Clinical and Experimental Medicine最新文献

Despite advancements in antiretroviral therapy, AIDS-related diffuse large B-cell lymphoma (AR-DLBCL) remains a major cause of morbidity and mortality. Compared to non-HIV-infected individuals, AR-DLBCL presents with considerable disease heterogeneity, which impairs the accuracy of current prognostic tools. This study aims to develop a novel prognostic model to enhance risk assessment for AR-DLBCL. We retrospectively analyzed 90 AR-DLBCL cases using univariate and multivariate analyses to identify clinical factors affecting overall survival (OS) and progression-free survival (PFS). A nomogram was created based on independent OS risk factors. The cohort had a median age of 43 years (range: 22-75), with 96.5% male patients. The median follow-up was 30 months (range: 1-139), with 5-year OS and PFS rates of 60.7% and 58.7%, respectively. Key prognostic factors for OS included decreased absolute lymphocyte count (p = 0.002), extranodal involvement (p = 0.005), reduced hemoglobin (Hb) levels (p = 0.004), Epstein-Barr virus (EBV) infection (p = 0.005), and elevated lactate dehydrogenase (LDH) levels (p = 0.018). The nomogram demonstrated robust predictive performance, with a 5-year receiver operating characteristic curve area under the curve of 0.949. Its C-index of 0.849 surpassed the International Prognostic Index (IPI) and age-adjusted IPI (aaIPI), which had C-index of 0.708 and 0.693, respectively. Additionally, the nomogram identified significant OS differences among low risk, intermediate-low risk, intermediate-high risk, and high-risk groups, with 5-year survival rates of 100%, 88%, 56%, and 8%, respectively. The model offers a personalized risk assessment for AR-DLBCL patients, facilitating precise prognosis prediction and informing individualized treatment strategies.

Background: Although alcohol has been illegal in Iran for over four decades, its consumption persists. This study aims to determine the prevalence and determinants of alcohol consumption in Tehran, the Middle East's third-largest city, using data from the Tehran Cohort Study (TeCS).

Methods: Our study encompasses data from 8420 individuals recorded between March 2016 and March 2019. We defined alcohol use as the lifetime consumption of alcoholic beverages and/or products. We calculated the age- and sex-weighted prevalence of alcohol use in addition to crude frequencies. We also determined the weighted prevalence of alcohol use in both genders. Multivariable logistic regressions were employed to investigate the adjusted odds ratios for the determinants of alcohol use.

Results: The mean age of participants was 53.8 ± 12.7 years. The lifetime prevalence of alcohol use was 9.9% (95% confidence interval [95% CI]: 8.3-11.8%) among the total population, with a prevalence of 3.3% (95% CI: 2.4-4.5%) among females and 16.6% (95% CI: 14.3-19.3%) among males. Alcohol use showed a decreasing trend with age in both sexes (women: 4.4% and men: 1.5% per year) as well as in the total population (1.7%). The geographical distribution of alcohol use in Tehran indicated a significantly higher concentration (95% CI: 6.5-13%) in the southern regions compared to other areas. Younger age, higher education levels, smoking, opium use, hyperlipidemia, physical activity, and being overweight determined a higher prevalence of alcohol use.

Conclusions: The prevalence of alcohol use in Tehran is significant and exceeds previous estimates. Policymakers must address the rising incidence of alcohol use, particularly among the younger population.

The critical involvement of circRNAs in tumour progression and development is becoming increasingly evident. This study aimed to identify novel cancer-promoting circRNAs and explore their potential contribution to the pathogenesis of hepatocellular carcinoma (HCC). Expression profiles of circRNAs, miRNAs, and mRNAs associated with HCC were predicted through interaction analysis using data from the GEO and TCGA databases. A circRNA-miRNA-mRNA network was constructed, and the biological functions of the target mRNAs were predicted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was generated to identify important hub genes. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to determine the key modules related to cancer-promoting circRNAs. OncomiR and GEPIA were used to investigate the correlation between miRNAs, mRNAs, and clinicopathological features, while TIMER was utilized to explore the relationship between gene expression and immune cell infiltration. A network of 18 cancer-promoting circRNAs in HCC was identified, which enhanced the expression of 141 downstream mRNAs through competitive binding with 10 miRNAs. GO, KEGG, and PPI network analyses revealed that E2F1, H2AFX, TOP2A, and RAD51 are key hub genes within the competitive endogenous RNA (ceRNA) network, primarily involved in cell cycle regulation, cancer-related pathways, and angiogenesis. WGCNA identified the "HCC DUcircRNA Module". Moreover, these core genes and key modules were closely associated with pathological stage, patient survival, and B-cell immune infiltration. We constructed a ceRNA network related to cancer-promoting circRNAs. The genes and key modules involved in this network may serve as potential therapeutic targets.

