Covariates Research Articles

Prognostic Value of Combined Detection of MMP-7 and ALP Levels in Children With Biliary Atresia Post-Kasai Surgery.

Biliary atresia (BA) remains a prevalent indication for pediatric liver transplantation (LT). We investigated the prognostic value of the serum matrix metalloproteinases 7 (MMP-7) and alkaline phosphatase (ALP) level combined detection for BA children post-Kasai surgery. This study retrospectively enrolled 85 BA children who underwent Kasai surgery. They were divided into the native liver (NL) and LT groups based on their three-year postoperative prognosis. Serum MMP-7 and ALP levels were measured by ELISA. The relationship of intraoperative serum MMP-7 and ALP levels with preoperative gamma-glutamyltransferase (GGT), and their impact on the risk of postoperative LT were analyzed by Pearson's correlation coefficient and Kaplan-Meier curves. The independent risk factors (IRFs) for postoperative LT and the predictive value of the serum MMP-7 and ALP level combined detection for postoperative LT in BA children were analyzed by Cox regression analysis and receiver operating characteristic (ROC) curves. MedCalc software compared the areas under the ROC curves (AUC). Significant differences were observed between the two groups in BA classification, postoperative jaundice clearance rate, and cholangitis occurrence. Intraoperative serum MMP-7 and ALP levels were higher in the LT group and positively correlated with preoperative GGT. High MMP-7 and ALP levels were IRFs for postoperative LT, while significant jaundice clearance was a protective factor. Combined MMP-7 and ALP detection (0.926 AUC, 91.30% sensitivity, 87.18% specificity) significantly improved the prediction for LT. High MMP-7 and ALP levels are IRFs for post-Kasai surgery LT in BA children, with their combination providing superior predictive value.

Impact of Perioperative Rehabilitation on Postoperative Length of Hospital Stay for Patients With Gastric Cancer.

Perioperative rehabilitation is effective in preventing postoperative complications and is associated with a shorter length of hospital stay after gastrectomy. However, its impact on short-term outcomes in patients without post-gastrectomy complications has not yet been clarified. This study aimed to evaluate the usefulness of perioperative rehabilitation beyond preventing postoperative complications. Of the 142 patients who underwent surgery for gastric cancer at our hospital between November 2017 and December 2022 and were treated according to the Enhanced Recovery After Surgery (ERAS) protocol during the perioperative period, 106 patients who were discharged without postoperative complications (with Clavien-Dindo classification < Grade 1) and did not undergo readmission within 30 days after surgery were included in the study. Perioperative rehabilitation was provided from August 2020. Patients were divided into the following two groups: Group A (with cancer rehabilitation; n=55) and Group B (without cancer rehabilitation; n=51), and their clinicopathological characteristics and short-term results were compared. Risk factor analysis was performed based on the number of days of postoperative hospitalization. The number of days of postoperative hospitalization in Group A (average 8.6 days) was significantly shorter than that in group B (average 9.9 days) (p=0.032). Multivariate analysis of postoperative hospital stay revealed that older age (p=0.003), female sex (p=0.043), heavy bleeding (p=0.026), and no rehabilitation (p=0.004) were independent risk factors. Even in patients without postoperative complications, perioperative rehabilitation for gastric cancer could be effective in shortening the postoperative hospital stay.

Stratification of Anatomical Imaging Features Between High-Risk and Non-High-Risk Groups in Neuroblastoma.

This study compared anatomical imaging features between high-risk and non-high-risk groups in neuroblastoma with at least one image-defined risk factor (IDRF). It also assessed the diagnostic performance of these features in identifying the high-risk group. A retrospective analysis of neuroblastoma patients with at least one IDRF was conducted. Imaging features, including estimated tumor volume and IDRFs, were compared between the two groups. The diagnostic performance of these features was assessed using receiver operating characteristic (ROC) curves, and the areas under the ROC curves (AUCs) along with their 95% confidence intervals (CIs) were calculated. Additionally, to internally validate their diagnostic performance, the bootstrap resampling method with 1000 bootstrap resamples was employed. The study included 255 patients (185 high-risk cases, 70 non-high-risk cases). Significant differences were found in estimated tumor volume and IDRF number between the high-risk and non-high-risk groups (P < 0.001). The estimated tumor volume and the IDRF number-based cluster were independent risk factors, and their combination achieved an AUC of 0.801 (95% CI: 0.747-0.848) for high-risk group diagnosis, with the average AUC of the 1000 bootstrap samples of 0.800 (95% CI: 0.798-0.802). In abdominal lesions, specific IDRF categories differed between high-risk and non-high-risk groups (P < 0.05). Our study reveals anatomical imaging differences between high-risk and non-high-risk groups in neuroblastoma with at least one IDRF.

