BACKGROUND Non-ST segment elevation myocardial infarction(NSTEMI)poses significant challenges in clinical management due to its diverse outcomes.Understanding the prognostic role of hematological parameters and derive...BACKGROUND Non-ST segment elevation myocardial infarction(NSTEMI)poses significant challenges in clinical management due to its diverse outcomes.Understanding the prognostic role of hematological parameters and derived ratios in NSTEMI patients could aid in risk stratification and improve patient care.AIM To evaluate the predictive value of hemogram-derived ratios for major adverse cardiovascular events(MACE)in NSTEMI patients,potentially improving clinical outcomes.METHODS A prospective,observational cohort study was conducted in 2021 at the Internal Medicine Clinic of the University Hospital in Tuzla,Bosnia and Herzegovina.The study included 170 patients with NSTEMI,who were divided into a group with MACE and a control group without MACE.Furthermore,the MACE group was subdivided into lethal and non-lethal groups for prognostic analysis.Alongside hematological parameters,an additional 13 hematological-derived ratios(HDRs)were monitored,and their prognostic role was investigated.RESULTS Hematological parameters did not significantly differ between non-ST segment elevation myocardial infarction(NSTEMI)patients with MACE and a control group at T1 and T2.However,significant disparities emerged in HDRs among NSTEMI patients with lethal and non-lethal outcomes post-MACE.Notably,neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)were elevated in lethal outcomes.Furthermore,C-reactive protein-to-lymphocyte ratio(CRP/Ly)at T1(>4.737)demonstrated predictive value[odds ratio(OR):3.690,P=0.024].Both NLR at T1(>4.076)and T2(>4.667)emerged as significant predictors,with NLR at T2 exhibiting the highest diagnostic performance,as indicated by an area under the curve of 0.811(95%CI:0.727-0.859)and OR of 4.915(95%CI:1.917-12.602,P=0.001),emphasizing its important role as a prognostic marker.CONCLUSION This study highlights the significant prognostic value of hemogram-derived indexes in predicting MACE among NSTEMI patients.During follow-up,NLR,PLR,and CRP/Ly offer important insights into the inflammatory processes underlying cardiovascular events.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is the most prevalent type of pan-creatic neoplasm.It is a highly aggressive lethal malignancy related to its delayed in diagnosis and limited response to treatments.The incidence...Pancreatic ductal adenocarcinoma(PDAC)is the most prevalent type of pan-creatic neoplasm.It is a highly aggressive lethal malignancy related to its delayed in diagnosis and limited response to treatments.The incidence and mortality of pancreatic cancer have been increasing over the years.Tumor budding is a proven independent,adverse prognostic factor in PDAC.It is helpful for improvement of prognosis in PDAC in early and precise diagnostic modalities.Tumor budding should be conveyed in pathology reports and taken into account by future onco-logic staging systems.展开更多
One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despit...One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.展开更多
In this editorial,we comment on an original article by Duan et al.Despite ad-vancements in the diagnosis and treatment of hepatocellular carcinoma(HCC),the identification of suitable prognostic factors remains challen...In this editorial,we comment on an original article by Duan et al.Despite ad-vancements in the diagnosis and treatment of hepatocellular carcinoma(HCC),the identification of suitable prognostic factors remains challenging.In their paper,Duan et al identified long non-coding RNAs(LncRNAs)to quantify ge-nomic instability(GI)by combining LncRNA expression and somatic mutation profiles.They confirmed that the GI-derived LncRNA signature(GI-LncSig)could be an independent prognostic factor with the area under the curve of 0.773.Fur-thermore,the authors stated that GI-LncSig may have a better predictive perfor-mance than TP53 mutation status alone.However,studies exploring genetic markers for predicting the prognosis of HCC are crucial for identifying thera-peutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of liver cancer.展开更多
AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine...AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.展开更多
AIM To evaluate the role of albumin at the time of ulcerative colitis(UC) diagnosis in predicting the clinical course of disease.METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs he...AIM To evaluate the role of albumin at the time of ulcerative colitis(UC) diagnosis in predicting the clinical course of disease.METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia(i.e.,≤ 3.5 gm/dl) or normal albumin levels(i.e.,> 3.5 gm/dl) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined asalbumin level ≤ 3.5 g/dl at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids(CS),thiopurines,anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients,but 92(11.4%) patients did not have their albumin levels checked at the time of UC diagnosis,and they were excluded. A total of 710 patients,who had albumin levels checked at time of UC diagnosis,were included in our study. Amongst them,536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use(adjusted HR = 1.7,95%CI: 1.3-2.3),higher likelihood of thiopurine or anti-TNF use(adjusted HR = 1.72,95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients,but it was not statistically significant(Adjusted HR = 1.7,95%CI: 0.90-3.25).CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis.展开更多
AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule...AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule and the most important predictors for outcome. METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed. RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD,and 140 (52.8%) of them were female. hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminanthepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012). CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal medicine stands out as the most common drug for DILD. While antitubercular drugs are found to be the primary etiological factor for fetal DILD, hepatic encephalopathy, ascites, jaundice, alcohol abuse and direct bilirubin levels are associated with the death of DILD patients.展开更多
