The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Cmyc,a proto-oncogene,is expressed at extremely low levels in mature neurons and is traditionally thought to have no function in these cells.However,recent studies suggest that Cmyc may play a crucial role in maintain...Cmyc,a proto-oncogene,is expressed at extremely low levels in mature neurons and is traditionally thought to have no function in these cells.However,recent studies suggest that Cmyc may play a crucial role in maintaining the health and function of mature dopaminergic neurons.This study assessed the role of Cmyc in dopaminergic neurons and its significance in Parkinson’s disease.We used a conditional knockout approach to specifically delete Cmyc in substantia nigra dopaminergic neurons of adult mice.Our findings showed that Cmyc deletion led to progressive neuron loss,Parkinson’s disease-like symptoms,downregulation of Klotho,and upregulation of senescence-associated inflammatory factors,along with enhanced oxidative stress and nitrated alpha-synuclein accumulation,ultimately causing neuronal death.In vitro experiments confirmed increased senescence in C-MYC knockout cells,which was partially reversible by KLOTHO overexpression.We conclude that low-level Cmyc expression is essential for maintaining the health of mature dopaminergic neurons and preventing neurodegeneration,and suggest the c-Myc/Klotho axis as a potential therapeutic target for age-related neurodegenerative diseases,including Parkinson’s disease.Our study introduces a novel mouse model for Parkinson’s disease that replicates a condition associated with normal aging,offering a valuable tool for future research into disease mechanisms and therapeutic strategies.展开更多
AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Com...AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.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
Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus...Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus(HR-HPV)infection.Methods Female patients(n=73)with HR-HPV infection were enrolled and divided into a high-grade squamous intraepithelial lesion(HSIL)group(n=33)and a non-HSIL(N-HSIL)group(n=40),which include low-grade squamous intraepithelial lesions and inflammation.Healthy screening subjects(n=31)with negative HR-HPV results were enrolled as a control group.We examined contemporaneous plasma and secretory cytokines from 25 study subjects to investigate the difference between systemic cytokine profiles and the local microenvironment immunity using the Wilcoxon matched-pairs signed rank test.The 12 cytokines from cervical secretions were compared between the three groups using the Mann-Whitney test,and logistic regression was used to analyze HSIL and N-HSIL.Results There were statistical differences in eight cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-1β,IL-12p70,IFN-α,and IL-8)between cervical secretion and plasma of the same patient,and seven cytokines were statistically different between the control and other two groups.We selected four independent variables(TNF-α,IFN-γ,IL-12p70,and IFN-α)commonly identified by univariate regression analysis and non-parametric tests for multivariate logistic regression analysis.Based on this model,HSIL could be predicted in patients with HR-HPV infection,with the area under the curve being 0.76.Conclusion The systemic cytokine profile cannot reflect the local microenvironment immunity,and the occurrence of HSIL is related to the cytokine levels in the cervical microenvironment.展开更多
Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)...Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.展开更多
Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-in...Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.展开更多
Objective Hemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders.This study aimed to characterize the clinical laboratory findings of hemocoagul...Objective Hemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders.This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection.Methods Wie retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1,2015 to March 31,2018.Clinical data were collected and investigated,including clinical manifestations,hemostatic and fibrinolytic parameters,dosage of hemocoagulase,the medication time,and the cryoprecipitate blood product infusion.Differences in fibrinogen,D-dimer,and fibrin/fibrinogen degradation products(FDP)before,during,and after the application of hemocoagulase injection were analyzed statistically.Results Plasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment(F=1.80,P<0.001),with the average decrease of 2.28 g/L(0.63-3.9 g/L).After withdrawal,fibrinogen level increased significantly compared to that during the medication(F=l.20,P<0.001),but was still lower than that before the medication(F=0.59,P=0.03).The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication(F=0.83,P=0.002;Wilcoxon-test,Z=-4.54,P<0.001).Spearman's correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemo coagulase(r=-0.17,P=0.40;r=-0.28,P=0.15;respectively)and the time of recovery from hypofibrinogenemia(r=-0.45,P=0.05;r=0.13,P=0.61;respectively).Conclusion Monitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection.Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.展开更多
