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
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
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
It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases ...It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.展开更多
Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe CO...Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe COVID-19.But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.Methods:We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 pa-tients upon admission and one-month after their discharge,comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.Results:Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients.These altered microbial metabolites included tryptophan,bile acids,fatty acids,amino acids,vitamins and those containing benzene.A total of 13 distinct microbial metabolites were identi-fied in COVID-19 patients compared to healthy controls.Notably,correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19.Furthermore,these metabolites did not restore to the normal levels one month after discharge.Importantly,two mi-crobial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.Conclusions:The microbial metabolites were altered in the acute and recovery stage,correlating with dis-ease severity of COVID-19.These results indicated the important role of gut microbiota in the progression of COVID-19,and facilitated the potential therapeutic microbial target for severe COVID-19 patients.展开更多
Lactylation is one of the post-translational modifications of proteins,a process in which lactyl residues bind to the lysine residues of proteins.This modification can alter the structure,stability,and function of pro...Lactylation is one of the post-translational modifications of proteins,a process in which lactyl residues bind to the lysine residues of proteins.This modification can alter the structure,stability,and function of proteins,which in turn regulates cellular metabolism,aging,and the onset of disease.This review classifies proteins with lactylation effects into histones and non-histone proteins and analyzes their functional roles when lactylation occurs.The in-depth exploration of lactylation is still in its infancy,and many aspects of its regulation,functional significance and therapeutic potential need to be further explored.展开更多
Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprote...Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprotein(AFP),and protein induced by vitamin K absence II(PIVKA-II)with/without AFP-L3,ASAP and GALAD models are potential diagnostic panels.The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases(CLDs).Methods:A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chi-nese hospitals.The etiologies of CLDs included hepatitis B virus(HBV),hepatitis C virus(HCV),alcoholic liver disease(ALD),and nonalcoholic fatty liver disease(NAFLD).Using area under the receiver operating characteristic curve(AUC)values,the diagnostic performances of ASAP and GALAD models were com-pared to detect HCC among patients with various etiologies of CLDs.Results:Among 248 HCC patients and 722 CLD controls,the ASAP model demonstrated the highest AUC(0.886)to detect HCC at any stage,outperforming the GALAD model(0.853,P=0.001),as well as any individual biomarker(0.687-0.799,all P<0.001).In the subgroup analysis of various CLDs etiologies,the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology.In addition,the ASAP model performed better in detecting early-stage(BCLC stage 0/A)HCC versus the GALAD model.Conclusions:Despite using one less laboratory variable(AFP-L3),the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various eti-ologies of CLDs-related HCC.展开更多
BACKGROUND Primary liver cancer(PLC)is characterized by high malignancy,rapid disease progression,and persistent high incidence and mortality rates,posing a significant public health challenge worldwide.Early diagnosi...BACKGROUND Primary liver cancer(PLC)is characterized by high malignancy,rapid disease progression,and persistent high incidence and mortality rates,posing a significant public health challenge worldwide.Early diagnosis and assessment of PLC are of great significance for guiding clinical treatment and improving patient prognosis.Alpha fetoprotein(AFP)and gamma-glutamyl transpeptidase(GGT)are commonly utilized tumor markers for the clinical diagnosis of PLC.They are ideal indicators for the detection of metastasis and recurrence after LC surgery.Nevertheless,not all patients with PLC secrete large amounts of AFP and GGT,which affects the accuracy of evaluating PLC by monitoring these two tumor markers alone.Cluster of differentiation 3 and 161 double-positive natural killer T(CD3^(+)CD161^(+)NKT)cell subsets are a class of molecules inextricably related to immune function and tumor occurrence and development.This research seeks to explore the clinical significance of CD3^(+)CD161^(+)NKT cell subsets combined with tumor markers AFP and GGT in the diagnosis of patients with PLC.AIM To probe the clinical significance of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT changes in the peripheral blood of individuals with PLC.METHODS The PLC group comprised 30 patients diagnosed with PLC who were admitted to our hospital between July 2022 and December 2023,whereas the control group consisted of 30 healthy individuals undergoing routine