[ Objective] To study the effects of diets with different com-to-soybean ratios on production performance of lactational Rex rabbits and select the best feed formula. [Method] A total of 80 lactational healthy Rex rab...[ Objective] To study the effects of diets with different com-to-soybean ratios on production performance of lactational Rex rabbits and select the best feed formula. [Method] A total of 80 lactational healthy Rex rabbits （similar age, body weight and delivery time） were randomly divided into five groups, 16 in each group. The Rex rabbits in group I were fed with corn-based meal diet, group II with soybean-based meal diet, group III with the developed corn-soybean meal diet, group IV with corn-soybean meal free diet, and group CK with conventional corn-soybean meal diet. During the lactation period, the changes in the lactation performance, growth rate of baby rabbits, weight and feed costs were observed. [ Result] The lactation performance of mother rabbits and the growth rate of baby rabbits in the experimental groups were similar to that in the control group. The weaning survival rate of the group III was the highest, but it was not significantly higher than that of the control group. The weaning survival rate of the other three groups was lower than that of the control group （P〈0.05）. The weight loss of mother rabbits in the group I, II and III was not significantly different from that of the control group, but the weight loss of the group IV was higher than that of the control group （ P 〈 0.01 ）. [ Conclusion] Diets with appropriate corn-to-soybean ratios not only reduce feed costs but also give the best feeding effects.展开更多
Objective:Lactation mastitis is a kind of disease with high incidence during puerperium.In the early stage,breast massage can effectively eliminate the symptoms.However,the value of breast massage is not fully known t...Objective:Lactation mastitis is a kind of disease with high incidence during puerperium.In the early stage,breast massage can effectively eliminate the symptoms.However,the value of breast massage is not fully known to the public,which restricts its promotion and popularization.One important reason is the absence of a multi-dimensional and overall evaluation of outcome.COS is strongly advocated internationally as the outcome in clinical research to promote the transformation of clinical evidence into practice.At present,there is no systematic review of the existing outcome.This protocol aims to provide a set of outcomes and outcome evaluation schemes for developing COS of breast massage in lactation mastitis early stage.Methods:We will search PubMed,Embase,Web of Science,CNKI,Wan-fang,VIP,SinoMed,Grey literature databases(master and doctoral thesis databases and conference literature databases of CNKI,Wan-fang and SinoMed),Clinical Trials Registry Platform portal,the Clinical Trials Registry,Australian,New Zealand Clinical Trials Registry,the Center Watch Registry,before March 1,2021.We will include randomized controlled trials and non-randomized trials,cohort studies,case series,case reports.We will assess the quality of outcome reporting according to the MOMENT,classify all outcomes using the OMERACT Filter 2.0 conceptual framework.Descriptive analysis will be performed for all categorical variables using frequency and mean.Result:This protocol aims to help guide the design of systematic review to summarize the existing outcomes,and comprehensively evaluate existing outcomes,classify outcomes and provide schemes of outcome evaluation for developing COS of breast massage in the early stage of lactation mastitis.Percentage and mean will be used to describe the extracted data.Conclusion:This is the first systematic review protocol to summarize outcomes,measurement instruments,assessment times,measurement frequencies,measurers about breast massage in the early stage of lactational mastitis.展开更多
Optimizing nitrogen utilization efficiency and mitigating nitrogen losses in cows plays a pivotal role in fostering economic sustainability within contemporary agricultural systems.Biochanin A(BCA),a natural component...Optimizing nitrogen utilization efficiency and mitigating nitrogen losses in cows plays a pivotal role in fostering economic sustainability within contemporary agricultural systems.Biochanin A(BCA),a natural component in red clover,has the potential to improve nitrogen metabolism in dairy cows.The primary objective of this study was to probe the impact of biochanin A supplementation on lactational performance,nitrogen metabolism,and blood metabolites in dairy cows.A complete randomized block design experiment was conducted over 28 d,involving 36 multiparous Holstein cows(comparable milk yield=37.1±2.90 kg,BW=642±70.0 kg,days in milk=92±8.0 d,and parity=2.4±0.50),which were allocated to three treatment groups:the Control group(with 0 g/d BCA),the Low group(with 10 g/d per cow BCA),and the High group(with 40 g/d per cow BCA).Biochanin A supplementation improved the lactational performance of cows by increasing milk yield by 6.3%(P=0.007)and feed efficiency by 12.7%(P=0.009).Total intestinal apparent digestibility was unaffected by BCA supplementation(P>0.05),but microbial nitrogen was increased by 30.0%(P=0.002)for promoting nitrogen utilization efficiency by 20.7%(P=0.004).Milk competent yields(protein,lactose,and non-fat milk solid)were increased with increasing BCA supplementation(P 0.05).BCA did not affect body health of dairy cows.Additionally,none of the plasma endocrine hormones were affected(P>0.05).A total of 95 significantly different metabolites were screened from the plasma metabolites of cows in the BCA-added and non-added groups.After performing an enrichment analysis of the metabolic pathways associated with the different metabolites,six specific pathways were identified:bile acid biosynthesis,aspartate metabolism,pyrimidine metabolism,arginine and proline metabolism,the urea cycle,and ammonia recycling.The inclusion of BCA is suggested to enhance milk yield and modulate nitrogen metabolism by influencing relevant metabolites within the metabolic pathways.展开更多
Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein ...Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.展开更多
BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify t...BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.展开更多