BACKGROUND Immunoinflammatory markers such as the peripheral blood neutrophil-tolymphocyte ratio(NLR)and the platelet-to-lymphocyte ratio(PLR)have gained considerable attention as prognostic markers in gastrointestina...BACKGROUND Immunoinflammatory markers such as the peripheral blood neutrophil-tolymphocyte ratio(NLR)and the platelet-to-lymphocyte ratio(PLR)have gained considerable attention as prognostic markers in gastrointestinal stromal tumors(GISTs).AIM To assess the prognostic value of Onodera’s Prognostic Nutritional Index(OPNI)for GISTs.METHODS All patients who had undergone surgical resection for a primary,localized GIST from 2009 to 2016 at our cancer center were initially and retrospectively identified.Recurrence-free survival(RFS)was calculated by the Kaplan-Meier method and compared by the log-rank test.We used multivariate Cox proportional hazard regression models to identify associations with outcome variables.RESULTS A total of 235 GISTs were identified and included for analysis under our inclusion criteria.Univariate and multivariate analyses both identified the OPNI as an independent prognostic marker,and the OPNI was associated with the primary site,tumor size,mitotic index,tumor rupture,necrosis,and modified NIH risk classification.Low OPNI(<51.30;hazard ratio=5.852;95% confidence interval:1.072–31.964;P=0.0414)was associated with worse RFS.The 2-and 5-year RFS rates of the patients with a low OPNI were 92.83% and 76.22%,respectively,whereas 100% and 98.41% were achieved by the patients with a high OPNI.CONCLUSION The preoperative OPNI is a novel and useful prognostic marker for GISTs.展开更多
Background:RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma(HCC),which is characterized by a mass of genetic and epigen...Background:RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma(HCC),which is characterized by a mass of genetic and epigenetic alterations.However,the treatment targeting these alterations is limited.Methods:We used comprehensive bioinformatics analysis to analyze the correlation between cancerassociated RNA methylation regulators and HCC malignant features in network datasets.Results:We identified two HCC subgroups(cluster 1 and 2),which had clearly distinct clinicopathological,biofunctional and prognostic characteristics,by consensus clustering.The cluster 2 subgroup correlated with malignancy of the primary tumor,higher tumor stage,higher histopathological grade and higher frequency of TP53 mutation,as well as with shorter survival when compared with cluster 1.Gene enrichment indicated that the cluster 2 correlated to the tumor malignancy signaling and biological processes.Based on these findings,an 11-gene risk signature was built,which not only was an independent prognostic marker but also had an excellent power to predict the tumor features.Conclusions:Our study indicated that RNA methylation regulators are vital for HCC malignant progression and provide an important evidence for RNA methylation,methylation regulators are actionable targets for anticancer drug discovery.展开更多
Objective: We planned this study to investigate the relation between serum adiponectin level and hepatocellular carcinoma (HCC): risk, features and prognosis. Methods: The study included 100 patients with HCC and 40 h...Objective: We planned this study to investigate the relation between serum adiponectin level and hepatocellular carcinoma (HCC): risk, features and prognosis. Methods: The study included 100 patients with HCC and 40 healthy control subjects. Adiponectin levels were determined by an enzyme-linked immunosorbent assay kit. Results: In the subset of patients with compensated cirrhosis, the mean serum adiponectin level was significantly lower in HCC cases compared to healthy controls (88.6 versus 115 ng/mL; P = 0.012). In addition, serum adiponectin levels correlated negatively with tumor size (P = 0.004) and were significantly lower in patients with vascular invasion and distant metastases (P = 0.03 and P = 0.02 respectively). Furthermore, the median overall survival was significantly higher in the high adiponectin group than the low adiponectin group (median 12.5 versus 9.5 months; log rank = 4.6, P = 0.03). Conclusion: Decreased circulating adiponectin level may play a role in the development of HCC and is a potential poor prognostic marker. These data should be validated in further prospective studies. Also the mechanisms by which adiponectin affect the course of HCC need to be clarified.展开更多
Objective:In order to find a genetic marker to predict the prognosis of patients with ovarian cancer based on multi-omics data. Methods:We download RNA-Seq SNP, CNV data and clinical follow-up information from TCGA da...Objective:In order to find a genetic marker to predict the prognosis of patients with ovarian cancer based on multi-omics data. Methods:We download RNA-Seq SNP, CNV data and clinical follow-up information from TCGA database and randomly divide them into training set and test set. GSE17260 dataset in GEO is taken as an external validation set. Prognosis-related genes, copy number difference genes and mutant genes are screened in the training set. After the integration of genes, the random forest algorithm is further used for feature selection, ultimately obtaining a robust biomarker. On this basis, a gene-related prognostic model is established and verified in the test set and verification set. Results:We have obtained 2097 prognostic related genes, 447 copy amplification genes, 1069 copy deletion genes and 654 significant mutations genes. Through the feature selection of random forest algorithm, five feature genes (PSMB1, COL6A6, SLC22A2, KLHL23 and CD3G) are obtained by integrating these genes, some of which have been reported to be related to tumor progress. Furthermore, the prognostic risk assessment model of 5-gene signature is established by Cox regression analysis. The model can evaluate the risk of patient samples in training set, test set and external verification set. 5-gene signature shows strong robustness and clinical independence. The results of GSEA analysis also show that the pathway of 5-gene signature enrichment is significantly related to the pathway and biological process of the occurrence and development of ovarian cancer. Conclusion:In this study, 5-gene signature is constructed as a new prognostic marker to predict the survival of patients with ovarian cancer.展开更多