AIM:To evaluate seroprevalence of hepatitis A virus (HAV) antibody and investigate demographic,clinical,and laboratory features of recent cases in Korea.METHODS:For the evaluation of hepatitis A seroprevalence,we anal...AIM:To evaluate seroprevalence of hepatitis A virus (HAV) antibody and investigate demographic,clinical,and laboratory features of recent cases in Korea.METHODS:For the evaluation of hepatitis A seroprevalence,we analyzed the data from 3127 subjects including,healthcare workers and patients who visited Konkuk University Hospital,a secondary referral center,from January to October 2009.The sera with positive IgM were excluded from seroprevalence data for total HAV antibody.We retrospectively reviewed the electronic medical records of 419 patients with HAV,who were diagnosed by the presence of serum IgM antibodies against HAV.All patients presented at Konkuk University Hospital between August 2005 and September 2008.RESULTS:Among 3127 sera tested,1428 (45.7%)were positive for anti-HAV antibody.The seroprevalence was very low in teenagers or those in their twenties,increased in those in their thirties,and was > 90% in older patients.In children younger than 10 years,seroprevalence was increased again.Most patients with HAV hepatitis were in their twenties and thirties.The γ-glutamyl transpeptidase increased with age and was significantly higher in patients older than 30 years.Indicators of severity,such as decreased albumin and increased bilirubin,were also more prominent in the older age group;however,the leukocyte count was higher and the frequency of leukopenia was lower in younger patients than in older adults.CONCLUSION:There has been an apparent epidemiological shift in HAV seroprevalence and a change in the peak age of HAV hepatitis.This study could provide baseline data of recent hepatitis A in Asia.展开更多
The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19.This study aimed to evaluate longitudinal change patterns of key laboratory tests in patients with COVID-1...The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19.This study aimed to evaluate longitudinal change patterns of key laboratory tests in patients with COVID-19,and identify independent prognostic factors by examining the associations between laboratory findings and outcomes of patients.This multicenter study included 56 patients with COVID-19 treated in Jilin Province,China,from January 21,2020 to March 5,2020.The laboratoryfindings,epidemiological characteristics and demographic data were extracted from electronic medical records.The average value of eosinophils and carbon dioxide combining power continued to significantly increase,while the average value of cardiac troponin I and mean platelet volume decreased throughout the course of the disease.The average value of lymphocytes approached the lower limit of the reference interval for the first 5 days and then rose slowly thereafter.The average value of thrombocytocrit peaked on day 7 and slowly declined thereafter.The average value of mean corpuscular volume and serum sodium showed an upward trend from day 8 and day 15,respectively.Age,sex,lactate dehydrogenase,platelet count and globulin level were included in the final model to predict the probability of recovery.The above parameters were verified in 24 patients with COVID-19 in another area of Jilin Province.The risk stratification and management of patients with COVID-19 could be improved according to the temporal trajectories of laboratory tests.展开更多
The Ebola virus(EBOV)is a member of the Orthoebolavirus genus,Filoviridae family,which causes severe hemorrhagic diseases in humans and non-human primates(NHPs),with a case fatality rate of up to 90%.The development o...The Ebola virus(EBOV)is a member of the Orthoebolavirus genus,Filoviridae family,which causes severe hemorrhagic diseases in humans and non-human primates(NHPs),with a case fatality rate of up to 90%.The development of countermeasures against EBOV has been hindered by the lack of ideal animal models,as EBOV requires handling in biosafety level(BSL)-4 facilities.Therefore,accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV.In this study,a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein(VSV-EBOV/GP)was constructed and applied as a surrogate virus,establishing a lethal infection in hamsters.Following infection with VSV-EBOV/GP,3-week-old female Syrian hamsters exhibited disease signs such as weight loss,multi-organ failure,severe uveitis,high viral loads,and developed severe systemic diseases similar to those observed in human EBOV patients.All animals succumbed at 2–3 days post-infection(dpi).Histopathological changes indicated that VSV-EBOV/GP targeted liver cells,suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV(WT EBOV).Notably,the pathogenicity of the VSV-EBOV/GP was found to be species-specific,age-related,gender-associated,and challenge route-dependent.Subsequently,equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model.Overall,this surrogate model represents a safe,effective,and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions,which would accelerate technological advances and breakthroughs in confronting Ebola virus disease.展开更多
Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 pandemic.However,approaches for its analysis by use of reverse transcription quantitative polymer...Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 pandemic.However,approaches for its analysis by use of reverse transcription quantitative polymerase chain reaction(RT-q PCR)are still far from standardized globally.To characterize inter-and intra-laboratory variability among results when using various methods deployed across Canada,aliquots from a real wastewater sample were spiked with surrogates of SARS-CoV-2(gamma-radiation inactivated SARS-CoV-2 and human coronavirus strain 229E[HCoV-229E])at low and high levels then provided"blind"to eight laboratories.Concentration estimates reported by individual laboratories were consistently within a 1.0-log_(10) range for aliquots of the same spiked condition.All laboratories distinguished between low-and high-spikes for both surrogates.As expected,greater variability was observed in the results amongst laboratories than within individual laboratories,but SARS-CoV-2 RNA concentration estimates for each spiked condition remained mostly within 1.0-log_(10) ranges.The no-spike wastewater aliquots provided yielded non-detects or trace levels(<20 gene copies/mL)of SARS-CoV-2 RNA.Detections appear linked to methods that included or focused on the solids fraction of the wastewater matrix and might represent in-situ SARS-CoV-2 to the wastewater sample.HCoV-229E RNA was not detected in the no-spike aliquots.Overall,all methods yielded comparable results at the conditions tested.Partitioning behavior of SARS-CoV-2 and spiked surrogates in wastewater should be considered to evaluate method effectiveness.A consistent method and laboratory to explore wastewater SARS-CoV-2 temporal trends for a given system,with appropriate quality control protocols and documented in adequate detail should succeed.展开更多
The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a ...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a unique physiological condition, and is characterized by altered immunity and elevated hormone levels to actively tolerate the semiallogeneic fetus, which undergoes a sudden and substantial fluctuation during the immediate postpartum period. Changes in clinical features, laboratory characteristics, and imaging features of pregnant women during the pre-partum and postpartum periods require further elucidation. Here, we retrospectively analyzed the clinical features, laboratory characteristics, and imaging features of eight pregnant cases of SARS-CoV-2 infection during the pre-partum and post-partum periods. Our results showed that four of the eight pregnant women were asymptomatic before delivery but became symptomatic post-partum. Correspondingly, white blood cell(WBC) counts increased and lymphocyte(LYMPH) counts decreased. C-reactive protein(CRP) levels in the serum also increased to a higher level than those in general pregnancy.Therefore, it is imperative to closely monitor laboratory parameters including the WBC count, LYMPH count, and CRP,along with other imaging features in chest CT scans, to promptly prevent, diagnose, and treat a SARS-CoV-2 infection during pregnancy.展开更多
The current rapidly rising 5^(th) wave of the Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2),dominated by the omicron variant,has clearly shown the challenges in monitoring,and tracing clinical cases of i...The current rapidly rising 5^(th) wave of the Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2),dominated by the omicron variant,has clearly shown the challenges in monitoring,and tracing clinical cases of infection.Omicron has been identified by the World Health Organization(WHO)as a variant of concern(VOC)on November 26^(th) of 2021,because of the reported higher risk of transmission,reinfection.展开更多
BACKGROUND D-dimer,a soluble degradation product of cross-linked fibrin,is commonly used as an important marker for the diagnosis of disseminated intravascular coagulation and differential diagnosis of thrombosis.Here...BACKGROUND D-dimer,a soluble degradation product of cross-linked fibrin,is commonly used as an important marker for the diagnosis of disseminated intravascular coagulation and differential diagnosis of thrombosis.Herein,we present a geriatric case with an unusually elevated D-dimer level.CASE SUMMARY An 82-year-old woman,admitted to the ward with a diagnosis of chronic heart failure,was noted to have a remarkably elevated D-dimer level,beyond the qualified range(>100 mg/L),utilizing the Innovating D-dimer for Sysmex CS-5100 System?.However,no evidence,including clinical symptoms,radiographic evidence of thromboembolic disease,and parallel fibrinogen degradation product values,suggested that this patient was at high risk of thrombopenia.To confirm the discrepancy,a series of approaches including sample dilution,re-analysis via alternative methods,and sample treatment with blockage of specific heterophilic antibodies were performed.A remarkable disappearance of the elevated D-dimer values was observed in the samples after they were subjected to these approaches(4.49,9.42,9.06,and 12.58 mg/L,respectively).This confirmed the presence of heterophilic antibodies in this case.In addition,a reduction in cardiac output due to the presence of cardiac failure could also be responsible for the existence of a hypercoagulable state in this case.CONCLUSION In conclusion,the presence of heterophilic antibodies should be considered when an elevated D-dimer value is not in conformity with the clinical evidence,and a viral infection should be considered when interference by a heterophilic antibody exists.展开更多
Dear Editor,We are writing to express concerns regarding the recent paper“A unique pseudo-eligibility analysis of longitudinal laboratory performance data from a transgender female competitive cyclist”by Hamilton et...Dear Editor,We are writing to express concerns regarding the recent paper“A unique pseudo-eligibility analysis of longitudinal laboratory performance data from a transgender female competitive cyclist”by Hamilton et al.[1].The authors assert that a sub-elite trans woman athlete can compete equitably in elite women’s cycling events after one year of gender-affirming hormone therapy(GAHT).However,this conclusion is not supported by the data presented.Furthermore,the authors’presentation of data from a single athlete as a basis for inferring the effects of testosterone suppression is fundamentally flawed.展开更多