Background:As a common breast disease in lactating women,lactational mastitis is clinically manifested as painful breast lumps and systemic symptoms.To a certain extent,this disease may affect the physical and mental ...Background:As a common breast disease in lactating women,lactational mastitis is clinically manifested as painful breast lumps and systemic symptoms.To a certain extent,this disease may affect the physical and mental health of lactating women and even the breastfeeding of infants.Objective:This study was conducted to evaluate the clinical efficacy of Lou’s Wentong Method in the comprehensive treatment of lactational mastitis and its effects on relevant symptoms.Methods:A total of 158 patients who were diagnosed with lactational mastitis in The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2022 to January 2024 were included in this study to conduct a retrospective analysis.The treatment method comprised oral administration of traditional Chinese medicine prescriptions guided by the concept of“Wentong zhi yong”(warming and dispersing therapy for treating abscesses),puncture and pus extraction for patients with abscess formation,and milk drainage for patients with milk stagnation.The clinical symptoms of these patients were collected according to the seven indexes in Lou’s quantitative scorecard for evaluating the condition of canker sores before and after treatment.Additionally,the improvement of each symptom after treatment,the total effective rate of the clinical treatment,and the total symptom evaluation score before and after treatment were also analyzed.Results:It was demonstrated that there were significant differences in the overall distribution of different severity symptoms(skin erythema,breast pain,number of lumps,size of lumps,breast abscesses,and body temperature)at three time points(P<0.01).The evaluation of these symptoms at different time points revealed that all symptoms were effectively mitigated over time.Meanwhile,the efficacy was assessed according to the efficacy index to evaluate the efficacy of Lou’s Wentong Method in the comprehensive treatment of lactational mastitis.The results corroborated the pronounced efficacy of Lou’s Wentong Method in treating lactational mastitis,exhibiting statistical significance(P<0.01).Conclusion:Lou’s Wentong Method has significant therapeutic effects in the comprehensive treatment of lactational mastitis.Furthermore,this method is conducive to alleviating the clinical symptoms of these patients as soon as possible and can reduce the pain of patients,thus promoting their recovery.展开更多
Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates...Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.展开更多
Both linoleic acid(18:2 n-6,LA)andα-linolenic acid(18:3 n-3,ALA)are essential fatty acids for infants.The contents of LA and ALA,and their ratio exhibited significant changes in human milk over the past 4 decades,whi...Both linoleic acid(18:2 n-6,LA)andα-linolenic acid(18:3 n-3,ALA)are essential fatty acids for infants.The contents of LA and ALA,and their ratio exhibited significant changes in human milk over the past 4 decades,which were not well summarized.Here,we summarized these values in 9898 human breast milk samples of 6664 mothers from 50 countries in 81 studies.A literature search was conducted using PubMed,Embase,and Web of Science between January 1980 and October 2023.The 95%confidence interval of LA/ALA ratio across lactation and gestation ranged from 14.24 to 31.26.The LA content was higher in China and Turkey(>20%)whereas the ALA content was below 1%in Africa.The LA/ALA ratio in countries along the Mediterranean coast exceeded 20 or even 30.LA and ALA contents increased significantly(P<0.01)while the ratio remained stable over the last 40 years.Multivariate meta-regression results showed that regions significantly(P<0.01)determined the LA,ALA,and LA/ALA ratio.Especially,maternal diet could definitely explain the variation while the effects of gestational age,lactation period was not significant.Clinical trials demonstrated that decreasing the LA/ALA ratio increased docosahexaenoic acid(22:6 n-3,DHA)status,reduced arachidonic acid(20:4 n-6,AA)contents,exerted no effect on the visual function of infants,and reached no consensus on growth.The current review aims to provide an overview on the LA and ALA contents and their ratio in human breast milk to raise concern in infant formula.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Objective To observe the clinical efficacy of Qinggan Tongru Formula(QTF)and probiotics(Clostridium butyricum Capsules)alone or in combination for lactational acute mastitis(AM),and to explore their effects on breast ...Objective To observe the clinical efficacy of Qinggan Tongru Formula(QTF)and probiotics(Clostridium butyricum Capsules)alone or in combination for lactational acute mastitis(AM),and to explore their effects on breast milk microbiota.Methods A total of 177 patients with AM during lactation(Gan-Wei stagnant heat syndrome)who visited the outpatient department of First Affiliated Hospital.展开更多
BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains u...BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.展开更多
Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L...Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L42)were balanced by parity(140 and 169 sows representing parity 1 to 2[P1-2]and 3 to 9[P3+],respectively)and assigned within parity to a 2×2 factorial arrangement.Factors included essential fatty acid(EFA)supplementation(control diets containing 1.2%linoleic and 0.15%α-linolenic acid or diets with 3.0%linoleic and 0.38%α-linolenic acid)and supplementation period(lactation or wean-to-breeding).Tallow(low EFA diets)or soybean oil(high EFA diets)were included at 4%in sorghum-soybean meal-wheat middlings-based diets to attain targeted EFA levels.Results High levels of EFA fed during lactation had no effect on feed intake or litter performance,but increased subsequent farrowing rate(P=0.027;82.1%vs.70.4%),tended to reduce the proportion of sows removed(P=0.070;12.4%vs.20.8%),decreased the number of total pigs born in the following litter(P=0.072;15.3 vs.16.2),and increased total pigs born alive per 100 sows weaned(P=0.062;1,122 vs.974),regardless of sow parity.Young sows(P1-2)consuming the high EFA diet during lactation displayed a shorter wean-to-estrus interval(P=0.035;4.2 vs.4.6),but P3+sows were unaffected.Increasing EFA intake for P3+sows,but not P1-2 sows,resulted in more sows bred by d 5(P=0.028;91.1%vs.81.7%)and more mummies in the subsequent litter(P=0.040;0.32 vs.0.16).Feeding increased EFA to P1-2 sows during the wean-to-breeding period decreased subsequent farrowing rate(P=0.042;72.0%vs.87.7%),and increased removal rate(P=0.003;28.8%vs.9.4%).Total pigs born alive per 100 sows weaned was reduced(P=0.007)in P1-2 sows when supplemented with EFA during wean-breeding(939 vs.1,149)but was not impacted in P3+sows(1,131 vs.982).Conclusions Supplemental EFA in lactation diets benefited subsequent reproduction of sows,regardless of parity.Increasing dietary levels of EFA during the wean-to-breeding period to younger sows negatively impacted subsequent reproduction.展开更多
