Cation-exchange high-performance liquid chromatography(CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It...Cation-exchange high-performance liquid chromatography(CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It's versatility, speed, reproducibility and convenience have made CE-HPLC the method of choice to initially screen for hemoglobin disorders. Despite its popularity, several methodological aspects of the technology remain obscure to pathologists and this may have consequences in specific situations. This paper discusses the basic principles of the technique, the initial quality control steps and the interpretation of various controls and variables that are available on the instrument output. Subsequent sections are devoted to methodological considerations that arise during reporting of cases. For instance, common problems of misidentified peaks, totals crossing 100%, causes of total area being above or below acceptable limits and the importance of pre-integration region peaks are dealt with. Ultimately, CE-HPLC remains an investigation, the reporting of which combines in-depth knowledge of the biological basics with more than a working knowledge of the technological aspects of the technique.展开更多
Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
To summarize the results of general survey, primary structure analysis and related functional studies of abnormal hemoglobins (Hbs) found in Hunan Province Data sources International Hb journals, Chinese biochemic...To summarize the results of general survey, primary structure analysis and related functional studies of abnormal hemoglobins (Hbs) found in Hunan Province Data sources International Hb journals, Chinese biochemical and biomedical journals and other articles relevant to hematology Study selection All Hb variants found in Hunan and identified by primary structure analysis during 1980-1991 were included Data extraction Data concerning 11 types of Hb variants found in 3 districts and 7 counties in Hunan Province were briefly documented Their frequencies of occurrence were calculated and their distributions among Han, Yao, Tujia and Dong ethnic groups were listed Results Thirty six cases with abnormal Hb were identified out of 7412 individuals screened in Hunan 11 different types of Hb variants were recognized by primary structure analysis in 19 propositi along with their family members, including 5 α chain variants, 4 β chain variants, 1 δ chain variant and 1 δ β chain fusion variant Oxygen equilibrium characteristics, reaction dynamics, the rate of globin chain synthesis (RGCS), morphology observation by electron microscopy and DNA analysis were all used in the functional studies of hemoglobinopathies Conclusions The average incidence of abnormal Hbs in Hunan is 0 486% In Jianghua County, whose inhabitants are mostly of the Yao ethnic group, the incidence is significantly higher (1 09%) Hb Jianghua [β120(GH3) LysIle] and Hb Shuangfeng (SF)[α27(B8) GluLys] were two new variants first reported in international literature; whereas Hb Lille [α74(EF3) AspAla], HbA 2 Flatbush [δ22(B4) AlaGlu] and Hb Lepore Boston [δ87(F3) β116(G18)] were the first three instances to be found in China Hb SF displayed an oxygen affinity 1 5 fold higher than that of HbA at pH 7 4 and 25℃ with its oxygen equilibrium curve shifted to the left Reticulocytes of Hb SF heterozygote showed unbalanced RGCS, quite similar to that found in β thalassemia minor Erythrocytes of Hb SF heterozygote were changed to spherocytes and began to lyse after incubation with sodium salicylate or sulfadiazine (pH 7 4, 37℃) for 2-4 h These findings explained the sudden attack of hemolytic anemia provoked by two drugs in Hb SF propositus The genotype of a patient with Hb Q H disease is identified as , / ,α Q by DNA restriction mapping展开更多
Land plants and algae form a supergroup, the Archaeplastida, believed to be monophyletic. We report the results of an analysis of the phylogeny of putative globins in the currently available genomes to bacterial and o...Land plants and algae form a supergroup, the Archaeplastida, believed to be monophyletic. We report the results of an analysis of the phylogeny of putative globins in the currently available genomes to bacterial and other eu- karyote hemoglobins （Hbs）. Archaeplastida genomes have 3/3 and 2/2 Hbs, with the land plant genomes having group 2 2/ 2 Hbs, except for the unexpected occurrence of two group 1 2/2 Hbs in Ricinus communis. Bayesian analysis shows that plant 3/3 Hbs are related to vertebrate neuroglobins and bacterial flavohemoglobins （FHbs）. We sought to define the bacterial groups, whose ancestors shared the precursors of Archaeplastida Hbs, via Bayesian and neighbor-joining anal- yses based on COBALTalignment of representative sets of bacterial 3/3 FHb-like globins and group I and 2 2/2 Hbs with the corresponding Archaeplastida Hbs. The results suggest that the Archaeplastida 3/3 and group 1 2/2 Hbs could have orig- inated from the horizontal gene transfers （HGTs） that accompanied the two generally accepted endosymbioses of a pro- teobacterium and a cyanobacterium with a eukaryote ancestor. In contrast, the origin of the group 2 212 Hbs unexpectedly appears to involve HGT from a bacterium ancestral to Chloroflexi, Deinococcales, Bacilli, and Actinomycetes. Furthermore, although intron positions and phases are mostly conserved among the land plant 3/3 and 2/2 globin genes, introns are absent in the algal 3/3 genes and intron positions and phases are highly variable in their 2/2 genes. Thus, introns are irrelevant to globin evolution in Archaeplastida.展开更多
The following asymmetric α1 99 Lys-α2 99 Lys cross-linked Fe(Ⅱ)-Co(Ⅱ) hybrid hemoglobins (Hbs) were first prepared from derivatives of hemoglobin C (β6 Glu-Lys) and human normal HbA: [α(Co)β(Fe)]A[α(Co)β(Co)]...The following asymmetric α1 99 Lys-α2 99 Lys cross-linked Fe(Ⅱ)-Co(Ⅱ) hybrid hemoglobins (Hbs) were first prepared from derivatives of hemoglobin C (β6 Glu-Lys) and human normal HbA: [α(Co)β(Fe)]A[α(Co)β(Co)]cXL, [α(Fe)β(Co)]A[α(Co)β(Co)]cXL, etc.Their 500 MHz 1H NMR and EPR spectra were measured in order to study the change in their tertiary and quaternary structure under atmosphere of deozy, oxy and carbon monoxide (with or without IHP). From the change of T and R marks in 1H NMR hydrogen bonding region, it is proved that oxygen molecules are first bonded to α(Fe) subunits rather than to β(Fe). The experimental phenomena provided further evidence that intermediate states of ligation are present in addition to T and R state during process of binding of oxygen to Hb. IHP facilitates transformation of T state to R state. The same conclusion can also be drawn from the results of EPR spectra at 77 K.展开更多