physical examinations at our hospital.Peripheral blood samples were harvested from both cohorts of patients.The levels of CD4^(+)NKT,CD8^(+)NKT,CD3^(+)CD56^(+)NKT,CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,and CD3-CD161^(+)NKT were measured by flow cytometry.Serum AFP content was determined using a fully automatic immunoassay analyzer,and serum GGT content was ascertained by a fully automatic biochemical analyzer.The diagnostic value of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT level alterations for PLC was evaluated by receiver operating characteristic curve analysis.RESULTS No significant disparities were observed in the counts of white blood cells,neutrophils,and platelets,as well as the levels of blood urea nitrogen and serum creatinine between the two groups(P>0.05).Lymphocytes,red blood cells,hemoglobin,total protein,albumin,and globulin were more attenuated in the PLC group than in the control group,while glutamic-pyruvic transaminase,glutamic oxalacetic transaminase,and carcinoembryonic antigen levels were increased in the PLC cohort compared with the control cohort,with statistical significance(P<0.05).No substantial difference was discovered in peripheral blood CD4^(+)NKT,CD8^(+)NKT,and CD3^(+)CD56^(+)NKT cells between the two cohorts(P>0.05).The percentage of CD8^(+)CD56^(+)NKT cells(8.35%±1.01%),CD3^(+)CD161^(+)NKT cells(14.36%±1.55%),and CD3-CD161^(+)NKT cells(12.08%±1.34%)in the PLC group was higher than that in the control group(P<0.05).The levels of AFP(335.71±20.89 ng/mL)and GGT(136.87±15.62 U/mL)in the PLC cohort were elevated within the PLC cohort compared with the control cohort(P<0.05).The sensitivity of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT alone for diagnosing PLC was 70.00%,83.33%,80.00%,56.67%,and 53.33%,respectively(P<0.05),with specificity rates of 66.67%,80.00%,76.67%,76.67%,and 66.67%,respectively(P<0.05).The area under the curve for combined detection was 0.898,with a sensitivity of 86.67%and a specificity of 80.00%(P<0.05).CONCLUSION The levels of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT in the peripheral blood of patients with PLC were markedly elevated.The combined detection of these five indicators can improve the sensitivity and specificity of PLC diagnosis,providing solid evidence for the early clinical diagnosis of PLC.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 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.
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].
基金supported by the Natural Science Foundation of Jiangsu Province of China,No.BK20211348(to SHQ)Xuzhou Basic Research Program,No.KC21030(to LYH)+1 种基金Leadership Program of Xuzhou Medical University,No.JBGS202203(to SHQ)Research Grant Council GRF of Hong Kong Special Administrative Region of China,No.17105220(to JGS)。
文摘It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.
基金supported by grants from the National Key R&D Program of China(2021YFA1301001)the Natural Science Founda-tion of China(82170668)+1 种基金the Sino-German Center for Research Promotion(GZ1546)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-045).
文摘Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe COVID-19.But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.Methods:We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 pa-tients upon admission and one-month after their discharge,comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.Results:Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients.These altered microbial metabolites included tryptophan,bile acids,fatty acids,amino acids,vitamins and those containing benzene.A total of 13 distinct microbial metabolites were identi-fied in COVID-19 patients compared to healthy controls.Notably,correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19.Furthermore,these metabolites did not restore to the normal levels one month after discharge.Importantly,two mi-crobial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.Conclusions:The microbial metabolites were altered in the acute and recovery stage,correlating with dis-ease severity of COVID-19.These results indicated the important role of gut microbiota in the progression of COVID-19,and facilitated the potential therapeutic microbial target for severe COVID-19 patients.
基金supported by the Natural Science Foundation of Guangdong Province(No.2024A1515010605,2022A1515140034)Discipline Construction Project of Guangdong Medical University(No.4SG24007G,4SG22302P)+1 种基金Medical Scientific Research Fund of Guangdong Province(No.B2024193)Dongguan Social Development and Scientific Technology Project,China(No.20231800936562).
文摘Lactylation is one of the post-translational modifications of proteins,a process in which lactyl residues bind to the lysine residues of proteins.This modification can alter the structure,stability,and function of proteins,which in turn regulates cellular metabolism,aging,and the onset of disease.This review classifies proteins with lactylation effects into histones and non-histone proteins and analyzes their functional roles when lactylation occurs.The in-depth exploration of lactylation is still in its infancy,and many aspects of its regulation,functional significance and therapeutic potential need to be further explored.
基金supported by grants from the National Natural Science Foundation of China(81972726 and 82273074)Abbott Diagnostics(ADD-China-2016).