BACKGROUND Liver transplantation(LT)is the preferred treatment for end-stage liver diseases.Early allograft failure(EAF)can result in death or retransplantation.One of the key factors predicting EAF is the degree of g...BACKGROUND Liver transplantation(LT)is the preferred treatment for end-stage liver diseases.Early allograft failure(EAF)can result in death or retransplantation.One of the key factors predicting EAF is the degree of graft injury,which is typically assessed by elevated alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels.Aminotransferase levels exceeding 5000 U/L within 48 hours of LT are indicative of poor short-term graft survival.AIM To investigate outcomes in liver transplant recipients with peak aminotransferase levels exceeding 5000 U/L and to identify predictors of EAF.METHODS Adult patients who underwent LT from a deceased(brain-dead)donor between 2011 and 2024 at Hospital de Clínicas de Porto Alegre were screened.Patients with peak AST or ALT levels>5000 U/L post-LT were included,excluding those with vascular thrombosis.EAF was defined as death or retransplantation within 90 days.A receiver operating characteristic curve were generated for each EAF predictor to determine the area under the curve(AUC).Sensitivity,specificity,negative predictive value,and positive predictive value were calculated for each predictor’s best cutoff,as defined by the Youden Index.Survival curves were plotted using the Kaplan-Meier method.RESULTS Between 2011 and 2024,341 patients underwent LT.Of these,29(8.5%)patients had AST and/or ALT levels exceeding 5000 U/L within the first 48 hours post-LT.Four patients were excluded due to vascular thrombosis,resulting in a study cohort of 25 patients.EAF were also observed in 11 patients.One-year and five-year graft survival rates were 51.7%and 42.6%,respectively.For patients without EAF,one-year and five-year graft survivals were 92.3%and 76.2%,respectively.The key predictors of EAF included serum factor V and arterial lactate levels on postoperative day(POD)1,with AUCs of 0.936 and 0.919,respectively.The optimal cutoff for EAF prediction were 26.2%for serum factor V and 9 mmol/L for arterial lactate.CONCLUSION Aminotransferase levels>5000 U/L were associated with high EAF risk.However,favorable graft function indicators on POD 1 were associated with long-term survival comparable to that of general LT recipients.Serum factor V and arterial lactate levels emerged as valuable prognostic markers.展开更多
Breast cancer(BC)has the highest prevalence among cancers specific to women,and its incidence rates are increasing in many countries.Subtypes of BC,including HER2-positive or triple-negative BC,exhibit differing treat...Breast cancer(BC)has the highest prevalence among cancers specific to women,and its incidence rates are increasing in many countries.Subtypes of BC,including HER2-positive or triple-negative BC,exhibit differing treatment responses;consequently,demand for personalized therapy is increasing,and relevant precision medicine strategies are under development.Aerobic glycolysis in cancer cells can lead to excessive lactate production,which in turn promotes lactylation and influences tumor cell behavior.Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors.Because lactate and lactylation are important in cancer,further investigation of the mechanisms underlying lactate metabolism and lactylation,and the development of therapeutic strategies targeting these processes,are topics of increasing interest.This review describes current research on lactate metabolism and lactylation in BC,thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.展开更多
BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and ...BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and stem cell biotherapies are often used to facilitate this process.Histone lactylation modifications are involved in the regulation of various diseases.Lactate dehydrogenase A(LDHA)has been shown to play an important role in exosomes.AIM To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells(BMSC-Exos).METHODS BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy,qNano,immunofluorescence and western blotting assay.The corresponding low expression cell lines were obtained using RNA interference transfection;LDHA expression in rat bone tissues after ACLR was analyzed by western blotting.The volume of newborn bone tissues was monitored by micro-computed tomography imaging.Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis,including hematoxylin and eosin and Safranin O-Fast green staining,respectively;LDHA levels of chondrocyte stem cells(CSPCs)after co-incubation with BMSC-Exos were analyzed by western blotting.Extracellularly secreted lactic acid content was determined by lactate assay kit.Cell viability was assessed by cell counting kit 8 assay,and the proliferation and differentiation ability of cells was further examined by the expression of collagen II,SOX9 and aggrecan.Histone H3K18 lactylation modification was analyzed by western blotting.H3K18 La binding on bone morphogenetic protein 7(BMP7)promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction;BMP7 promoter activity was analyzed by dual luciferase reporter gene;BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting.Then,the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA,BMP7,collagen II,SOX9,aggrecan,extracellular lactate content,and cell counting kit 8 assay.RESULTS The spherical nanosized BMSC-Exos could be uptaken by CSPCs.LDHA was highly expressed in BMSC-Exos,which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue,as well as significantly increased the regeneration of tendon and fibrocartilage.Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs,cell viability,and the expression of markers related to cell proliferation and differentiation,including collagen II,SOX9,and aggrecan;LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification;high LDHA expression reversed the knockdown of BMP7,further increasing the proliferation and differentiation of CSPCs,thereby inducing cartilage formation.CONCLUSION LDHA in BMSC-Exos promotes BMP7 expression via H3K18 lactylation modification,which further promotes tendon-bone healing after ACLR.展开更多
