416,95%CI:2.093–2.735)were positively correlated with the severity of severe pneumonia.Conclusion:The expression level of IL-17D in the serum of patients with severe pneumonia is higher than the normal threshold and is positively correlated with disease severity.
基金Supported by Young Talent Project of Air Force Medical Center,No.2022YXQN008and Rapid Response Project of Air Force Medical University,No.2023KXKT041.
文摘BACKGROUND Depression,anxiety,and insomnia were found out that were significant relevance to the mental health impact of the coronavirus disease 2019(COVID-19)lock-down.AIM To examine the interrelationships among perceived severity,anxiety,depression,insomnia,and sense of security in Chinese community residents during the COVID-19 lockdown period.METHODS Participants were selected using simple random sampling from four large gated communities in Chengdu,China.All participants were invited to complete a survey that included the Perceived Severity Questionnaire,Security Question-naire,Patient Health Questionnaire-9,Generalized Anxiety Disorder 7-item,and Insomnia Severity Index-7.In total,568 valid questionnaires were gathered.Co-rrelation analysis and structural equation models were used to explore the rela-RESULTS The observed prevalence rates of anxiety,depression,and insomnia among residents during lockdown were 27.5%,17.6%,and 16.0%,respectively.Correlation analysis showed that both perceived severity and sense of security were positively correlated with anxiety,depression,and insomnia[Pearson’s r was perceived severity and anxiety r=0.44(P<0.01);with depression r=0.48(P<0.01);with insomnia r=0.43(P<0.01);security with anxiety r=-0.65(P<0.01);with depression r=-0.65(P<0.01);with insomnia r=-0.53(P<0.01)].Structural equation modeling and bootstrap tests revealed that sense of security acted as a significant mediator in the relationship between perceived severity and emotional and sleep disorders(anxiety,depression,and insomnia).CONCLUSION This study demonstrates that sense of security is a significant predictor of emotional and sleep disorders(namely,depression,anxiety,and insomnia)among residents during the COVID-19 lockdown,with sense of security acting as a mediating factor.These findings suggest that mental health interventions for Chinese community residents during lockdowns may benefit from developing community-based educational programs to reduce perceived severity and ensuring the stable supply of essential resources and promoting social support networks to enhance the sense of security.
基金providing by the Shenzhen City Nanshan District Science and Technology Plan Project(Medical and Health Category)(Grant No.2018073)。
文摘Objective:To assess whether there is a correlation between CT scan severity score and pulmonary function in Interstitial Lung Disease,and provide a more reliable basis for clinical diagnosis and treatment.Materials and Methods:Sixty patients with clinical diagnosis of Interstitial Lung Disease(ILD)were collected,and chest CT and pulmonary function tests were performed at the same time.Here DLCO%and FEV1%were used as the pulmonary function indexes.The severity of the patients was assessed by CT scores as mild(range,1~10),moderate(range 11~20),and severe(range 21~30).Correlation analysis was carried out between CT score and pulmonary function index,and the lung function parameters of patients at three grades were compared between groups and pairwise among the means.Results:As per the CT severity classification,there were 13 mild cases,31 moderate cases,and 16 severe cases.CT score was negatively correlated with DLCO%and FEV1%.R value was-0.814 and-0.797,respectively;The comparison of the mean value of DLCO%and FEV1%among the three groups and the pairings of the mean value of DLCO%and FEV1%were statistically significant.Conclusion:There was good correlation between CT score of ILD and the pulmonary function index.The pulmonary function index of patients with different CT severity grading was statistically significant,which can provide a new basis for the clinical evaluation and diagnosis of the disease.
文摘A recent single-center retrospective study proposed novel combinations of hematological parameters and scoring systems for predicting severe acute pancre-atitis.While these combinations showed promising predictive performance,several limitations warrant consideration,including the lack of calibration,the absence of key inflammatory markers such as procalcitonin,and practical challenges in integrating these models into routine clinical workflows.To improve predictive accuracy and clinical applicability,prospective validation and the inclusion of additional variables are recommended.