Developing a Prognostic Model for Predicting the Risk of Outcome in Patients With Novel Bunyavirus Infection: A Retrospective Study.

The study aims to investigate the key risk factors influencing the prognosis of patients with severe fever with thrombocytopenia syndrome (SFTS) and develop a prognostic warning model based on these factors. A total of 264 SFTS patients treated at Tongji Hospital from April 1, 2023, to July 30, 2024, were included as the research sample. Retrospective analysis was conducted based on the final prognostic status of the patients, dividing them into a survival group (n = 165) and a death group (n = 99). Univariate and multivariate analyses were performed along with LASSO and logistic regression on baseline information and the first laboratory indicators within 24 h after admission to identify independent risk factors affecting prognosis. A warning model was constructed based on these factors. The analysis revealed that age (OR = 1.098, 95% CI: 1.054-1.149, p < 0.001), presence of consciousness disorders (OR = 2.506, 95% CI: 1.042-6.187, p = 0.042), BUN (OR = 1.248, 95% CI: 1.154-1.369, p < 0.001), and viral load (OR = 3.598, 95% CI: 2.572-5.288, p < 0.001) were identified as independent risk factors significantly impacting the prognosis of SFTS patients. A nomogram warning model was developed incorporating these four risk factors, which demonstrated excellent predictive performance (ROC = 0.917, 95% CI: 0.882-0.948, p < 0.001). The prognostic risk prediction model successfully established for SFTS patients in this study exhibits robust predictive performance, and it is anticipated to serve as a practical clinical tool for predicting disease progression and prognosis in SFTS patients.

Identification and validation VAT1 in gastric cancer through bioinformatics and experimental analysis.

This study investigated the expression pattern of Vesicular Amine Transporter 1 (VAT1) in gastric cancer (GC) and its impact on prognosis, alongside evaluating its potential as a biomarker for immunotherapy and chemotherapy. Analysis of transcriptomic data, supported by experimental validation, revealed that VAT1 is highly expressed in GC and is associated with poor prognosis. Kaplan-Meier and ROC analyses demonstrated VAT1's potential in GC diagnosis, while multivariate analysis confirmed its role as an independent risk factor. Gene set enrichment analysis indicated that VAT1 plays a role in regulating the MAPK signaling pathway and epithelial-mesenchymal transition (EMT) in GC. Immune infiltration analysis showed a positive correlation between VAT1 and immune cells, particularly macrophages, and a negative correlation with chemotherapy sensitivity. In vitro and in vivo experiments further confirmed VAT1's critical role in promoting GC cell proliferation and inhibiting apoptosis. Overall, VAT1 holds significant value not only in GC diagnosis and prognosis but also as a potential target for immunotherapy and overcoming drug resistance.

COMPREHENSIVE CHARACTERIZATION OF CYTOKINES IN PATIENTS UNDER EXTRACORPOREAL MEMBRANE OXYGENATION: EVIDENCE FROM INTEGRATED BULK AND SINGLE-CELL RNA SEQUENCING DATA USING MULTIPLE MACHINE LEARNING APPROACHES.

Background : Extracorporeal membrane oxygenation (ECMO) is an effective technique for providing short-term mechanical support to the heart, lungs, or both. During ECMO treatment, the inflammatory response, particularly involving cytokines, plays a crucial role in pathophysiology. However, the potential effects of cytokines on patients receiving ECMO are not comprehensively understood. Methods : We acquired three ECMO support datasets, namely two bulk and one single-cell RNA sequencing (RNA-seq), from the Gene Expression Omnibus (GEO) combined with hospital cohorts to investigate the expression pattern and potential biological processes of cytokine-related genes (CRGs) in patients under ECMO. Subsequently, machine learning approaches, including support vector machine (SVM), random forest (RF), modified Lasso penalized regression, extreme gradient boosting (XGBoost), and artificial neural network (ANN), were applied to identify hub CRGs, thus developing a prediction model called CRG classifier. The predictive and prognostic performance of the model was comprehensively evaluated in GEO and hospital cohorts. Finally, we mechanistically analyzed the relationship between hub cytokines, immune cells, and pivotal molecular pathways. Results : Analyzing bulk and single-cell RNA-seq data revealed that most CRGs were significantly differentially expressed; the enrichment scores of cytokine and cytokine-cytokine receptor (CCR) interaction were significantly higher during ECMO. Based on multiple machine learning algorithms, nine key CRGs (CCL2, CCL4, IFNG, IL1R2, IL20RB, IL31RA, IL4, IL7, and IL7R) were used to develop the CRG classifier. The CRG classifier exhibited excellent prognostic values (AUC > 0.85), serving as an independent risk factor. It performed better in predicting mortality and yielded a larger net benefit than other clinical features in GEO and hospital cohorts. Additionally, IL1R2, CCL4, and IL7R were predominantly expressed in monocytes, NK cells, and T cells, respectively. Their expression was significantly positively correlated with the relative abundance of corresponding immune cells. Gene set variation analysis (GSVA) revealed that para-inflammation, complement and coagulation cascades, and IL6/JAK/STAT3 signaling were significantly enriched in the subgroup that died after receiving ECMO. Spearman correlation analyses and Mantel tests revealed that the expression of hub cytokines (IL1R2, CCL4, and IL7R) and pivotal molecular pathways scores (complement and coagulation cascades, IL6/JAK/STAT3 signaling, and para-inflammation) were closely related. Conclusion : A predictive model (CRG classifier) comprising nine CRGs based on multiple machine learning algorithms was constructed, potentially assisting clinicians in guiding individualized ECMO treatment. Additionally, elucidating the underlying mechanistic pathways of cytokines during ECMO will provide new insights into its treatment.

