Cardiovascular immunology research in Wuhan Union Hospital began in 1991.Anti-heart antibodies in dilated cardiomyopathy and acute viral myocarditis began to be reported from 1993.It was found that a new autoantibody ...Cardiovascular immunology research in Wuhan Union Hospital began in 1991.Anti-heart antibodies in dilated cardiomyopathy and acute viral myocarditis began to be reported from 1993.It was found that a new autoantibody against L-type calcium channel results in ventricular tachycardia and sudden death in patients with dilated cardiomyopathy.Through the Intervention Study of Diltiazem in Dilated Cardiomyopathy,diltiazem was verifi ed to reduce mortality and the chronic heart failure hospitalization rate signifi cantly in patients with dilated cardiomyopathy.The autoantibodies against angiotensin II receptor type 1 andα1-adrenoceptor were associated with the increased recurrence of and death from stroke in hypertensive patients.Through many clinical and experimental studies,the functional imbalance of T-cell subsets was suggested to mediate myocardial injury and chronic heart failure,which provided a new theoretical basis for immunoregulation therapy for heart failure.The first antihypertensive polypeptide vaccine(ATRQβ-001)was invented.In addition to these achievements,there will be more research on cardiovascular immunology in Wuhan Union Hospital in the future.展开更多
The coronavirus disease (COVID‑19) has claimed thousands of lives. The patients have been quarantined and treated in special shelter hospitals,and mild illness accounts for the majority of the total number of patients...The coronavirus disease (COVID‑19) has claimed thousands of lives. The patients have been quarantined and treated in special shelter hospitals,and mild illness accounts for the majority of the total number of patients. This article reports one case of the first batches of infected medicalstaff, who got infected with 2019 novel coronavirus and later discharged 2 weeks after receiving treatment and nursing care in Wuhan UnionHospital. Considering all aspects of the patient’s hospitalization, the patient was performed ward environment management, medical nursing,symptomatic treatment, nutrition management, vital signs monitoring, observation and nursing, psychological assessment and support, andinfection protection and management. As the earliest successful case of cure, the patient’s manifestations are classical and common. Moreover,we hope to share it with colleagues to fight against COVID‑19 for reference. The treatment and nursing guidelines can be applied to treat a largenumber of mild cases, thus improving the discharge rate of patients and reducing the pressure of epidemic situation.展开更多
Prognostic factors are biological or physical characteristics of a patient or the patient＇s cancer that can be used to predict the outcome of the individual. The prognosis of childhood acute lymphoblastic leukemia （...Prognostic factors are biological or physical characteristics of a patient or the patient＇s cancer that can be used to predict the outcome of the individual. The prognosis of childhood acute lymphoblastic leukemia （ALL） has been improved greatly in the past 40 years, reaching a long-term event free survival （EFS） of about 75% and overall survival of about 80% in developed countries.3-6 The same result has also been achieved in China. The ALL-XH-99 Protocol at Shanghai Children＇s Medical Center adopted early intensification treatment and triple intrathecal chemotherapy with high-dose methotrexate treatment for all patients and intensive chemotherapy in median risk （MR） and high risk （HR） patients. More intensive chemotherapy might cause more complications. In order to reevaluate the outcome of childhood ALL treated with the ALL-XH-99 Protocol and to fully elucidate the prognostic factors and the sequelae, a retrospective analysis was carried out to evaluate patients diagnosed with childhood ALL who were treated with the ALL-XH-99 Protocol in the past decade.展开更多
AIM:To investigate the demographics,risk factors,clinical presentation,treatments and outcomes of Acanthamoeba keratitis(AK)in a tertiary referral hospital in central China.METHODS:In this noncomparative,retrospective...AIM:To investigate the demographics,risk factors,clinical presentation,treatments and outcomes of Acanthamoeba keratitis(AK)in a tertiary referral hospital in central China.METHODS:In this noncomparative,retrospective study,a total of 21 AK patients were enrolled between April 2020 and March 2023.All patients underwent anterior segment photography,in vivo confocal microscopy(IVCM),bestcorrected visual acuity(BCVA)and anterior segment optical coherence tomography(AS-OCT).RESULTS:The most common potential predisposing factors were contact lens wearing(71.4%),mostly were students,and organic trauma(23.8%),mainly by outdoor workers.And 80.9%of patients were initially misdiagnosed with herpes keratitis.The clinical features were radial keratoneuritis 42.8%(n=9),crude salt-like granular dense infiltration 28.6%(n=6),and corneal ring infiltration 28.6%(n=6).Fifteen patients were completely cured by medical therapy,and six patients with corneal ring infiltration feature were performed conjunctival flap covering surgery(CFCS),three of them later underwent secondary deep anterior lamellar keratoplasty(DALK).All patients completed their follow-up at the Union Hospital,with a total of 20 patients(95.2%)had improved visual acuity after treatment,1 had no change.Corneal scarring and vascularization were the two most common complications of AK in this study,with incidence rates of 85.7%and 28.6%,respectively.CONCLUSION:In central China,AK occurs predominantly in contact lens wearers,mainly in students with myopia prevention and control.The radial keratoneuritis with crude salt-like granular dense infiltration can generally be effectively managed with medications.In contrast,corneal ring infiltration necessitates immediate surgical intervention.The CFCS combined with secondary DALK is effective for patients with high-risk AK in this condition.展开更多
Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal micro...Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.展开更多
Traumatic spinal cord injury often leads to the disintegration of nerve cells and axons,resulting in a substantial accumulation of myelin debris that can persist for years.The abnormal buildup of myelin debris at site...Traumatic spinal cord injury often leads to the disintegration of nerve cells and axons,resulting in a substantial accumulation of myelin debris that can persist for years.The abnormal buildup of myelin debris at sites of injury greatly impedes nerve regeneration,making the clearance of debris within these microenvironments crucial for effective post-spinal cord injury repair.In this review,we comprehensively outline the mechanisms that promote the clearance of myelin debris and myelin metabolism and summarize their roles in spinal cord injury.First,we describe the composition and characteristics of myelin debris and explain its effects on the injury site.Next,we introduce the phagocytic cells involved in myelin debris clearance,including professional phagocytes(macrophages and microglia)and non-professional phagocytes(astrocytes and microvascular endothelial cells),as well as other cells that are also proposed to participate in phagocytosis.Finally,we focus on the pathways and associated targets that enhance myelin debris clearance by phagocytes and promote lipid metabolism following spinal cord injury.Our analysis indicates that myelin debris phagocytosis is not limited to monocyte-derived macrophages,but also involves microglia,astrocytes,and microvascular endothelial cells.By modulating the expression of genes related to phagocytosis and lipid metabolism,it is possible to modulate lipid metabolism disorders and influence inflammatory phenotypes,ultimately affecting the recovery of motor function following spinal cord injury.Additionally,therapies such as targeted mitochondrial transplantation in phagocytic cells,exosome therapy,and repeated trans-spinal magnetic stimulation can effectively enhance the removal of myelin debris,presenting promising potential for future applications.展开更多