In the 21st century,the determination of alert thresholds remains the most challenging and controversial issue in clinical pediatrics.Pre-analytical,analytical,and postanalytical matters will consolidate or undermine ...In the 21st century,the determination of alert thresholds remains the most challenging and controversial issue in clinical pediatrics.Pre-analytical,analytical,and postanalytical matters will consolidate or undermine the fate of any laboratory process.Pre-analytical issues need to be cleared off before the laboratory physician can dispatch the result to the pediatrician in charge.Once it is cleared off,the classification of essential laboratory results is paramount.It is more than an academic exercise and may be subdivided in the order of priority we handle it to inform promptly and safely the primary physicians.Currently,we are applying new modes of making sure relevant information is transmitted without interrupting the standard workflow of the primary physicians in charge for the child,who eventually need a fast line of action for results that may be lifethreatening.展开更多
Since our Department for Dialysis performs the Peritoneal Equilibration Test （PET） to monitor peritoneal dialysis adequacy, our Laboratory has been asked to collaborate on calculating clearances and transport charac...Since our Department for Dialysis performs the Peritoneal Equilibration Test （PET） to monitor peritoneal dialysis adequacy, our Laboratory has been asked to collaborate on calculating clearances and transport characteristics of patients. This collaboration is ongoing since 2003, despite the Baxter-PD Adequest software having appeared. Our aim is to emphasize the importance of the laboratory in the selection of formulas and specifically in solving the problem of determining creatinine concentration in PETs, and to recommend the cooperation between the laboratory and the dialysis department. Since creatinine determination is encumbered by recommendations for correcting elevated creatinine levels because of the influence of glucose in PETs, we compared results of dialysates determined as serum and as urine. Until now we had 86 patients on continuous ambulatory peritoneal dialysis （CAPD）. Method for determining patients＇ creatinine remains Jaffe kinetic uncompesated although the analyzers and the corresponding reagenses were changed in the laboratory. We have achieved the complete cooperation and confidence in the result, and with the PET test performed strictly according to the protocol, increasingly better results for clearences, Kt/V and transport characteristics. All this helps with treatment planning and analyzing patients＇ quality of life.展开更多
Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation ...Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.展开更多
Dear Editor,On March 8–15,2022,a board of international scientists assembled in Lyon to evaluate the carcinogenicity of cobalt metal,cobalt(Ⅱ)salts,antimony trioxide,and weaponsgrade tungsten alloy harboring nickel ...Dear Editor,On March 8–15,2022,a board of international scientists assembled in Lyon to evaluate the carcinogenicity of cobalt metal,cobalt(Ⅱ)salts,antimony trioxide,and weaponsgrade tungsten alloy harboring nickel and cobalt[1].The 131st International Agency for Research on Cancer(IARC)Monograph is the result of a 6–9-month work of perusing the literature,slide evaluation,data interpretation,and interim meetings.The assessment of cobalt,antimony,and nickelcontaining alloys will have tremendous consequences for the industry,health,and defense departments[1].展开更多
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金supported by the National Natural Science Foundation of China,No.81671263(to XX)Scientific Research and Innovation Team,Education Department of Anhui Province,China,No.2023AH010072(to XX)+1 种基金the Natural Science Foundation of Anhui Province,No.2208085MH221(to XX)The Key Projects for National Science Research of Education Department of Anhui Province,No.KJ2021A0851(to YD).
文摘Cmyc,a proto-oncogene,is expressed at extremely low levels in mature neurons and is traditionally thought to have no function in these cells.However,recent studies suggest that Cmyc may play a crucial role in maintaining the health and function of mature dopaminergic neurons.This study assessed the role of Cmyc in dopaminergic neurons and its significance in Parkinson’s disease.We used a conditional knockout approach to specifically delete Cmyc in substantia nigra dopaminergic neurons of adult mice.Our findings showed that Cmyc deletion led to progressive neuron loss,Parkinson’s disease-like symptoms,downregulation of Klotho,and upregulation of senescence-associated inflammatory factors,along with enhanced oxidative stress and nitrated alpha-synuclein accumulation,ultimately causing neuronal death.In vitro experiments confirmed increased senescence in C-MYC knockout cells,which was partially reversible by KLOTHO overexpression.We conclude that low-level Cmyc expression is essential for maintaining the health of mature dopaminergic neurons and preventing neurodegeneration,and suggest the c-Myc/Klotho axis as a potential therapeutic target for age-related neurodegenerative diseases,including Parkinson’s disease.Our study introduces a novel mouse model for Parkinson’s disease that replicates a condition associated with normal aging,offering a valuable tool for future research into disease mechanisms and therapeutic strategies.