The globin superfamily,central to oxygen(O_(2))cascade dynamics,exemplifies how canalization—evolutionary stabilization of phenotypic traits—enables vertebrates to thrive in extreme environments.In birds,hemoglobins...The globin superfamily,central to oxygen(O_(2))cascade dynamics,exemplifies how canalization—evolutionary stabilization of phenotypic traits—enables vertebrates to thrive in extreme environments.In birds,hemoglobins(Hbs)serve as a paradigm of this process,with structural and functional canalization underpinning their exceptional aerobic capacity and elevational diversification.Despite significant advances of globins in our understanding of avian aerobic adaptation,a comprehensive synthesis of functional diversity,molecular evolution,and structural innovation is essential to fully elucidate their canalized roles in O_(2)homeostasis.Integrating perspectives on globin functional diversity and structural evolution,this review examines how chance(mutation/fixation biases)and contingency(historical genetic/epistatic constraints)shape Hb divergence and parallelism,thereby bridging molecular mechanisms with physiological adaptation in birds.We highlight how avian Hbs,canalized through compensatory substitutions and allosteric regulation,achieves a balance between evolutionary robustness and adaptive plasticity.However,critical gaps remain persist:the roles of understudied globins(e.g.,neuroglobin,globin E)and the mechanisms of genetic assimilation in migratory taxa.We propose an integrative framework that incorporates ecological divergence(elevation,flight endurance),phylogenetic timescales,and systems biology to unravel how canalization directs adaptive compromise.By focusing on birds within the amniotes,this synthesis advances a cohesive model for vertebrate evolution,wherein canalized globins reconcile metabolic precision with ecological innovation.Ultimately,this review refines hypotheses of O_(2)cascade evolution and calls for cross-disciplinary studies to decode the genetic and physiological architecture underlying adaptive canalization in extreme environments.展开更多
Objective:This study aimed to determine the effect of a culture-specificbehavior modificationprogram on glycated hemoglobin(HbA1c)and blood pressure among adults with diabetes and hypertension.Methods:This study was a...Objective:This study aimed to determine the effect of a culture-specificbehavior modificationprogram on glycated hemoglobin(HbA1c)and blood pressure among adults with diabetes and hypertension.Methods:This study was a single-blind randomized controlled trial design.From January to May 2024,a total of 60 patients with uncontrolled type 2 diabetes and hypertension from the primary care unit of a hospital in northeastern(Isan)Thailand were recruited.The intervention group received the usual care supplemented by a culture-specificbehavior modificationprogramm implemented through interactive classes and online web application consisting of information,motivation,and behavioral skills(diet,exercise,and medication use),the control group received the usual care.HbA1c and blood pressure measurements were collected at both baseline and at 12 weeks.Results:A total of 51 patients completed the study,the intervention group(n=26)and control group(n=25),respectively.After 12 weeks,23.1%of patients in the intervention group could maintain their HbA1c<7.0%;those with poorly controlled HbA1c decreased from 7.7%at baseline to 3.8%at 12 weeks.After 12 weeks,69.2%of intervention group participants could maintain systolic blood pressure<130 mmHg and 53.8%could keep diastolic blood pressure<80 mmHg.Analysis revealed that HbA1c,systolic and diastolic blood pressure levels in the intervention group were lower than the control group after the intervention(P<0.05).There was a statistically significantdifference a linear combination of HbA1c and blood pressure(systolic and diastolic BP levels)between time and group(P<0.05).Conclusion:These results suggest that healthcare providers can incorporate elements of this program to manage blood glucose and blood pressure effectively.Future studies should consider a longitudinal design with a larger sample size and include outcomes of lipid levels to confirmlong-term motivation.展开更多
ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a ...ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.展开更多
Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the ...Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.展开更多
BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of ...BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin(HbA1c)≥10%and varying backgrounds of glycemic control.METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months.Participants were categorized into four groups based on prior glycemic history:Newly diagnosed,previously well controlled with recent worsening,previously off-target but now worsening,and HbA1c consistently above 10%.HbA1c levels were monitored quarterly,and patients received medical,educational,and dietary support as needed.The analysis focused on the success rates of good glycemic control and the associated factors within each group.RESULTS The study showed significant improvements in HbA1c levels in all participants.The most significant improvement was observed in individuals newly diagnosed with diabetes:65%achieved an HbA1c target of≤7%.The results varied between participants with different glycemic control histories,followed by decreasing success rates:39%in participants with previously good glycemic control,21%in participants whose glycemic control had deteriorated compared to before,and only 10%in participants with persistently poor control,with mean HbA1c levels of 6.3%,7.7%,8.2%,and 9.7%,respectively.After one year,65.2%of the“newly diagnosed patients”,39.3%in the“previously controlled group”,21.9%in the“previously off-target but now worsened'”group and 10%in the“poorly controlled from the start”group had achieved HbA1c levels of 7 and below.CONCLUSION In poorly controlled diabetes,the rate at which treatment goals are achieved is associated with the glycemic background characteristics,emphasizing the need for tailored strategies.Therefore,different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.展开更多
BACKGROUND Advanced gastric cancer is characterized by fast tumor growth and aggressive biological behavior.During neoadjuvant chemotherapy,patients are at risk of distant metastasis or local progression.Anemia is a f...BACKGROUND Advanced gastric cancer is characterized by fast tumor growth and aggressive biological behavior.During neoadjuvant chemotherapy,patients are at risk of distant metastasis or local progression.Anemia is a frequent complication in these patients.AIM To analyze whether changes in hemoglobin and hematocrit can predict the survival and efficacy of neoadjuvant chemotherapy in patients with advanced gastric cancer.METHODS The clinical data of 185 patients with advanced gastric cancer admitted to the Third Affiliated Hospital of Chengdu Medical College,Pidu District People’s Hospital,Chengdu,China,between January 2016 and January 2021,were retrospectively analyzed.All patients underwent a tegafur+oxaliplatin+apatinib chemotherapy regimen.According to the efficacy of chemotherapy,they were divided into an effective group(complete or partial response,n=121)and an ineffective group(stable disease or disease progression,n=64).The factors related to chemotherapy efficacy in patients with advanced gastric cancer were analyzed by univariate and logistic multivariate analyses.The 3-year survival rates of the patients with different hemoglobin and hematocrit levels were compared.RESULTS Univariate analysis showed that the proportion of patients with a tumor diameter>5 cm,non-tubular adenocarcinoma,lymph node metastasis,hematocrit<33%,low mean red blood cell(RBC)protein content,low RBC distribution width,hemoglobin<107 g/L,and platelets>266×109/L in the ineffective group were significantly higher than those in the effective group(P<0.05).Logistic multivariate analysis showed that a tumor diameter>5 cm,lymph node metastasis,≤3 chemotherapy cycles,hematocrit<33%,and hemoglobin<107 g/L are risk factors for neoadjuvant chemotherapy failure in advanced gastric cancer(P<0.05).The 1-year,2-year,and 3-year survival rates in the effective group were 93.39%,83.47%,and 60.33%,respectively.These rates were significantly higher than those in the ineffective group(P<0.05).The 1-year,2-year,and 3-year survival rates of patients with hematocrit<33%were 74.67%,49.33%,and 29.33%,respectively,which were significantly lower than those of patients with hematocrit≥33%(P<0.05).The 1-year,2-year,and 3-year survival rates of patients with hemoglobin<107 g/L were 80.39%,58.82%,and 39.22%,respectively,which were significantly lower than those of patients with hemoglobin≥107 g/L(P<0.05).CONCLUSION Hematocrit<33%and hemoglobin<107 g/L are risk factors for chemotherapy failure in patients with advanced gastric cancer.They are associated with poorer prognosis and reduced 3-year survival rates.