Lactate,as a metabolite,plays a significant role in a number of fields,including medical diagnostics,exercise physiology and food science.Traditional methods for lactate measurement often involve expensive and cumbers...Lactate,as a metabolite,plays a significant role in a number of fields,including medical diagnostics,exercise physiology and food science.Traditional methods for lactate measurement often involve expensive and cumbersome instrumentation.This study developed a portable and low-cost lactate measurement system,including independently detectable hardware circuits and user-friendly embedded software,computer,and smartphone applications.The experiment verified that the relative error of the detection current in the device circuit was less than 1%.The electrochemical performance was measured by comparing the[Fe(CN)_(6)]^(3−)/[Fe(CN)_(6)]^(4−)solution with the desktop electrochemical workstation CHI660E,and a nearly consistent chronoamperometry(CA)curve was obtained.Two modified lactate sensors were used for CA testing of lactate.Within the concentration range of 0.1 mmol·L^(−1)to 20 mmol·L^(−1),there was a good linear relationship between lactate concentration and steady-state current,with a correlation coefficient(R2)greater than 0.99 and good repeatability,demonstrating the reliability of the developed device.The lactate measurement system developed in this study not only provides excellent detection performance and reliability,but also achieves portability and low cost,providing a new solution for lactate measurement.展开更多
An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors co...An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors contributes to a highly acidic microenvironment that promotes cancer cell survival and resistance to therapies.However,existing lactate depletion agents,primarily enzymes and macromolecules,fall short of clinical applications due to poor stability and their ability to only perform solitary lactate depletion without interfering with the transport process.Consequently,the development of stable molecules that deplete lactate and interfere with lactate transport is critically needed.Therefore,in this study,chlorin e6(Ce6)-gadolinium chloride(GdCl_(3))-flavin adenine dinucleotide(FAD)/tamoxifen(TAM)molecular chelates were prepared.The chelates fully interfered with lactate transport,depleted lactate in the tumor microenvironment,mitigated photodynamic therapy resistance,and realized synergistic photodynamic-hormonal therapy.FAD has promising capabilities in regulating lactate levels and mitigating acidic microenvironments.However,a strategy for depleting lactate by chelating the coenzyme FAD to form nanoparticles has not yet been reported.Tamoxifen disrupts tumor development and interferes with lactate transport by binding to estrogen receptor and inhibiting the expression of monocarboxylate transporter.In addition,coupling with Gd^(3+)increased the solubility of Ce6,thereby improving the photodynamic therapy effectiveness.This innovative strategy improves therapeutic efficacy and offers a promising approach for breast cancer treatment.展开更多
Background Lactational performance depends heavily on age,health,and nutrition.L-Citrulline(Cit)is an effective precursor of L-arginine(Arg),an amino acid that has important roles in synthesis of nitric oxide(NO)and p...Background Lactational performance depends heavily on age,health,and nutrition.L-Citrulline(Cit)is an effective precursor of L-arginine(Arg),an amino acid that has important roles in synthesis of nitric oxide(NO)and polyamines.Ruminal microbes degrade extracellular Arg;however,extracellular L-citrulline(Cit)is not degraded by ruminal microbes due to lack of uptake and can be fed unencapsulated as a precursor for Arg.As NO is a vasodilator,an increase in blood flow and transport of molecules to mammary tissue may enhance lactational performance and milk composition.Increases in polyamine production may increase milk protein synthesis within mammary tissue,thus increasing milk protein content.This study determined,for the first time,effects of dietary Cit supplementation on milk production and milk composition of Alpine dairy goats.Methods Does were synchronized to estrus and bred to Alpine bucks.Parturition was induced on d 149 of gestation and does were suckled overnight allowing kid(s)to obtain colostrum before being milked 24 h later(d 1 of lactation).Does were assigned to either control(CON,n=24)or Cit(CIT,n=23)diets.The isonitrogenous control diet consisted of 97.63%basal diet and 2.37%supplement(1.37%L-alanine and 1.00%soybean hydrogenated oil).The CIT supplemented diet consisted of 97.63%basal diet and 2.37%supplement(0.5%Cit,0.5%L-glutamine,1%soybean hydrogenated oil,0.37%cornstarch).Diets were group fed ad-libitum by treatment group.Blood samples were collected on d 0 and 30 of lactation,milk volumes measured twice daily,and on d 10,20,and 40 of lactation,milk samples were collected.Results CIT-treated does had greater daily milk production(P<0.05)and there was an effect of day of lactation on daily milk production(P<0.0001).Sire had significant effect on daily milk production as well(P<0.05).Milk compositional analyses revealed Cit supplementation increased solid-non-fat(SNF;P<0.05)and protein(P<0.05)content in milk.Conclusions Our novel results indicate that dietary supplementation of Cit fed ad-libitum in Alpine does increased daily milk yield,milk SNF content,and protein content.Supplemental Cit may be a proxy for Arg in goats to enhance lactational performance.展开更多
Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response an...Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.展开更多
基金funded by National Special Research Fundfor Public Welfare ( Agriculture) of China ( 3-52,meat rabbit)
文摘[ Objective] To study the effects of diets with different com-to-soybean ratios on production performance of lactational Rex rabbits and select the best feed formula. [Method] A total of 80 lactational healthy Rex rabbits （similar age, body weight and delivery time） were randomly divided into five groups, 16 in each group. The Rex rabbits in group I were fed with corn-based meal diet, group II with soybean-based meal diet, group III with the developed corn-soybean meal diet, group IV with corn-soybean meal free diet, and group CK with conventional corn-soybean meal diet. During the lactation period, the changes in the lactation performance, growth rate of baby rabbits, weight and feed costs were observed. [ Result] The lactation performance of mother rabbits and the growth rate of baby rabbits in the experimental groups were similar to that in the control group. The weaning survival rate of the group III was the highest, but it was not significantly higher than that of the control group. The weaning survival rate of the other three groups was lower than that of the control group （P〈0.05）. The weight loss of mother rabbits in the group I, II and III was not significantly different from that of the control group, but the weight loss of the group IV was higher than that of the control group （ P 〈 0.01 ）. [ Conclusion] Diets with appropriate corn-to-soybean ratios not only reduce feed costs but also give the best feeding effects.