基金Supported by the National Natural Science Foundation of China(No.81873686)Natural Science Foundation of Hunan Province(No.2023JJ30715)+4 种基金Scientific Research Project of Hunan Provincial Health Commission(No.A202303018385)Health Research Project of Hunan Provincial Health Commission(No.W20243024)Distinguished Professor of the Lotus Scholars Award Program of Hunan ProvinceSublimation Scholars Project of Central South UniversityWisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202109).
文摘AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.
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supported by the National Key Research and Development Program of China(2023YFC2308800)the Natural Science Foundation of Shanghai(25ZR1402053)the Key Discipline of Public Health of the Shanghai Municipal Health Commission(Grant No.GWVI-11.1-07).
文摘Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus(HR-HPV)infection.Methods Female patients(n=73)with HR-HPV infection were enrolled and divided into a high-grade squamous intraepithelial lesion(HSIL)group(n=33)and a non-HSIL(N-HSIL)group(n=40),which include low-grade squamous intraepithelial lesions and inflammation.Healthy screening subjects(n=31)with negative HR-HPV results were enrolled as a control group.We examined contemporaneous plasma and secretory cytokines from 25 study subjects to investigate the difference between systemic cytokine profiles and the local microenvironment immunity using the Wilcoxon matched-pairs signed rank test.The 12 cytokines from cervical secretions were compared between the three groups using the Mann-Whitney test,and logistic regression was used to analyze HSIL and N-HSIL.Results There were statistical differences in eight cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-1β,IL-12p70,IFN-α,and IL-8)between cervical secretion and plasma of the same patient,and seven cytokines were statistically different between the control and other two groups.We selected four independent variables(TNF-α,IFN-γ,IL-12p70,and IFN-α)commonly identified by univariate regression analysis and non-parametric tests for multivariate logistic regression analysis.Based on this model,HSIL could be predicted in patients with HR-HPV infection,with the area under the curve being 0.76.Conclusion The systemic cytokine profile cannot reflect the local microenvironment immunity,and the occurrence of HSIL is related to the cytokine levels in the cervical microenvironment.
基金supported by Guangdong Province Basic and Applied Basic Research Fund Project(2023A1515220104)Open Fund of Key Laboratory of Hepatoaplenic Surgery,Ministry of Education(Award Number:GPKF202407).
文摘Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.
基金supported by grants from the Knut and Alice Wallenberg foundation(P-OB,JRZ,and AK)the Swedish Research Council(JRZ and AK),Centrum för idrottsforskning(AK and JRZ)+7 种基金the NovoNordisk Foundation Metabolic Stress Associated Molecules(MSAM)consortium NNF15SA0018346 and Metabolite-related Inflammation and Disease(MeRIAD)consortium Grant number 0064142(AK)the Swedish Diabetes Foundation(AK and JRZ)the European Foundation for the Study of Diabetes(JRZ and AK)the Region Stockholm(ALF project)(JRZ and KC)the Strategic Research Program in Diabetes at Karolinska Institutet(JRZ and AK)supported by the Strategic Research Programme in Diabetes(SRP Diabetes)for use of the Seahorse flux analyzer.Human islets were made possible through the Juvenile Diabetes Research Foundation(JDRF)award 31-2008-416(European Coordinating Infrastructure for Islet Transplantation(ECIT),Islet for Basic Research program)AK holds a Distinguished Investigator Grant within Endocrinology and Metabolism from the Novo Nordisk Foundation(NNF24OC0088739)JRZ received the 2024 European Association for the Study of Diabetes(ESAD)-Novo Nordisk Foundation Diabetes Prize for Excellence(NNF24SA0092609).
文摘Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.