Background: Several animal models, including dogs, have been useful to compare the pathogenesis of mammary neoplasm in humans, showing biological parallelism in the growth and development of breast cancer. The causes ...Background: Several animal models, including dogs, have been useful to compare the pathogenesis of mammary neoplasm in humans, showing biological parallelism in the growth and development of breast cancer. The causes of cancer could be attributed to change in several tumor suppressor genes. The relationship between molecule associated to senescence and clinical prognosis of patients affected by mammary cancer is little known. Beyond a collection of data, the major interest of the present study was to carry out a clinical follow-up of patients affected by these tumors, through association with new molecular markers by immunohistochemical technic. Upon completing the study, 15 patients survived, while 45 died. In the case of malignant neoplasms, 40 patients died because of the illness. The type of surgery most used by veterinarian surgeons was the simple lumpectomy, followed by the regional mastectomy. Sentinel node was removed by surgery only when clearly affected. Result: Markings against steroid hormones were positive. Regarding the markings against HER2 and Ki-67, they were negative in all cases. The markings against P53 and CD31 were all positives. Markings against molecules associated with cellular senescence were all positives. No statistical differences were found in immunomarcation for the different antigens used as clinical prognosis factors in mammary neoplasms. Conclusions: According to the study conditions, the survival of patients affected by breast tumors is directly related to diagnosis and malignancy histological grade, but not to animal breed, number of affected glands or patient reproductive status. On the other hand, immunohistochemical markings were not related to the patient prognosis. For this reason, it is important to highlight the persistance of a high percentage of mammary neoplasm cases clinically diagnosed with poor results on patient survival. Thus, educating owners and veterinarians for using diagnostic available tools to improve the prognosis after surgical animals affected by breast cancer is quite necessary.展开更多
Gastric cancer(GC)remains a leading cause of cancer-related mortality worldwide,necessitating the identification of reliable prognostic indicators to enhance treatment outcomes.Recent research has highlighted the trig...Gastric cancer(GC)remains a leading cause of cancer-related mortality worldwide,necessitating the identification of reliable prognostic indicators to enhance treatment outcomes.Recent research has highlighted the triglyceride-glucose(TyG)index as a potential surrogate marker for insulin resistance,which may significantly influence the prognosis of patients undergoing immunotherapy combined with chemotherapy.In this context,the study by Yao et al demonstrates that a high TyG index correlates with improved overall survival and progressionfree survival in advanced GC patients receiving sintilimab and chemotherapy.Specifically,patients in the high TyG group had a significantly longer median progression-free survival of 9.8 months[95%confidence interval(CI):9.2-10.9]compared to 8.0 months(95%CI:7.5-8.5)in the low TyG group(hazard ratio=0.58,95%CI:0.43-0.79,P<0.001).Similarly,the median overall survival was significantly longer in the high TyG group at 23.1 months(95%CI:21.2-NA)vs 16.5 months(95%CI:13.9-18.3)in the low TyG group(hazard ratio=0.30,95%CI:0.21-0.42,P<0.001).These findings underscore the strong prognostic potential of the TyG index in guiding treatment strategies for advanced GC.These findings underscore the need for further investigation into the TyG index’s role as a prognostic tool and its underlying mechanisms in influencing treatment efficacy.We advocate for additional multicenter studies to validate these results and explore the TyG index’s applicability across diverse patient populations,ultimately aiming to refine treatment strategies and improve patient outcomes in advanced GC.展开更多
The retrospective cohort study by Zuo et al investigates the interplay between microsatellite instability(MSI)status,nutritional indicators,and inflammatory profiles in colorectal cancer(CRC).Analyzing 56 patients,the...The retrospective cohort study by Zuo et al investigates the interplay between microsatellite instability(MSI)status,nutritional indicators,and inflammatory profiles in colorectal cancer(CRC).Analyzing 56 patients,the study reveals that MSI-high tumors are associated with significantly lower serum albumin,body mass index,and absolute lymphocyte counts,alongside elevated neutrophil-tolymphocyte ratios compared to microsatellite stable tumors.These findings highlight distinct immunological and nutritional profiles in MSI-high CRC,suggesting potential clinical utility in risk stratification and personalized treat-ment.While the study underscores the importance of MSI status in CRC mana-gement,its single-center design and limited sample size warrant validation through multicenter trials.This article contextualizes these findings within the broader landscape of CRC research,emphasizing the need for integrating bio-markerdriven strategies into clinical practice to optimize outcomes for patients with differing MSI statuses.展开更多
Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension （IPAH）.Date sources We searched literature from PubMed and CNKI databases both ...Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension （IPAH）.Date sources We searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.Study selection Data about mortality and cut-off value are from clinical trials and identified by analysis.Results IPAH is an unexplained,progressive,and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance.The diagnosis is difficult,mortality of IPAH is high,and the survival periods are only 2-3 years after diagnosis.Investigations in recent years have identified a range of prognostic markers for IPAH,including the 6-minute walking test,red blood cell distribution width,and platelet levels,as well as imaging findings.Changes in these markers are important sources of information to predict the prognosis of patients with IPAH,which carries significant benefits for treatment planning.Conclusion Even though the prognosis of IPAH has been investigated,the mortality is also high.More accurate and meaningful assessment for the prognosis of IPAH is required.展开更多
Lysosomal acidification dysfunction has been implicated as a key driving factor in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Multiple genetic factors have b...Lysosomal acidification dysfunction has been implicated as a key driving factor in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Multiple genetic factors have been linked to lysosomal de-acidification through impairing the vacuolar-type ATPase and ion channels on the organelle membrane.Similar lysosomal abnormalities are also present in sporadic forms of neurodegeneration,although the underlying pathogenic mechanisms are unclear and remain to be investigated.Importantly,recent studies have revealed early occurrence of lysosomal acidification impairment before the onset of neurodegeneration and late-stage pathology.However,there is a lack of methods for organelle pH monitoring in vivo and a dearth of lysosome-acidifying therapeutic agents.Here,we summarize and present evidence for the notion of defective lysosomal acidification as an early indicator of neurodegeneration and urge the critical need for technological advancement in developing tools for lysosomal pH monitoring and detection both in vivo and for clinical applications.We further discuss current preclinical pharmacological agents that modulate lysosomal acidification,including small molecules and nanomedicine,and their potential clinical translation into lysosome-targeting therapies.Both timely detection of lysosomal dysfunction and development of therapeutics that restore lysosomal function represent paradigm shifts in targeting neurodegenerative diseases.展开更多
The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism...The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism,tumo-rigenesis,and tumor development.However,how DDX1 functions in various cancers remains unclear.Here,we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases.DDX1 is highly expressed in breast cancer(BRCA),cholangiocarcinoma(CHOL),and colon adenocarcinoma(COAD),but it is lowly expressed in renal cancers,including kidney renal clear cell carcinoma(KIRC),kidney chromophobe(KICH),and kidney renal papillary cell carcinoma(KIRP).Low expression of DDX1 in KIRC is cor-related with a good prognosis of overall survival(OS)and disease-free survival(DFS).Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma(ACC),bladder urothelial carcinoma(BLCA),KICH,and liver hepatocellular carcinoma(LIHC).Also,the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer(OV)but decreased in KIRC.Immune infiltration analysis exhibited that DDX1 expression affected CD8+T cells,and it was significantly associated with MSI(microsatellite instability),TMB(tumor mutational burden),and ICT(immune checkpoint blockade therapy)in tumors.In addition,the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines.DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database.Thus,our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.展开更多
Background:Nucleolar protein 6(NOL6)is a nucleolar RNA-associated protein that is highly conserved between species.It has been proved to be associated with the prognosis of liver cancer.However,the underlying mechanis...Background:Nucleolar protein 6(NOL6)is a nucleolar RNA-associated protein that is highly conserved between species.It has been proved to be associated with the prognosis of liver cancer.However,the underlying mechanism has not been fully established.This study aimed to assess the relationship between NOL6 and liver cancer prognosis.Methods:We constructed anNOL6-short hairpin RNA(shRNA)-expressing lentivirus.Through viral transfection,cell growth assay and fluorescence-activated cell sorting,we evaluated the effect of shRNA-mediatedNOL6 knockdown on the proliferation,colony formation,and apoptosis of hepatocellular carcinoma(HCC)cells.The relationship betweenNOL6 expression and HCC patient survival has been established through bioinformatics analysis.We also explored the downstream molecular regulatory network ofNOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.Results:IncreasedNOL6 expression was detected in HCC cells compared to normal controls;HCC patients with highNOL6 expression had poorer prognoses than those with low expression.NOL6 knockdown inhibited HCC cell proliferation,apoptosis,and colony formation.Also,MAPK8,CEBPA,andFOSL1 were selected as potential downstream genes ofNOL6.Conclusions:NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes.Moreover,NOL6 is considered to be associated with poor prognosis in HCC patients.展开更多
BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT s...BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.展开更多
This letter offered commentary on the recently published article by Wang et al that investigated the relationship between iron metabolism disorders and sepsis-associated liver injury(SALI).The original study identifie...This letter offered commentary on the recently published article by Wang et al that investigated the relationship between iron metabolism disorders and sepsis-associated liver injury(SALI).The original study identified serum iron and total iron-binding capacity as potential predictive markers of SALI,contributing important insights to critical care hepatology.In this correspondence several methodological considerations that may influence the interpretation and general-izability of the findings were discussed.These include the limitations of a single-center design,the lack of serial biomarker measurements,the omission of hepcidin(a central iron regulatory hormone)as a measured variable,and the exclusive reliance on biochemical criteria for diagnosing liver injury.The potential value of incorporating imaging modalities and additional iron-related markers such as ferritin and transferrin saturation were also highlighted.The aim was to reinforce the importance of a comprehensive approach to iron metabolism in sepsis and to suggest future directions for clinical research that may enhance the diagnostic and prognostic utility of iron-related biomarkers in SALI.展开更多