The morbidity rate of primary cardiac tumors(PCTs)is only 0.0138%.[1]Calcified amorphous tumors(CATs)are a particularly rare entity with only a few cases reported in the literature,and account for only 2.47%of PCTs.[2...The morbidity rate of primary cardiac tumors(PCTs)is only 0.0138%.[1]Calcified amorphous tumors(CATs)are a particularly rare entity with only a few cases reported in the literature,and account for only 2.47%of PCTs.[2]CATs can occur at any age and have been identified at various intracardiac locations.The clinical manifestations of patients are related to the location and size of the lesion.展开更多
The misfolding,aggregation,and deposition of alpha-synuclein into Lewy bodies are pivotal events that trigger pathological changes in Parkinson's disease.Extracellular vesicles are nanosized lipidbilayer vesicles ...The misfolding,aggregation,and deposition of alpha-synuclein into Lewy bodies are pivotal events that trigger pathological changes in Parkinson's disease.Extracellular vesicles are nanosized lipidbilayer vesicles secreted by cells that play a crucial role in intercellular communication due to their diverse cargo.Among these,brain-derived extracellular vesicles,which are secreted by various brain cells such as neurons,glial cells,and Schwann cells,have garnered increasing attention.They serve as a promising tool for elucidating Parkinson's disease pathogenesis and for advancing diagnostic and therapeutic strategies.This review highlights the recent advancements in our understanding of brain-derived extracellular vesicles released into the blood and their role in the pathogenesis of Parkinson's disease,with specific emphasis on their involvement in the aggregation and spread of alpha-synuclein.Brain-derived extracellular vesicles contribute to disease progression through multiple mechanisms,including autophagy-lysosome dysfunction,neuroinflammation,and oxidative stress,collectively driving neurodegeneration in Parkinson's disease.Their application in Parkinson's disease diagnosis is a primary focus of this review.Recent studies have demonstrated that brainderived extracellular vesicles can be isolated from peripheral blood samples,as they carryα-synuclein and other key biomarkers such as DJ-1 and various micro RNAs.These findings highlight the potential of brain-derived extracellular vesicles,not only for the early diagnosis of Parkinson's disease but also for disease progression monitoring and differential diagnosis.Additionally,an overview of explorations into the potential therapeutic applications of brain-derived extracellular vesicles for Parkinson's disease is provided.Therapeutic strategies targeting brain-derived extracellular vesicles involve modulating the release and uptake of pathological alpha-synuclein-containing brain-derived extracellular vesicles to inhibit the spread of the protein.Moreover,brain-derived extracellular vesicles show immense promise as therapeutic delivery vehicles capable of transporting drugs into the central nervous system.Importantly,brain-derived extracellular vesicles also play a crucial role in neural regeneration by promoting neuronal protection,supporting axonal regeneration,and facilitating myelin repair,further enhancing their therapeutic potential in Parkinson's disease and other neurological disorders.Further clarification is needed of the methods for identifying and extracting brain-derived extracellular vesicles,and large-scale cohort studies are necessary to validate the accuracy and specificity of these biomarkers.Future research should focus on systematically elucidating the unique mechanistic roles of brain-derived extracellular vesicles,as well as their distinct advantages in the clinical translation of methods for early detection and therapeutic development.展开更多
Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important...Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important regulator of cellular stress responses and has been confirmed to play a critical role in the occurrence of various diseases.However,the mechanisms by which hypoxia-inducible factor 1αis related to epilepsy and neuronal ferroptosis remain unclear.In this study,we used a pentylentetrazole-induced chronic epilepsy mouse model and treated the mice with intraperitoneal administration of PX-478,a hypoxia-inducible factor-1αinhibitor.Our results showed that PX-478 significantly prolonged the latency of epilepsy,reduced seizure severity,and shortened seizure duration.PX-478 also alleviated neuronal damage in the hippocampal CA1 and CA2 regions,reduced levels of reactive oxygen species and malondialdehyde,and increased levels of superoxide dismutase,catalase,and glutathione peroxidase.Transmission electron microscopy showed that PX-478 treatment reduced mitochondrial damage in the hippocampal neurons of epileptic mice,and significantly improved mitochondrial length and area.Additionally,PX-478 preferentially reduced Fe^(2+)levels and the expression of cyclooxygenase-2,ferritin heavy chain 1 and transferrin in the hippocampus of epileptic mice.It also inhibited the activity of the hypoxia-inducible factor 1α/heme oxygenase-1 pathway.In summary,these findings suggest that PX-478 has the potential to treat epilepsy by inhibiting the hypoxia-inducible factor 1α/heme oxygenase-1 pathway,alleviating oxidative stress,and reducing ferroptosis in hippocampal neurons.展开更多
Glucagon-like peptide-1 receptor agonists,originally developed for the treatment of type 2 diabetes mellitus,have been suggested as a potential disease-modifying treatment for Parkinson’s disease.Some clinical trials...Glucagon-like peptide-1 receptor agonists,originally developed for the treatment of type 2 diabetes mellitus,have been suggested as a potential disease-modifying treatment for Parkinson’s disease.Some clinical trials of glucagon-like peptide-1 receptor agonists have demonstrated that they can alleviate motor dysfunction and improve quality of life for patients with Parkinson’s disease.However,the mechanisms underlying the neuroprotective effects of glucagon-like peptide-1 receptor agonists have yet to be elucidated.In this study,we usedα-synuclein preformed fibrils to generate in vitro and in vivo models of Parkinson’s disease and investigated the effects of a short-acting glucagon-like peptide-1 receptor agonist,lixisenatide,on the propagation ofα-synuclein pathology.We found that lixisenatide reducedα-synuclein phosphorylation,aggregation,and propagation in cells treated withα-synuclein preformed fibrils,and that these effects were accompanied by decreased mitochondrial dysfunction and apoptosis.Additionally,lixisenatide treatment alleviated motor dysfunction and dopaminergic cell neurodegeneration 20 weeks after stereotactic injection ofα-synuclein preformed fibrils into the striatum of wild-type mice.In addition,lixisenatide inhibitedα-synuclein phosphorylation and seeding between neurons,mediated by neuronal lymphocyte-activation gene 3 expression.This study provides new insights into the mechanism underlying the disease-modifying effects of glucagon-like peptide-1 receptor agonists in the treatment of Parkinson’s disease.展开更多
The continuous extension of human life expectancy and the global trend of population aging have contributed to a marked increase in the incidence of musculoskeletal diseases,with fractures and osteoporosis being promi...The continuous extension of human life expectancy and the global trend of population aging have contributed to a marked increase in the incidence of musculoskeletal diseases,with fractures and osteoporosis being prominent examples.Consequently,promoting bone regeneration is a crucial medical challenge that demands immediate attention.As early as the mid-20th century,researchers revealed that electrical stimulation could effectively promote the healing and regeneration of bone tissue.This is achieved by mimicking the endogenous electric field within bone tissue,which influences cellular behavior and molecular mechanisms.In recent years,electroactive hydrogels responsive to electric field stimulation have been developed and applied to regulate cell functions at different stages of bone regeneration.This paper elaborates on the regulatory effects of electrical stimulation on MSCs,macrophages,and vascular endothelial cells during the process of bone regeneration.It also involves the activation of relevant ion channels and signaling pathways.Subsequently,it comprehensively reviews various electric-field-responsive hydrogels developed in recent years,covering aspects such as material selection,preparation methods,characteristics,and their applications in bone regeneration.Ultimately,it provides an objective summary of the existing deficiencies in hydrogel materials and research,and looks ahead to future development directions.展开更多