基金supported by the National Key Research and Development Program of China(NKPs)(2022YFC2604101).
文摘Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019(COVID19).In older individuals,a dysregulated immune response to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection contributes to disease severity;however,the underlying mechanism remains elusive.In this study,we established an aging mouse model of COVID-19,successfully replicating the development of a relatively severe disease in older adults.Further single-cell transcriptome analysis revealed a distinct immune cell landscape in the infected lungs,accompanied by an over-activated inflammatory response,especially in aging mice.Compared to young mice,aging mice showed extensive neutrophil activation,NETosis,and a dramatic decrease in the number of alveolar macrophages(AMs).Moreover,as important executors of efferocytosis,AMs exhibited a low efferocytotic gene signature and downregulation of multiple efferocytosis receptors in aged mice.Further analysis indicated that the efferocytosis of neutrophils,whether undergoing apoptosis or NETosis,was compromised after SARS-CoV-2 infection.Since efferocytosis is a key process in inflammatory resolution,impaired efferocytosis may contribute to hyperinflammation in aging lungs.Our study reveals the characteristics and role of efferocytosis in aging mice after SARS-CoV-2 infection and provides valuable insights for the potential treatment of COVID-19.
基金supported by Osmaniye Korkut Ata University Scientific Research Projects Unit(Project No:OKüBAP-2024-PT1-015)。
文摘Soil liquefaction,a seismic-induced phenomenon,is of significant concern in geotechnical engineering due to its potential to cause severe structural damage and ground instability during earthquakes.This study explores the prediction of the Liquefaction Severity Index(LSI)by integrating extensive borehole investigation data with seismic records from the Kahramanmara?(M_(w)7.8)and Hatay(M_(w)6.4)earthquakes that occurred in 2023.Nine machine learning models,Random Forest(RF),M5P,REPTree,IBk,Random Tree(RT),Gaussian Processes(GP),SMOreg,Locally Weighted Learning(LWL),and Linear Regression(LR),were employed with 10-fold cross-validation to ensure reliable predictions.Twelve geotechnical and seismic parameters,groundwater level,earthquake magnitude,peak ground acceleration,V_(s30),dominant frequency,dominant period,longitudinal wave velocity,dynamic modulus of elasticity,dynamic shear modulus,modulus of incompressibility,standard penetration test(SPT)values,and cyclic stress ratio(CSR)values,were utilized as inputs.The analysis results were evaluated with respect to RMSE,MAE,R2,RAE,P/M,error category limits,Taylor diagram,and relative importance of input parameters.Among the models,Random Forest outperformed with an R2 of 0.94,MAE of 2.35,with minimal prediction errors,followed by M5P and REPTree.Error analysis indicated that 80%of Random Forest and REPTree predictions fell within±7,while M5P showed slightly higher variability.Model-based feature ranking demonstrated that Cyclic Stress Ratio(CSR),Ground Water Level(GWL),and Standard Penetration Test(SPT)value emerged as dominant predictors.These findings highlight the study’s contribution to developing a reliable,datadriven framework for LSI prediction,offering a robust basis for improving site-specific liquefaction risk assessment and informed geotechnical decisionmaking in future seismic events.
文摘This study examines the interaction between emotional states(anxiety and depression)and tinnitus severity in individuals undergoing a four-month sound therapy intervention.43 participants(28 males and 15 females)of a study on four-month sound therapy of tinnitus were recruited and their tinnitus severity(Tinnitus Handicap Inventory,THI,and Tinnitus Functional Index,TFI)and emotional state(Hospitalary Anxiety and Depression Scale,HADS)were assessed before and after finishing the treatment.The participants,predominantly with moderate tinnitus,showed a significant reduction in tinnitus-related distress,with a mean reduction of approximately 30 points on both the THI and the TFI.Analysis revealed significant gender differences,with women experiencing higher baseline tinnitus distress but higher response to sound therapy.Emotional state assessments revealed moderate levels of anxiety and depression at baseline,which decreased significantly after therapy,particularly in women.Correlational analyses revealed a strong relationship between changes in emotional state and tinnitus severity,with reductions in anxiety and depression associated with improved tinnitus outcomes.The results highlight the complex relationship between emotional well-being and tinnitus severity and underline the potential of sound therapy to alleviate both emotional distress and tinnitus symptoms.