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a major complication of diabetes mellitus,and anemia is commonly observed in diabetic patients.However,the relationship between anemia and the risk of developing DFUs remains u...BACKGROUND Diabetic foot ulcers(DFUs)are a major complication of diabetes mellitus,and anemia is commonly observed in diabetic patients.However,the relationship between anemia and the risk of developing DFUs remains unclear.AIM To investigate the relationship between anemia and the risk of DFUs in diabetic patients through a meta-analysis.METHODS A systematic search was conducted across PubMed,Embase,and Web of Science databases to identify studies that reported the co-occurrence of anemia and DFUs in diabetic patients.The primary outcome was an association between anemia and DFU risk,expressed as odds ratios(ORs).Secondary outcomes included the risk of DFU per 1-g/dL decrease in hemoglobin and the difference in hemoglobin le-vels between patients with and without DFU.Statistical analyses were performed using random-effects models to account for heterogeneity.RESULTS Sixteen studies involving 170,949 diabetic patients were included in the analysis.The results indicated a significant association between anemia and an increased risk of DFUs(eight studies,n=166173,OR:2.72,95%CI:1.73–4.25,P<0.001;I2=93%).Subgroup analyses sup-ported consistent findings across various patient characteristics,analytic models,and study quality scores(P for subgroup differences,all>0.05).Additionally,each 1-g/dL decrease in hemoglobin was associated with an excess risk of DFUs(four studies,n=2543,OR:1.65,95%CI:1.21–2.27,P=0.002;I2=68%).Furthermore,diabetic patients with DFUs exhibited significantly lower hemoglobin levels compared to those without DFUs(nine studies,n=3986,mean difference:-2.13 g/dL,95%CI:-2.58 to-1.68,P<0.001;I2=90%).CONCLUSION Anemia can be associated with an increased risk of DFUs in diabetic patients.Monitoring and managing anemia in diabetic population may help mitigate the risk of DFUs,emphasizing the need for early interventions.Further research is required to investigate the underlying mechanisms and potential therapeutic strategies.展开更多
BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of co...BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.展开更多
Background:Lipemia,characterized by elevated triglyceride levels in blood samples,is a prevalent preanalytical interferent in clinical hematology.It leads to erroneous measurements of key complete blood count(CBC)para...Background:Lipemia,characterized by elevated triglyceride levels in blood samples,is a prevalent preanalytical interferent in clinical hematology.It leads to erroneous measurements of key complete blood count(CBC)parameters,including falsely elevated hemoglobin(Hgb)and platelet(PLT)counts.These inaccuracies can compromise diagnostic reliability and patient management.Objective:This review systematically evaluates existing correction methods for lipemic interference in CBC analysis,comparing their efficacy,limitations,and applicability in clinical settings.Methods:We analyze saline replacement,formula-based correction,instrument-specific algorithms,and emerging technologies,supported by experimental and clinical validation data.Conclusion:An optimized,context-dependent strategy is proposed,integrating multiple correction approaches based on lipemia severity.Future research directions,including artificial intelligence(AI)-enhanced corrections and standardized protocols,are discussed to advance hematology testing accuracy.展开更多
Flooding can lead to oxygen deprivation in rapeseed,negatively affecting its growth and development and ul-timately reducing yields.Vitreoscilla hemoglobin(VHb),a bacterial hemoglobin with a high oxygen-binding affini...Flooding can lead to oxygen deprivation in rapeseed,negatively affecting its growth and development and ul-timately reducing yields.Vitreoscilla hemoglobin(VHb),a bacterial hemoglobin with a high oxygen-binding affinity,plays a key role in enhancing oxygen uptake and metabolic efficiency under low-oxygen conditions.Through genetic transformation,we overexpressed the VHb gene in rapeseed,which resulted in significant im-provements in survival rate,root length,and biomass under submerged conditions.Additionally,we observed that transgenic plants developed adventitious roots in response to submergence stress.These transgenic plants also exhibited increased activities of ethanol dehydrogenase and pyruvate decarboxylase-enzymes associated with anaerobic respiration.Our findings indicate that VHb enhances flooding tolerance in rapeseed by promoting adventitious root formation and strengthening the plant's capacity for fermentation metabolism under anaerobic conditions.展开更多
BACKGROUND Despite laparoscopic total hysterectomy provided more benefits to patients and has become one of the most commonly used surgical methods for total hysterectomy.However,vaginal cuff dehiscence is a serious c...BACKGROUND Despite laparoscopic total hysterectomy provided more benefits to patients and has become one of the most commonly used surgical methods for total hysterectomy.However,vaginal cuff dehiscence is a serious complication after laparoscopic total hysterectomy and so far,there are limited studies on vaginal cuff dehiscence after a total hysterectomy.AIM To investigate the factors influencing vaginal cuff dehiscence after laparoscopic hysterectomy and the psychological state of the patients.METHODS This study retrospectively,univariately,and multivariately analyzed the clinical data of patients who experienced vaginal cuff dehiscence after laparoscopic hysterectomy in Yuyao People’s Hospital from January 2015 to December 2021.Logistic regression was utilized to analyze the high-risk factors of vaginal cuff dehiscence.RESULTS Among 1459 cases with laparoscopic hysterectomy,9 reported vaginal cuff dehiscence postoperatively,with an incidence of 0.617%.Univariate logistic regression analysis revealed that preoperative hemoglobin value[odds ratio(OR)=5.12,P=0.016],vaginal cuff suture method(OR=0.26,P=0.048),and postoperative first sexual lifetime(OR=15.86,P=0.002)were associated with vaginal cuff dehiscence following laparoscopic hysterectomy.Multivariate logistic regression analysis revealed that preoperative hemoglobin value of<90 g/L(OR=5.17,P=0.015)and time interval between postoperative first sexual life and operation of<3 months(OR=54.00,P=0.004)are independent risk factors for vaginal cuff dehiscence after laparoscopic hysterectomy.CONCLUSION Postoperative hemoglobin and the time interval between postoperative first sexual life and operation were the independent factors of developing vaginal cuff dehiscence after laparoscopic hysterectomy.展开更多