Estrogen deficiency after menopause accelerates bone loss by stimulating osteoclast formation and activity,but the molecular pathways that link estrogen signaling to osteoclast regulation remain incompletely defined.H...Estrogen deficiency after menopause accelerates bone loss by stimulating osteoclast formation and activity,but the molecular pathways that link estrogen signaling to osteoclast regulation remain incompletely defined.Here,we identify the sialyltransferase ST3GAL-I as a key mediator of RANKL-induced osteoclastogenesis.RANKL activates c-FOS to drive ST3GAL1 transcription,whereas estrogen-bound ERαcompetes with TRAF6 and suppresses this c-FOS–dependent induction.In a clinical cohort of pre-menopausal and post-menopausal women with or without osteoporosis,serum total andα-2,3-linked sialic acid levels increased with age and were highest in post-menopausal osteoporotic patients.Single-cell RNA sequencing of human bone revealed that osteoclasts form a prominent cluster only after menopause,where FOS,CTSK,and ST3GAL1 are strongly co-expressed,and the estrogen-responsive gene PGR is down-regulated.Additionally,in vivo experiments showed that sialidase treatment in estrogen-deficient models effectively reduced osteoclast-mediated bone loss,mimicking the effects of estradiol.These findings define a direct molecular link between loss of estrogen and activation of a FOS–ST3GAL1 sialylation pathway in osteoclasts,providing mechanistic insight into the enhanced bone resorption characteristic of post-menopausal osteoporosis.展开更多
Objective This study aims to investigate the joint associations of sarcopenia and social isolation with mortality risk.Methods Using data from the Chinese Longitudinal Healthy Longevity Survey(CLHLS)and the UK Biobank...Objective This study aims to investigate the joint associations of sarcopenia and social isolation with mortality risk.Methods Using data from the Chinese Longitudinal Healthy Longevity Survey(CLHLS)and the UK Biobank,sarcopenia was diagnosed according to European and Asian Working Groups for Sarcopenia criteria.Social isolation was assessed using standardized questionnaires,including questions on solitude,frequency of social activities,contact with others,and marital status(for the CLHLS only).Results During the follow-up period,8,249 deaths occurred in the CLHLS and 26,670 deaths in the UK Biobank groups.While no significant interaction was observed between sarcopenia and social isolation in predicting all-cause mortality in the CLHLS cohort,the association between social isolation and mortality was stronger among individuals with sarcopenia in the UK Biobank(P-interaction=0.03,relative risk due to interaction:0.23,95%confidence interval[CI]:0.06–0.41).Further joint analyses showed that participants with sarcopenia and high levels of social isolation had the highest mortality risk(hazard ration[HR]:1.99;95%CI:[1.74–2.28]in the CLHLS and 1.69[1.55–1.85]in the UK Biobank)compared to those without either condition.Conclusion The combination of social isolation and sarcopenia synergistically increases the risk of mortality in middle-aged and older adults across diverse populations.展开更多
Hydrogels are widely employed in various cutting-edge fields due to their excellent flexibility and tunability.However,hydrogels undergo significant swelling when immersed in seawater or other ionic solutions,leading ...Hydrogels are widely employed in various cutting-edge fields due to their excellent flexibility and tunability.However,hydrogels undergo significant swelling when immersed in seawater or other ionic solutions,leading to a severe decline in their performance.Herein,we develop a composite hydrogel(PAH)with anti-swelling capability in different solution environments,constructed through hydrogen bonding interactions between rigid aramid nanofibers(ANF)and flexible poly(vinyl alcohol)(PVA).The dense three-dimensional skeleton within PAH not only dissipates energy to enhance its strength and toughness but also effectively inhibits water molecule penetration.Even after immersion in different ionic solutions,PAH maintains its structural integrity(equilibrium swelling ratio of only 0.1%),while retaining excellent mechanical properties.This work provides a simple and effective strategy for improving the anti-swelling ability of hydrogels in different solutions,offering insights for broadening the application scope of hydrogels.展开更多
DNA methylation is an important promising biomarker for cancer diagnosis and monitoring.Therefore,the assessment of DNA methylation levels is helpful for the prognosis and diagnosis of cancer.However,it is still a hug...DNA methylation is an important promising biomarker for cancer diagnosis and monitoring.Therefore,the assessment of DNA methylation levels is helpful for the prognosis and diagnosis of cancer.However,it is still a huge challenge to sensitively and accurately quantify the levels of DNA methylation in clinical sample.In this work,we proposed a protospacer adjacent motif(PAM)-free mediated CRISPR-Cas12a ultra-sensitive and quantitative DNA methylation detection method.Through recognizing the ds DNA with toehold region,CRISPR-Cas12a not only got rid of the limitation of PAM,but also improved its distinction ability for single Cp G site methylation,nearly 5-fold that of conventional PAM-containing ds DNA.We further introduced assist-strand and design an artificial mismatch to greatly improve the ability to distinguish single Cp G methylation site.Our results showed that the discrimination factor was >200.Then,we constructed toe-ds DNA by using “heating and freezing”,which made our method universally applicable and feasible.In addition,we greatly simplified the difficulty of primer design.Our method detected four highly methylated genes acyl carrier protein(ACP),CLV3/ESR-related(CLE),Disabled(DAB) and Homeobox(HOX) with a detection limit of 0.01 % and excellent linearity in DNA methylation standards.Then,we verified the clinical utility of this method in 29 hepatocellular carcinomas,11 ovarian cancers and4 health people.In conclusion,we have successfully constructed a PAM-free CRISPR-Cas12a DNA methylation quantification method,which achieves high congruence in sensitivity,specificity and universality,fully demonstrating its significant clinical application value.展开更多
Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features ...Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features of human RCT scars,characterized by disruption of tendon architecture,disorganized collagen fibrils,and imbalance in type Ⅰ/Ⅲ collagen ratios and fibril diameters.Using single-cell RNA sequencing of tendon stumps from patients with RCT,we deconvolved the cellular and molecular landscape of the fibrotic scarring microenvironment.Heterogenous pro-fibrotic subclusters were identified and validated to participate into scar formation,including tendon stem cell,senescent tenocyte,SOX9-driven pro-fibrotic macrophage,and pro-fibrotic endothelial cells undergoing endothelial-mesenchymal transition(EndoMT).Furthermore,we found that osteopontin and TGF-βsignaling were key drivers of extracellular matrix deposition,and their blockade ameliorated fibrotic scarring after RCT.Collectively,our study dissected the dynamic scarring microenvironment in human RCT and highlights potential therapeutic targets for preventing pathological scar formation.展开更多