基金Supported by the National Key Research and Development Program of China,No.2024YFC2707801the Science and Technology Innovation Commission of Shenzhen,No.JCYJ20230807143800002.
文摘BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.
基金Supported by National Natural Sciences Foundation of China,No.82301700Liaoning Province Natural Science Foundation Project,No.2024-MS-157+2 种基金Youth Talent Cultivation Fund Key Project of Dalian Medical UniversityScientific Research Projects from Wuhan Municipal Health Commission,No.WX23Z26Science and Technology of Liaoning Province,No.2023-MS-266.
文摘In this editorial,we critically evaluate the recent article by Niu et al,which ex-plores the potential of phospholipase D2(PLD2)as a biomarker for stratifying disease severity in acute pancreatitis(AP).AP is a clinically heterogeneous inflam-matory condition that requires reliable biomarkers for early and accurate classi-fication of disease severity.PLD2,an essential regulator of neutrophil migration and inflammatory responses,has emerged as a promising candidate.Although current biomarkers such as C-reactive protein and procalcitonin provide general indications of inflammation,they lack specificity regarding the molecular mechanisms underlying AP progression.Recent studies,including the research conducted by Niu et al,suggest an inverse correlation between PLD2 expression and AP severity,offering both diagnostic insights and mechanistic understanding.This editorial critically evaluates the role of PLD2 as a biomarker in the broader context of AP research.Evidence indicates that decreased levels of PLD2 are associated with increased neutrophil chemotaxis and cytokine release,con-tributing to pancreatic and systemic inflammation.However,several challenges remain,including the need for large-scale validation and functional studies to establish causation,and standardization of measurement protocols.Additionally,further investigation into the temporal dynamics of PLD2 expression and its variability across diverse populations is warranted.Looking ahead,PLD2 holds the potential to revolutionize AP management by integrating molecular diagnostics with precision medicine.The utilization of large-scale multi-omics approaches and advancements in diagnostic platforms could position PLD2 as a fundamental biomarker for early diagnosis,prognosis,and potentially therapeutic targeting.While promising,it is crucial to conduct critical evaluations and rigorous validations of PLD2’s role to ensure its efficacy in improving patient outcomes.
文摘Objective:To investigate the value of dynamic monitoring of serum interleukin(IL)-33 and tumor necrosis factor(TNF)-αlevels in the early diagnosis,severity assessment and prognosis of acute pancreatitis(AP)combined with abdominal CT radiomics and intestinal microbiota data.Methods:A total of 170 AP patients were admitted immediately after the onset of the disease and divided into MAP group(85 cases)and SAP group(85 cases).The levels of serum IL-33,TNF-α,IL-6,and HMGB1,as well as the expression of miRNA-155 in extracellular vesicles(EVs),were dynamically monitored at multiple time points(0 h,6 h,12 h,24 h,3 d,5 d,7 d,14 d)after admission.Abdominal CT radiomics analyzed the texture characteristics of pancreatic necrosis,and stool samples collected at admission were metagenomic sequencing of the gut microbiome.The Acute Pancreatitis Severity Bedside Index(BISAP)score is calculated within 48 hours of admission.Multivariate regression analysis assessed the independent effects of various factors on the prognosis of mortality groups.Results:Serum IL-33 and TNF-αlevels in SAP patients were significantly higher than those in MAP patients(p<0.05)at all time points,peaked on day 3,and decreased with treatment.The levels of these cytokines in patients with SIRS were also higher than in patients without SIRS(p<0.05).The serum IL-33,TNF-αlevels and BISAP scores in the mortality group were higher than those in the survival group(p<0.05).Multivariate regression analysis showed that serum IL-33(OR=3.21,95%CI:1.12–9.23,p=0.03),TNF-α(OR=4.05,95%CI:1.37–11.96,p=0.01),and BISAP score(OR=5.67,95%CI:1.83–17.54,p<0.01)were independent prognostic risk factors.Spearman correlation analysis showed that serum IL-33 and TNF-αlevels were positively correlated with BISAP scores(r=0.68,p<0.01;r=0.73,p<0.01).Conclusion:Dynamic monitoring of serum IL-33 and TNF-αlevels combined with BISAP score has important clinical value for early diagnosis,severity assessment,treatment guidance and prognosis evaluation of AP,and provides a basis for accurate diagnosis and treatment.