Glycogen accumulation is a typical feature in clear cell renal cell carcinoma (ccRCC). It has been reported that glycogen metabolism-related genes can promote the progression of ccRCC, but its role in molecular typing, prognosis, immune infiltration, and immunotherapy response has rarely been reported. We applied an unsupervised clustering approach for molecular typing of ccRCC. The least absolute shrinkage and selection operator regression (LASSO) was used for prognostic model construction. The robustness of the model is evaluated by multicenter mutual verification. Weighted gene co-expression network analysis (WGCNA) was used to explore potential biological mechanisms. RT-qPCR was used to identify mRNA relative expression. We found ccRCC can be divided into two subtypes based on glycogen metabolism-related genes, and the prognosis of patients between the two subtypes is significantly different. Furthermore, we constructed a prognostic model for ccRCC patients based on glycogen metabolism-related genes using LASSO algorithm. We found that the model has a strong prognostic effect. Subsequently, we explored the underlying mechanisms through WGCNA and found that the model is associated with immune-related signaling pathways. Finally, we also found that this prognostic model can be used as a marker of response to immunotherapy in patients with advanced ccRCC. In conclusion, glycogen metabolism-related genes have critical value in molecular typing and prognosis evaluation of ccRCC.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Immunotherapy, particularly PD-1 inhibitors, has revolutionized the treatment landscape for NSCLC. However, the predictive biomarkers for PD-1 inhibitor therapy are still limited. Serum cytokines have emerged as potential biomarkers for predicting treatment outcomes. This meta-analysis aims to investigate the predictive value of serum cytokines in PD-1 inhibitor therapy for NSCLC. We conducted a comprehensive literature search in major databases, including PubMed, Google scholar, Embase, and Cochrane database, with a focus on literature published up until October 22, 2024. Studies investigating the association between serum cytokine levels and treatment outcomes in NSCLC patients receiving PD-1 inhibitor therapy were included. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The meta-analysis revealed that elevated IL-6 levels were significantly associated with poorer PFS in NSCLC patients (HR = 2.30, 95% CI [1.39-3.80], P = 0.001). Additionally, high IL-10 expression was related to poorer PFS in NSCLC after therapy (HR = 2.45, 95% CI [1.26-4.76], P = 0.009). In contrast, no significant associations were found between OS and the expression of various cytokines, including IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, IL-1β, TNF-α, and IL-12p70. This meta-analysis demonstrates that elevated IL-6 and IL-10 levels are significantly associated with poorer PFS in NSCLC patients receiving PD-1 inhibitor therapy. These findings suggest that serum cytokine levels may serve as predictive biomarkers for treatment outcomes. Further studies are needed to validate these results and explore the underlying mechanisms.

Hepatitis B virus (HBV) infection remains a major global health challenge, affecting approximately 296 million people and causing significant mortality annually. Despite vaccination efforts, HBV prevalence persists, particularly in low- and middle-income regions and endemic areas like China. HBV is closely associated with various kidney diseases, including acute kidney injury, chronic kidney disease, and glomerulonephritis, through mechanisms such as immune complex deposition, direct viral invasion, and chronic inflammation. Patients undergoing hemodialysis or kidney transplantation are at increased risk of HBV infection and reactivation, highlighting the need for effective preventive and therapeutic measures. This review examines the classification and clinical features of HBV-associated nephropathy, focusing on membranous nephropathy and membranoproliferative glomerulonephritis. It explores the pathogenesis, emphasizing immune complex deposition and podocyte apoptosis. Antiviral therapy, particularly with nucleos(t)ide analogs like entecavir and tenofovir (including TAF and TMF), demonstrates superior efficacy and safety compared to older agents such as lamivudine and adefovir. While interferon therapy offers benefits, its use is limited by adverse effects. Additionally, individualized treatment strategies for specific populations, including pregnant women and HIV co-infected patients, are crucial. Addressing HBV-associated nephropathy requires enhanced surveillance, timely antiviral intervention, and tailored therapeutic approaches to improve patient outcomes.

Haemophagocytic lymphohistiocytosis (HLH) is a serious condition characterised by uncontrolled hyperinflammation. Etoposide has been used as a treatment option in paediatric HLH; however, its effectiveness and the necessity for adult induction therapy remain unclear. This systematic review and meta-analysis aimed to assess the effectiveness of etoposide-based induction therapy in adult HLH, focusing on overall response (OR). A systematic literature search was conducted to identify relevant studies on 11 December 2023, resulting in the inclusion of seven studies in the analysis. The pooled data demonstrated a significant improvement in OR with etoposide-based therapy in adult patients with HLH (1.95, 95% CI 1.51-2.53), compared with non-etoposide-treated patients. Furthermore, overall survival improved with etoposide treatment (1.25, 95% CI 1.03-1.52). Our analysis revealed the potential benefit of etoposide-based therapy in adult patients with HLH. Therefore, etoposide should be considered as a timely and early therapeutic option for the management of adult HLH.