文摘Objective Hemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders.This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection.Methods Wie retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1,2015 to March 31,2018.Clinical data were collected and investigated,including clinical manifestations,hemostatic and fibrinolytic parameters,dosage of hemocoagulase,the medication time,and the cryoprecipitate blood product infusion.Differences in fibrinogen,D-dimer,and fibrin/fibrinogen degradation products(FDP)before,during,and after the application of hemocoagulase injection were analyzed statistically.Results Plasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment(F=1.80,P<0.001),with the average decrease of 2.28 g/L(0.63-3.9 g/L).After withdrawal,fibrinogen level increased significantly compared to that during the medication(F=l.20,P<0.001),but was still lower than that before the medication(F=0.59,P=0.03).The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication(F=0.83,P=0.002;Wilcoxon-test,Z=-4.54,P<0.001).Spearman's correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemo coagulase(r=-0.17,P=0.40;r=-0.28,P=0.15;respectively)and the time of recovery from hypofibrinogenemia(r=-0.45,P=0.05;r=0.13,P=0.61;respectively).Conclusion Monitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection.Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.
文摘AIM:To evaluate seroprevalence of hepatitis A virus (HAV) antibody and investigate demographic,clinical,and laboratory features of recent cases in Korea.METHODS:For the evaluation of hepatitis A seroprevalence,we analyzed the data from 3127 subjects including,healthcare workers and patients who visited Konkuk University Hospital,a secondary referral center,from January to October 2009.The sera with positive IgM were excluded from seroprevalence data for total HAV antibody.We retrospectively reviewed the electronic medical records of 419 patients with HAV,who were diagnosed by the presence of serum IgM antibodies against HAV.All patients presented at Konkuk University Hospital between August 2005 and September 2008.RESULTS:Among 3127 sera tested,1428 (45.7%)were positive for anti-HAV antibody.The seroprevalence was very low in teenagers or those in their twenties,increased in those in their thirties,and was > 90% in older patients.In children younger than 10 years,seroprevalence was increased again.Most patients with HAV hepatitis were in their twenties and thirties.The γ-glutamyl transpeptidase increased with age and was significantly higher in patients older than 30 years.Indicators of severity,such as decreased albumin and increased bilirubin,were also more prominent in the older age group;however,the leukocyte count was higher and the frequency of leukopenia was lower in younger patients than in older adults.CONCLUSION:There has been an apparent epidemiological shift in HAV seroprevalence and a change in the peak age of HAV hepatitis.This study could provide baseline data of recent hepatitis A in Asia.
基金supported by grants from Jilin Science and Technology Development Program(No.20170623092TC-09,to Dr.Jiancheng Xu,No.20190304110YY to Dr.Jiancheng Xu,No.20200404171YY to Dr.Qi Zhou)the First Hospital Translational Funding for Scientific and Technological Achievements(No.JDYYZH-1902002 to Dr.Jiancheng Xu)。
文摘The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19.This study aimed to evaluate longitudinal change patterns of key laboratory tests in patients with COVID-19,and identify independent prognostic factors by examining the associations between laboratory findings and outcomes of patients.This multicenter study included 56 patients with COVID-19 treated in Jilin Province,China,from January 21,2020 to March 5,2020.The laboratoryfindings,epidemiological characteristics and demographic data were extracted from electronic medical records.The average value of eosinophils and carbon dioxide combining power continued to significantly increase,while the average value of cardiac troponin I and mean platelet volume decreased throughout the course of the disease.The average value of lymphocytes approached the lower limit of the reference interval for the first 5 days and then rose slowly thereafter.The average value of thrombocytocrit peaked on day 7 and slowly declined thereafter.The average value of mean corpuscular volume and serum sodium showed an upward trend from day 8 and day 15,respectively.Age,sex,lactate dehydrogenase,platelet count and globulin level were included in the final model to predict the probability of recovery.The above parameters were verified in 24 patients with COVID-19 in another area of Jilin Province.The risk stratification and management of patients with COVID-19 could be improved according to the temporal trajectories of laboratory tests.
基金supported by National Key R&D Program of China(grant number 2023YFC2605500)Jilin Province Youth Talent Support Project(grant number QT202208)+1 种基金the Ministry of Science and Technology of the People's Republic of China(grant number 2022YFC0867900)Nation Key Research and Development Program of China,New technology of rapid of pathogens in laboratory animals(grant number 2021YFF07033600).