基金This work is supported by Education Science Research Project of Beijing University of Chinese Medicine(XJYB2029)Fundamental Research Funds for the Central Universities(2020-JYB-ZDGG-082).
文摘Objective:Lactation mastitis is a kind of disease with high incidence during puerperium.In the early stage,breast massage can effectively eliminate the symptoms.However,the value of breast massage is not fully known to the public,which restricts its promotion and popularization.One important reason is the absence of a multi-dimensional and overall evaluation of outcome.COS is strongly advocated internationally as the outcome in clinical research to promote the transformation of clinical evidence into practice.At present,there is no systematic review of the existing outcome.This protocol aims to provide a set of outcomes and outcome evaluation schemes for developing COS of breast massage in lactation mastitis early stage.Methods:We will search PubMed,Embase,Web of Science,CNKI,Wan-fang,VIP,SinoMed,Grey literature databases(master and doctoral thesis databases and conference literature databases of CNKI,Wan-fang and SinoMed),Clinical Trials Registry Platform portal,the Clinical Trials Registry,Australian,New Zealand Clinical Trials Registry,the Center Watch Registry,before March 1,2021.We will include randomized controlled trials and non-randomized trials,cohort studies,case series,case reports.We will assess the quality of outcome reporting according to the MOMENT,classify all outcomes using the OMERACT Filter 2.0 conceptual framework.Descriptive analysis will be performed for all categorical variables using frequency and mean.Result:This protocol aims to help guide the design of systematic review to summarize the existing outcomes,and comprehensively evaluate existing outcomes,classify outcomes and provide schemes of outcome evaluation for developing COS of breast massage in the early stage of lactation mastitis.Percentage and mean will be used to describe the extracted data.Conclusion:This is the first systematic review protocol to summarize outcomes,measurement instruments,assessment times,measurement frequencies,measurers about breast massage in the early stage of lactational mastitis.
基金supported by research programs from the National Key R&D Program of China (2022YFD1301000)the Agri-cultural Science and Technology Innovation Program (CAAS-ZDRW202308)+1 种基金the Agricultur al Science and Technology Innovation Program (ASTIP-IAS12)the State Key Laboratory of Animal Nutrition and Feeding (2004DA125184G2108).
文摘Optimizing nitrogen utilization efficiency and mitigating nitrogen losses in cows plays a pivotal role in fostering economic sustainability within contemporary agricultural systems.Biochanin A(BCA),a natural component in red clover,has the potential to improve nitrogen metabolism in dairy cows.The primary objective of this study was to probe the impact of biochanin A supplementation on lactational performance,nitrogen metabolism,and blood metabolites in dairy cows.A complete randomized block design experiment was conducted over 28 d,involving 36 multiparous Holstein cows(comparable milk yield=37.1±2.90 kg,BW=642±70.0 kg,days in milk=92±8.0 d,and parity=2.4±0.50),which were allocated to three treatment groups:the Control group(with 0 g/d BCA),the Low group(with 10 g/d per cow BCA),and the High group(with 40 g/d per cow BCA).Biochanin A supplementation improved the lactational performance of cows by increasing milk yield by 6.3%(P=0.007)and feed efficiency by 12.7%(P=0.009).Total intestinal apparent digestibility was unaffected by BCA supplementation(P>0.05),but microbial nitrogen was increased by 30.0%(P=0.002)for promoting nitrogen utilization efficiency by 20.7%(P=0.004).Milk competent yields(protein,lactose,and non-fat milk solid)were increased with increasing BCA supplementation(P 0.05).BCA did not affect body health of dairy cows.Additionally,none of the plasma endocrine hormones were affected(P>0.05).A total of 95 significantly different metabolites were screened from the plasma metabolites of cows in the BCA-added and non-added groups.After performing an enrichment analysis of the metabolic pathways associated with the different metabolites,six specific pathways were identified:bile acid biosynthesis,aspartate metabolism,pyrimidine metabolism,arginine and proline metabolism,the urea cycle,and ammonia recycling.The inclusion of BCA is suggested to enhance milk yield and modulate nitrogen metabolism by influencing relevant metabolites within the metabolic pathways.
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金supported by Applied Basic Research Joint Fund Project of Yunnan Province,No.202301AY070001-200Middle-aged Academic and Technical Training Project for High-Level Talents,No.202105AC160065+1 种基金Yunnan Clinical Medical Center for Neurological and Cardiovascular Diseases,No.YWLCYXZX2023300077Key Clinical Specialty of Neurology in Yunnan Province,No.300064(all to CL)。
文摘Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.
基金supported by grants from National Natural Science Foundation of China (82402543)National High Level Hospital Clinical Research Funding (2022-PUMCH-B-109)+2 种基金CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-020)Opening Foundation of Agile and Intelligent Computing Key Laboratory of Sichuan ProvinceSpecial Research Fund for Central Universities,Peking Union Medical College (3332024120)
文摘BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.