Liver cancer ranks among the deadliest cancers worldwide. Entosis, a recently uncovered method of cell death, has not yet been fully explored for its relevance to HCC. A bioinformatics analysis was performed to determine the expression and mutational landscapes of Entosis-related genes (ERGs). A subset of differentially expressed Entosis-related genes (DEERGs) was generated. A risk model for entosis was subsequently constructed employing LASSO and Cox regression methodologies. The correlations among ERGs, genes associated with risk, the developed risk model, and the immune context of the tumour were explored. Furthermore, the study investigated the varying drug sensitivities between high-risk and slight-risk patient groups. The expression patterns of four pivotal risk genes were delineated via qRT‒PCR and WB. A prognostic model comprising four DEERGs (KIF18A, SPP1, LCAT and TRIB3) was developed. The ability of this model to predict the survival outcomes of patients with HCC was confirmed through receiver operating characteristic curve analysis. Patients were grouped according to their risk assessments, revealing that the low-risk population demonstrated a more favourable survival outcome than did the high-risk population. The high-risk population presented reduced tumour stroma, immune and ESTIMATE scores, along with an increased proportion of cancer stem cells and tumour mutation burden. Additionally, a connection between the risk model and the responsiveness of various chemotherapy drugs as well as the efficacy of immunotherapies in patients was noted. These findings provide significant guidance for the development of targeted clinical treatment strategies. qRT‒PCR and WB analysis revealed that the gene expression of KIF18A and SPP1 were elevated in HCCLM3 cells compared with that in THLE2 cells; whereas, the expression level of LCAT and TIRB3 was decreased. The four genes KIF18A, SPP1, LCAT and TRIB3 could effectively predict the survival prognosis of patients with liver cancer. KIF18A and SPP1 were elevated in HCC tissues compared with that in THLE2 cells.

To explore value of semi-quantitative scoring based on musculoskeletal ultrasound in diagnosis and disease assessment of gouty arthritis (GA). Ninety patients with suspected GA who received in our hospital from January 2022 to December 2023 were retrospectively selected as the study objects. The puncture results of joint synovial fluid or crystal material in the joint cavity were used as the gold standard, and the patients 'joint effusion, synovitis, bone erosion and tenosynovitis were counted. Compare the musculoskeletal ultrasound semi-quantitative score with the puncture results of joint synovial fluid or crystal material in the joint cavity to diagnose different pathological types of GA and evaluate the diagnostic efficiency of musculoskeletal ultrasound semi-quantitative score in diagnosing different pathological types of GA. Use correlation analysis to analyze the correlation between patients with the musculoskeletal ultrasound semi-quantitative score results, IL-6 and DAS28 scores, and typical musculoskeletal ultrasound and MRI examination results. There was no significant difference between the musculoskeletal ultrasound semi-quantitative score and the puncture results of joint synovial fluid or crystal material in the joint cavity. There was no significant difference between the examination results of different lesion types (P > 0.05). The puncture results of joint synovial fluid or crystal material in the joint cavity were used as the gold standard, the sensitivity of musculoskeletal ultrasound semi-quantitative scoring in diagnosing synovial thickening, joint effusion, bone erosion, and tendon/tendon sheath inflammation in GA patients was 92.86% (26/28), 96.00% (24/25), 95.24% (20/21), and 75.00% (12/16), respectively. The specificity values were 93.55% (58/62), 96.92% (63/65), 95.65% (66/69), and 98.65% (73/74) respectively. The accuracy rates were 93.33% (84/90), 96.67% (87/90), 95.56% (86/90), and 94.44% (85/90), respectively. According to Pearson linear correlation analysis, as the semi-quantitative scoring increased, there was a positive correlation with erythrocyte sedimentation rate, IL-6, and DAS28 scores (r = 0.729, 0.584, 0.773, P < 0.001). Observation of their serological indicators showed that there were significant differences in serological indicators between patients with different semi-quantitative scores (P < 0.05). Semi-quantitative scoring based on musculoskeletal ultrasound has high value in the diagnosis and assessment of gouty arthritis, and is worth further use.

Overcoming cancer and enhancing patient survival are becoming increasingly challenging due to the uncontrolled growth and metastasis of colorectal cancer cells. In order to provide effective cancer treatment and minimize the malignancy of cancer cells, it is necessary to understand how complex signaling networks contribute to their invasion and proliferation. The signal transducer and activator of transcription 3 (STAT3) is a promising target due to its involvement in various cellular functions, including apoptosis, immunosuppression, cell invasion, migration, and proliferation. Dysregulation of STAT3 signaling is associated with diseases, particularly colorectal cancer. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs, are essential for the progression, apoptosis, and metastasis of CRC as they regulate key signaling pathways such as STAT3 signaling and contribute to gene regulation at the epigenetic, transcriptional, and post-transcriptional levels. Moreover, lncRNAs have a key function in regulating immune cells function through STAT3. In this study, we comprehensively reviewed the regulatory roles of different lncRNAs on STAT3 and the mutual effects of this pathway in various aspects of carcinogenesis, including proliferation, apoptosis, metastasis, drug resistance, and angiogenesis. Moreover, we investigate the effects of lncRNA/STAT3 axis on the function of different immune cells that play critical role in the tumor microenvironment.