Background:Mastitis seriously affects the mammary health of humans and animals.Studies have found that inflammation and oxidative stress play key roles in the occur-rence and development of mastitis.Therefore,in-depth...Background:Mastitis seriously affects the mammary health of humans and animals.Studies have found that inflammation and oxidative stress play key roles in the occur-rence and development of mastitis.Therefore,in-depth research on related molecular mechanisms is of great significance.Methods:Postpartum mice were anesthetized with pentobarbital and administered lipopolysaccharide to develop the mouse mastitis model.Proteomic analysis was per-formed to compare protein expression in mitochondria-associated endoplasmic retic-ulum membranes(MAM)from two mouse mammary gland groups.Western blot was used to detect the expression of MAM-related proteins in mitochondria.AlphaFold3 was used to predict the molecular structures of phosphofurin acidic cluster sorting protein 2(PACS2)and mitofusin 2(MFN2)and their interaction levels.The MFN2-PACS2 interaction was investigated using co-immunoprecipitation and small interfer-ing RNA.Results:The results showed that the inflammation level in the mammary gland tissue of mice with mastitis significantly increased,the total antioxidant capacity decreased,and the expression of MAM-related proteins MFN2 and PACS2 was significantly downregulated.In cell experiments,overexpression of MFN2 can inhibit inflamma-tion and oxidative stress responses,and promote the interaction between MFN2 and PACS2 to affect the formation of MAMs.Conclusion:In summary,this study suggests that mastitis can alter the expression of MAM-related proteins in mouse breast tissue.The interaction between MFN2 and PACS2 regulates the formation of MAMs.Overexpression of MFN2 can promote the formation of MAMs and inhibit inflammation and oxidative stress response in mam-mary epithelial cells.Our results provided a new theoretical basis and potential thera-peutic targets for the prevention and treatment of mastitis.展开更多
Coronary artery disease （CAD） is a multifactorial disease in which inflammation plays a central role. This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte rat...Coronary artery disease （CAD） is a multifactorial disease in which inflammation plays a central role. This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio （NLR）, the Global Registry of Acute Coronary Events （GRACE） score with in-hospital mortality of elderly patients with acute myocardial infarction （AMI） in an attempt to explore the prognostic value of these indices for elderly AMI patients. One thousand consecutive CAD patients were divided into two groups based on age 60. The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records. The NLR and GRACE score were calculated. In the elderly （〉60 years）, patients with non-ST-elevation myocardial infarction （NSTEMI） and ST-elevation myocardial infarction （STEMI） had significantly higher NLR than did those with unstable angina （UA） and stable angina pectoris （SAP） （P〈0.01）. The NLR was considerably elevated in older AMI patients compared with their younger counterparts （〈60 years） （P〈0.05）. In elderly AMI patients, the NLR was considerably higher in the high-risk group than in both the low-risk and mediumrisk groups based on the GRACE score （P〈0.05 and P〈0.01, respectively）, and the NLR was positively correlated with the GRACE score （r=0.322, P〈0.001）. Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group （P〈0.05）. By curve receiver operator characteristic curve （ROC） analysis, the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve （AUC） 0.771 and 0.787, respectively, P〈0.001]. It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.展开更多
An emerging infectious disease was identified as severe fever with thrombocytopenia syn- drome （SFTS） in central China since late March 2009. We found the patients with SFTS had severe clinical symptoms, and progres...An emerging infectious disease was identified as severe fever with thrombocytopenia syn- drome （SFTS） in central China since late March 2009. We found the patients with SFTS had severe clinical symptoms, and progressed rapidly to multiple organ dysfunction syndrome （MODS） with high fatality rate of 25%-30%. The aim of this study was to assess the significance of risk factors predicting the development of MODS and death in SFTS patients. Consecutive SFTS admissions between May 2009 and September 2011 were analyzed for parameters of organ function during hospitalization using Marshall scoring system for MODS, and platelet counts were recorded on admission and at 24, 48, 72 h and one week after admission. We investigated the kinetics of organ failures and analyzed the associa- tion between age, platelet count and development of MODS or death. A total of 92 SFTS patients were enrolled in this study. Among them, 32 patients with dysfunction of over 4 organs were identified, 45% of them died within 72 h, 72% died within 5 days, and 76% died within 7 days after admission. We also found cumulative Marshall score was significantly higher in death patients （11.76＋2.05） than in survival patients （4.22~1.98） （P〈0.001）. In addition, SFTS patients had older age and lower platelet counts in MODS and death groups. Furthermore, we also observed that there was a close correlation between platelet count on admission and Marshall score （P〈0.001）. High Marshall score, advanced age and lower platelet counts were the main risk factors for the development of MODS, and those factors could predict mortality in SFTS patients, suggesting prompt treatment and close monitoring of severe complications, especially MODS, are of great importance in saving patients＇ lives.展开更多
This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and ...This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and guide the rational drug use,improve the drug specificity and provide a basis for drug therapy.The study adopts a prospective,multi-center,large sample size,centralized hospital monitoring system.We selected five leading hospitals in Hubei province,and observed the inpatients who received the ornidazole injection from July 1,2015 to October 31,2015.The basic information of patients was recorded,as well as the drug use and adverse events.The statistical analysis was performed based on these data.A total of 4396 individuals were enrolled in this study,most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections,and surgical treatment of anaerobic infections,abdominal infections and pelvic infections.The irrational drug use existed mainly in the prescribing and administration process,including unreasonable dosing frequency,rapid intravenous drip speed and extended duration of drug use.Eleven cases of adverse reactions were collected during the monitoring,incidence rate of adverse reactions was 2.5‰;adverse drug reactions occurred within 30 min.The study results fully reflected the usage of ornidazole injection in the real world.Based on the study,we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection.Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.展开更多
文摘Cardiovascular immunology research in Wuhan Union Hospital began in 1991.Anti-heart antibodies in dilated cardiomyopathy and acute viral myocarditis began to be reported from 1993.It was found that a new autoantibody against L-type calcium channel results in ventricular tachycardia and sudden death in patients with dilated cardiomyopathy.Through the Intervention Study of Diltiazem in Dilated Cardiomyopathy,diltiazem was verifi ed to reduce mortality and the chronic heart failure hospitalization rate signifi cantly in patients with dilated cardiomyopathy.The autoantibodies against angiotensin II receptor type 1 andα1-adrenoceptor were associated with the increased recurrence of and death from stroke in hypertensive patients.Through many clinical and experimental studies,the functional imbalance of T-cell subsets was suggested to mediate myocardial injury and chronic heart failure,which provided a new theoretical basis for immunoregulation therapy for heart failure.The first antihypertensive polypeptide vaccine(ATRQβ-001)was invented.In addition to these achievements,there will be more research on cardiovascular immunology in Wuhan Union Hospital in the future.
