Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite ou...Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite outgrowth remains unknown.Here,we found that spastin interacted with ubiquitin and was significantly degraded by K48-mediated poly-ubiquitination.Cullin3 facilitated spastin degradation and ubiquitination.RING-box protein 1,but not RING-box protein 2,acted synergistically with Cullin3 protein to regulate spastin degradation.Overexpression of Culin3 or BRX1 markedly suppressed spastin expression,and inhibited spastin-mediated microtubule severing and promotion of neurite outgrowth.Moreover,USP14 interacted directly with spastin to mediate its deubiquitination.USP14 overexpression significantly increased spastin expression and suppressed its ubiquitination and degradation.Although co-expression of spastin and USP14 did not enhance microtubule severing,it did increase neurite length in hippocampal neurons.Taken together,these findings elucidate the intricate regulatory mechanisms of spastin turnover,highlighting the roles of the Cullin-3–Ring E3 ubiquitin ligase complex and USP14 in orchestrating its ubiquitination and degradation.The dynamic interplay between these factors governs spastin stability and function,ultimately influencing microtubule dynamics and neuronal morphology.These insights shed light on potential therapeutic targets for neurodegenerative disorders associated with spastin defects.展开更多
This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to ...This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to age-related immune dysfunction,whereas EEN has been demonstrated to improve clinical prognosis,reduce infection and complication rates,and shor ten hospital stays.However,ongoing debates exist regarding the optimal timing,route selection,and complication management of EEN.Through a systematic review of the literature,this study synthesizes current evidence on EEN in elderly SAP populations,critically examines unresolved clinical controversies,and proposes future research priorities to inform evidence-based practice.展开更多
Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based c...Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based chain rescue is crucial in managing severe trauma.A patient with chest and abdominal injuries and hemorrhagic shock was transferred from an ambulance to our hospital.Our trauma team-initiated pre-hospital first aid,utilized an emergency green channel,and conducted rapid ultrasound,collaborating across disciplines.The patient eventually recovered and was discharged.展开更多
A case of imported severe falciparum malaria with spontaneous splenic rupture was reported in this paper.The patient,an African migrant worker,developed hemolytic anemia,sepsis,thrombocytopenia,coagulation dysfunction...A case of imported severe falciparum malaria with spontaneous splenic rupture was reported in this paper.The patient,an African migrant worker,developed hemolytic anemia,sepsis,thrombocytopenia,coagulation dysfunction,liver failure,renal insufficiency,electrolyte disturbance and other clinical manifestations after returning to the local area.Plasmodium falciparum was found by peripheral blood smearscopy and was diagnosed as severe falciparum malaria.After standardized anti-malaria treatment,plasma exchange+cytokine adsorption therapy,the establishment of“forewarning-forewarning-prevention-emergency”predictive nursing management model,the establishment of an integrated nursing team,the division of medical care is clear,professional knowledge is complementary,after three months of regular follow-up,the patient has no malaria recurrence,no refire,the function of all organs returned to normal.展开更多
Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.S...Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.Standard classification methods fail to address these dual challenges,limiting their real-world performance.In this paper,a novel,three-phase training framework is proposed that learns a robust ordinal classifier directly from noisy labels.The approach synergistically combines a rank-based ordinal regression backbone with a cooperative,semi-supervised learning strategy to dynamically partition the data into clean and noisy subsets.A hybrid training objective is then employed,applying a supervised ordinal loss to the clean set.The noisy set is simultaneously trained using a dualobjective that combines a semi-supervised ordinal loss with a parallel,label-agnostic contrastive loss.This design allows themodel to learn fromthe entire noisy subset while using contrastive learning to mitigate the risk of error propagation frompotentially corrupt supervision.Extensive experiments on a new,large-scale,multi-site clinical dataset validate our approach.Themethod achieves state-of-the-art performance with 80.71%accuracy and a 76.86%F1-score,significantly outperforming existing approaches,including a 2.26%improvement over the strongest baseline method.This work provides not only a robust solution for a practical medical imaging problem but also a generalizable framework for other tasks plagued by noisy ordinal labels.展开更多
Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To over...Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.展开更多
Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is sig...Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.展开更多
Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given th...Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.展开更多
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
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