BACKGROUND Objective and accurate assessment of blood loss during pancreaticoduodenectomy(PD)is crucial for ensuring the safety and efficacy of the procedure.While the visual method remains the most common clinical me...BACKGROUND Objective and accurate assessment of blood loss during pancreaticoduodenectomy(PD)is crucial for ensuring the safety and efficacy of the procedure.While the visual method remains the most common clinical metric,many scholars argue that it significantly differs from actual blood loss and is inherently subjective.AIM To assess blood loss in PD via delta hemoglobin(ΔHb)and compare it with the visual method to predict bleeding-related risk factors.METHODS In this retrospective analysis,1722 patients who underwent PD from 2017 to 2022 at Shandong Provincial Hospital were divided into three groups:Open PD(OPD),laparoscopic PD(LPD),and conversion to OPD(CTOPD).IntraoperativeΔHb(IΔHb)was calculated via preoperative and 72-hour-postoperative hemoglobin concentrations,and its association with visually obtained estimated blood loss(EBL)was analyzed.PerioperativeΔHb(PΔHb)was calculated via preoperative and predischarge hemoglobin concentrations.We compared the differences in IΔHb and PΔHb among the three groups,and performed univariate and multi-variate regression analyses of IΔHb and PΔHb.RESULTS The preoperative general information of patients showed no statistically si-gnificant difference among the three groups(P>0.05).The IΔHb in the OPD,LPD,and CTOPD groups were 22.00(12.00,36.00),21.00(10.00,33.00),and 33.00(18.12,52.24)g/L,respectively;And the PΔHb in the OPD,LPD,and CTOPD groups were 25.87(13.51,42.00),25.00(14.00,45.00),and 37.48(21.64,59.65)g/L,respectively,values significantly differed(P<0.05).IΔHb and EBL were significantly correlated(r=0.337,P<0.001).The results of univariate and multivariate regression analyses indicated that American Society of Anesthesiologists(ASA)classification IV[95%confidence interval(CI):2.330-37.811,P=0.049]and preoperative total bilirubin>200μmol/L(95%CI:2.805-8.673,P<0.001)were independent risk factors for IΔHb(P<0.05),and ASA classification IV(95%CI:45.934-105.485,P<0.001),body mass index>24 kg/m2(95%CI:1.285-9.890,P=0.011),and preoperative total bilirubin>200μmol/L(95%CI:6.948-16.797,P<0.001)were independent risk factors for PΔHb(P<0.05).CONCLUSION There is a correlation between IΔHb and EBL in PD,so we can assess the patients’intraoperative blood loss by theΔHb method.ASA classification IV,body mass index>24 kg/m²,and preoperative total bilirubin>200μmol/L increased perioperative bleeding risk.展开更多
AIM:To evaluate retinal hemoglobin oxygen saturation in myopic eyes by scanning laser ophthalmoscope(SLO)and to assess its correlations with different severity of myopia.METHODS:Sixty-one eyes from 61 patients were in...AIM:To evaluate retinal hemoglobin oxygen saturation in myopic eyes by scanning laser ophthalmoscope(SLO)and to assess its correlations with different severity of myopia.METHODS:Sixty-one eyes from 61 patients were included and subdivided into three groups according to their refractive errors:high myopia group[20 eyes,spherical equivalent(SE)≤-6 D];low and moderate myopia(22 eyes,-6.0<SE≤-0.5 D);normal(19 eyes,-0.5<SE<+0.5 D).All subjects underwent SLO imaging with dual lasers(532 nm and 633 nm).The oxygen saturations of hemoglobin in arteries(SO_(2)A)and veins(SO_(2)V),and their differences(SO_(2)AV)were estimated from the optical densities of the vessels on the images at the two wavelengths.Pearson’s or Spearman’s rank correlation coefficient were calculated to assess the correlation between retinal hemoglobin oxygen saturation and refractive error/axial length(AL).RESULTS:For the retinal oxygen saturation,the SO_(2)V in high myopia group(73.21%±21.42%)was significantly higher than that in normal group(55.81%±21.69%)and low and moderate myopia group(56.88%±13.83%,P<0.05).The SE was significantly correlated with SO_(2)A(r=-0.30)and SO_(2)V(r=-0.36;P<0.05),and AL was also significantly correlated with SO_(2)A(r=0.27)and SO_(2)V(r=0.30;P<0.05).No significant correlations were found between SO_(2)AV and SE and AL(P>0.05).CONCLUSION:SO_(2)A and SO_(2)V increased in more myopic eye based on SLO measurements.Further studies are warranted to investigate the changes of retinal hemoglobin oxygen saturation in myopia with different methods.展开更多
Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans...Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin switching.Here,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at onset.Gene-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb F.Finally,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control regions.This study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.展开更多
Background Diabetic cardiomyopathy(DCM)represents a severe cardiovascular complication of diabetes mellitus,characterized by insidious onset,diagnostic challenges in early stages,and poor prognosis.Current diagnosis o...Background Diabetic cardiomyopathy(DCM)represents a severe cardiovascular complication of diabetes mellitus,characterized by insidious onset,diagnostic challenges in early stages,and poor prognosis.Current diagnosis of DCM primarily relies on imaging techniques,lacking convenient and effective early biomarkers.Method Using a case-control study design,we enrolled 50 DCM patients(DCM group)and 50 diabetes-only patients(control group)diagnosed at our hospital between January 2023 and January 2025.Demographic data were collected from all participants.Serum levels of hemoglobinA1c(HbAlc),interleukin-1β(IL-1β),and superoxide dismutase(SOD)were measured and compared between groups.Logistic regression analysis was performed to identify DCM risk factors,while receiver operating characteristic(ROC)curve analysis evaluated the diagnostic value of individual and combined biomarkers for DCM screening.Results The levels of HbAlc and IL-1βin the DCM group were higher than those in the control group,and the level of SOD was lower than that in the control group(P<0.05).Multivariate Logistic regression analysis showed that HbAlc,IL-1βand SOD were all independent risk factors for DCM.The results of the ROC curve showed that the areas under curve(AUC)of HbA1c,IL-1β,and SOD levels in diagnosing DCM patients were 0.673,0.783,and 0.728,respectively.The AUC predicted by the combination of the three was 0.836,which was higher than that detected by any above single index(P<0.05).Conclusions DCM patients exhibited significantly higher HbAlc and IL-1βlevels but lower SOD activity compared to the controls.Each biomarker demonstrated significant diagnostic value for DCM,and their combination yielded superior diagnostic performance compared to any single marker.展开更多
文摘Cation-exchange high-performance liquid chromatography(CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It's versatility, speed, reproducibility and convenience have made CE-HPLC the method of choice to initially screen for hemoglobin disorders. Despite its popularity, several methodological aspects of the technology remain obscure to pathologists and this may have consequences in specific situations. This paper discusses the basic principles of the technique, the initial quality control steps and the interpretation of various controls and variables that are available on the instrument output. Subsequent sections are devoted to methodological considerations that arise during reporting of cases. For instance, common problems of misidentified peaks, totals crossing 100%, causes of total area being above or below acceptable limits and the importance of pre-integration region peaks are dealt with. Ultimately, CE-HPLC remains an investigation, the reporting of which combines in-depth knowledge of the biological basics with more than a working knowledge of the technological aspects of the technique.
