BACKGROUND:Given the high prevalence and serious health threats of Metabolic dysfunction-associated steatotic liver disease (MASLD) in older people, uncovering the pathological features of MASLD in the context of age is critically important. This study aimed to perform serum metabolomics analysis for older adults with MASLD to identify potential biomarkers and involved metabolic disturbances. METHODS:30 older subjects with MASLD and 30 healthy individuals were included (age > 65). Sex-stratified metabolomics analysis was applied by using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). Partial least squares discriminant analysis (PLS-DA) was utilized to identify differential metabolites between groups. The distinct and shared pathways of MASLD in older men and older women were explored using MetaboAnalyst 6.0. Machine learning algorithms are applied to screen for optimal biomarkers. Receiver operating characteristics (ROC) curve analysis was applied to test the predictive ability of biomarkers. Spearman's correlation analysis was conducted to evaluate the correlation of metabolic biomarkers with biochemical parameters. The differences in phosphatidylcholine concentration were externally validated in other 60 older adults. Finally, in the aged mice MASLD model, the mRNA expression levels of the rate-limiting enzyme of phosphatidylcholine synthesis (PCYT1A and PEMT) were detected. RESULTS:Principal components analysis (PCA) and PLS-DA exhibited pronounced metabolic separations between the MASLD and HC groups in both older males and females. 14 shared metabolites were selected by the least absolute shrinkage and selection operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Finally, 6 metabolites significantly dysregulated in older MASLD patients (|logFC| > 0.5) would be determined as the optimal metabolic markers, including: PC 18:1_22:6, 2'-Deoxyuridine-5-monophosphate, porphobilinogen, uridine, all-trans-13,14-Dihydroretinol and D-Ribulose 1,5-bisphosphate. Notably, a marked difference in serum phosphatidylcholine levels in the elderly between the MASLD group and the healthy group was confirmed by external validation (p < 0.001). The significant downregulation of PCYT1A mRNA expression was also found in the aged mice MASLD model. CONCLUSIONS:This study depicts the metabolic features of MASLD in the older population. Our finding explores promising biomarkers for diagnosis and provides more perspectives on molecular mechanisms and potential targets for MASLD in the context of aging.

Kinesin Family Member 3C (KIF3C) assumes a crucial role in various biological processes of specific human cancers. Nevertheless, there exists a paucity of systematic assessments pertaining to the contribution of KIF3C in human malignancies. We conducted an extensive analysis of KIF3C, covering its expression profile, prognostic relevance, molecular function, tumor immunity, and drug sensitivity. Functional enrichment analysis was also carried out. In addition, we conducted in vitro experiments to substantiate the role of KIF3C in gastric cancer (GC). KIF3C expression demonstrated consistent elevation in various tumors compared to their corresponding normal tissues. We further unveiled that heightened KIF3C expression served as a prognostic indicator, and its elevated levels correlated with unfavorable clinical outcomes, encompassing reduced OS, DSS, and PFS in several cancer types. Notably, KIF3C expression exhibited positive associations with the pathological stages of several cancers. Moreover, KIF3C demonstrated varying relationships with the infiltration of various distinct immune cell types in gastric cancer. Functional analysis outcomes indicated that KIF3C played a role in the PI3K-AKT signaling pathway. Drug sensitivity unveiled a positive relationship between KIF3C in gastric cancer and the IC50 values of the majority of identified anti-cancer drugs. Additionally, KIF3C knockdown reduced the proliferation, migration, and invasion capabilities, increased apoptosis, and led to alterations in the cell cycle of gastric cancer cells. Our research has revealed the significant and functional role of KIF3C as a tumorigenic gene in diverse cancer types. These findings indicate that KIF3C may serve as a promising target for the treatment of gastric cancer.

Background:Hepatocellular carcinoma (HCC), which is characterized by its high malignancy, generally exhibits poor response to immunotherapy. As part of the tumor microenvironment, basement membranes (BMs) are involved in tumor development and immune activities. Presently, there is no integrated analysis linking the basement membrane with immune checkpoints, especially from the perspective of lncRNA. Methods:Based on transcriptome data from The Cancer Genome Atlas, BMs-related and immune checkpoint-related lncRNAs were identified. By applying univariable Cox regression and Machine learning (LASSO and SVM-RFE algorithm), a 10-lncRNA prognosis signature was constructed. The prognostic significance of this signature was assessed by survival analysis. GSEA, ssGSEA, and drug sensitivity analysis were conducted to investigate potential functional pathways, immune status, and clinical implications of guiding individual treatments in HCC. Finally, the promoting migration effect of LINC01224 was validated via in vitro experiments. Results:The multiple Cox regression, receiver operating characteristic curves, and stratified survival analysis of clinical subgroups exhibited the robust prognostic ability of the lncRNA signature. Results of the GSEA and drug sensitivity analysis revealed significant differences in potential functional pathways and response to drugs between the two risk groups. In addition, the risk level of HCC patients was distinctly correlated with immune cell infiltration status. More importantly, LINC01224 was independently associated with the OS of HCC patients (P < 0.05), suppressing the expression of LINC01224 inhibited the migration of HCC cells. Conclusion:This study developed a reliable signature for the prognosis of HCC based on BM and immune checkpoint related lncRNA, revealing that LINC01224 might be a prognostic biomarker for HCC associated with the progression of HCC.

