Utilizing resequencing big data to facilitate Brassica vegetable breeding:tracing introgression pedigree and developing highly specific markers for clubroot resistance

Clubroot caused by Plasmodiophora brassicae is a devastating disease of Cruciferous crops.Developing cultivars with clubroot resistance(CR)is the most effective control measure.For the two major Brassica vegetable species B.rapa and B.oleracea,several commercial cultivars with unclear CR pedigrees have been intensively used as CR donors in breeding.However,the continuous occurrence of CR-breaking makes the CR pedigree underlying these cultivars one of the breeders'most urgent concerns.The complex intraspecific diversity of these two major Brassica vegetables has also limited the applicability of CR markers in different breeding programs.Here we first traced the pedigree underlying two kinds of CR that have been widely applied in breeding by linkage and introgression analyses based on public resequencing data.In B.rapa,a major locus CRzi8 underlying the CR of the commercial CR donor‘DegaoCR117’was identified.CRzi8 was further shown to have been introgressed from turnip(B.rapa ssp.rapifera)and that it carried a potential functional allele of Crr1a.The turnip introgression carried CRb^(c),sharing the same coding sequence with the CRb that was also identified from chromosome C07 of B.oleracea CR cultivars with different morphotypes.Within natural populations,variation analysis of linkage intervals of CRzi8,PbBa8.1,CRb,and CRb^(c)yielded easily resolved InDel markers(>20 bp)for these fundamental CR genes.The specificity of these markers was tested in diverse cultivars panels,and each exhibited high reliability in breeding.Our research demonstrates the value of the practice of applying resequencing big data to solve urgent concerns in breeding programs.

Hyperhomocysteinemia and Associated Biological Markers in a Congolese Population of Type 2 Diabetes Mellitus in Brazzaville

The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerative complications in type 2 diabetics. The aim of this work was to study hyperhomocysteinemia and other biochemical markers associated with T2D in the Congolese population. This was an analytical case-control study carried out between October 2022 and October 2023. The study population consisted of 150 subjects including 100 T2D patients and 50 control subjects. The main clinical data were collected on a pre-established form. Homocysteine determination was carried out by the sandwich ELISA method. The other biochemical markers were measured by colorimetric enzymatic methods. Hyperhomocysteinemia was present in 27.3% (41/150) of the entire study population. Type 2 diabetics had a frequency of hyperhomocysteinemia of 36% (36/100) and control 10% (5/50) (p = 0.001). The mean hyperhomocysteinemia concentration was 31.9 μmol/l with extremes ranging from 18 to 103 μmol/l. Means of biological markers between diabetics and controls showed a statistically significant difference (p = 0.01). The risk factors associated with this HHcy were: sex (OR = 3.5), age (OR = 9.4), sedentary lifestyle (OR = 3.4) and glycosylated hemoglobin (OR = 12) with a p-value <0.05 respectively. Our results suggest that hyperhomocysteinemia can be considered as a predictive biomarker in the bioclinic of Congolese type 2 diabetic patients.

Evaluating combined bevacizumab and XELOX in advanced colorectal cancer: Serum markers carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 199 analysis

BACKGROUND Colorectal cancer ranks third and second among common and fatal cancers.The treatment of metastatic colorectal cancer(mCRC)is generally based on XELOX in clinical practice,which includes capecitabine(CAP)and oxaliplatin.Serum tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125 and CA199 are prognostic factors for various tumors.AIM To investigate evaluating combined bevacizumab(BEV)and XELOX in advanced colorectal cancer:Serum markers CEA,CA125,CA199 analysis.METHODS In this retrospective study,a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received.The control group was treated with XELOX plus CAP(n=47),while the observation group was treated with XELOX plus CAP and BEV(n=47).Several indexes were assessed in both groups,including disease control rate(DCR),incidence of adverse effects,serum marker levels(CEA,CA125,and CA19)and progression-free survival(PFS).RESULTS After 9 wk of treatment,the serum levels of CEA,CA199 and CA125 in the observation group were significantly lower than those in the control group(P<0.05).Moreover,the PFS of the observation group(9.12±0.90 mo)was significantly longer than that of the control group(6.49±0.64 mo).Meanwhile,there was no statistically significant difference in the incidence of adverse reactions and DCR between the two groups during maintenance therapy(P>0.05).CONCLUSION On the basis of XELOX treatment,the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.