基金supported by the Zhejiang Provincial Administration of Traditional Chinese Medicine,the national medical masters inheritance studio construction project(GZS2021006).
文摘Background:As a common breast disease in lactating women,lactational mastitis is clinically manifested as painful breast lumps and systemic symptoms.To a certain extent,this disease may affect the physical and mental health of lactating women and even the breastfeeding of infants.Objective:This study was conducted to evaluate the clinical efficacy of Lou’s Wentong Method in the comprehensive treatment of lactational mastitis and its effects on relevant symptoms.Methods:A total of 158 patients who were diagnosed with lactational mastitis in The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2022 to January 2024 were included in this study to conduct a retrospective analysis.The treatment method comprised oral administration of traditional Chinese medicine prescriptions guided by the concept of“Wentong zhi yong”(warming and dispersing therapy for treating abscesses),puncture and pus extraction for patients with abscess formation,and milk drainage for patients with milk stagnation.The clinical symptoms of these patients were collected according to the seven indexes in Lou’s quantitative scorecard for evaluating the condition of canker sores before and after treatment.Additionally,the improvement of each symptom after treatment,the total effective rate of the clinical treatment,and the total symptom evaluation score before and after treatment were also analyzed.Results:It was demonstrated that there were significant differences in the overall distribution of different severity symptoms(skin erythema,breast pain,number of lumps,size of lumps,breast abscesses,and body temperature)at three time points(P<0.01).The evaluation of these symptoms at different time points revealed that all symptoms were effectively mitigated over time.Meanwhile,the efficacy was assessed according to the efficacy index to evaluate the efficacy of Lou’s Wentong Method in the comprehensive treatment of lactational mastitis.The results corroborated the pronounced efficacy of Lou’s Wentong Method in treating lactational mastitis,exhibiting statistical significance(P<0.01).Conclusion:Lou’s Wentong Method has significant therapeutic effects in the comprehensive treatment of lactational mastitis.Furthermore,this method is conducive to alleviating the clinical symptoms of these patients as soon as possible and can reduce the pain of patients,thus promoting their recovery.
基金funded by the Sichuan Science and Technology Program(2021ZDZX0009)the earmarked fund from the National Natural Science Foundation of China(31972577)。
文摘Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.
基金supported by National Key R&D Program of China(2021YFD2100700).
文摘Both linoleic acid(18:2 n-6,LA)andα-linolenic acid(18:3 n-3,ALA)are essential fatty acids for infants.The contents of LA and ALA,and their ratio exhibited significant changes in human milk over the past 4 decades,which were not well summarized.Here,we summarized these values in 9898 human breast milk samples of 6664 mothers from 50 countries in 81 studies.A literature search was conducted using PubMed,Embase,and Web of Science between January 1980 and October 2023.The 95%confidence interval of LA/ALA ratio across lactation and gestation ranged from 14.24 to 31.26.The LA content was higher in China and Turkey(>20%)whereas the ALA content was below 1%in Africa.The LA/ALA ratio in countries along the Mediterranean coast exceeded 20 or even 30.LA and ALA contents increased significantly(P<0.01)while the ratio remained stable over the last 40 years.Multivariate meta-regression results showed that regions significantly(P<0.01)determined the LA,ALA,and LA/ALA ratio.Especially,maternal diet could definitely explain the variation while the effects of gestational age,lactation period was not significant.Clinical trials demonstrated that decreasing the LA/ALA ratio increased docosahexaenoic acid(22:6 n-3,DHA)status,reduced arachidonic acid(20:4 n-6,AA)contents,exerted no effect on the visual function of infants,and reached no consensus on growth.The current review aims to provide an overview on the LA and ALA contents and their ratio in human breast milk to raise concern in infant formula.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
文摘Objective To observe the clinical efficacy of Qinggan Tongru Formula(QTF)and probiotics(Clostridium butyricum Capsules)alone or in combination for lactational acute mastitis(AM),and to explore their effects on breast milk microbiota.Methods A total of 177 patients with AM during lactation(Gan-Wei stagnant heat syndrome)who visited the outpatient department of First Affiliated Hospital.
基金Supported by National Natural Science Foundation of China,No.82360136Jiangxi Clinical Research Center for Gastroenterology,No.20223BCG74011.
文摘BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.
文摘Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L42)were balanced by parity(140 and 169 sows representing parity 1 to 2[P1-2]and 3 to 9[P3+],respectively)and assigned within parity to a 2×2 factorial arrangement.Factors included essential fatty acid(EFA)supplementation(control diets containing 1.2%linoleic and 0.15%α-linolenic acid or diets with 3.0%linoleic and 0.38%α-linolenic acid)and supplementation period(lactation or wean-to-breeding).Tallow(low EFA diets)or soybean oil(high EFA diets)were included at 4%in sorghum-soybean meal-wheat middlings-based diets to attain targeted EFA levels.Results High levels of EFA fed during lactation had no effect on feed intake or litter performance,but increased subsequent farrowing rate(P=0.027;82.1%vs.70.4%),tended to reduce the proportion of sows removed(P=0.070;12.4%vs.20.8%),decreased the number of total pigs born in the following litter(P=0.072;15.3 vs.16.2),and increased total pigs born alive per 100 sows weaned(P=0.062;1,122 vs.974),regardless of sow parity.Young sows(P1-2)consuming the high EFA diet during lactation displayed a shorter wean-to-estrus interval(P=0.035;4.2 vs.4.6),but P3+sows were unaffected.Increasing EFA intake for P3+sows,but not P1-2 sows,resulted in more sows bred by d 5(P=0.028;91.1%vs.81.7%)and more mummies in the subsequent litter(P=0.040;0.32 vs.0.16).Feeding increased EFA to P1-2 sows during the wean-to-breeding period decreased subsequent farrowing rate(P=0.042;72.0%vs.87.7%),and increased removal rate(P=0.003;28.8%vs.9.4%).Total pigs born alive per 100 sows weaned was reduced(P=0.007)in P1-2 sows when supplemented with EFA during wean-breeding(939 vs.1,149)but was not impacted in P3+sows(1,131 vs.982).Conclusions Supplemental EFA in lactation diets benefited subsequent reproduction of sows,regardless of parity.Increasing dietary levels of EFA during the wean-to-breeding period to younger sows negatively impacted subsequent reproduction.