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
文摘To summarize the results of general survey, primary structure analysis and related functional studies of abnormal hemoglobins (Hbs) found in Hunan Province Data sources International Hb journals, Chinese biochemical and biomedical journals and other articles relevant to hematology Study selection All Hb variants found in Hunan and identified by primary structure analysis during 1980-1991 were included Data extraction Data concerning 11 types of Hb variants found in 3 districts and 7 counties in Hunan Province were briefly documented Their frequencies of occurrence were calculated and their distributions among Han, Yao, Tujia and Dong ethnic groups were listed Results Thirty six cases with abnormal Hb were identified out of 7412 individuals screened in Hunan 11 different types of Hb variants were recognized by primary structure analysis in 19 propositi along with their family members, including 5 α chain variants, 4 β chain variants, 1 δ chain variant and 1 δ β chain fusion variant Oxygen equilibrium characteristics, reaction dynamics, the rate of globin chain synthesis (RGCS), morphology observation by electron microscopy and DNA analysis were all used in the functional studies of hemoglobinopathies Conclusions The average incidence of abnormal Hbs in Hunan is 0 486% In Jianghua County, whose inhabitants are mostly of the Yao ethnic group, the incidence is significantly higher (1 09%) Hb Jianghua [β120(GH3) LysIle] and Hb Shuangfeng (SF)[α27(B8) GluLys] were two new variants first reported in international literature; whereas Hb Lille [α74(EF3) AspAla], HbA 2 Flatbush [δ22(B4) AlaGlu] and Hb Lepore Boston [δ87(F3) β116(G18)] were the first three instances to be found in China Hb SF displayed an oxygen affinity 1 5 fold higher than that of HbA at pH 7 4 and 25℃ with its oxygen equilibrium curve shifted to the left Reticulocytes of Hb SF heterozygote showed unbalanced RGCS, quite similar to that found in β thalassemia minor Erythrocytes of Hb SF heterozygote were changed to spherocytes and began to lyse after incubation with sodium salicylate or sulfadiazine (pH 7 4, 37℃) for 2-4 h These findings explained the sudden attack of hemolytic anemia provoked by two drugs in Hb SF propositus The genotype of a patient with Hb Q H disease is identified as , / ,α Q by DNA restriction mapping
文摘Land plants and algae form a supergroup, the Archaeplastida, believed to be monophyletic. We report the results of an analysis of the phylogeny of putative globins in the currently available genomes to bacterial and other eu- karyote hemoglobins （Hbs）. Archaeplastida genomes have 3/3 and 2/2 Hbs, with the land plant genomes having group 2 2/ 2 Hbs, except for the unexpected occurrence of two group 1 2/2 Hbs in Ricinus communis. Bayesian analysis shows that plant 3/3 Hbs are related to vertebrate neuroglobins and bacterial flavohemoglobins （FHbs）. We sought to define the bacterial groups, whose ancestors shared the precursors of Archaeplastida Hbs, via Bayesian and neighbor-joining anal- yses based on COBALTalignment of representative sets of bacterial 3/3 FHb-like globins and group I and 2 2/2 Hbs with the corresponding Archaeplastida Hbs. The results suggest that the Archaeplastida 3/3 and group 1 2/2 Hbs could have orig- inated from the horizontal gene transfers （HGTs） that accompanied the two generally accepted endosymbioses of a pro- teobacterium and a cyanobacterium with a eukaryote ancestor. In contrast, the origin of the group 2 212 Hbs unexpectedly appears to involve HGT from a bacterium ancestral to Chloroflexi, Deinococcales, Bacilli, and Actinomycetes. Furthermore, although intron positions and phases are mostly conserved among the land plant 3/3 and 2/2 globin genes, introns are absent in the algal 3/3 genes and intron positions and phases are highly variable in their 2/2 genes. Thus, introns are irrelevant to globin evolution in Archaeplastida.
基金This work has been supported by Research Grant HL14508 from the National Heart, Lung and Blood Institute, U.S.A
文摘The following asymmetric α1 99 Lys-α2 99 Lys cross-linked Fe(Ⅱ)-Co(Ⅱ) hybrid hemoglobins (Hbs) were first prepared from derivatives of hemoglobin C (β6 Glu-Lys) and human normal HbA: [α(Co)β(Fe)]A[α(Co)β(Co)]cXL, [α(Fe)β(Co)]A[α(Co)β(Co)]cXL, etc.Their 500 MHz 1H NMR and EPR spectra were measured in order to study the change in their tertiary and quaternary structure under atmosphere of deozy, oxy and carbon monoxide (with or without IHP). From the change of T and R marks in 1H NMR hydrogen bonding region, it is proved that oxygen molecules are first bonded to α(Fe) subunits rather than to β(Fe). The experimental phenomena provided further evidence that intermediate states of ligation are present in addition to T and R state during process of binding of oxygen to Hb. IHP facilitates transformation of T state to R state. The same conclusion can also be drawn from the results of EPR spectra at 77 K.