Background: Myc-associated zinc-finger protein (MAZ) is a transcription factor, which has been confirmed to be abnormally expressed in many tumors and involved in regulating the proliferation, migration, apoptosis, and autophagy of tumor cells. Currently, there is a lack of comprehensive analysis of MAZ in pan-cancer, and the mechanism of MAZ in hepatocellular carcinoma (HCC) and its association with immunotherapy remains unclear. Methods: The expression, prognostic mutation, sCNA, and tumor immunity characteristics of MAZ in 33 types of tumors were analyzed by The Cancer Genome Atlas (TCGA), GEPIA, and TIMER databases. The association of MAZ expression levels with drug sensitivity, immunotherapy, immune checkpoints, and HLA-associated genes was further analyzed. Transwell, CCK-8, wound healing, and flow cytometry verified that MAZ affected the malignant cell behavior of HCC. The signaling pathways and cellular functions affected by MAZ in HCC were revealed by GSEA enrichment analysis. Results: The expression level of MAZ was up-regulated, and the high expression of MAZ indicated a high-risk prognostic factor in most tumors, including ACC, BLCA, KIRP, LIHC, PRAD, SKCM, and THCA (p < 0.05). MAZ expression was positively correlated with the sensitivity of most chemotherapy drugs (p < 0.05). HLA-DQB2, HLA-H, and most immune checkpoint genes were remarkably up-regulated in the high MAZ expression group (p < 0.05). GSEA analysis revealed that MAZ expression was highly correlated with the intracellular immune-related functions and cancer-related signaling pathway, including the B cell receptor signaling pathway, complement activation, humoral immune response, TGF-beta signaling pathway, and Wnt signaling pathway. The overexpression of MAZ in HCC cells could promote the abilities of cell proliferation and migration and inhibit tumor cell apoptosis. Conclusion: Our study revealed that MAZ might play a role in promoting the progression of HCC. It was closely related to the tumor microenvironment, immune cell infiltration, and immune escape in pan-cancer. Moreover, this study provides new insights into MAZ as a prognostic marker and potential therapeutic target in HCC.

Abstract In recent years, although there has been a decline in the incidence and mortality rates of gastric cancer, it continues to represent a substantial burden on both the human healthcare and society at large. The challenges in early diagnosis of gastric cancer are attributed to its invasive nature and the absence of specific biomarkers. Kinesin family members (KIFs) have emerged as crucial contributors to tumor development. In this research, we explore a dataset acquired from the TCGA to investigate the potential value of KIFs in gastric cancer (GC). Initially, we explored the mutational features of KIFs. Then, in order to clarify their putative biological roles, we selected KIFs that were differentially expressed and carried out GO functional annotation and KEGG pathway analysis. Utilizing Cox regression analysis, we carried out anticipating models relied on the signatures of four KIFs (KIF3C, KIF17, KIF24, and KIFC3). The results revealed that our risk score derived from these models acts as an independent prognostic variable for GC. Additionally, a nomogram was developed to evaluate the outlook of patients with GC. The observed association between the risk score and infiltration of immune cell indicates that the four KIFs signatures could have a crucial influence on the immune microenvironment of GC. To summarize, our investigation revealed the possible molecular pathways linked to KIFs in GC and constructed a predictive framework that shows potential in directing individualized therapy and prognostic evaluation for GC individuals.