文摘The Ebola virus(EBOV)is a member of the Orthoebolavirus genus,Filoviridae family,which causes severe hemorrhagic diseases in humans and non-human primates(NHPs),with a case fatality rate of up to 90%.The development of countermeasures against EBOV has been hindered by the lack of ideal animal models,as EBOV requires handling in biosafety level(BSL)-4 facilities.Therefore,accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV.In this study,a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein(VSV-EBOV/GP)was constructed and applied as a surrogate virus,establishing a lethal infection in hamsters.Following infection with VSV-EBOV/GP,3-week-old female Syrian hamsters exhibited disease signs such as weight loss,multi-organ failure,severe uveitis,high viral loads,and developed severe systemic diseases similar to those observed in human EBOV patients.All animals succumbed at 2–3 days post-infection(dpi).Histopathological changes indicated that VSV-EBOV/GP targeted liver cells,suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV(WT EBOV).Notably,the pathogenicity of the VSV-EBOV/GP was found to be species-specific,age-related,gender-associated,and challenge route-dependent.Subsequently,equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model.Overall,this surrogate model represents a safe,effective,and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions,which would accelerate technological advances and breakthroughs in confronting Ebola virus disease.
基金supported by a CHEO (Children’s Hospital of Eastern Ontario) CHAMO (Children’s Hospital Academic Medical Organization) grant, awarded to Dr.Alex E.Mac Kenziesupported by the “Next generation solutions to ensure healthy water resources for future generations” funded by the Global Water Futures program, Canada First Research Excellence Fund (#419205)+7 种基金supported by the Canada Research Chairs Program of the Natural Sciences and Engineering Research Council of Canada (NSERC)supported by funding from NSERC Discovery and Strategic Grant Programssupported by funding from an NSERC Discovery Grantsupported by the NSERC Alliance COVID-19 Grantby Mitacs through the Mitacs Accelerate programsupported by Canadian Institutes of Health Research (CIHR), Alberta Innovates, Alberta Health-Water for Life Strategysupported by the BC center for Disease Control, BC center for Disease Control Foundation for Public Health and Metro Vancouversupported by the Canada Research Chairs Program of NSERC。
文摘Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 pandemic.However,approaches for its analysis by use of reverse transcription quantitative polymerase chain reaction(RT-q PCR)are still far from standardized globally.To characterize inter-and intra-laboratory variability among results when using various methods deployed across Canada,aliquots from a real wastewater sample were spiked with surrogates of SARS-CoV-2(gamma-radiation inactivated SARS-CoV-2 and human coronavirus strain 229E[HCoV-229E])at low and high levels then provided"blind"to eight laboratories.Concentration estimates reported by individual laboratories were consistently within a 1.0-log_(10) range for aliquots of the same spiked condition.All laboratories distinguished between low-and high-spikes for both surrogates.As expected,greater variability was observed in the results amongst laboratories than within individual laboratories,but SARS-CoV-2 RNA concentration estimates for each spiked condition remained mostly within 1.0-log_(10) ranges.The no-spike wastewater aliquots provided yielded non-detects or trace levels(<20 gene copies/mL)of SARS-CoV-2 RNA.Detections appear linked to methods that included or focused on the solids fraction of the wastewater matrix and might represent in-situ SARS-CoV-2 to the wastewater sample.HCoV-229E RNA was not detected in the no-spike aliquots.Overall,all methods yielded comparable results at the conditions tested.Partitioning behavior of SARS-CoV-2 and spiked surrogates in wastewater should be considered to evaluate method effectiveness.A consistent method and laboratory to explore wastewater SARS-CoV-2 temporal trends for a given system,with appropriate quality control protocols and documented in adequate detail should succeed.
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a unique physiological condition, and is characterized by altered immunity and elevated hormone levels to actively tolerate the semiallogeneic fetus, which undergoes a sudden and substantial fluctuation during the immediate postpartum period. Changes in clinical features, laboratory characteristics, and imaging features of pregnant women during the pre-partum and postpartum periods require further elucidation. Here, we retrospectively analyzed the clinical features, laboratory characteristics, and imaging features of eight pregnant cases of SARS-CoV-2 infection during the pre-partum and post-partum periods. Our results showed that four of the eight pregnant women were asymptomatic before delivery but became symptomatic post-partum. Correspondingly, white blood cell(WBC) counts increased and lymphocyte(LYMPH) counts decreased. C-reactive protein(CRP) levels in the serum also increased to a higher level than those in general pregnancy.Therefore, it is imperative to closely monitor laboratory parameters including the WBC count, LYMPH count, and CRP,along with other imaging features in chest CT scans, to promptly prevent, diagnose, and treat a SARS-CoV-2 infection during pregnancy.
文摘The current rapidly rising 5^(th) wave of the Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2),dominated by the omicron variant,has clearly shown the challenges in monitoring,and tracing clinical cases of infection.Omicron has been identified by the World Health Organization(WHO)as a variant of concern(VOC)on November 26^(th) of 2021,because of the reported higher risk of transmission,reinfection.