基金supported by the National Natural Science Foundation of China(NSFC 31900313)to X.Z.the Central guide local science and technology development funds(XZ202301YD0007C)to L.Y.+1 种基金NSFC(32471572)National Key Research and Development Program of China(2024YFC2310303)to D.L。
文摘The globin superfamily,central to oxygen(O_(2))cascade dynamics,exemplifies how canalization—evolutionary stabilization of phenotypic traits—enables vertebrates to thrive in extreme environments.In birds,hemoglobins(Hbs)serve as a paradigm of this process,with structural and functional canalization underpinning their exceptional aerobic capacity and elevational diversification.Despite significant advances of globins in our understanding of avian aerobic adaptation,a comprehensive synthesis of functional diversity,molecular evolution,and structural innovation is essential to fully elucidate their canalized roles in O_(2)homeostasis.Integrating perspectives on globin functional diversity and structural evolution,this review examines how chance(mutation/fixation biases)and contingency(historical genetic/epistatic constraints)shape Hb divergence and parallelism,thereby bridging molecular mechanisms with physiological adaptation in birds.We highlight how avian Hbs,canalized through compensatory substitutions and allosteric regulation,achieves a balance between evolutionary robustness and adaptive plasticity.However,critical gaps remain persist:the roles of understudied globins(e.g.,neuroglobin,globin E)and the mechanisms of genetic assimilation in migratory taxa.We propose an integrative framework that incorporates ecological divergence(elevation,flight endurance),phylogenetic timescales,and systems biology to unravel how canalization directs adaptive compromise.By focusing on birds within the amniotes,this synthesis advances a cohesive model for vertebrate evolution,wherein canalized globins reconcile metabolic precision with ecological innovation.Ultimately,this review refines hypotheses of O_(2)cascade evolution and calls for cross-disciplinary studies to decode the genetic and physiological architecture underlying adaptive canalization in extreme environments.
基金supported by the 90th Anniversary of Chulalong-korn University Scholarship(Ratchadaphiseksomphot Endowment Fund)。
文摘Objective:This study aimed to determine the effect of a culture-specificbehavior modificationprogram on glycated hemoglobin(HbA1c)and blood pressure among adults with diabetes and hypertension.Methods:This study was a single-blind randomized controlled trial design.From January to May 2024,a total of 60 patients with uncontrolled type 2 diabetes and hypertension from the primary care unit of a hospital in northeastern(Isan)Thailand were recruited.The intervention group received the usual care supplemented by a culture-specificbehavior modificationprogramm implemented through interactive classes and online web application consisting of information,motivation,and behavioral skills(diet,exercise,and medication use),the control group received the usual care.HbA1c and blood pressure measurements were collected at both baseline and at 12 weeks.Results:A total of 51 patients completed the study,the intervention group(n=26)and control group(n=25),respectively.After 12 weeks,23.1%of patients in the intervention group could maintain their HbA1c<7.0%;those with poorly controlled HbA1c decreased from 7.7%at baseline to 3.8%at 12 weeks.After 12 weeks,69.2%of intervention group participants could maintain systolic blood pressure<130 mmHg and 53.8%could keep diastolic blood pressure<80 mmHg.Analysis revealed that HbA1c,systolic and diastolic blood pressure levels in the intervention group were lower than the control group after the intervention(P<0.05).There was a statistically significantdifference a linear combination of HbA1c and blood pressure(systolic and diastolic BP levels)between time and group(P<0.05).Conclusion:These results suggest that healthcare providers can incorporate elements of this program to manage blood glucose and blood pressure effectively.Future studies should consider a longitudinal design with a larger sample size and include outcomes of lipid levels to confirmlong-term motivation.
基金Supported by the National Key R D Program of China,No.2022YFC2010102Natural Science Foundation of Hunan Province,No.2021JC0003+1 种基金National Natural Science Foundation of China,No.82070812the Sinocare Diabetes Foundation,No.LYF2022039.
文摘ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.
文摘Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.
文摘BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin(HbA1c)≥10%and varying backgrounds of glycemic control.METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months.Participants were categorized into four groups based on prior glycemic history:Newly diagnosed,previously well controlled with recent worsening,previously off-target but now worsening,and HbA1c consistently above 10%.HbA1c levels were monitored quarterly,and patients received medical,educational,and dietary support as needed.The analysis focused on the success rates of good glycemic control and the associated factors within each group.RESULTS The study showed significant improvements in HbA1c levels in all participants.The most significant improvement was observed in individuals newly diagnosed with diabetes:65%achieved an HbA1c target of≤7%.The results varied between participants with different glycemic control histories,followed by decreasing success rates:39%in participants with previously good glycemic control,21%in participants whose glycemic control had deteriorated compared to before,and only 10%in participants with persistently poor control,with mean HbA1c levels of 6.3%,7.7%,8.2%,and 9.7%,respectively.After one year,65.2%of the“newly diagnosed patients”,39.3%in the“previously controlled group”,21.9%in the“previously off-target but now worsened'”group and 10%in the“poorly controlled from the start”group had achieved HbA1c levels of 7 and below.CONCLUSION In poorly controlled diabetes,the rate at which treatment goals are achieved is associated with the glycemic background characteristics,emphasizing the need for tailored strategies.Therefore,different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.
文摘BACKGROUND Advanced gastric cancer is characterized by fast tumor growth and aggressive biological behavior.During neoadjuvant chemotherapy,patients are at risk of distant metastasis or local progression.Anemia is a frequent complication in these patients.AIM To analyze whether changes in hemoglobin and hematocrit can predict the survival and efficacy of neoadjuvant chemotherapy in patients with advanced gastric cancer.METHODS The clinical data of 185 patients with advanced gastric cancer admitted to the Third Affiliated Hospital of Chengdu Medical College,Pidu District People’s Hospital,Chengdu,China,between January 2016 and January 2021,were retrospectively analyzed.All patients underwent a tegafur+oxaliplatin+apatinib chemotherapy regimen.According to the efficacy of chemotherapy,they were divided into an effective group(complete or partial response,n=121)and an ineffective group(stable disease or disease progression,n=64).The factors related to chemotherapy efficacy in patients with advanced gastric cancer were analyzed by univariate and logistic multivariate analyses.The 3-year survival rates of the patients with different hemoglobin and hematocrit levels were compared.RESULTS Univariate analysis showed that the proportion of patients with a tumor diameter>5 cm,non-tubular adenocarcinoma,lymph node metastasis,hematocrit<33%,low mean red blood cell(RBC)protein content,low RBC distribution width,hemoglobin<107 g/L,and platelets>266×109/L in the ineffective group were significantly higher than those in the effective group(P<0.05).Logistic multivariate analysis showed that a tumor diameter>5 cm,lymph node metastasis,≤3 chemotherapy cycles,hematocrit<33%,and hemoglobin<107 g/L are risk factors for neoadjuvant chemotherapy failure in advanced gastric cancer(P<0.05).The 1-year,2-year,and 3-year survival rates in the effective group were 93.39%,83.47%,and 60.33%,respectively.These rates were significantly higher than those in the ineffective group(P<0.05).The 1-year,2-year,and 3-year survival rates of patients with hematocrit<33%were 74.67%,49.33%,and 29.33%,respectively,which were significantly lower than those of patients with hematocrit≥33%(P<0.05).The 1-year,2-year,and 3-year survival rates of patients with hemoglobin<107 g/L were 80.39%,58.82%,and 39.22%,respectively,which were significantly lower than those of patients with hemoglobin≥107 g/L(P<0.05).CONCLUSION Hematocrit<33%and hemoglobin<107 g/L are risk factors for chemotherapy failure in patients with advanced gastric cancer.They are associated with poorer prognosis and reduced 3-year survival rates.