文摘The coronavirus disease (COVID‑19) has claimed thousands of lives. The patients have been quarantined and treated in special shelter hospitals,and mild illness accounts for the majority of the total number of patients. This article reports one case of the first batches of infected medicalstaff, who got infected with 2019 novel coronavirus and later discharged 2 weeks after receiving treatment and nursing care in Wuhan UnionHospital. Considering all aspects of the patient’s hospitalization, the patient was performed ward environment management, medical nursing,symptomatic treatment, nutrition management, vital signs monitoring, observation and nursing, psychological assessment and support, andinfection protection and management. As the earliest successful case of cure, the patient’s manifestations are classical and common. Moreover,we hope to share it with colleagues to fight against COVID‑19 for reference. The treatment and nursing guidelines can be applied to treat a largenumber of mild cases, thus improving the discharge rate of patients and reducing the pressure of epidemic situation.
文摘Prognostic factors are biological or physical characteristics of a patient or the patient＇s cancer that can be used to predict the outcome of the individual. The prognosis of childhood acute lymphoblastic leukemia （ALL） has been improved greatly in the past 40 years, reaching a long-term event free survival （EFS） of about 75% and overall survival of about 80% in developed countries.3-6 The same result has also been achieved in China. The ALL-XH-99 Protocol at Shanghai Children＇s Medical Center adopted early intensification treatment and triple intrathecal chemotherapy with high-dose methotrexate treatment for all patients and intensive chemotherapy in median risk （MR） and high risk （HR） patients. More intensive chemotherapy might cause more complications. In order to reevaluate the outcome of childhood ALL treated with the ALL-XH-99 Protocol and to fully elucidate the prognostic factors and the sequelae, a retrospective analysis was carried out to evaluate patients diagnosed with childhood ALL who were treated with the ALL-XH-99 Protocol in the past decade.
基金Supported by National Natural Science Foundation of China(No.82171025No.82070934)+3 种基金the Fundamental Research Funds for the Central Universities(HUST:2019kfyXMBZ065)the Key Research and Development Program of Hubei Province(No.2021BCA146)the Clinical Research Foundation of Wuhan Union Hospital(No.2021xhlcyj03)the Hubei Province Health and Family Planning Scientific Research Project(No.WJ2023M035).
文摘AIM:To investigate the demographics,risk factors,clinical presentation,treatments and outcomes of Acanthamoeba keratitis(AK)in a tertiary referral hospital in central China.METHODS:In this noncomparative,retrospective study,a total of 21 AK patients were enrolled between April 2020 and March 2023.All patients underwent anterior segment photography,in vivo confocal microscopy(IVCM),bestcorrected visual acuity(BCVA)and anterior segment optical coherence tomography(AS-OCT).RESULTS:The most common potential predisposing factors were contact lens wearing(71.4%),mostly were students,and organic trauma(23.8%),mainly by outdoor workers.And 80.9%of patients were initially misdiagnosed with herpes keratitis.The clinical features were radial keratoneuritis 42.8%(n=9),crude salt-like granular dense infiltration 28.6%(n=6),and corneal ring infiltration 28.6%(n=6).Fifteen patients were completely cured by medical therapy,and six patients with corneal ring infiltration feature were performed conjunctival flap covering surgery(CFCS),three of them later underwent secondary deep anterior lamellar keratoplasty(DALK).All patients completed their follow-up at the Union Hospital,with a total of 20 patients(95.2%)had improved visual acuity after treatment,1 had no change.Corneal scarring and vascularization were the two most common complications of AK in this study,with incidence rates of 85.7%and 28.6%,respectively.CONCLUSION:In central China,AK occurs predominantly in contact lens wearers,mainly in students with myopia prevention and control.The radial keratoneuritis with crude salt-like granular dense infiltration can generally be effectively managed with medications.In contrast,corneal ring infiltration necessitates immediate surgical intervention.The CFCS combined with secondary DALK is effective for patients with high-risk AK in this condition.
基金supported by the National Key R&D Program of China(2023YFD1801100)China National Postdoctoral Program for Innovative Talents(BX20230140)China Postdoctoral Science Foundation(2023M741348)。
文摘Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WL)the International Cooperative Project of Talent Cultivation“Xinghai Project”at the China-Japan Union Hospital of Jilin University,No.XHLH202404(to WL)+1 种基金the Science and Technology Development Plan of Jilin Province,No.YDZJ202201ZYTS038(to WL)Jilin Provincial Finance Program,No.2022SCZ10(to WL)。
文摘Traumatic spinal cord injury often leads to the disintegration of nerve cells and axons,resulting in a substantial accumulation of myelin debris that can persist for years.The abnormal buildup of myelin debris at sites of injury greatly impedes nerve regeneration,making the clearance of debris within these microenvironments crucial for effective post-spinal cord injury repair.In this review,we comprehensively outline the mechanisms that promote the clearance of myelin debris and myelin metabolism and summarize their roles in spinal cord injury.First,we describe the composition and characteristics of myelin debris and explain its effects on the injury site.Next,we introduce the phagocytic cells involved in myelin debris clearance,including professional phagocytes(macrophages and microglia)and non-professional phagocytes(astrocytes and microvascular endothelial cells),as well as other cells that are also proposed to participate in phagocytosis.Finally,we focus on the pathways and associated targets that enhance myelin debris clearance by phagocytes and promote lipid metabolism following spinal cord injury.Our analysis indicates that myelin debris phagocytosis is not limited to monocyte-derived macrophages,but also involves microglia,astrocytes,and microvascular endothelial cells.By modulating the expression of genes related to phagocytosis and lipid metabolism,it is possible to modulate lipid metabolism disorders and influence inflammatory phenotypes,ultimately affecting the recovery of motor function following spinal cord injury.Additionally,therapies such as targeted mitochondrial transplantation in phagocytic cells,exosome therapy,and repeated trans-spinal magnetic stimulation can effectively enhance the removal of myelin debris,presenting promising potential for future applications.