Identification of new cotton fiber-quality QTL by multiple genomic analyses and development of markers for genomic breeding

Cotton fiber is one of the main raw materials for the textile industry.In recent years,many cotton fiber quality QTL have been identified,but few were applied in breeding.In this study,a genome wide association study(GWAS)of fiber-quality traits in 265 upland cotton breeding intermediate lines(GhBreeding),combined with genome-wide selective sweep analysis(GSSA)and genomic selection(GS),revealed 25 QTL.Most of these QTL were ignored by only using GWAS.The CRISPR/Cas9 mutants of GhMYB_D13 had shorter fiber,which indicates the credibility of QTL to a certain extent.Then these QTL were verified in other cotton natural populations,5 stable QTL were found having broad potential for application in breeding.Additionally,among these 5 stable QTL,superior genotypes of 4 showed an enrichment in most improved new varieties widely cultivated currently.These findings provide insights for how to identify more QTL through combined multiple genomic analysis to apply in breeding.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Recent progress in hair follicle stem cell markers and their regulatory roles

Hair follicle stem cells(HFSCs)in the bulge are a multipotent adult stem cell population.They can periodically give rise to new HFs and even regenerate the epidermis and sebaceous glands during wound healing.An increasing number of biomarkers have been used to isolate,label,and trace HFSCs in recent years.Considering more detailed data from single-cell transcriptomics technology,we mainly focus on the important HFSC molecular markers and their regulatory roles in this review.

New markers of fibrosis in hepatitis C:A step towards the Holy Grail?

In the present issue of the World Journal of Hepatology,Ferrassi et al examine the problem of liver fibrosis staging in chronic hepatitis C.They identify novel biomarkers in an effort to predict accurate fibrosis staging with the aid of the metabolome of Hepatitis C patients.Overall I think Ferrassi et al took a different approach in identifying fibrosis biomarkers,by looking at the patients’metabolome.Their biomarkers clearly separate patients from controls.They can also separate out,patients with minimal fibrosis(F0-F1 stage)and patients with cirrhosis(F4 stage).Obviously,if these biomarkers were to be widely used,tests for all the important metabolites would need to be readily available for use in hospitals or outpatient setting and that may prove difficult and above all,costly.Nevertheless,this step could eventually lead to a metabolomic approach for novel biomarkers of Fibrosis.Obviously,it would need to be validated,but could represent a step towards the Holy Grail of Hepatology.

Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents:A metaanalysis

BACKGROUND Obesity in children and adolescents is a serious problem,and the efficacy of exercise therapy for these patients is controversial.AIM To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers.METHODS The PubMed,Web of Science,and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October 2023.The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children.RESULTS In total,1010 patients from 28 studies were included.Exercise therapy reduced the levels of fasting blood glucose(FBG)[standardized mean difference(SMD):-0.78;95%confidence interval(CI):-1.24 to-0.32,P=0.0008],fasting insulin(FINS)(SMD:-1.55;95%CI:-2.12 to-0.98,P<0.00001),homeostatic model assessment for insulin resistance(HOMA-IR)(SMD:-1.58;95%CI:-2.20 to-0.97,P<0.00001),interleukin-6(IL-6)(SMD:-1.31;95%CI:-2.07 to-0.55,P=0.0007),C-reactive protein(CRP)(SMD:-0.64;95%CI:-1.21 to-0.08,P=0.03),and leptin(SMD:-3.43;95%CI:-5.82 to-1.05,P=0.005)in overweight and obese children.Exercise training increased adiponectin levels(SMD:1.24;95%CI:0.30 to 2.18,P=0.01)but did not improve tumor necrosis factor-alpha(TNF-α)levels(SMD:-0.80;95%CI:-1.77 to 0.18,P=0.11).CONCLUSION In summary,exercise therapy improves glucose metabolism by reducing levels of FBG,FINS,HOMA-IR,as well as improves inflammatory status by reducing levels of IL-6,CRP,leptin,and increasing levels of adiponectin in overweight and obese children.There was no statistically significant effect between exercise training and levels of TNF-α.Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.