基金Supported by General Program of Hainan Natural Science Foundation,No.824MS143.
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a major complication of diabetes mellitus,and anemia is commonly observed in diabetic patients.However,the relationship between anemia and the risk of developing DFUs remains unclear.AIM To investigate the relationship between anemia and the risk of DFUs in diabetic patients through a meta-analysis.METHODS A systematic search was conducted across PubMed,Embase,and Web of Science databases to identify studies that reported the co-occurrence of anemia and DFUs in diabetic patients.The primary outcome was an association between anemia and DFU risk,expressed as odds ratios(ORs).Secondary outcomes included the risk of DFU per 1-g/dL decrease in hemoglobin and the difference in hemoglobin le-vels between patients with and without DFU.Statistical analyses were performed using random-effects models to account for heterogeneity.RESULTS Sixteen studies involving 170,949 diabetic patients were included in the analysis.The results indicated a significant association between anemia and an increased risk of DFUs(eight studies,n=166173,OR:2.72,95%CI:1.73–4.25,P<0.001;I2=93%).Subgroup analyses sup-ported consistent findings across various patient characteristics,analytic models,and study quality scores(P for subgroup differences,all>0.05).Additionally,each 1-g/dL decrease in hemoglobin was associated with an excess risk of DFUs(four studies,n=2543,OR:1.65,95%CI:1.21–2.27,P=0.002;I2=68%).Furthermore,diabetic patients with DFUs exhibited significantly lower hemoglobin levels compared to those without DFUs(nine studies,n=3986,mean difference:-2.13 g/dL,95%CI:-2.58 to-1.68,P<0.001;I2=90%).CONCLUSION Anemia can be associated with an increased risk of DFUs in diabetic patients.Monitoring and managing anemia in diabetic population may help mitigate the risk of DFUs,emphasizing the need for early interventions.Further research is required to investigate the underlying mechanisms and potential therapeutic strategies.
文摘BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.
文摘Background:Lipemia,characterized by elevated triglyceride levels in blood samples,is a prevalent preanalytical interferent in clinical hematology.It leads to erroneous measurements of key complete blood count(CBC)parameters,including falsely elevated hemoglobin(Hgb)and platelet(PLT)counts.These inaccuracies can compromise diagnostic reliability and patient management.Objective:This review systematically evaluates existing correction methods for lipemic interference in CBC analysis,comparing their efficacy,limitations,and applicability in clinical settings.Methods:We analyze saline replacement,formula-based correction,instrument-specific algorithms,and emerging technologies,supported by experimental and clinical validation data.Conclusion:An optimized,context-dependent strategy is proposed,integrating multiple correction approaches based on lipemia severity.Future research directions,including artificial intelligence(AI)-enhanced corrections and standardized protocols,are discussed to advance hematology testing accuracy.
基金supported by National Key Research and Development Program of China(2023YFD1201403)The Science and Technology Innovation Program of Hunan Province(2023RC1077)+2 种基金Key Research and Development Projects of Hunan Provincial(2023NK2012)Hunan Provincial Science and Technology Talent Promotion Project(2023 TJ-Z09)The Hunan Agricultural Science and Technology Innovation Fund Project(2024CX096).
文摘Flooding can lead to oxygen deprivation in rapeseed,negatively affecting its growth and development and ul-timately reducing yields.Vitreoscilla hemoglobin(VHb),a bacterial hemoglobin with a high oxygen-binding affinity,plays a key role in enhancing oxygen uptake and metabolic efficiency under low-oxygen conditions.Through genetic transformation,we overexpressed the VHb gene in rapeseed,which resulted in significant im-provements in survival rate,root length,and biomass under submerged conditions.Additionally,we observed that transgenic plants developed adventitious roots in response to submergence stress.These transgenic plants also exhibited increased activities of ethanol dehydrogenase and pyruvate decarboxylase-enzymes associated with anaerobic respiration.Our findings indicate that VHb enhances flooding tolerance in rapeseed by promoting adventitious root formation and strengthening the plant's capacity for fermentation metabolism under anaerobic conditions.
文摘BACKGROUND Despite laparoscopic total hysterectomy provided more benefits to patients and has become one of the most commonly used surgical methods for total hysterectomy.However,vaginal cuff dehiscence is a serious complication after laparoscopic total hysterectomy and so far,there are limited studies on vaginal cuff dehiscence after a total hysterectomy.AIM To investigate the factors influencing vaginal cuff dehiscence after laparoscopic hysterectomy and the psychological state of the patients.METHODS This study retrospectively,univariately,and multivariately analyzed the clinical data of patients who experienced vaginal cuff dehiscence after laparoscopic hysterectomy in Yuyao People’s Hospital from January 2015 to December 2021.Logistic regression was utilized to analyze the high-risk factors of vaginal cuff dehiscence.RESULTS Among 1459 cases with laparoscopic hysterectomy,9 reported vaginal cuff dehiscence postoperatively,with an incidence of 0.617%.Univariate logistic regression analysis revealed that preoperative hemoglobin value[odds ratio(OR)=5.12,P=0.016],vaginal cuff suture method(OR=0.26,P=0.048),and postoperative first sexual lifetime(OR=15.86,P=0.002)were associated with vaginal cuff dehiscence following laparoscopic hysterectomy.Multivariate logistic regression analysis revealed that preoperative hemoglobin value of<90 g/L(OR=5.17,P=0.015)and time interval between postoperative first sexual life and operation of<3 months(OR=54.00,P=0.004)are independent risk factors for vaginal cuff dehiscence after laparoscopic hysterectomy.CONCLUSION Postoperative hemoglobin and the time interval between postoperative first sexual life and operation were the independent factors of developing vaginal cuff dehiscence after laparoscopic hysterectomy.