文摘The morbidity rate of primary cardiac tumors(PCTs)is only 0.0138%.[1]Calcified amorphous tumors(CATs)are a particularly rare entity with only a few cases reported in the literature,and account for only 2.47%of PCTs.[2]CATs can occur at any age and have been identified at various intracardiac locations.The clinical manifestations of patients are related to the location and size of the lesion.
基金supported by the National Natural Science Foundation of China,No.822712782019 Wuhan Huanghe Talents Program+3 种基金2020 Wuhan Medical Research Project,No.20200206010123032021 Hubei Youth Top-notch Talent Training Program2022 Outstanding Youth Project of Natural Science Foundation of Hubei Province,No.2022CFA106Medical Research Program of Huatongguokang,No.2023HT036(all to NX)。
文摘The misfolding,aggregation,and deposition of alpha-synuclein into Lewy bodies are pivotal events that trigger pathological changes in Parkinson's disease.Extracellular vesicles are nanosized lipidbilayer vesicles secreted by cells that play a crucial role in intercellular communication due to their diverse cargo.Among these,brain-derived extracellular vesicles,which are secreted by various brain cells such as neurons,glial cells,and Schwann cells,have garnered increasing attention.They serve as a promising tool for elucidating Parkinson's disease pathogenesis and for advancing diagnostic and therapeutic strategies.This review highlights the recent advancements in our understanding of brain-derived extracellular vesicles released into the blood and their role in the pathogenesis of Parkinson's disease,with specific emphasis on their involvement in the aggregation and spread of alpha-synuclein.Brain-derived extracellular vesicles contribute to disease progression through multiple mechanisms,including autophagy-lysosome dysfunction,neuroinflammation,and oxidative stress,collectively driving neurodegeneration in Parkinson's disease.Their application in Parkinson's disease diagnosis is a primary focus of this review.Recent studies have demonstrated that brainderived extracellular vesicles can be isolated from peripheral blood samples,as they carryα-synuclein and other key biomarkers such as DJ-1 and various micro RNAs.These findings highlight the potential of brain-derived extracellular vesicles,not only for the early diagnosis of Parkinson's disease but also for disease progression monitoring and differential diagnosis.Additionally,an overview of explorations into the potential therapeutic applications of brain-derived extracellular vesicles for Parkinson's disease is provided.Therapeutic strategies targeting brain-derived extracellular vesicles involve modulating the release and uptake of pathological alpha-synuclein-containing brain-derived extracellular vesicles to inhibit the spread of the protein.Moreover,brain-derived extracellular vesicles show immense promise as therapeutic delivery vehicles capable of transporting drugs into the central nervous system.Importantly,brain-derived extracellular vesicles also play a crucial role in neural regeneration by promoting neuronal protection,supporting axonal regeneration,and facilitating myelin repair,further enhancing their therapeutic potential in Parkinson's disease and other neurological disorders.Further clarification is needed of the methods for identifying and extracting brain-derived extracellular vesicles,and large-scale cohort studies are necessary to validate the accuracy and specificity of these biomarkers.Future research should focus on systematically elucidating the unique mechanistic roles of brain-derived extracellular vesicles,as well as their distinct advantages in the clinical translation of methods for early detection and therapeutic development.
基金supported by the Science and Technology Development Plan Project of Jilin Province,No.YDZJ202401157ZYTS(to SL).
文摘Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important regulator of cellular stress responses and has been confirmed to play a critical role in the occurrence of various diseases.However,the mechanisms by which hypoxia-inducible factor 1αis related to epilepsy and neuronal ferroptosis remain unclear.In this study,we used a pentylentetrazole-induced chronic epilepsy mouse model and treated the mice with intraperitoneal administration of PX-478,a hypoxia-inducible factor-1αinhibitor.Our results showed that PX-478 significantly prolonged the latency of epilepsy,reduced seizure severity,and shortened seizure duration.PX-478 also alleviated neuronal damage in the hippocampal CA1 and CA2 regions,reduced levels of reactive oxygen species and malondialdehyde,and increased levels of superoxide dismutase,catalase,and glutathione peroxidase.Transmission electron microscopy showed that PX-478 treatment reduced mitochondrial damage in the hippocampal neurons of epileptic mice,and significantly improved mitochondrial length and area.Additionally,PX-478 preferentially reduced Fe^(2+)levels and the expression of cyclooxygenase-2,ferritin heavy chain 1 and transferrin in the hippocampus of epileptic mice.It also inhibited the activity of the hypoxia-inducible factor 1α/heme oxygenase-1 pathway.In summary,these findings suggest that PX-478 has the potential to treat epilepsy by inhibiting the hypoxia-inducible factor 1α/heme oxygenase-1 pathway,alleviating oxidative stress,and reducing ferroptosis in hippocampal neurons.
基金supported by the National Natural Science Foundation of China,No.82271446(to JX).
文摘Glucagon-like peptide-1 receptor agonists,originally developed for the treatment of type 2 diabetes mellitus,have been suggested as a potential disease-modifying treatment for Parkinson’s disease.Some clinical trials of glucagon-like peptide-1 receptor agonists have demonstrated that they can alleviate motor dysfunction and improve quality of life for patients with Parkinson’s disease.However,the mechanisms underlying the neuroprotective effects of glucagon-like peptide-1 receptor agonists have yet to be elucidated.In this study,we usedα-synuclein preformed fibrils to generate in vitro and in vivo models of Parkinson’s disease and investigated the effects of a short-acting glucagon-like peptide-1 receptor agonist,lixisenatide,on the propagation ofα-synuclein pathology.We found that lixisenatide reducedα-synuclein phosphorylation,aggregation,and propagation in cells treated withα-synuclein preformed fibrils,and that these effects were accompanied by decreased mitochondrial dysfunction and apoptosis.Additionally,lixisenatide treatment alleviated motor dysfunction and dopaminergic cell neurodegeneration 20 weeks after stereotactic injection ofα-synuclein preformed fibrils into the striatum of wild-type mice.In addition,lixisenatide inhibitedα-synuclein phosphorylation and seeding between neurons,mediated by neuronal lymphocyte-activation gene 3 expression.This study provides new insights into the mechanism underlying the disease-modifying effects of glucagon-like peptide-1 receptor agonists in the treatment of Parkinson’s disease.