Abstract Background Kinesin Family Member 3C (KIF3C) assumes a crucial role in various biological processes and has been engaged in the initiation and deveopment of specific human cancers. Nevertheless, there exists a paucity of systematic assessments pertaining to the contribution of KIF3C in human malignancies. Furthermore, the significance of KIF3C in the context of diagnosing and prognosticating gastric cancer (GC) has yet to be thoroughly investigated. As a result, this study endeavors to undertake a comprehensive analysis of KIF3C and assess its potential diagnostic and prognostic value in GC. Methods We conducted an extensive analysis of Kinesin Family Member 3C (KIF3C), covering its expression profile, prognostic relevance, molecular function, tumor immunity, and drug sensitivity. Functional enrichment analysis was also carried out for gastric cancer using publicly accessible databases. In addition, we conducted in vitro experiments to substantiate the role of KIF3C in gastric cancer (GC). Results KIF3C expression demonstrated consistent elevation in various tumors in comparison to their corresponding normal tissues. Our study further unveiled that heightened KIF3C expression served as a prognostic indicator, and its elevated levels correlated with unfavorable clinical outcomes, encompassing reduced OS, DSS, and PFS in several cancer types. Notably, KIF3C expression exhibited positive associations with the pathological stages of BLCA, BRCA, COAD, COADREAD, KIRP, LIHC, LUNG, and THCA. Furthermore, KIF3C expression displayed distinct associations with 60 immune checkpoints, immunoregulators, TMB, and MSI. Moreover, KIF3C demonstrated varying relationships with the infiltration of various distinct immune cell types in gastric cancer. Functional analysis outcomes indicated that KIF3C played a role in the PI3K-AKT signaling pathway. Our analysis of drug sensitivity unveiled a positive relationship between KIF3C in gastric cancer and the IC50 values of the majority of identified anti-cancer drugs. Additionally, our cellular experiments demonstrated that KIF3C knockdown reduced the proliferation, migration, and invasion capabilities, increased apoptosis, and led to alterations in the cell cycle of gastric cancer cells. Conclusion Our research has revealed the significant and functional role of KIF3C as an tumorigenic gene in diverse cancer types. Additionally, we observed elevated KIF3C level in gastric cancer cells, and this upregulation was notably linked to an unfavorable prognosis among gastric cancer patients. These findings indicate that KIF3C may serve as a promising target for the treatment of gastric cancer.

Purpose: Autophagy plays a crucial role in the initiation and progression of gastric cancer (GC). However, the role of autophagy-related lncRNAs in GC remains unknown. This study aimed to investigate the prognostic value of the autophagy-related lncRNA signature and its role in the tumor immune microenvironment (TIME) of GC. Methods: RNA-sequencing (RNA-seq) and clinical data of GC patients were extracted from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were performed to identify the autophagy-related lncRNA prognostic signature which was validated in the test set and entire set. The survival and predictive performance were analyzed based on the Kaplan-Meier and ROC curves. Furthermore, the CIBERSORT algorithm was applied to explore the relationship between this signature and the immune cell infiltration. To elucidate the potential functions of autophagy-related lncRNAs in GC, we constructed the lncRNA-mRNA co-expression network and performed enrichment analysis. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) were further performed to compare the different statuses between the high-risk and low-risk groups. Results: We identified 5 autophagy-related lncRNAs (AL355574.1, AC010768.2, AP000695.2, AC087286.2, and HAGLR) to construct a prognostic signature. This signature could be an independent prognostic indicator for GC patients and had a higher prediction efficiency than other clinicopathological parameters. Furthermore, patients in the high-risk score group had a stronger immunosuppressive microenvironment than the low-risk group. The enrichment analysis for mRNAs co-expressed with these lncRNAs indicated that autophagy-related signaling pathways were remarkably enriched. PCA and GSEA further revealed different autophagy and immune statuses in the high-and low-risk groups. Conclusion: The 5 autophagy-related lncRNA signature has significant clinical implications in prognosis prediction of GC. Meanwhile, our study elucidates the critical role of the autophagy-related lncRNA signature in the TIME of GC.

Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

目的:探讨结直肠癌(CRC)组织人源长寿保障基因2(LASS2)、同源异型盒基因B7(HOXB7)表达与凋亡指数(AJ)及预后的关系.方法:选择2013年10月至2015年4月期间在我院接受治疗的105例CRC患者作为研究对象.检测其CRC组织以及癌旁组织中LASS2、HOXB7表达以及AI,分析LASS2、HOXB7表达与临床病理特征的关系,采用Kaplan-Meier生存曲线分析不同LASS2、HOXB7表达患者总生存率的差异,Cox比例风险回归分析CRC患者预后的影响因素.结果:CRC组织中LASS2阳性率低于癌旁正常组织,而HOXB7阳性率高于癌旁正常组织(P＜0.05),CRC组织中AI低于癌旁正常组织(P＜0.05).经Spreaman相关性分析显示CRC组织LASS2阳性率和AI呈正相关关系,而HOXB7阳性率和AI呈负相关关系(P＜0.05).LASS2表达与临床分期、浸润深度和淋巴结转移有关(P＜0.05),而HOXB7表达与临床分期和淋巴结转移有关(P＜0.05).HOXB7表达阳性患者的生存率低于HOXB7表达阴性患者,而LASS2表达阳性患者的生存率高于LASS2表达阴性患者(P＜0.05).Cox比例风险回归分析结果显示,临床分期为Ⅲ期、有淋巴结转移、LASS2阴性表达、HOXB7阳性表达以及AI＜2.0％均是影响CRC患者预后的危险因素(P＜0.05).结论:在CRC组织中HOXB7阳性率升高,而LASS2阳性率以及AI下降,且与临床分期以及淋巴结转移密切相关.LASS2、HOXB7表达及AI与CRC患者的生存和预后联系密切.