Laparoscopic vs open surgery for gastric cancer: Assessing time, recovery, complications, and markers

BACKGROUND Gastric cancer(GC)is one of the most common cancers worldwide.Morbidity and mortality have increased in recent years,making it an urgent issue to address.La-paroscopic radical surgery(LRS)is a crucial method for treating patients with GC;However,its influence on tumor markers is still under investigation.The data of 194 patients treated at Chongqing University Cancer Hospital bet-ween January 2018 and January 2019 were retrospectively analyzed.Patients who underwent traditional open surgery and LRS were assigned to the control(n=90)and observation groups(n=104),respectively.Independent sample t-tests andχ2 tests were used to compare the two groups based on clinical efficacy,changes in tumor marker levels after treatment,clinical data,and the incidence of posto-perative complications.To investigate the association between tumor marker levels and clinical efficacy in patients with GC,three-year recurrence rates in the two groups were compared.RESULTS Patients in the observation group had a shorter duration of operation,less in-traoperative blood loss,an earlier postoperative eating time,and a shorter hospital stay than those in the control group(P<0.05).No significant difference was observed between the two groups regarding the number of lymph node dissections(P>0.05).After treatment,the overall response rate in the control group was significantly lower than that in the observation group(P=0.001).Furthermore,after treatment,the levels of carbohydrate antigen 19-9,cancer antigen 72-4,carcinoembryonic antigen,and cancer antigen 125 decreased significantly.The observation group also exhibited a significantly lower incidence rate of postoperative complications compared to the control group(P<0.001).Additionally,the two groups did not significantly differ in terms of three-year survival and recurrence rates(P>0.05).CONCLUSION LRS effectively treats early gastric cancer by reducing intraoperative bleeding,length of hospital stays,and postoperative complications.It also significantly lowers tumor marker levels,thus improving the short-term prognosis of the disease.

Research Progress on Application of Molecular Markers in Breeding of Camellia oleifera

Camellia oleifera is an important woody oil tree species unique to China.It is known as the world s four major woody oil crops along with olive,oil palm and coconut.It is known as the‘king of oil’because of its high oil content.With the increase of people's attention to the yield of Camellia oleifera,its high yield has become the focus.In traditional breeding model,judgment is performed by phenotypic traits,but this method is single and easily affected by the environment,and can no longer meet the demand.In contrast,molecular marker breeding is not affected by the environment,and is stable and efficient and capable of accurately mapping target genes,so it has attracted much attention.In this paper,the research progress on C.oleifera germplasm resources diversity,DNA fingerprinting construction,genetic linkage map construction and QTL mapping was summarized,and the application of SSR molecular marker technique combined with association analysis in C.oleifera breeding in recent years was discussed,in order to provide new ideas for high-yield breeding of C.oleifera.

Preoperative blood markers and intra-abdominal infection after colorectal cancer resection

BACKGROUND Colorectal cancer(CRC)has one of the highest morbidity and mortality rates among digestive tract tumors.Intra-abdominal infection(IAI)is a common postoperative complication that affects the clinical outcomes of patients with CRC and hinders their rehabilitation process.However,the factors influencing abdominal infection after CRC surgery remain unclear;further,prediction models are rarely used to analyze preoperative laboratory indicators and postoperative complications.AIM To explore the predictive value of preoperative blood markers for IAI after radical resection of CRC.METHODS The data of 80 patients who underwent radical resection of CRC in the Anorectal Surgery Department of Suzhou Hospital affiliated with Anhui Medical University were analyzed.These patients were categorized into IAI(n=15)and non-IAI groups(n=65)based on whether IAI occurred.Influencing factors were compared;general data and laboratory indices of both groups were identified.The relationship between the indicators was assessed.Further,a nomogram prediction model was developed and evaluated;its utility and clinical applic-ability were assessed.RESULTS The risk factors for IAI after radical resection of CRC were neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and carcinoembryonic antigen(CEA)levels.NLR was correlated with PLR and SII(r=0.604,0.925,and 0.305,respectively),while PLR was correlated with SII(r=0.787).The nomogram prediction model demonstrated an area under the curve of 0.968[95%confidence interval(CI):0.948-0.988]in the training set(n=60)and 0.926(95%CI:0.906-0.980)in the validation set(n=20).The average absolute errors of the calibration curves for the training and validation sets were 0.032 and 0.048,respectively,indicating a good model fit.The decision curve analysis curves demonstrated high net income above the 5%threshold,indicating the clinical practicality of the model.CONCLUSION The nomogram model constructed using NLR,PLR,SII,and CEA levels had good accuracy and reliability in predicting IAI after radical resection of CRC,potentially aiding clinical treatment decision-making.