Effects of gut microbiota and metabolites on pancreatitis: a 2-sample Mendelian randomization study.

Acute pancreatitis (AP) and chronic pancreatitis (CP) have high incidences and poor prognoses. The early screening of at-risk populations still awaits further study. The limitation was mainly based on observational studies, with limited sample size and the presence of confounding factors. This study used a 2-sample Mendelian randomization (MR) analysis based on publicly available data from genome-wide association studies to reveal the causal effect of gut microbiota and metabolites on pancreatitis. This study collected summary statistics on gut microbiota, metabolites, AP, and CP. A 2-sample MR analysis was performed using MR-Egger, inverse variance-weighted, MR Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median. The 2-sample MR showed that only Eubacterium coprostanoligenes was an independent protective factor for AP among all gut microbiota, and the other microbiota were not significant for pancreatitis. Unsaturated fatty acids in metabolites are protective factors for both AP (odds ratio [OR], 0.730; 95% CI, 0.593-0.899; P=.003) and CP (OR, 0.660; 95% CI, 0.457-0.916; P=.013). Furthermore, carnitine was a protective factor CP, and glucose was an independent risk factor for CP. This study provides potential evidence of the causal role of gut microbiota and metabolites on pancreatitis, which may be conducive for designing microbiome and metabolite interventions on AP or CP in the future.

Prognostic value of tumor regression grade (TRG) in patients with gastric/gastroesophageal junction cancer treated by peri-operative chemotherapy and surgery: A single-center experience (Institut Mutualiste Montsouris, Paris, France).

486 Background: Management of locally advanced gastric and gastroesophageal junction (GOJ) cancer relies on peri-operative chemotherapy and radical surgery. Response to neoadjuvant chemotherapy can be evaluated by Mandard Tumor Regression Grade (TRG) performed on the removed specimens. The aim of this study was to investigate the prognostic value of TRG, in terms of post-surgical disease-free survival (DFS) and overall survival (OS). Methods: Retrospective analysis of all consecutive patients (Jan 2010 to Dec 2021) who underwent oncological gastrectomy for gastric or GOJ adenocarcinoma after neoadjuvant chemotherapy was performed. TRG was evaluated according to Mandard classification, ranging from 1 (complete pathological response) to 5 (absence of response), TRG 1-2 being considered as “good responders” and TRG 3-5 as “bad responders”. Univariate and multivariate analysis were performed for DFS and OS. Results: One hundred and ninety-nine patients were included, 157 treated with FOLFOX and 42 with FOLFOX + Taxanes (either FLOT or FOLFOX + Abraxane). TRG 1-2 was observed in 30% in patients (pts) treated with FOLFOX and 24% in pts treated with FOLFOX + Taxanes. With a median follow-up over 5 years (yrs), median DFS and OS were not reached (DFS rates at 3, 5 and 10yrs of 66.5%, 64.1% and 55.7%, respectively; OS rates at 3, 5 and 10yrs of 75.6%, 66.8% and 60.4%, respectively). In univariate analysis, TRG 1-2 was significantly associated with favorable outcome compared to TRG 3-5 in terms of DFS (HR 2.4, p-value 0.0056) and OS (HR 2.6, p-value 0.0061), as well as ECOG at diagnosis (0 vs. 1), ypT stage (yp T0-2 vs. yp T3-4), ypN stage (ypN- vs. ypN+), tumor localization (antrum + body vs. cardia + esophagus), and lymphatic, vascular and peri nervous embolisms (negative vs. positive) for both DFS and OS. However, in multivariate analysis (selection backward Cox-model), only ypT stage and vascular embolisms for DFS, and ypT and ypN stages for OS were found to be independent prognostic factors. Conclusions: Although TRG is a prognostic factor in patients with gastric or GOJ cancer, it does not appear as an independent factor for DFS and OS in this series of 199 pts. These results raise the issue of “good responder” definition, especially for TRG 3. Prognostic impact of TRG needs to be investigated for patients treated with combination of immune checkpoint inhibitors and chemotherapy in neoadjuvant regimens.