文摘Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprotein(AFP),and protein induced by vitamin K absence II(PIVKA-II)with/without AFP-L3,ASAP and GALAD models are potential diagnostic panels.The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases(CLDs).Methods:A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chi-nese hospitals.The etiologies of CLDs included hepatitis B virus(HBV),hepatitis C virus(HCV),alcoholic liver disease(ALD),and nonalcoholic fatty liver disease(NAFLD).Using area under the receiver operating characteristic curve(AUC)values,the diagnostic performances of ASAP and GALAD models were com-pared to detect HCC among patients with various etiologies of CLDs.Results:Among 248 HCC patients and 722 CLD controls,the ASAP model demonstrated the highest AUC(0.886)to detect HCC at any stage,outperforming the GALAD model(0.853,P=0.001),as well as any individual biomarker(0.687-0.799,all P<0.001).In the subgroup analysis of various CLDs etiologies,the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology.In addition,the ASAP model performed better in detecting early-stage(BCLC stage 0/A)HCC versus the GALAD model.Conclusions:Despite using one less laboratory variable(AFP-L3),the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various eti-ologies of CLDs-related HCC.
文摘BACKGROUND Primary liver cancer(PLC)is characterized by high malignancy,rapid disease progression,and persistent high incidence and mortality rates,posing a significant public health challenge worldwide.Early diagnosis and assessment of PLC are of great significance for guiding clinical treatment and improving patient prognosis.Alpha fetoprotein(AFP)and gamma-glutamyl transpeptidase(GGT)are commonly utilized tumor markers for the clinical diagnosis of PLC.They are ideal indicators for the detection of metastasis and recurrence after LC surgery.Nevertheless,not all patients with PLC secrete large amounts of AFP and GGT,which affects the accuracy of evaluating PLC by monitoring these two tumor markers alone.Cluster of differentiation 3 and 161 double-positive natural killer T(CD3^(+)CD161^(+)NKT)cell subsets are a class of molecules inextricably related to immune function and tumor occurrence and development.This research seeks to explore the clinical significance of CD3^(+)CD161^(+)NKT cell subsets combined with tumor markers AFP and GGT in the diagnosis of patients with PLC.AIM To probe the clinical significance of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT changes in the peripheral blood of individuals with PLC.METHODS The PLC group comprised 30 patients diagnosed with PLC who were admitted to our hospital between July 2022 and December 2023,whereas the control group consisted of 30 healthy individuals undergoing routine physical examinations at our hospital.Peripheral blood samples were harvested from both cohorts of patients.The levels of CD4^(+)NKT,CD8^(+)NKT,CD3^(+)CD56^(+)NKT,CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,and CD3-CD161^(+)NKT were measured by flow cytometry.Serum AFP content was determined using a fully automatic immunoassay analyzer,and serum GGT content was ascertained by a fully automatic biochemical analyzer.The diagnostic value of CD3^(+)CD161^(+)NKT cell subsets and AFP and GGT level alterations for PLC was evaluated by receiver operating characteristic curve analysis.RESULTS No significant disparities were observed in the counts of white blood cells,neutrophils,and platelets,as well as the levels of blood urea nitrogen and serum creatinine between the two groups(P>0.05).Lymphocytes,red blood cells,hemoglobin,total protein,albumin,and globulin were more attenuated in the PLC group than in the control group,while glutamic-pyruvic transaminase,glutamic oxalacetic transaminase,and carcinoembryonic antigen levels were increased in the PLC cohort compared with the control cohort,with statistical significance(P<0.05).No substantial difference was discovered in peripheral blood CD4^(+)NKT,CD8^(+)NKT,and CD3^(+)CD56^(+)NKT cells between the two cohorts(P>0.05).The percentage of CD8^(+)CD56^(+)NKT cells(8.35%±1.01%),CD3^(+)CD161^(+)NKT cells(14.36%±1.55%),and CD3-CD161^(+)NKT cells(12.08%±1.34%)in the PLC group was higher than that in the control group(P<0.05).The levels of AFP(335.71±20.89 ng/mL)and GGT(136.87±15.62 U/mL)in the PLC cohort were elevated within the PLC cohort compared with the control cohort(P<0.05).The sensitivity of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT alone for diagnosing PLC was 70.00%,83.33%,80.00%,56.67%,and 53.33%,respectively(P<0.05),with specificity rates of 66.67%,80.00%,76.67%,76.67%,and 66.67%,respectively(P<0.05).The area under the curve for combined detection was 0.898,with a sensitivity of 86.67%and a specificity of 80.00%(P<0.05).CONCLUSION The levels of CD8^(+)CD56^(+)NKT,CD3^(+)CD161^(+)NKT,CD3-CD161^(+)NKT,AFP,and GGT in the peripheral blood of patients with PLC were markedly elevated.The combined detection of these five indicators can improve the sensitivity and specificity of PLC diagnosis,providing solid evidence for the early clinical diagnosis of PLC.