基金Supported by Financiamento e IncentivoàPesquisa of Hospital de Clínicas de Porto Alegre,No.170271.
文摘BACKGROUND Liver transplantation(LT)is the preferred treatment for end-stage liver diseases.Early allograft failure(EAF)can result in death or retransplantation.One of the key factors predicting EAF is the degree of graft injury,which is typically assessed by elevated alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels.Aminotransferase levels exceeding 5000 U/L within 48 hours of LT are indicative of poor short-term graft survival.AIM To investigate outcomes in liver transplant recipients with peak aminotransferase levels exceeding 5000 U/L and to identify predictors of EAF.METHODS Adult patients who underwent LT from a deceased(brain-dead)donor between 2011 and 2024 at Hospital de Clínicas de Porto Alegre were screened.Patients with peak AST or ALT levels>5000 U/L post-LT were included,excluding those with vascular thrombosis.EAF was defined as death or retransplantation within 90 days.A receiver operating characteristic curve were generated for each EAF predictor to determine the area under the curve(AUC).Sensitivity,specificity,negative predictive value,and positive predictive value were calculated for each predictor’s best cutoff,as defined by the Youden Index.Survival curves were plotted using the Kaplan-Meier method.RESULTS Between 2011 and 2024,341 patients underwent LT.Of these,29(8.5%)patients had AST and/or ALT levels exceeding 5000 U/L within the first 48 hours post-LT.Four patients were excluded due to vascular thrombosis,resulting in a study cohort of 25 patients.EAF were also observed in 11 patients.One-year and five-year graft survival rates were 51.7%and 42.6%,respectively.For patients without EAF,one-year and five-year graft survivals were 92.3%and 76.2%,respectively.The key predictors of EAF included serum factor V and arterial lactate levels on postoperative day(POD)1,with AUCs of 0.936 and 0.919,respectively.The optimal cutoff for EAF prediction were 26.2%for serum factor V and 9 mmol/L for arterial lactate.CONCLUSION Aminotransferase levels>5000 U/L were associated with high EAF risk.However,favorable graft function indicators on POD 1 were associated with long-term survival comparable to that of general LT recipients.Serum factor V and arterial lactate levels emerged as valuable prognostic markers.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82302626)Gusu Health Talent Project of Suzhou,China(Grant No.GSWS2022076)Suzhou Key Laboratory of Intelligent Critical Illness Biomarkers Translational Research Project(Grant No.SZS2024029)。
文摘Breast cancer(BC)has the highest prevalence among cancers specific to women,and its incidence rates are increasing in many countries.Subtypes of BC,including HER2-positive or triple-negative BC,exhibit differing treatment responses;consequently,demand for personalized therapy is increasing,and relevant precision medicine strategies are under development.Aerobic glycolysis in cancer cells can lead to excessive lactate production,which in turn promotes lactylation and influences tumor cell behavior.Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors.Because lactate and lactylation are important in cancer,further investigation of the mechanisms underlying lactate metabolism and lactylation,and the development of therapeutic strategies targeting these processes,are topics of increasing interest.This review describes current research on lactate metabolism and lactylation in BC,thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.
文摘BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and stem cell biotherapies are often used to facilitate this process.Histone lactylation modifications are involved in the regulation of various diseases.Lactate dehydrogenase A(LDHA)has been shown to play an important role in exosomes.AIM To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells(BMSC-Exos).METHODS BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy,qNano,immunofluorescence and western blotting assay.The corresponding low expression cell lines were obtained using RNA interference transfection;LDHA expression in rat bone tissues after ACLR was analyzed by western blotting.The volume of newborn bone tissues was monitored by micro-computed tomography imaging.Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis,including hematoxylin and eosin and Safranin O-Fast green staining,respectively;LDHA levels of chondrocyte stem cells(CSPCs)after co-incubation with BMSC-Exos were analyzed by western blotting.Extracellularly secreted lactic acid content was determined by lactate assay kit.Cell viability was assessed by cell counting kit 8 assay,and the proliferation and differentiation ability of cells was further examined by the expression of collagen II,SOX9 and aggrecan.Histone H3K18 lactylation modification was analyzed by western blotting.H3K18 La binding on bone morphogenetic protein 7(BMP7)promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction;BMP7 promoter activity was analyzed by dual luciferase reporter gene;BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting.Then,the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA,BMP7,collagen II,SOX9,aggrecan,extracellular lactate content,and cell counting kit 8 assay.RESULTS The spherical nanosized BMSC-Exos could be uptaken by CSPCs.LDHA was highly expressed in BMSC-Exos,which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue,as well as significantly increased the regeneration of tendon and fibrocartilage.Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs,cell viability,and the expression of markers related to cell proliferation and differentiation,including collagen II,SOX9,and aggrecan;LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification;high LDHA expression reversed the knockdown of BMP7,further increasing the proliferation and differentiation of CSPCs,thereby inducing cartilage formation.CONCLUSION LDHA in BMSC-Exos promotes BMP7 expression via H3K18 lactylation modification,which further promotes tendon-bone healing after ACLR.