Ischemic colitis (IC) is the most prevalent ischemic injury of thegastrointestinal tract. Clinical features of IC such as acute abdominal pain, hematochezia,and diarrhea are similar to those of acute mesenteric ischemia, inflammatorybowel disease, or infectious bowel disease, and their relative ambiguity candelay diagnosis and treatment. To comprehensively detail the current state ofdiagnostic methods and available drug therapies for detecting and treating IC,this review aims to provide a concise and practical summary of thecorresponding literature. PubMed and Cochrane Library were searched toretrieve all published studies reporting the diagnostic methods and drugtherapies in patients with ischemic colitis. The search strategy of drugtherapy includes human and animal data. Colonoscopy combined with histopathologicalbiopsy is the standard of diagnosis for the IC. Most patients respond well tothe conservative treatment, and surgical consultation is needed when conservativetreatment is ineffective. Studies of potential drug therapy have beendeveloped, including phosphodiesterase type 5 inhibitors, pentoxifylline,rebamipide, prostaglandin E1, and polydeoxyribonucleotide. Accurate diagnoses and effective treatmentshave helped reduce the mortality rate and improve prognoses for patientsafflicted with IC, and corresponding drug therapies have been constantlyupdated as new research has emerged.

Objective: To investigate the efficacy of radiofrequency ablation (RFA) in combination with hepatic arterial chemoembolization (HACE) in the treatment of primary hepatic carcinoma (PHC) and its effect on the serum markers. Methods: A total of 74 patients with PHC who were admitted to our hospital from February 2013 to January 2014 were randomly allocated to the experimental group (n=37) and the control group (n=37) in terms of a random number table. The patients in the control group received HACE whereas those in the experimental group underwent RFA plus HACE. The adverse events during treatment, the efficacy 2 months after treatment, the recurrence rate, the survival rate and the degree of tumor necrosis 3 years after surgery were compared between the two groups. In addition, the changes in serum markers before and after treatment were observed in the two groups. Results: Two months after treatment, glutamyl transpeptidase (GGT) lowered significantly in the experimental group as compared with the control group (P=0.000), so was alpha fetoprotein (AFP). And the difference was significant between the two groups (P=0.000). The overall clinical response and the rate of tumor complete necrosis were significantly higher in the experimental group (P=0.017, P=0.000, respectively). The 3-year recurrence rate was markedly lower (P=0.027), but the survival rate was strikingly higher in the experimental group (P=0.006). Furthermore, no significant differences were noted in the incidence of adverse events between the two groups (P=0.662). Conclusion: The protocol of RFA in combination with HACE in PHC was associated with greatly improved serum markers, reduced recurrence rate and enhanced survival rate of patients with PHC. Therefore, it is a safe and effective alternative for treatment of PHC.

OBJECTIVE To investigate the effects and safety of pantoprazole on the treatment of peptic ulcer bleeding related with nonsteroidal anti-inflammatory drugs(NSAIDs). METHODS 80 patients(between 65 to 85 years old and were all given NSAIDs for 7 days) with peptic ulcer bleeding diagnosed by endoscope were randomly divided in two groups: pantoprazole group(treatment group) and famotidine group(control group).The treatment group received pantoprazole 40 mg,q12 h,the control group received famotidine 20 mg,q12 h by intravenous drip for 5 days. RESULTS After 3 days of treatment the excellent rates were 80% in pantoprazole group and 25% in famotidine group(P<0.05).After 5 days of treatments the total effective rates were 92.5% in pantoprazole group and 60% in famotidine group(P>0.05). CONCLUSION Pantoprazole has more distinguished therapeutic effect than famotidine in peptic ulcer bleeding related with NSAIDs in the aged.