基金supported by the National Science Foundation of China(No.82272491)。
文摘The continuous extension of human life expectancy and the global trend of population aging have contributed to a marked increase in the incidence of musculoskeletal diseases,with fractures and osteoporosis being prominent examples.Consequently,promoting bone regeneration is a crucial medical challenge that demands immediate attention.As early as the mid-20th century,researchers revealed that electrical stimulation could effectively promote the healing and regeneration of bone tissue.This is achieved by mimicking the endogenous electric field within bone tissue,which influences cellular behavior and molecular mechanisms.In recent years,electroactive hydrogels responsive to electric field stimulation have been developed and applied to regulate cell functions at different stages of bone regeneration.This paper elaborates on the regulatory effects of electrical stimulation on MSCs,macrophages,and vascular endothelial cells during the process of bone regeneration.It also involves the activation of relevant ion channels and signaling pathways.Subsequently,it comprehensively reviews various electric-field-responsive hydrogels developed in recent years,covering aspects such as material selection,preparation methods,characteristics,and their applications in bone regeneration.Ultimately,it provides an objective summary of the existing deficiencies in hydrogel materials and research,and looks ahead to future development directions.
基金funded by a grant from the National Natural Science Foundation of China(82572785,82172489,82172449)funding for young investigators of PLA(2022-JCJQ-QT-004)。
文摘Estrogen deficiency after menopause accelerates bone loss by stimulating osteoclast formation and activity,but the molecular pathways that link estrogen signaling to osteoclast regulation remain incompletely defined.Here,we identify the sialyltransferase ST3GAL-I as a key mediator of RANKL-induced osteoclastogenesis.RANKL activates c-FOS to drive ST3GAL1 transcription,whereas estrogen-bound ERαcompetes with TRAF6 and suppresses this c-FOS–dependent induction.In a clinical cohort of pre-menopausal and post-menopausal women with or without osteoporosis,serum total andα-2,3-linked sialic acid levels increased with age and were highest in post-menopausal osteoporotic patients.Single-cell RNA sequencing of human bone revealed that osteoclasts form a prominent cluster only after menopause,where FOS,CTSK,and ST3GAL1 are strongly co-expressed,and the estrogen-responsive gene PGR is down-regulated.Additionally,in vivo experiments showed that sialidase treatment in estrogen-deficient models effectively reduced osteoclast-mediated bone loss,mimicking the effects of estradiol.These findings define a direct molecular link between loss of estrogen and activation of a FOS–ST3GAL1 sialylation pathway in osteoclasts,providing mechanistic insight into the enhanced bone resorption characteristic of post-menopausal osteoporosis.
基金supported by grants from the National Key Research and Development Program of China(No.2023YFC3606300,No.2022YFC3600300)the National Natural Science Foundation of China(No.82325043)the National Key Research and Development Program of Hubei Province(2022BCA036)。
文摘Objective This study aims to investigate the joint associations of sarcopenia and social isolation with mortality risk.Methods Using data from the Chinese Longitudinal Healthy Longevity Survey(CLHLS)and the UK Biobank,sarcopenia was diagnosed according to European and Asian Working Groups for Sarcopenia criteria.Social isolation was assessed using standardized questionnaires,including questions on solitude,frequency of social activities,contact with others,and marital status(for the CLHLS only).Results During the follow-up period,8,249 deaths occurred in the CLHLS and 26,670 deaths in the UK Biobank groups.While no significant interaction was observed between sarcopenia and social isolation in predicting all-cause mortality in the CLHLS cohort,the association between social isolation and mortality was stronger among individuals with sarcopenia in the UK Biobank(P-interaction=0.03,relative risk due to interaction:0.23,95%confidence interval[CI]:0.06–0.41).Further joint analyses showed that participants with sarcopenia and high levels of social isolation had the highest mortality risk(hazard ration[HR]:1.99;95%CI:[1.74–2.28]in the CLHLS and 1.69[1.55–1.85]in the UK Biobank)compared to those without either condition.Conclusion The combination of social isolation and sarcopenia synergistically increases the risk of mortality in middle-aged and older adults across diverse populations.
基金supported by the National Natural Science Foundation of China(No.52573131)the National Key Research and Development Program of China(No.2020YFA0710303)。
文摘Hydrogels are widely employed in various cutting-edge fields due to their excellent flexibility and tunability.However,hydrogels undergo significant swelling when immersed in seawater or other ionic solutions,leading to a severe decline in their performance.Herein,we develop a composite hydrogel(PAH)with anti-swelling capability in different solution environments,constructed through hydrogen bonding interactions between rigid aramid nanofibers(ANF)and flexible poly(vinyl alcohol)(PVA).The dense three-dimensional skeleton within PAH not only dissipates energy to enhance its strength and toughness but also effectively inhibits water molecule penetration.Even after immersion in different ionic solutions,PAH maintains its structural integrity(equilibrium swelling ratio of only 0.1%),while retaining excellent mechanical properties.This work provides a simple and effective strategy for improving the anti-swelling ability of hydrogels in different solutions,offering insights for broadening the application scope of hydrogels.
基金financially supported by the Natural Science Foundation of Wuhan City (Chenguang Project) (No.2024040801020331)the Natural Science Foundation of Hubei Province of China (No.2023AFB402)+1 种基金the National Key Research and Development Program of China (No.2023YFE0210200)Interdisciplinary Research Program of HUST。
文摘DNA methylation is an important promising biomarker for cancer diagnosis and monitoring.Therefore,the assessment of DNA methylation levels is helpful for the prognosis and diagnosis of cancer.However,it is still a huge challenge to sensitively and accurately quantify the levels of DNA methylation in clinical sample.In this work,we proposed a protospacer adjacent motif(PAM)-free mediated CRISPR-Cas12a ultra-sensitive and quantitative DNA methylation detection method.Through recognizing the ds DNA with toehold region,CRISPR-Cas12a not only got rid of the limitation of PAM,but also improved its distinction ability for single Cp G site methylation,nearly 5-fold that of conventional PAM-containing ds DNA.We further introduced assist-strand and design an artificial mismatch to greatly improve the ability to distinguish single Cp G methylation site.Our results showed that the discrimination factor was >200.Then,we constructed toe-ds DNA by using “heating and freezing”,which made our method universally applicable and feasible.In addition,we greatly simplified the difficulty of primer design.Our method detected four highly methylated genes acyl carrier protein(ACP),CLV3/ESR-related(CLE),Disabled(DAB) and Homeobox(HOX) with a detection limit of 0.01 % and excellent linearity in DNA methylation standards.Then,we verified the clinical utility of this method in 29 hepatocellular carcinomas,11 ovarian cancers and4 health people.In conclusion,we have successfully constructed a PAM-free CRISPR-Cas12a DNA methylation quantification method,which achieves high congruence in sensitivity,specificity and universality,fully demonstrating its significant clinical application value.