基金supported by National Natural Science Foundation of China(No.62006092)Natural Science Research Project of Anhui Educational Committee(No.2023AH030081)+1 种基金2023 New Era Education Provincial Quality Engineering Project(Graduate Education)(No.2023cxcysj103)2024 New Era Education Provincial Quality Engineering Project(Graduate Education)。
文摘Lactate,as a metabolite,plays a significant role in a number of fields,including medical diagnostics,exercise physiology and food science.Traditional methods for lactate measurement often involve expensive and cumbersome instrumentation.This study developed a portable and low-cost lactate measurement system,including independently detectable hardware circuits and user-friendly embedded software,computer,and smartphone applications.The experiment verified that the relative error of the detection current in the device circuit was less than 1%.The electrochemical performance was measured by comparing the[Fe(CN)_(6)]^(3−)/[Fe(CN)_(6)]^(4−)solution with the desktop electrochemical workstation CHI660E,and a nearly consistent chronoamperometry(CA)curve was obtained.Two modified lactate sensors were used for CA testing of lactate.Within the concentration range of 0.1 mmol·L^(−1)to 20 mmol·L^(−1),there was a good linear relationship between lactate concentration and steady-state current,with a correlation coefficient(R2)greater than 0.99 and good repeatability,demonstrating the reliability of the developed device.The lactate measurement system developed in this study not only provides excellent detection performance and reliability,but also achieves portability and low cost,providing a new solution for lactate measurement.
基金supported by the National Natural Science Foundation of China(No.82373206)Zhejiang Provincial Natural Science Foundation of China under Grant No LHDMZ24H300002National Key Research and Development Program of China(No.2022YFE0107800,2023YFA1008603).
文摘An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors contributes to a highly acidic microenvironment that promotes cancer cell survival and resistance to therapies.However,existing lactate depletion agents,primarily enzymes and macromolecules,fall short of clinical applications due to poor stability and their ability to only perform solitary lactate depletion without interfering with the transport process.Consequently,the development of stable molecules that deplete lactate and interfere with lactate transport is critically needed.Therefore,in this study,chlorin e6(Ce6)-gadolinium chloride(GdCl_(3))-flavin adenine dinucleotide(FAD)/tamoxifen(TAM)molecular chelates were prepared.The chelates fully interfered with lactate transport,depleted lactate in the tumor microenvironment,mitigated photodynamic therapy resistance,and realized synergistic photodynamic-hormonal therapy.FAD has promising capabilities in regulating lactate levels and mitigating acidic microenvironments.However,a strategy for depleting lactate by chelating the coenzyme FAD to form nanoparticles has not yet been reported.Tamoxifen disrupts tumor development and interferes with lactate transport by binding to estrogen receptor and inhibiting the expression of monocarboxylate transporter.In addition,coupling with Gd^(3+)increased the solubility of Ce6,thereby improving the photodynamic therapy effectiveness.This innovative strategy improves therapeutic efficacy and offers a promising approach for breast cancer treatment.
基金supported by funding from Texas A&M AgriLife ResearchPrairie View A&M University International Center for Goat Research。
文摘Background Lactational performance depends heavily on age,health,and nutrition.L-Citrulline(Cit)is an effective precursor of L-arginine(Arg),an amino acid that has important roles in synthesis of nitric oxide(NO)and polyamines.Ruminal microbes degrade extracellular Arg;however,extracellular L-citrulline(Cit)is not degraded by ruminal microbes due to lack of uptake and can be fed unencapsulated as a precursor for Arg.As NO is a vasodilator,an increase in blood flow and transport of molecules to mammary tissue may enhance lactational performance and milk composition.Increases in polyamine production may increase milk protein synthesis within mammary tissue,thus increasing milk protein content.This study determined,for the first time,effects of dietary Cit supplementation on milk production and milk composition of Alpine dairy goats.Methods Does were synchronized to estrus and bred to Alpine bucks.Parturition was induced on d 149 of gestation and does were suckled overnight allowing kid(s)to obtain colostrum before being milked 24 h later(d 1 of lactation).Does were assigned to either control(CON,n=24)or Cit(CIT,n=23)diets.The isonitrogenous control diet consisted of 97.63%basal diet and 2.37%supplement(1.37%L-alanine and 1.00%soybean hydrogenated oil).The CIT supplemented diet consisted of 97.63%basal diet and 2.37%supplement(0.5%Cit,0.5%L-glutamine,1%soybean hydrogenated oil,0.37%cornstarch).Diets were group fed ad-libitum by treatment group.Blood samples were collected on d 0 and 30 of lactation,milk volumes measured twice daily,and on d 10,20,and 40 of lactation,milk samples were collected.Results CIT-treated does had greater daily milk production(P<0.05)and there was an effect of day of lactation on daily milk production(P<0.0001).Sire had significant effect on daily milk production as well(P<0.05).Milk compositional analyses revealed Cit supplementation increased solid-non-fat(SNF;P<0.05)and protein(P<0.05)content in milk.Conclusions Our novel results indicate that dietary supplementation of Cit fed ad-libitum in Alpine does increased daily milk yield,milk SNF content,and protein content.Supplemental Cit may be a proxy for Arg in goats to enhance lactational performance.
基金supported by National Nature Science Foundation of China(32102552 and 32172741).
文摘Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.