文摘BACKGROUND Non-ST segment elevation myocardial infarction(NSTEMI)poses significant challenges in clinical management due to its diverse outcomes.Understanding the prognostic role of hematological parameters and derived ratios in NSTEMI patients could aid in risk stratification and improve patient care.AIM To evaluate the predictive value of hemogram-derived ratios for major adverse cardiovascular events(MACE)in NSTEMI patients,potentially improving clinical outcomes.METHODS A prospective,observational cohort study was conducted in 2021 at the Internal Medicine Clinic of the University Hospital in Tuzla,Bosnia and Herzegovina.The study included 170 patients with NSTEMI,who were divided into a group with MACE and a control group without MACE.Furthermore,the MACE group was subdivided into lethal and non-lethal groups for prognostic analysis.Alongside hematological parameters,an additional 13 hematological-derived ratios(HDRs)were monitored,and their prognostic role was investigated.RESULTS Hematological parameters did not significantly differ between non-ST segment elevation myocardial infarction(NSTEMI)patients with MACE and a control group at T1 and T2.However,significant disparities emerged in HDRs among NSTEMI patients with lethal and non-lethal outcomes post-MACE.Notably,neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)were elevated in lethal outcomes.Furthermore,C-reactive protein-to-lymphocyte ratio(CRP/Ly)at T1(>4.737)demonstrated predictive value[odds ratio(OR):3.690,P=0.024].Both NLR at T1(>4.076)and T2(>4.667)emerged as significant predictors,with NLR at T2 exhibiting the highest diagnostic performance,as indicated by an area under the curve of 0.811(95%CI:0.727-0.859)and OR of 4.915(95%CI:1.917-12.602,P=0.001),emphasizing its important role as a prognostic marker.CONCLUSION This study highlights the significant prognostic value of hemogram-derived indexes in predicting MACE among NSTEMI patients.During follow-up,NLR,PLR,and CRP/Ly offer important insights into the inflammatory processes underlying cardiovascular events.
文摘Pancreatic ductal adenocarcinoma(PDAC)is the most prevalent type of pan-creatic neoplasm.It is a highly aggressive lethal malignancy related to its delayed in diagnosis and limited response to treatments.The incidence and mortality of pancreatic cancer have been increasing over the years.Tumor budding is a proven independent,adverse prognostic factor in PDAC.It is helpful for improvement of prognosis in PDAC in early and precise diagnostic modalities.Tumor budding should be conveyed in pathology reports and taken into account by future onco-logic staging systems.
文摘One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.
基金Supported by The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘In this editorial,we comment on an original article by Duan et al.Despite ad-vancements in the diagnosis and treatment of hepatocellular carcinoma(HCC),the identification of suitable prognostic factors remains challenging.In their paper,Duan et al identified long non-coding RNAs(LncRNAs)to quantify ge-nomic instability(GI)by combining LncRNA expression and somatic mutation profiles.They confirmed that the GI-derived LncRNA signature(GI-LncSig)could be an independent prognostic factor with the area under the curve of 0.773.Fur-thermore,the authors stated that GI-LncSig may have a better predictive perfor-mance than TP53 mutation status alone.However,studies exploring genetic markers for predicting the prognosis of HCC are crucial for identifying thera-peutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of liver cancer.
基金Supported by the Major State Basic Research Development Program (973 Program) of China (No. 2003CB515507) and Science and Technology Fund by Department of Education of Anhui Province
文摘AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.
文摘AIM To evaluate the role of albumin at the time of ulcerative colitis(UC) diagnosis in predicting the clinical course of disease.METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia(i.e.,≤ 3.5 gm/dl) or normal albumin levels(i.e.,> 3.5 gm/dl) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined asalbumin level ≤ 3.5 g/dl at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids(CS),thiopurines,anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients,but 92(11.4%) patients did not have their albumin levels checked at the time of UC diagnosis,and they were excluded. A total of 710 patients,who had albumin levels checked at time of UC diagnosis,were included in our study. Amongst them,536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use(adjusted HR = 1.7,95%CI: 1.3-2.3),higher likelihood of thiopurine or anti-TNF use(adjusted HR = 1.72,95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients,but it was not statistically significant(Adjusted HR = 1.7,95%CI: 0.90-3.25).CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis.
文摘AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule and the most important predictors for outcome. METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed. RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD,and 140 (52.8%) of them were female. hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminanthepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012). CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal medicine stands out as the most common drug for DILD. While antitubercular drugs are found to be the primary etiological factor for fetal DILD, hepatic encephalopathy, ascites, jaundice, alcohol abuse and direct bilirubin levels are associated with the death of DILD patients.