The clinical treatment of severe trauma withsternoclavicular joint injury is challenging,primarilydue to the irregular shape of the bones surrounding thesternoclavicular joint,as well as the posterior clavicle beingcl...The clinical treatment of severe trauma withsternoclavicular joint injury is challenging,primarilydue to the irregular shape of the bones surrounding thesternoclavicular joint,as well as the posterior clavicle beingclose to the aorta and mediastinal organs.^([1])These patientsnot only suffer direct injuries to the sternoclavicularjoint,but also frequently experience severe injuries toother body parts.The systemic physiological disordersand multi-organ dysfunction caused by severe traumaincrease the surgery di?culty and mortality risk.^([2])展开更多
Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While mos...Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.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
Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has ...Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.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
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
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:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of ...BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of severe trauma,providing a reliable research tool.METHODS:Male C57BL/6J mice(aged 8-10 weeks and weighting approximately 20 g)were used to establish the severe trauma model.Under anesthesia,a midshaft femoral fracture was created and packed with sterile cotton.A midline incision was made from the inguinal region to the sternum,exposing the abdominal organs for 30 min.The right femoral artery was cannulated to induce controlled blood loss at 30%,35%,40%,and 50%of the total blood volume.Survival rates were monitored for 24 h post-induction.In the mice that experienced 30%blood loss,the mean arterial pressure,body temperature,blood gas parameters,peripheral blood inflammatory markers,and major organ pathological changes were assessed.RESULTS:Mice with femoral fractures,soft tissue injuries,abdominal organ exposure,and 30%blood loss exhibited stable survival rates.Increased blood loss significantly reduced survival rates.Mean arterial pressure decreased initially,recovering within 0-15 min and returning to baseline by 50 min.Similarly,the body temperature decreased initially and gradually recovered to baseline within 50 min.Levels of peripheral blood inflammatory markers remained elevated for 12 h post-injury.Distant organs,including intestines,lungs,liver,spleen and kidneys,displayed varying degrees of injury.CONCLUSION:The established mouse model replicates the pathophysiological responses to severe trauma,indicating stability and reproducibility,which could be an useful tool for further trauma research.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
基金supported by the National Natural Science Foundation of China,No.32071033(to MT)Basic and Applied Basic Research Foundation of Guangdong Province,Nos.2023A1515010140(to MT),2022A1515140169(to MT),2022A1515111096(to ZC)+3 种基金Science and Technology Project of Guangzhou,Nos.202201010015(to YL),2023A03J0790(to TJ)Basic and Applied Basic Research Foundation of Guangzhou,No.2023A04J1285(to ZC)Medical Research Foundation of Guangdong Province,No.A2023147(to ZC)Health Science and Technology Project of Guangzhou,No.20221A011039(to TJ)。
文摘Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite outgrowth remains unknown.Here,we found that spastin interacted with ubiquitin and was significantly degraded by K48-mediated poly-ubiquitination.Cullin3 facilitated spastin degradation and ubiquitination.RING-box protein 1,but not RING-box protein 2,acted synergistically with Cullin3 protein to regulate spastin degradation.Overexpression of Culin3 or BRX1 markedly suppressed spastin expression,and inhibited spastin-mediated microtubule severing and promotion of neurite outgrowth.Moreover,USP14 interacted directly with spastin to mediate its deubiquitination.USP14 overexpression significantly increased spastin expression and suppressed its ubiquitination and degradation.Although co-expression of spastin and USP14 did not enhance microtubule severing,it did increase neurite length in hippocampal neurons.Taken together,these findings elucidate the intricate regulatory mechanisms of spastin turnover,highlighting the roles of the Cullin-3–Ring E3 ubiquitin ligase complex and USP14 in orchestrating its ubiquitination and degradation.The dynamic interplay between these factors governs spastin stability and function,ultimately influencing microtubule dynamics and neuronal morphology.These insights shed light on potential therapeutic targets for neurodegenerative disorders associated with spastin defects.
基金supported by the Scientific Research Project of the Health Commission of Shanxi Province(No.2024003)。
文摘This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to age-related immune dysfunction,whereas EEN has been demonstrated to improve clinical prognosis,reduce infection and complication rates,and shor ten hospital stays.However,ongoing debates exist regarding the optimal timing,route selection,and complication management of EEN.Through a systematic review of the literature,this study synthesizes current evidence on EEN in elderly SAP populations,critically examines unresolved clinical controversies,and proposes future research priorities to inform evidence-based practice.
基金Jiangsu Provincial Hospital Association Hospital Management Innovation Research Fund(Project Ni.:JSYGY-3-2025-267)。
文摘Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based chain rescue is crucial in managing severe trauma.A patient with chest and abdominal injuries and hemorrhagic shock was transferred from an ambulance to our hospital.Our trauma team-initiated pre-hospital first aid,utilized an emergency green channel,and conducted rapid ultrasound,collaborating across disciplines.The patient eventually recovered and was discharged.