基金Supported by the Shandong Provincial Natural Science Foundation General Project,No.ZR2020MH248.
文摘BACKGROUND Objective and accurate assessment of blood loss during pancreaticoduodenectomy(PD)is crucial for ensuring the safety and efficacy of the procedure.While the visual method remains the most common clinical metric,many scholars argue that it significantly differs from actual blood loss and is inherently subjective.AIM To assess blood loss in PD via delta hemoglobin(ΔHb)and compare it with the visual method to predict bleeding-related risk factors.METHODS In this retrospective analysis,1722 patients who underwent PD from 2017 to 2022 at Shandong Provincial Hospital were divided into three groups:Open PD(OPD),laparoscopic PD(LPD),and conversion to OPD(CTOPD).IntraoperativeΔHb(IΔHb)was calculated via preoperative and 72-hour-postoperative hemoglobin concentrations,and its association with visually obtained estimated blood loss(EBL)was analyzed.PerioperativeΔHb(PΔHb)was calculated via preoperative and predischarge hemoglobin concentrations.We compared the differences in IΔHb and PΔHb among the three groups,and performed univariate and multi-variate regression analyses of IΔHb and PΔHb.RESULTS The preoperative general information of patients showed no statistically si-gnificant difference among the three groups(P>0.05).The IΔHb in the OPD,LPD,and CTOPD groups were 22.00(12.00,36.00),21.00(10.00,33.00),and 33.00(18.12,52.24)g/L,respectively;And the PΔHb in the OPD,LPD,and CTOPD groups were 25.87(13.51,42.00),25.00(14.00,45.00),and 37.48(21.64,59.65)g/L,respectively,values significantly differed(P<0.05).IΔHb and EBL were significantly correlated(r=0.337,P<0.001).The results of univariate and multivariate regression analyses indicated that American Society of Anesthesiologists(ASA)classification IV[95%confidence interval(CI):2.330-37.811,P=0.049]and preoperative total bilirubin>200μmol/L(95%CI:2.805-8.673,P<0.001)were independent risk factors for IΔHb(P<0.05),and ASA classification IV(95%CI:45.934-105.485,P<0.001),body mass index>24 kg/m2(95%CI:1.285-9.890,P=0.011),and preoperative total bilirubin>200μmol/L(95%CI:6.948-16.797,P<0.001)were independent risk factors for PΔHb(P<0.05).CONCLUSION There is a correlation between IΔHb and EBL in PD,so we can assess the patients’intraoperative blood loss by theΔHb method.ASA classification IV,body mass index>24 kg/m²,and preoperative total bilirubin>200μmol/L increased perioperative bleeding risk.
基金Supported by Shantou Science and Technology Project(No.190917155269927)2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant(No.2020LKSFG06B).
文摘AIM:To evaluate retinal hemoglobin oxygen saturation in myopic eyes by scanning laser ophthalmoscope(SLO)and to assess its correlations with different severity of myopia.METHODS:Sixty-one eyes from 61 patients were included and subdivided into three groups according to their refractive errors:high myopia group[20 eyes,spherical equivalent(SE)≤-6 D];low and moderate myopia(22 eyes,-6.0<SE≤-0.5 D);normal(19 eyes,-0.5<SE<+0.5 D).All subjects underwent SLO imaging with dual lasers(532 nm and 633 nm).The oxygen saturations of hemoglobin in arteries(SO_(2)A)and veins(SO_(2)V),and their differences(SO_(2)AV)were estimated from the optical densities of the vessels on the images at the two wavelengths.Pearson’s or Spearman’s rank correlation coefficient were calculated to assess the correlation between retinal hemoglobin oxygen saturation and refractive error/axial length(AL).RESULTS:For the retinal oxygen saturation,the SO_(2)V in high myopia group(73.21%±21.42%)was significantly higher than that in normal group(55.81%±21.69%)and low and moderate myopia group(56.88%±13.83%,P<0.05).The SE was significantly correlated with SO_(2)A(r=-0.30)and SO_(2)V(r=-0.36;P<0.05),and AL was also significantly correlated with SO_(2)A(r=0.27)and SO_(2)V(r=0.30;P<0.05).No significant correlations were found between SO_(2)AV and SE and AL(P>0.05).CONCLUSION:SO_(2)A and SO_(2)V increased in more myopic eye based on SLO measurements.Further studies are warranted to investigate the changes of retinal hemoglobin oxygen saturation in myopia with different methods.
基金supported by the National Natural Science Foundation of China(U20A20353 to X.Xu and 81900185 to Y.Ye).
文摘Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin switching.Here,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at onset.Gene-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb F.Finally,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control regions.This study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.
基金supported by Dongguan Social Development Science and Technology Program(No.202218009016172)。
文摘Background Diabetic cardiomyopathy(DCM)represents a severe cardiovascular complication of diabetes mellitus,characterized by insidious onset,diagnostic challenges in early stages,and poor prognosis.Current diagnosis of DCM primarily relies on imaging techniques,lacking convenient and effective early biomarkers.Method Using a case-control study design,we enrolled 50 DCM patients(DCM group)and 50 diabetes-only patients(control group)diagnosed at our hospital between January 2023 and January 2025.Demographic data were collected from all participants.Serum levels of hemoglobinA1c(HbAlc),interleukin-1β(IL-1β),and superoxide dismutase(SOD)were measured and compared between groups.Logistic regression analysis was performed to identify DCM risk factors,while receiver operating characteristic(ROC)curve analysis evaluated the diagnostic value of individual and combined biomarkers for DCM screening.Results The levels of HbAlc and IL-1βin the DCM group were higher than those in the control group,and the level of SOD was lower than that in the control group(P<0.05).Multivariate Logistic regression analysis showed that HbAlc,IL-1βand SOD were all independent risk factors for DCM.The results of the ROC curve showed that the areas under curve(AUC)of HbA1c,IL-1β,and SOD levels in diagnosing DCM patients were 0.673,0.783,and 0.728,respectively.The AUC predicted by the combination of the three was 0.836,which was higher than that detected by any above single index(P<0.05).Conclusions DCM patients exhibited significantly higher HbAlc and IL-1βlevels but lower SOD activity compared to the controls.Each biomarker demonstrated significant diagnostic value for DCM,and their combination yielded superior diagnostic performance compared to any single marker.