基金Supported by the National Natural Science Foundation of China,No.81672083 and No.81702071
文摘BACKGROUND D-dimer,a soluble degradation product of cross-linked fibrin,is commonly used as an important marker for the diagnosis of disseminated intravascular coagulation and differential diagnosis of thrombosis.Herein,we present a geriatric case with an unusually elevated D-dimer level.CASE SUMMARY An 82-year-old woman,admitted to the ward with a diagnosis of chronic heart failure,was noted to have a remarkably elevated D-dimer level,beyond the qualified range(>100 mg/L),utilizing the Innovating D-dimer for Sysmex CS-5100 System?.However,no evidence,including clinical symptoms,radiographic evidence of thromboembolic disease,and parallel fibrinogen degradation product values,suggested that this patient was at high risk of thrombopenia.To confirm the discrepancy,a series of approaches including sample dilution,re-analysis via alternative methods,and sample treatment with blockage of specific heterophilic antibodies were performed.A remarkable disappearance of the elevated D-dimer values was observed in the samples after they were subjected to these approaches(4.49,9.42,9.06,and 12.58 mg/L,respectively).This confirmed the presence of heterophilic antibodies in this case.In addition,a reduction in cardiac output due to the presence of cardiac failure could also be responsible for the existence of a hypercoagulable state in this case.CONCLUSION In conclusion,the presence of heterophilic antibodies should be considered when an elevated D-dimer value is not in conformity with the clinical evidence,and a viral infection should be considered when interference by a heterophilic antibody exists.
文摘Dear Editor,We are writing to express concerns regarding the recent paper“A unique pseudo-eligibility analysis of longitudinal laboratory performance data from a transgender female competitive cyclist”by Hamilton et al.[1].The authors assert that a sub-elite trans woman athlete can compete equitably in elite women’s cycling events after one year of gender-affirming hormone therapy(GAHT).However,this conclusion is not supported by the data presented.Furthermore,the authors’presentation of data from a single athlete as a basis for inferring the effects of testosterone suppression is fundamentally flawed.
文摘In the 21st century,the determination of alert thresholds remains the most challenging and controversial issue in clinical pediatrics.Pre-analytical,analytical,and postanalytical matters will consolidate or undermine the fate of any laboratory process.Pre-analytical issues need to be cleared off before the laboratory physician can dispatch the result to the pediatrician in charge.Once it is cleared off,the classification of essential laboratory results is paramount.It is more than an academic exercise and may be subdivided in the order of priority we handle it to inform promptly and safely the primary physicians.Currently,we are applying new modes of making sure relevant information is transmitted without interrupting the standard workflow of the primary physicians in charge for the child,who eventually need a fast line of action for results that may be lifethreatening.
文摘Since our Department for Dialysis performs the Peritoneal Equilibration Test （PET） to monitor peritoneal dialysis adequacy, our Laboratory has been asked to collaborate on calculating clearances and transport characteristics of patients. This collaboration is ongoing since 2003, despite the Baxter-PD Adequest software having appeared. Our aim is to emphasize the importance of the laboratory in the selection of formulas and specifically in solving the problem of determining creatinine concentration in PETs, and to recommend the cooperation between the laboratory and the dialysis department. Since creatinine determination is encumbered by recommendations for correcting elevated creatinine levels because of the influence of glucose in PETs, we compared results of dialysates determined as serum and as urine. Until now we had 86 patients on continuous ambulatory peritoneal dialysis （CAPD）. Method for determining patients＇ creatinine remains Jaffe kinetic uncompesated although the analyzers and the corresponding reagenses were changed in the laboratory. We have achieved the complete cooperation and confidence in the result, and with the PET test performed strictly according to the protocol, increasingly better results for clearences, Kt/V and transport characteristics. All this helps with treatment planning and analyzing patients＇ quality of life.
基金supported by the Chengdu University of Traditional Chinese Medicine"Xinglin Scholars"Program,China(Grant No.:MPRC2023014).
文摘Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.
文摘Dear Editor,On March 8–15,2022,a board of international scientists assembled in Lyon to evaluate the carcinogenicity of cobalt metal,cobalt(Ⅱ)salts,antimony trioxide,and weaponsgrade tungsten alloy harboring nickel and cobalt[1].The 131st International Agency for Research on Cancer(IARC)Monograph is the result of a 6–9-month work of perusing the literature,slide evaluation,data interpretation,and interim meetings.The assessment of cobalt,antimony,and nickelcontaining alloys will have tremendous consequences for the industry,health,and defense departments[1].