基金“Artificial Liver Special Fund”of Beijing Gan Dan Xiang Zhao Public Welfare Foundation(Project No.:iGandanF-1082024-RGG055)。
文摘A case of imported severe falciparum malaria with spontaneous splenic rupture was reported in this paper.The patient,an African migrant worker,developed hemolytic anemia,sepsis,thrombocytopenia,coagulation dysfunction,liver failure,renal insufficiency,electrolyte disturbance and other clinical manifestations after returning to the local area.Plasmodium falciparum was found by peripheral blood smearscopy and was diagnosed as severe falciparum malaria.After standardized anti-malaria treatment,plasma exchange+cytokine adsorption therapy,the establishment of“forewarning-forewarning-prevention-emergency”predictive nursing management model,the establishment of an integrated nursing team,the division of medical care is clear,professional knowledge is complementary,after three months of regular follow-up,the patient has no malaria recurrence,no refire,the function of all organs returned to normal.
文摘Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.Standard classification methods fail to address these dual challenges,limiting their real-world performance.In this paper,a novel,three-phase training framework is proposed that learns a robust ordinal classifier directly from noisy labels.The approach synergistically combines a rank-based ordinal regression backbone with a cooperative,semi-supervised learning strategy to dynamically partition the data into clean and noisy subsets.A hybrid training objective is then employed,applying a supervised ordinal loss to the clean set.The noisy set is simultaneously trained using a dualobjective that combines a semi-supervised ordinal loss with a parallel,label-agnostic contrastive loss.This design allows themodel to learn fromthe entire noisy subset while using contrastive learning to mitigate the risk of error propagation frompotentially corrupt supervision.Extensive experiments on a new,large-scale,multi-site clinical dataset validate our approach.Themethod achieves state-of-the-art performance with 80.71%accuracy and a 76.86%F1-score,significantly outperforming existing approaches,including a 2.26%improvement over the strongest baseline method.This work provides not only a robust solution for a practical medical imaging problem but also a generalizable framework for other tasks plagued by noisy ordinal labels.
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
基金The Korea Centers for Disease Control and Prevention,Grant/Award Number:2022-ER1701-00,2022-NI-041-02,2024-ER1702-00 and 2025-NI-014-00。
文摘Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.
文摘Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.
基金funded by grants Pronaii 302979A1-S-9005 CONACyT (México) from RMDA。
文摘Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.
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.
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.
文摘The clinical treatment of severe trauma withsternoclavicular joint injury is challenging,primarilydue to the irregular shape of the bones surrounding thesternoclavicular joint,as well as the posterior clavicle beingclose to the aorta and mediastinal organs.^([1])These patientsnot only suffer direct injuries to the sternoclavicularjoint,but also frequently experience severe injuries toother body parts.The systemic physiological disordersand multi-organ dysfunction caused by severe traumaincrease the surgery di?culty and mortality risk.^([2])
基金supported by National Natural Science Foundation of China(81272737).
文摘Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.
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 the National Natural Science Foundation of China(32170144 and 32470146).
文摘Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.
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 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 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.
基金supported by the National Natural Science Foundation of China(82102315).
文摘BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of severe trauma,providing a reliable research tool.METHODS:Male C57BL/6J mice(aged 8-10 weeks and weighting approximately 20 g)were used to establish the severe trauma model.Under anesthesia,a midshaft femoral fracture was created and packed with sterile cotton.A midline incision was made from the inguinal region to the sternum,exposing the abdominal organs for 30 min.The right femoral artery was cannulated to induce controlled blood loss at 30%,35%,40%,and 50%of the total blood volume.Survival rates were monitored for 24 h post-induction.In the mice that experienced 30%blood loss,the mean arterial pressure,body temperature,blood gas parameters,peripheral blood inflammatory markers,and major organ pathological changes were assessed.RESULTS:Mice with femoral fractures,soft tissue injuries,abdominal organ exposure,and 30%blood loss exhibited stable survival rates.Increased blood loss significantly reduced survival rates.Mean arterial pressure decreased initially,recovering within 0-15 min and returning to baseline by 50 min.Similarly,the body temperature decreased initially and gradually recovered to baseline within 50 min.Levels of peripheral blood inflammatory markers remained elevated for 12 h post-injury.Distant organs,including intestines,lungs,liver,spleen and kidneys,displayed varying degrees of injury.CONCLUSION:The established mouse model replicates the pathophysiological responses to severe trauma,indicating stability and reproducibility,which could be an useful tool for further trauma research.
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.