基金jointly General Research Fund(17121619)of the Research Grant Council of Hong KongGuangdong Basic and Applied Basic Research Foundation(2024A1515010104 and 2023A1515220095)Scientific Research Foundation of Peking University Shenzhen Hospital(KYQD202100X)。
文摘Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic cells in disc degeneration has been reported,yet their nature and origin remain elusive.In this study,we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.We found that disc degeneration severity is associated with an enrichment of fibrocyte phenotype,characterized by CD45 and collagen I dual positivity,and expression of myofibroblast markerα-smooth muscle actin.Refined clustering and classification distinguished the fibrocyte-like populations as subtypes in the NP cells-and immunocytes-clusters,expressing disc degeneration markers HTRA1 and ANGPTL4 and genes related to response to TGF-β.In injury-induced mouse disc degeneration model,fibrocytes were found recruited into the NP undergoing fibrosis and adopted a myofibroblast phenotype.Depleting the fibrocytes in CD11b-DTR mice in which myeloid-derived lineages were ablated by diphtheria toxin could markedly attenuate fibrous modeling and myofibroblast formation in the NP of the degenerative discs,and prevent disc height loss and histomorphological abnormalities.Marker analysis supports that disc degeneration progression is dependent on a function of CD45^(+)COL1A1^(+)andαSMA^(+)cells.Our findings reveal that myeloid-derived fibrocytes play a pivotal role in NP fibrosis and may therefore be a target for modifying disc degeneration and promoting its repair.
基金supported by the National Natural Science Foundation of China(Nos.62375144 and 12404345)the Tianjin Foundation of Natural Science(No.22JCZDJC00160)+1 种基金the China Postdoctoral Science Foundation(No.2023M731787)the Fundamental Research Funds for the Central Universities,Nankai University(No.63241331).
文摘Distinguishing the severity of burned skin from structural optical coherence tomography(OCT)intensity maps remains a challenging task,and functional imaging from an elastic perspective can improve the accuracy of burned skin examination.As a functional extension of OCT,optical coherence elastography(OCE)can reveal the mechanical properties of samples while inheriting the imaging advantages of OCT.In this study,we used OCE to reveal the shear modulus and anisotropy parameters of burned skin before and after burning.A porcine skin burn model was constructed at a series of burned time durations and tested by elastic anisotropy imaging.Normal skin after hydration maintains good consistency in shear modulus.Interestingly,the shear modulus and longitudinal modulus of the burned skin show a tendency to stepwise increase with increasing burned times.A dataset was constructed by sampling the modulus parameters of burned skin maps through a scratch window,and its category was automatically identi¯ed by Kmeans and density peak clustering(DPC)algorithms with good agreement.The elastic anisotropy-based skin burn assessment method shows a prospect to be supplemented into the nondestructive means of burned skin examination.