基金Supported by Health Commission of Shanxi Province,No.2020130 and No.2020TD27the Science and Technology Planning Project of Yangzhou City,No.YZ2018092。
文摘BACKGROUND Immunoinflammatory markers such as the peripheral blood neutrophil-tolymphocyte ratio(NLR)and the platelet-to-lymphocyte ratio(PLR)have gained considerable attention as prognostic markers in gastrointestinal stromal tumors(GISTs).AIM To assess the prognostic value of Onodera’s Prognostic Nutritional Index(OPNI)for GISTs.METHODS All patients who had undergone surgical resection for a primary,localized GIST from 2009 to 2016 at our cancer center were initially and retrospectively identified.Recurrence-free survival(RFS)was calculated by the Kaplan-Meier method and compared by the log-rank test.We used multivariate Cox proportional hazard regression models to identify associations with outcome variables.RESULTS A total of 235 GISTs were identified and included for analysis under our inclusion criteria.Univariate and multivariate analyses both identified the OPNI as an independent prognostic marker,and the OPNI was associated with the primary site,tumor size,mitotic index,tumor rupture,necrosis,and modified NIH risk classification.Low OPNI(<51.30;hazard ratio=5.852;95% confidence interval:1.072–31.964;P=0.0414)was associated with worse RFS.The 2-and 5-year RFS rates of the patients with a low OPNI were 92.83% and 76.22%,respectively,whereas 100% and 98.41% were achieved by the patients with a high OPNI.CONCLUSION The preoperative OPNI is a novel and useful prognostic marker for GISTs.
文摘Background:RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma(HCC),which is characterized by a mass of genetic and epigenetic alterations.However,the treatment targeting these alterations is limited.Methods:We used comprehensive bioinformatics analysis to analyze the correlation between cancerassociated RNA methylation regulators and HCC malignant features in network datasets.Results:We identified two HCC subgroups(cluster 1 and 2),which had clearly distinct clinicopathological,biofunctional and prognostic characteristics,by consensus clustering.The cluster 2 subgroup correlated with malignancy of the primary tumor,higher tumor stage,higher histopathological grade and higher frequency of TP53 mutation,as well as with shorter survival when compared with cluster 1.Gene enrichment indicated that the cluster 2 correlated to the tumor malignancy signaling and biological processes.Based on these findings,an 11-gene risk signature was built,which not only was an independent prognostic marker but also had an excellent power to predict the tumor features.Conclusions:Our study indicated that RNA methylation regulators are vital for HCC malignant progression and provide an important evidence for RNA methylation,methylation regulators are actionable targets for anticancer drug discovery.
基金Supported by a grant from the Project Funding Unit, University of Mansoura, Egypt
文摘Objective: We planned this study to investigate the relation between serum adiponectin level and hepatocellular carcinoma (HCC): risk, features and prognosis. Methods: The study included 100 patients with HCC and 40 healthy control subjects. Adiponectin levels were determined by an enzyme-linked immunosorbent assay kit. Results: In the subset of patients with compensated cirrhosis, the mean serum adiponectin level was significantly lower in HCC cases compared to healthy controls (88.6 versus 115 ng/mL; P = 0.012). In addition, serum adiponectin levels correlated negatively with tumor size (P = 0.004) and were significantly lower in patients with vascular invasion and distant metastases (P = 0.03 and P = 0.02 respectively). Furthermore, the median overall survival was significantly higher in the high adiponectin group than the low adiponectin group (median 12.5 versus 9.5 months; log rank = 4.6, P = 0.03). Conclusion: Decreased circulating adiponectin level may play a role in the development of HCC and is a potential poor prognostic marker. These data should be validated in further prospective studies. Also the mechanisms by which adiponectin affect the course of HCC need to be clarified.
文摘Objective:In order to find a genetic marker to predict the prognosis of patients with ovarian cancer based on multi-omics data. Methods:We download RNA-Seq SNP, CNV data and clinical follow-up information from TCGA database and randomly divide them into training set and test set. GSE17260 dataset in GEO is taken as an external validation set. Prognosis-related genes, copy number difference genes and mutant genes are screened in the training set. After the integration of genes, the random forest algorithm is further used for feature selection, ultimately obtaining a robust biomarker. On this basis, a gene-related prognostic model is established and verified in the test set and verification set. Results:We have obtained 2097 prognostic related genes, 447 copy amplification genes, 1069 copy deletion genes and 654 significant mutations genes. Through the feature selection of random forest algorithm, five feature genes (PSMB1, COL6A6, SLC22A2, KLHL23 and CD3G) are obtained by integrating these genes, some of which have been reported to be related to tumor progress. Furthermore, the prognostic risk assessment model of 5-gene signature is established by Cox regression analysis. The model can evaluate the risk of patient samples in training set, test set and external verification set. 5-gene signature shows strong robustness and clinical independence. The results of GSEA analysis also show that the pathway of 5-gene signature enrichment is significantly related to the pathway and biological process of the occurrence and development of ovarian cancer. Conclusion:In this study, 5-gene signature is constructed as a new prognostic marker to predict the survival of patients with ovarian cancer.