基金supported by the National Natural Science Foundation of China(NO.82230085,82272572,82030071)National Key Research and Development Program of China(NO.2022YFC2010204)Natural Science Foundation of Hunan Province(NO.2024JJ6637)。
文摘Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features of human RCT scars,characterized by disruption of tendon architecture,disorganized collagen fibrils,and imbalance in type Ⅰ/Ⅲ collagen ratios and fibril diameters.Using single-cell RNA sequencing of tendon stumps from patients with RCT,we deconvolved the cellular and molecular landscape of the fibrotic scarring microenvironment.Heterogenous pro-fibrotic subclusters were identified and validated to participate into scar formation,including tendon stem cell,senescent tenocyte,SOX9-driven pro-fibrotic macrophage,and pro-fibrotic endothelial cells undergoing endothelial-mesenchymal transition(EndoMT).Furthermore,we found that osteopontin and TGF-βsignaling were key drivers of extracellular matrix deposition,and their blockade ameliorated fibrotic scarring after RCT.Collectively,our study dissected the dynamic scarring microenvironment in human RCT and highlights potential therapeutic targets for preventing pathological scar formation.
基金National Natural Science Foundation of China,Grant/Award Number:32302826 and 32372961Jilin Provincial Special Project for Health Research Talents,Grant/Award Number:2020SCZ40China Postdoctoral Science Foundation,Grant/Award Number:2023M740623。
文摘Background:Mastitis seriously affects the mammary health of humans and animals.Studies have found that inflammation and oxidative stress play key roles in the occur-rence and development of mastitis.Therefore,in-depth research on related molecular mechanisms is of great significance.Methods:Postpartum mice were anesthetized with pentobarbital and administered lipopolysaccharide to develop the mouse mastitis model.Proteomic analysis was per-formed to compare protein expression in mitochondria-associated endoplasmic retic-ulum membranes(MAM)from two mouse mammary gland groups.Western blot was used to detect the expression of MAM-related proteins in mitochondria.AlphaFold3 was used to predict the molecular structures of phosphofurin acidic cluster sorting protein 2(PACS2)and mitofusin 2(MFN2)and their interaction levels.The MFN2-PACS2 interaction was investigated using co-immunoprecipitation and small interfer-ing RNA.Results:The results showed that the inflammation level in the mammary gland tissue of mice with mastitis significantly increased,the total antioxidant capacity decreased,and the expression of MAM-related proteins MFN2 and PACS2 was significantly downregulated.In cell experiments,overexpression of MFN2 can inhibit inflamma-tion and oxidative stress responses,and promote the interaction between MFN2 and PACS2 to affect the formation of MAMs.Conclusion:In summary,this study suggests that mastitis can alter the expression of MAM-related proteins in mouse breast tissue.The interaction between MFN2 and PACS2 regulates the formation of MAMs.Overexpression of MFN2 can promote the formation of MAMs and inhibit inflammation and oxidative stress response in mam-mary epithelial cells.Our results provided a new theoretical basis and potential thera-peutic targets for the prevention and treatment of mastitis.
基金This project was supported by a grant from Hubei Natural Science Foundation of China （No. 2013CKB011）.
文摘Coronary artery disease （CAD） is a multifactorial disease in which inflammation plays a central role. This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio （NLR）, the Global Registry of Acute Coronary Events （GRACE） score with in-hospital mortality of elderly patients with acute myocardial infarction （AMI） in an attempt to explore the prognostic value of these indices for elderly AMI patients. One thousand consecutive CAD patients were divided into two groups based on age 60. The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records. The NLR and GRACE score were calculated. In the elderly （〉60 years）, patients with non-ST-elevation myocardial infarction （NSTEMI） and ST-elevation myocardial infarction （STEMI） had significantly higher NLR than did those with unstable angina （UA） and stable angina pectoris （SAP） （P〈0.01）. The NLR was considerably elevated in older AMI patients compared with their younger counterparts （〈60 years） （P〈0.05）. In elderly AMI patients, the NLR was considerably higher in the high-risk group than in both the low-risk and mediumrisk groups based on the GRACE score （P〈0.05 and P〈0.01, respectively）, and the NLR was positively correlated with the GRACE score （r=0.322, P〈0.001）. Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group （P〈0.05）. By curve receiver operator characteristic curve （ROC） analysis, the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve （AUC） 0.771 and 0.787, respectively, P〈0.001]. It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.
基金supported by the National Natural Science Foundation of China (No. 81171638)
文摘An emerging infectious disease was identified as severe fever with thrombocytopenia syn- drome （SFTS） in central China since late March 2009. We found the patients with SFTS had severe clinical symptoms, and progressed rapidly to multiple organ dysfunction syndrome （MODS） with high fatality rate of 25%-30%. The aim of this study was to assess the significance of risk factors predicting the development of MODS and death in SFTS patients. Consecutive SFTS admissions between May 2009 and September 2011 were analyzed for parameters of organ function during hospitalization using Marshall scoring system for MODS, and platelet counts were recorded on admission and at 24, 48, 72 h and one week after admission. We investigated the kinetics of organ failures and analyzed the associa- tion between age, platelet count and development of MODS or death. A total of 92 SFTS patients were enrolled in this study. Among them, 32 patients with dysfunction of over 4 organs were identified, 45% of them died within 72 h, 72% died within 5 days, and 76% died within 7 days after admission. We also found cumulative Marshall score was significantly higher in death patients （11.76＋2.05） than in survival patients （4.22~1.98） （P〈0.001）. In addition, SFTS patients had older age and lower platelet counts in MODS and death groups. Furthermore, we also observed that there was a close correlation between platelet count on admission and Marshall score （P〈0.001）. High Marshall score, advanced age and lower platelet counts were the main risk factors for the development of MODS, and those factors could predict mortality in SFTS patients, suggesting prompt treatment and close monitoring of severe complications, especially MODS, are of great importance in saving patients＇ lives.
文摘This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and guide the rational drug use,improve the drug specificity and provide a basis for drug therapy.The study adopts a prospective,multi-center,large sample size,centralized hospital monitoring system.We selected five leading hospitals in Hubei province,and observed the inpatients who received the ornidazole injection from July 1,2015 to October 31,2015.The basic information of patients was recorded,as well as the drug use and adverse events.The statistical analysis was performed based on these data.A total of 4396 individuals were enrolled in this study,most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections,and surgical treatment of anaerobic infections,abdominal infections and pelvic infections.The irrational drug use existed mainly in the prescribing and administration process,including unreasonable dosing frequency,rapid intravenous drip speed and extended duration of drug use.Eleven cases of adverse reactions were collected during the monitoring,incidence rate of adverse reactions was 2.5‰;adverse drug reactions occurred within 30 min.The study results fully reflected the usage of ornidazole injection in the real world.Based on the study,we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection.Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.