基金supported by a grant from the Excellent Talent Training Special Fund,Xicheng District of Beijing(20110046)
文摘BACKGROUND: Although pneumonia severity index(PSI) is widely used to evaluate the severity of community-acquired pneumonia(CAP), the calculation of PSI is very complicated. The present study aimed to evaluate the role of B-type natriuretic peptide(BNP) in predicting the severity of CAP.METHODS: For 202 patients with CAP admitted to the emergency department, BNP levels, cardiac load indexes, inf lammatory indexes including C-reactive protein(CRP), white blood cell count(WBC), and PSI were detected. The correlation between the indexes and PSI was investigated. BNP levels for survivor and non-survivor groups were compared, and a receiver operating characteristic(ROC) curve analysis was performed on the BNP levels versus PSI.RESULTS: The BNP levels increased with CAP severity(r=0.782, P<0.001). The BNP levels of the high-risk group(PSI classes IV and V) were signifi cantly higher than those of the low-risk group(PSI classes I–III)(P<0.001). The BNP levels were signifi cantly higher in the non-survivor group than in the survivor group(P<0.001). In addition, there were positive correlations between BNP levels and PSI scores(r=0.782, P<0.001). The BNP level was highly accurate in predicting the severity of CAP(AUC=0.952). The optimal cut-off point of BNP level for distinguishing high-risk patients from low-risk ones was 125.0 pg/m L, with a sensitivity of 0.891 and a specifi city of 0.946. Moreover, BNP level was accurate in predicting mortality(AUC=0.823). Its optimal cut-off point for predicting death was 299.0 pg/m L, with a sensitivity of 0.675 and a specifi city of 0.816. Its negative predictive cut-off value was 0.926, and the positive predictive cut-off value was 0.426.CONCLUSION: BNP level is positively correlated with the severity of CAP, and may be used as a biomarker for evaluating the severity of CAP.
基金Supported by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support “Yangfan” Project,No.ZYLX201802Beijing Municipal Administration of Hospitals’ Youth Program,No.QML20170105National Natural Science Foundation of China,No.81374004 and 81773931
文摘BACKGROUND Acute pancreatitis(AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and death. However, scoring systems are complicated and time consuming, and the predictive values for the clinical course are vague.AIM To determine whether the dynamic changes in presepsin levels can be used to evaluate the severity of disease and outcome of AP.METHODS In this multicentric cohort study, 133 patients with AP were included. Clinical severity was dynamically evaluated using the 2012 revised Atlanta Classification. Blood presepsin levels were measured at days 1, 3, 5 and 7 after admission by chemiluminescent enzyme immunoassay.RESULTS The median concentration of presepsin increased and the clearance rate of presepsin decreased with disease severity and organ failure in AP patients. The presepsin levels on days 3, 5 and 7 were independent predictors of moderately severe and severe AP with time-specific area under the curve(AUC) values of 0.827, 0.848 and 0.867, respectively. The presepsin levels positively correlated with bedside index of severity in AP, Ranson, acute physiology and chronic health evaluation II, computed tomography severity index and Marshall scores. Presepsin levels on days 3, 5 and 7 were independent predictors of 28-d mortality of AP patients with AUC values of 0.781, 0.846 and 0.843, respectively.CONCLUSION Blood presepsin levels within 7 d of admission were associated with and may be useful to dynamically predict the severity of disease course and 28-d mortality in AP patients.
文摘A spatial analysis of drought characteristics in the Limpopo basin is undertaken to evaluate its regional implications to water management challenges. In this study, drought duration, frequency and severity are investigated. In addition drought Severity-Area-Frequency (SAF) curves were constructed. The entire Limpopo River Basin is subdivided into four homogeneous regions based on topographic and climate variations in the basin, which was constructed with the K-Means Clustering algorithm. Using the medium range time series of the Standardized Precipitation Index (SPI) as an indicator of drought for each homogeneous region, monthly and annual SAF curves and maps of probability of drought occurrence were produced. The results indicated localized severe droughts in higher frequencies compared to moderate to severe low frequency droughts spread over wider areas in the basin. The approach can be used to develop improved drought indicators to assess the relationship between drought hazard and vulnerability and to enhance the performance of methods currently used for drought forecasting. In general, this preliminary investigation reveals that the western part of the basin will face a higher risk of drought when compared to other regions of the Limpopo Basin in terms of the medium-term drought patterns. The Limpopo Basin is water stressed and livelihood challenges remain high, thus impacts of droughts and related resilience options should be taken into account in the formulation of regional sustainable water resources development strategies.