Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms:A Chinese multicenter study of 12-year experience

BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

Construction and validation of somatic mutation-derived long noncoding RNAs signatures of genomic instability to predict prognosis of hepatocellular carcinoma

BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.

Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.

Bioinformatics analysis and experimental validation of cystathionine-gamma-lyase as a potential prognosis biomarker in hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.

Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.

Exploring impedance spectrum for lithium-ion batteries diagnosis and prognosis:A comprehensive review

Lithium-ion batteries have extensive usage in various energy storage needs,owing to their notable benefits of high energy density and long lifespan.The monitoring of battery states and failure identification are indispensable for guaranteeing the secure and optimal functionality of the batteries.The impedance spectrum has garnered growing interest due to its ability to provide a valuable understanding of material characteristics and electrochemical processes.To inspire further progress in the investigation and application of the battery impedance spectrum,this paper provides a comprehensive review of the determination and utilization of the impedance spectrum.The sources of impedance inaccuracies are systematically analyzed in terms of frequency response characteristics.The applicability of utilizing diverse impedance features for the diagnosis and prognosis of batteries is further elaborated.Finally,challenges and prospects for future research are discussed.

Impact of preoperative inflammatory and nutritional markers on the prognosis of patients with peritoneal metastasis of colorectal cancer

BACKGROUND Identifying patients with peritoneal metastasis(PMs)of colorectal cancer(CRC)who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery.Inflammatory and nutritional indicators play essential roles in cancer development and metastasis.AIM To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM.METHODS We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018.Patients’demographics,overall survival(OS),and preoperative inflammatory and nutritional markers were evaluated.The Kaplan-Meier method and log-rank test were used to estimate differences.RESULTS Of the 133 patients,94(70.6%)had normal hemoglobin(Hb)and 54(40.6%)had a high neutrophil-to-lymphocyte ratio(NLR).The median OS(mOS)was significantly lower for patients with high NLR(7.9 months)than for those with low NLR(25.4 months;P=0.002).Similarly,patients with normal Hb had a longer mOS(18.5 months)than those with low Hb(6.3 months;P<0.001).Multivariate analysis identified age,carbohydrate antigen 199 levels,NLR,Hb,and peritoneal cancer index as independent predictors of OS.Based on these findings,a nomogram was constructed,which demonstrated a good capacity for prediction,with a C-index of 0.715(95%confidence interval:0.684-0.740).Furthermore,the 1-and 2-year survival calibration plots showed good agreement between predicted and actual OS rates.The areas under the curve for the 1-and 2-year survival predictions of the nomogram were 0.6238 and 0.6234,respectively.CONCLUSION High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM.The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM,indicating its potential as a valuable prognostic tool for this patient population.

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.

Protein tyrosine phosphatase non-receptor Ⅱ:A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma

BACKGROUND The incidence of primary liver cancer is increasing year by year.In 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of cases.HCC is the most common primary liver cancer.China has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese people.The onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when diagnosed.Therefore,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of patients.Protein tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further studied.AIM To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in HCC.METHODS The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and immunoblotting.The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features.Finally,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining.RESULTS The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways,including cancer-related pathways,the Notch signaling pathway,and the MAPK signaling pathway.Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways,such as the epithelial mesenchymal transition process.A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group.CONCLUSION This study investigated PTPN2 from multiple biological perspectives,revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.

Systematic review of risk factors,prognosis,and management of colorectal signet-ring cell carcinoma

BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CSRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CSRCC.METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were included.Studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.RESULTS In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CSRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CSRCC is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.Surgery is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation.As such,diagnostic modalities and therapeutic approach should be tailored accordingly.

Nomogram predicting the prognosis of primary liver cancer after radiofrequency ablation combined with transcatheter arterial chemoembolization

BACKGROUND The incidence and mortality rates of primary hepatocellular carcinoma(HCC)are high,and the conventional treatment is radiofrequency ablation(RFA)with transcatheter arterial chemoembolization(TACE);however,the 3-year survival rate is still low.Further,there are no visual methods to effectively predict their prognosis.AIM To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model.METHODS Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded.We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software(version 4.1.2).Internal verification was performed using the bootstrapping technique.The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index(CI),calibration curve,and receiver operating characteristic RESULTS Of the 150 patients treated with RFA and TACE,92(61.33%)developed recurrence and metastasis.Logistic regression analysis identified six variables,and a predictive model was created.The internal validation results of the model showed a CI of 0.882.The correction curve trend of the prognosis prediction model was always near the diagonal,and the mean absolute error before and after internal validation was 0.021.The area under the curve of the prediction model after internal verification was 0.882[95%confidence interval(95%CI):0.820-0.945],with a specificity of 0.828 and sensitivity of 0.656.According to the Hosmer-Lemeshow test,χ^(2)=3.552 and P=0.895.The predictive model demonstrated a satisfactory calibration,and the decision curve analysis demonstrated its clinical applicability.CONCLUSION The prognosis of patients with HCC after RFA and TACE is affected by several factors.The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.

Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

Longitudinal investigation of mineral composition in human milk and its correlation with infant anthropometric outcomes among Tibetan mother-infant dyads during the first 6 months postpartum

Nutrients in human milk,including minerals,relate growth and development of breast-fed infants.Tibetan mother-infant dyads possess unique characteristics on early nutrition due to their featured long-lasting lifestyle.This study longitudinally investigated the relationship between the mineral composition in human milk and the Z-scores of infants among Tibetan mother-infant dyads during their first 6 months postpartum through a prospective cohort study.The results show that the minerals of Na,Mg,K,Ca,Cu,Zn,and Se were of higher levels in colostrum than other lactation stages.Several minerals were below the recommended values for infants according to Chinese dietary guidelines.Besides,a large proportion of infant Z-scores were below-2 as lactation period continued.Multivariate statistical analysis revealed that classifications and correlations in varying degrees were observed between minerals in human milk and infant Z-scores.These findings will be advantageous for research upon Chinese early nutrition and progress of tailor-made infant formula.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

The impact of cerebral small vessel disease burden on prognosis in patients with acute coronary syndrome

Background Acute coronary syndrome(ACS)presents with a variable prognosis,posing significant public health challenges.This study investigated the potential link between cerebral small vessel disease(CSVD)burden and outcomes in patients with ACS.Methods In this retrospective cohort study,ACS patients admitted to Beijing Friendship Hospital,Capital Medical Universi-ty,Beijing,China from January 2020 to October 2021,were analyzed.CSVD burden was assessed using magnetic resonance ima-ging markers,including white matter lesions,lacunar infarcts,cerebral microbleeds,and enlarged perivascular spaces.The correl-ation between CSVD burden and clinical outcomes,including major adverse cardiovascular and cerebrovascular events,myocar-dial infarction(MI),target vessel revascularization,stroke,and mortality was examined over a one-year follow-up.Results Out of 248 patients,216 patients were categorized into the low score group(LSG-CSVD)and 32 patients were categor-ized into the high score group(HSG-CSVD).Patients in the HSG-CSVD group exhibited significantly worse prognosis,with an el-evated risk of major adverse cardiovascular and cerebrovascular events,MI,and target vessel revascularization.After adjusting for age,sex,hypertension,troponin T,and estimated glomerular filtration rate,a significantly higher risk of MI was observed in the HSG-CSVD group(HR=4.51,95%CI:1.53-13.26,P=0.006).Subgroup analysis by age and sex consistently demonstrated in-creased adverse outcomes in the HSG-CSVD.Conclusions The study highlights a direct association between increased CSVD burden and poorer ACS outcomes,particular-ly in MI risk.These findings underscore the importance of considering CSVD burden as a crucial prognostic factor in ACS manag-ement,facilitating risk stratification and guiding personalized treatment strategies.

GRIK1 promotes glioblastoma malignancy and is a novel prognostic factor of poor prognosis

Primary tumors of the central nervous system(CNS)are classified into over 100 different histological types.The most common type of glioma is derived from astrocytes,and the most invasive glioblastoma(WHO IV)accounts for over 57%of these tumors.Glioblastoma(GBM)is the most common and fatal tumor of the CNS,with strong growth and invasion capabilities,which makes complete surgical resection almost impossible.Despite various treatment methods such as surgery,radiotherapy,and chemotherapy,glioma is still an incurable disease,and the median survival time of patients with GBM is shorter than 15 months.Thus,molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis.Glutamate ionotropic receptor kainate type subunit 1(GRIK1)is essential for brain function and is involved in many mental and neurological diseases.However,GRIK1’s pathogenic roles and mechanisms in GBM are still unknown.Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM,consistent with The Cancer Genome Atlas database.Knockdown of GRIK1 retarded GBM cells growth,migration,and invasion.Taken together,these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.