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers

BACKGROUND Portal vein thrombosis(PVT),a complication of liver cirrhosis,is a major public health concern.PVT prediction is the most effective method for PVT diagnosis and treatment.AIM To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.METHODS Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved.Following a 1:1 propensity score matching 572 patients with cirrhosis were screened,and relevant clinical data were collected.PVT risk factors were identified using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression analysis.Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables.A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT,and its predictive performance was verified using a receiver operating characteristic curve(ROC),calibration curves,and decision curve analysis(DCA).Finally,a network calculator was constructed based on the nomograms.RESULTS This study enrolled 286 cirrhosis patients with PVT and 286 without PVT.LASSO analysis revealed 13 variables as strongly associated with PVT occurrence.Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors,including etiology,ascites,gastroesophageal varices,platelet count,D-dimer,portal vein diameter,portal vein velocity,aspartate transaminase to neutrophil ratio index,and platelet-to-lymphocyte ratio.LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables.A nomogram was constructed based on the screened independent risk factors.The nomogram had excellent predictive performance,with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups,respectively.Calibration curves and DCA revealed its good clinical performance.Finally,the optimal cutoff value for the total nomogram score was 0.513.The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706,respectively.CONCLUSION A nomogram for predicting PVT occurrence was successfully developed and validated,and a network calculator was constructed.This can enable clinicians to rapidly and easily identify high PVT risk groups.

Serum tumor markers:Can they clinically implicate in type 2 diabetes mellitus?

“Serum tumor markers expression(CA19-9,CA242,and CEA)and its clinical implications in type 2 diabetes mellitus”authored by Meng and Shi presents an observational case-control study investigating the correlation between tumor markers and type 2 diabetes mellitus(T2DM).The study explores the diagnostic accuracy of tumor markers,particularly cancer antigen 19-9(CA19-9),CA242,and carcinoembryonic antigen,in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%,employing receiver operating characteristic curve analysis.Though study offers valuable insights into the potential utility of tumor markers in clinical practice,caution is advised regarding routine tumor marker testing due to challenges such as limited availability and cost.Additionally,the study overlooks potential confounding factors like smoking and alcohol consumption.Variations in CA19-9 and CA242 expression underscore the complex interplay between tumor markers and systemic diseases,warranting further investigation into their diagnostic and prognostic implications.While Meng and Shi represent a significant contribution to the field,more extensive research is needed to fully elucidate the role of tumor markers in diabetes management and beyond.

Diagnostic significance of complete blood cell count and hemogramderived markers for neonatal sepsis at Southwest Public Hospitals,Ethiopia

BACKGROUND Neonatal sepsis is defined as an infection-related condition characterized by signs and symptoms of bacteremia within the first month of life.It is the leading cause of mortality and morbidity among newborns.While several studies have been conducted in other parts of world to assess the usefulness of complete blood count parameters and hemogram-derived markers as early screening tools for neonatal sepsis,the associations between sepsis and its complications with these blood parameters are still being investigated in our setting and are not yet part of routine practice.AIM To evaluate the diagnostic significance of complete blood cell count hemogramderived novel markers for neonatal sepsis among neonates attending public hospitals in the southwest region of Oromia,Ethiopia,through a case control study.METHODS A case control study was conducted from October 2021 to October 2023 Sociodemographic,clinical history,and laboratory test results data were collected using structured questionnaires.The collected data were entered into Epi-data 3.1 version and exported to SPSS-25 for analysis.Chi-square,independent sample ttest,and receiver operator characteristics curve of curve were used for analysis.A P-value of less than 0.05 was considered statistically significant.RESULTS In this study,significant increases were observed in the following values in the case group compared to the control group:In white blood cell(WBC)count,neutrophils,monocyte,mean platelet volume(MPV),neutrophils to lymphocyte ratio,monocyte to lymphocyte ratio(MLR),red blood cell width to platelet count ratio(RPR),red blood width coefficient variation,MPV to RPR,and platelet to lymphocyte ratio.Regarding MLR,a cut-off value of≥0.26 was found,with a sensitivity of 68%,a specificity of 95%,a positive predictive value(PPV)of 93.2%,and a negative predictive value(NPV)of 74.8%.The area under the curve(AUC)was 0.828(P<0.001).For WBC,a cutoff value of≥11.42 was identified,with a sensitivity of 55%,a specificity of 89%,a PPV of 83.3%,and a NPV of 66.4%.The AUC was 0.81(P<0.001).Neutrophils had a sensitivity of 67%,a specificity of 81%,a PPV of 77.9%,and a NPV of 71.1%.The AUC was 0.801,with a cut-off value of≥6.76(P=0.001).These results indicate that they were excellent predictors of neonatal sepsis diagnosis.CONCLUSION The findings of our study suggest that certain hematological parameters and hemogram-derived markers may have a potential role in the diagnosis of neonatal sepsis.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