基金the Sao Paulo Research Foundation(FAPESP),Brazil,which provided financial support for Francisco Pedraza-Ordonez through the Post-doctoral Fellowship2011/23737-3.
文摘Background: Several animal models, including dogs, have been useful to compare the pathogenesis of mammary neoplasm in humans, showing biological parallelism in the growth and development of breast cancer. The causes of cancer could be attributed to change in several tumor suppressor genes. The relationship between molecule associated to senescence and clinical prognosis of patients affected by mammary cancer is little known. Beyond a collection of data, the major interest of the present study was to carry out a clinical follow-up of patients affected by these tumors, through association with new molecular markers by immunohistochemical technic. Upon completing the study, 15 patients survived, while 45 died. In the case of malignant neoplasms, 40 patients died because of the illness. The type of surgery most used by veterinarian surgeons was the simple lumpectomy, followed by the regional mastectomy. Sentinel node was removed by surgery only when clearly affected. Result: Markings against steroid hormones were positive. Regarding the markings against HER2 and Ki-67, they were negative in all cases. The markings against P53 and CD31 were all positives. Markings against molecules associated with cellular senescence were all positives. No statistical differences were found in immunomarcation for the different antigens used as clinical prognosis factors in mammary neoplasms. Conclusions: According to the study conditions, the survival of patients affected by breast tumors is directly related to diagnosis and malignancy histological grade, but not to animal breed, number of affected glands or patient reproductive status. On the other hand, immunohistochemical markings were not related to the patient prognosis. For this reason, it is important to highlight the persistance of a high percentage of mammary neoplasm cases clinically diagnosed with poor results on patient survival. Thus, educating owners and veterinarians for using diagnostic available tools to improve the prognosis after surgical animals affected by breast cancer is quite necessary.
文摘Gastric cancer(GC)remains a leading cause of cancer-related mortality worldwide,necessitating the identification of reliable prognostic indicators to enhance treatment outcomes.Recent research has highlighted the triglyceride-glucose(TyG)index as a potential surrogate marker for insulin resistance,which may significantly influence the prognosis of patients undergoing immunotherapy combined with chemotherapy.In this context,the study by Yao et al demonstrates that a high TyG index correlates with improved overall survival and progressionfree survival in advanced GC patients receiving sintilimab and chemotherapy.Specifically,patients in the high TyG group had a significantly longer median progression-free survival of 9.8 months[95%confidence interval(CI):9.2-10.9]compared to 8.0 months(95%CI:7.5-8.5)in the low TyG group(hazard ratio=0.58,95%CI:0.43-0.79,P<0.001).Similarly,the median overall survival was significantly longer in the high TyG group at 23.1 months(95%CI:21.2-NA)vs 16.5 months(95%CI:13.9-18.3)in the low TyG group(hazard ratio=0.30,95%CI:0.21-0.42,P<0.001).These findings underscore the strong prognostic potential of the TyG index in guiding treatment strategies for advanced GC.These findings underscore the need for further investigation into the TyG index’s role as a prognostic tool and its underlying mechanisms in influencing treatment efficacy.We advocate for additional multicenter studies to validate these results and explore the TyG index’s applicability across diverse patient populations,ultimately aiming to refine treatment strategies and improve patient outcomes in advanced GC.
文摘The retrospective cohort study by Zuo et al investigates the interplay between microsatellite instability(MSI)status,nutritional indicators,and inflammatory profiles in colorectal cancer(CRC).Analyzing 56 patients,the study reveals that MSI-high tumors are associated with significantly lower serum albumin,body mass index,and absolute lymphocyte counts,alongside elevated neutrophil-tolymphocyte ratios compared to microsatellite stable tumors.These findings highlight distinct immunological and nutritional profiles in MSI-high CRC,suggesting potential clinical utility in risk stratification and personalized treat-ment.While the study underscores the importance of MSI status in CRC mana-gement,its single-center design and limited sample size warrant validation through multicenter trials.This article contextualizes these findings within the broader landscape of CRC research,emphasizing the need for integrating bio-markerdriven strategies into clinical practice to optimize outcomes for patients with differing MSI statuses.
基金This work was supported by a grant from the Beijing Natural Science Foundation （No. 7121014）.
文摘Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension （IPAH）.Date sources We searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.Study selection Data about mortality and cut-off value are from clinical trials and identified by analysis.Results IPAH is an unexplained,progressive,and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance.The diagnosis is difficult,mortality of IPAH is high,and the survival periods are only 2-3 years after diagnosis.Investigations in recent years have identified a range of prognostic markers for IPAH,including the 6-minute walking test,red blood cell distribution width,and platelet levels,as well as imaging findings.Changes in these markers are important sources of information to predict the prognosis of patients with IPAH,which carries significant benefits for treatment planning.Conclusion Even though the prognosis of IPAH has been investigated,the mortality is also high.More accurate and meaningful assessment for the prognosis of IPAH is required.