Assessment of molecular markers and marker-assisted selection for drought tolerance in barley(Hordeum vulgare L.)

This review updates the present status of the field of molecular markers and marker-assisted selection(MAS),using the example of drought tolerance in barley.The accuracy of selected quantitative trait loci(QTLs),candidate genes and suggested markers was assessed in the barley genome cv.Morex.Six common strategies are described for molecular marker development,candidate gene identification and verification,and their possible applications in MAS to improve the grain yield and yield components in barley under drought stress.These strategies are based on the following five principles:(1)Molecular markers are designated as genomic‘tags’,and their‘prediction’is strongly dependent on their distance from a candidate gene on genetic or physical maps;(2)plants react differently under favourable and stressful conditions or depending on their stage of development;(3)each candidate gene must be verified by confirming its expression in the relevant conditions,e.g.,drought;(4)the molecular marker identified must be validated for MAS for tolerance to drought stress and improved grain yield;and(5)the small number of molecular markers realized for MAS in breeding,from among the many studies targeting candidate genes,can be explained by the complex nature of drought stress,and multiple stress-responsive genes in each barley genotype that are expressed differentially depending on many other factors.

Fast tracking alien gene discovery by molecular markers in a late flowering Chinese cabbage-cabbage translocation line‘AT7–4'

Flowering time is an important agronomic trait of Chinese cabbage with late flowering being a primary breeding objective.In our previous work,we obtained Chinese cabbage-cabbage translocation lines that contained several beneficial cabbage genes.Cabbage-specific molecular markers show that these genes were coming from chromosome C01 of cabbage.In this study,we investigated the inheritance of flowering time in a couple of translocation lines and analyzed the transmission rate of molecular markers in the offspring.Consequently,we obtained the late flowering Chinese cabbage-cabbage translocation line‘AT7–4’in which the flowering time was later than that of‘85–1’by about 7 days under 4-week vernalization.Based on previous studies of the genomes of Chinese cabbage and cabbage,we located the cabbage-specific molecular markers that were closely linked at the top of the chromosome A01 in the F2mapping population generated by self-crossing F1s derived from a cross between the translocation line‘AT7–4’and Chinese cabbage‘14–36’.Five flowering-related genes in the alien fragment were found by functional annotation and their molecular markers were developed.This study lays the foundation for the future improvement of Chinese cabbage varieties using A-C translocation lines.

Efficacy of concurrent chemoradiotherapy with thalidomide and S-1 for esophageal carcinoma and its influence on serum tumor markers

BACKGROUND Although the current conventional treatment strategies for esophageal carcinoma(EC)have been proven effective,they are often accompanied by serious adverse events.Therefore,it is still necessary to continue to explore new therapeutic strategies for EC to improve the clinical outcome of patients.AIM To elucidate the clinical efficacy of concurrent chemoradiotherapy(CCRT)with thalidomide(THAL)and S-1(tegafur,gimeracil,and oteracil potassium capsules)in the treatment of EC as well as its influence on serum tumor markers(STMs).METHODS First,62 patients with EC treated at the Zibo 148 Hospital between November 2019 and November 2022 were selected and grouped according to the received treatment.Among these,30 patients undergoing CCRT with cis-platinum and 5-fluorouracil were assigned to the control group(Con),and 32 patients receiving CCRT with THAL and S-1 were assigned to the research group(Res).Second,inter-group comparisons were carried out with respect to curative efficacy,incidence of drug toxicities,STMs[carbohydrate antigen 125(CA125)and macrophage inflammatory protein-3α(MIP-3α)],angiogenesis-related indicators[vascular endothelial growth factor(VEGF);VEGF receptor-1(VEGFR-1);basic fibroblast growth factor(bFGF);angiogenin-2(Ang-2)],and quality of life(QoL)[QoL core 30(QLQ-C30)]after one month of treatment.RESULTS The analysis showed no statistical difference in the overall response rate and disease control rate between the two patient cohorts;however,the incidences of grade I–II myelosuppression and gastrointestinal reactions were significantly lower in the Res than in the Con.Besides,the post-treatment CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels in the Res were markedly lower compared with the pre-treatment levels and the corresponding post-treatment levels in the Con.Furthermore,more evident improvements in QLQ-C30 scores from the dimensions of physical,role,emotional,and social functions were determined in the Res.CONCLUSION The above results demonstrate the effectiveness of THAL+S-1 CCRT for EC,which contributes to mild side effects and significant reduction of CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels,thus inhibiting tumors from malignant progression and enhancing patients’QoL.

Study on Quality Markers of Poria cocos Based on UPLC-Q-TOF-MS and Network Pharmacology Technology

[Objectives]To analyze the main chemical components of traditional Chinese medicine(TCM)Poria cocos by liquid chromatography-mass spectrometry,and explore the active components for P.cocos in the treatment of primary dysmenorrhea(PD)by network pharmacology to predict its quality markers(Q-marker).[Methods]Ultra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UPLC-Q-TOF-MS)in positive and negative ion mode was used to collect high quality MS and MS/MS data of Poria cocos,and qualitative characterization of the components in Poria cocos was performed using Analyst TF 1.7.1 and PeakView 2.2 software with reference to internal databases and literature.Taking the above identified chemical components as the research object,we used network pharmacology to discover the potential effective components and their key targets of PD,and metabolic pathway enrichment analysis of the core targets was performed to screen the Q-marker of P.cocos based on the five principles of Q-marker of TCM.[Results]UPLC-Q-TOF-MS technique was used to identify 41 chemical components of P.cocos,including 3 amino acids,26 triterpenoids,4 lactones,7 organic acids and 1 adenosine.It was more likely to lose H 2O and CO 2 during cleavage and break at the carbonyl group.The triterpenoids were mainly in the form of[M-H]-peaks in negative ion mode,which was easy to lose some structural fragments such as H 2O,CH 3COOH,CH 4,CO 2,etc.Further network pharmacological analysis showed that 302 targets of chemical components of P.cocos,518 targets of PD,28 common targets of component and disease,and 27 core targets such as PTGS2,ESR1,TNF,IL1B were observed by PPI interactions network analysis.451 biological processes such as hormone response and inflammatory response regulation were obtained by GO enrichment analysis.KEGG enrichment analysis showed that 89 pathways including PI3K/Akt signaling pathway,IL-17 signaling pathway and TNF signaling pathway were obtained.The connectivity value of components was analyzed.The core components with the connectivity value greater than 10,including poricoic acid A,polyporenic acid,polyporenic acid C,and 25-hydroxy-3-epidehydrotumoric acid were selected,while the key targets with the connectivity value greater than 15 included TNF,PTGS2,IL1B and CASP3.Molecular docking between core components and key targets was performed,and most of the docking energy was less than-5 kcal/mol,indicating that the binding between the active components and target proteins of P.cocos was relatively stable,so 23 active components of P.cocos were determined.Following the five principles of Q-marker,four possible Q-markers of P.cocos were predicted,including poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epidehydrotumoric acid.[Conclusions]P.cocos was mainly composed of triterpenoids,its effect on the treatment of PD may be achieved mainly by poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epi-dehydrotumoric acid acting on PTGS2,ESR1,TNF,IL1B and other targets to regulate PI3K/Akt signaling pathway,IL-17 signaling pathway,TNF signaling pathway,etc.Based on these active components,poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epi-dehydrotumoric acid could be taken as Q-markers of P.cocos,which provided a solid basis for further improving the quality standard of P.cocos.

Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients

BACKGROUND Coronary artery disease(CAD)is a major cause of death worldwide,and India contributes to about one-fifth of total CAD deaths.The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine(CML)in heart muscle,which correlates with fibrosis.AIM To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes.METHODS We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin(HbA1c)levels(group I:HbA1c≥6.5;group II:HbA1c<6.5).We analyzed the levels of lipoproteins,plasma HbA1c levels,CML,interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α),and nitric oxide.RESULTS Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had moresevere CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the leftanterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter.Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide ascompared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596,P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Oddsratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantlyassociated with diabetic CAD at unadjusted and adjusted levels with covariates.