基金supported by a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship(021207-00001)Nanyang Technological University(NTU)Singapore and a Mistletoe Research Fellowship(022522-00001)+1 种基金the Momental Foundation USA.J.Z.is supported by a Presidential Postdoctoral Fellowship(021229-00001)from NTU Singapore and an Open Fund Young Investigator Research Grant(OF-YIRG)(MOH-001147)the National Medical Research Council(NMRC)Singapore.
文摘Lysosomal acidification dysfunction has been implicated as a key driving factor in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Multiple genetic factors have been linked to lysosomal de-acidification through impairing the vacuolar-type ATPase and ion channels on the organelle membrane.Similar lysosomal abnormalities are also present in sporadic forms of neurodegeneration,although the underlying pathogenic mechanisms are unclear and remain to be investigated.Importantly,recent studies have revealed early occurrence of lysosomal acidification impairment before the onset of neurodegeneration and late-stage pathology.However,there is a lack of methods for organelle pH monitoring in vivo and a dearth of lysosome-acidifying therapeutic agents.Here,we summarize and present evidence for the notion of defective lysosomal acidification as an early indicator of neurodegeneration and urge the critical need for technological advancement in developing tools for lysosomal pH monitoring and detection both in vivo and for clinical applications.We further discuss current preclinical pharmacological agents that modulate lysosomal acidification,including small molecules and nanomedicine,and their potential clinical translation into lysosome-targeting therapies.Both timely detection of lysosomal dysfunction and development of therapeutics that restore lysosomal function represent paradigm shifts in targeting neurodegenerative diseases.
基金supported by grants from the National Natural Science Foundation of China(82071782)the Shanghai Committee of Science and Technology(20XD1400800)to JL.
文摘The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism,tumo-rigenesis,and tumor development.However,how DDX1 functions in various cancers remains unclear.Here,we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases.DDX1 is highly expressed in breast cancer(BRCA),cholangiocarcinoma(CHOL),and colon adenocarcinoma(COAD),but it is lowly expressed in renal cancers,including kidney renal clear cell carcinoma(KIRC),kidney chromophobe(KICH),and kidney renal papillary cell carcinoma(KIRP).Low expression of DDX1 in KIRC is cor-related with a good prognosis of overall survival(OS)and disease-free survival(DFS).Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma(ACC),bladder urothelial carcinoma(BLCA),KICH,and liver hepatocellular carcinoma(LIHC).Also,the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer(OV)but decreased in KIRC.Immune infiltration analysis exhibited that DDX1 expression affected CD8+T cells,and it was significantly associated with MSI(microsatellite instability),TMB(tumor mutational burden),and ICT(immune checkpoint blockade therapy)in tumors.In addition,the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines.DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database.Thus,our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.
基金supported by a grant from the Natural Science Foundation(No.81370069)。
文摘Background:Nucleolar protein 6(NOL6)is a nucleolar RNA-associated protein that is highly conserved between species.It has been proved to be associated with the prognosis of liver cancer.However,the underlying mechanism has not been fully established.This study aimed to assess the relationship between NOL6 and liver cancer prognosis.Methods:We constructed anNOL6-short hairpin RNA(shRNA)-expressing lentivirus.Through viral transfection,cell growth assay and fluorescence-activated cell sorting,we evaluated the effect of shRNA-mediatedNOL6 knockdown on the proliferation,colony formation,and apoptosis of hepatocellular carcinoma(HCC)cells.The relationship betweenNOL6 expression and HCC patient survival has been established through bioinformatics analysis.We also explored the downstream molecular regulatory network ofNOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.Results:IncreasedNOL6 expression was detected in HCC cells compared to normal controls;HCC patients with highNOL6 expression had poorer prognoses than those with low expression.NOL6 knockdown inhibited HCC cell proliferation,apoptosis,and colony formation.Also,MAPK8,CEBPA,andFOSL1 were selected as potential downstream genes ofNOL6.Conclusions:NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes.Moreover,NOL6 is considered to be associated with poor prognosis in HCC patients.
基金Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University,2022-LCYJ-PY-17CIMF-CSPEN Project,Z-2017-24-2211Project of Chinese Hospital Reform and Development Institute,Nanjing University and Aid project of Nanjing Drum Tower Hospital Health,Education&Research Foundation,NDYG2022090。
文摘BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.
文摘This letter offered commentary on the recently published article by Wang et al that investigated the relationship between iron metabolism disorders and sepsis-associated liver injury(SALI).The original study identified serum iron and total iron-binding capacity as potential predictive markers of SALI,contributing important insights to critical care hepatology.In this correspondence several methodological considerations that may influence the interpretation and general-izability of the findings were discussed.These include the limitations of a single-center design,the lack of serial biomarker measurements,the omission of hepcidin(a central iron regulatory hormone)as a measured variable,and the exclusive reliance on biochemical criteria for diagnosing liver injury.The potential value of incorporating imaging modalities and additional iron-related markers such as ferritin and transferrin saturation were also highlighted.The aim was to reinforce the importance of a comprehensive approach to iron metabolism in sepsis and to suggest future directions for clinical research that may enhance the diagnostic and prognostic utility of iron-related biomarkers in SALI.