Prevalence and factor associated with depressive symptoms in patients with osteoarthritis: A cross-sectional study.

Osteoarthritis (OA) is a prevalent degenerative joint condition. Among OA patients, depressive symptoms are the most frequent psychiatric disorder, negatively impacting both prognosis and quality of life. This study analyzed the independent factors associated with the development of depressive symptoms in patients with OA and constructed a nomogram to assess the risk of developing depressive symptoms. An analysis was conducted on data from 2093 OA patients in the NHANES database, covering 2007 to 2014. A training set and a validation set were randomly assigned to participants in a 7:3 ratio. Variables significantly associated with depressive symptoms in OA patients were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression analyses and nomograms were constructed. Its performance and clinical relevance were assessed using receiver operating characteristic (ROC) curves, C indices, calibration curves, and decision curves. Among the 2093 OA patients, 357 were assessed as having depressive symptoms. There are eight independent relevant factors, which are gender, age, poverty-to-income ratio (PIR), race, educational attainment, smoking status, diabetes, and sleep disorder. The AUC values of the training and validation sets were 0.718 (95%CI: 0.683-0.752) and 0.733 (95%CI: 0.678-0.788). Calibration and decision curve analyses showed that this nomogram exhibits high accuracy, good discrimination, and potential clinical benefits on both training and validation sets. We screened to obtain factors associated with depressive symptoms in patients with OA. Dynamic nomograms enable the combination of individual relevant factors for better assessing and managing high-risk OA groups.

Rizatriptan loaded Bilosomes for Nose to Brain Delivery: Fabrication, Statistical Optimization, and Biological Evaluation

Rizatriptan (RTP) is an anti-migraine drug and after oral administration, it exhibits low bioavailability (45%) due to high first-pass hepatic metabolism. Therefore, to resolve this issue, RTP-loaded bilosomes (BLSs) for brain delivery through the intranasal route were developed. RTP-BLSs were prepared by the thin-film hydration technique and optimized by the L9 Taguchi model. Bile salt (sodium glycocholate, mg), surfactant (Span 40, mg), and edge activator (Cremophor RH 40, mg) were selected as independent factors and their influence was observed on vesicle size (nm) and entrapment efficiency (%). Selected optimized RTP-BLSs (F5) have low vesicle size (204.70 ± 5.8 nm) and polydispersity index (0.260 ± 0.022), good entrapment efficiency (78.32 ± 3.1%), and high zeta potential (-27.6 ± 1.67 mV). The optimized RTP-BLSs exhibited a more sustained released profile (96.41 ± 4.48 % in 24 h) than RTP-Sol (98.65 ± 3.46 % RTP released in 4 h). The flux and apparent permeability coefficient for optimized RTP-BLSs were calculated and found to be 1.069 ± 0.026 μg.cm-2.h1 and 10.690×10-4 ± 0.262×10-4 cm.h-1) and comparatively (P<0.05) better than RTP-Sol (0.548 ± 0.148 μg.cm-2.h-1 and 5.481×10-4 ± 1.476 ×10-4 cm.h-1). The relative bioavailability of RTP formulated within the optimized RTP-BLSs administered intranasally was 2.94 ± 0.78-fold higher than the one obtained with RTP-Sol. The optimized RTP-BLSs showed 1.91 ± 0.15-fold higher absolute bioavailability as compared to intravenous administration RTP-BLSs. The optimized RTP-BLSs showed 64.18 ± 2.34% nose-to-brain drug transport, while RTP-Sol exhibited 20.72 ± 1.46% after intranasal administration. The optimized RTP-BLSs showed a significantly higher brain drug targeting efficiency (279.16 ± 6.37%) as compared to RTP-Sol (126.15 ± 4.79%) given intranasally. From our findings, it can be concluded that the developed BLSs are novel alternative RTP carriers for direct nose-to-brain delivery for the improvement of brain drug targeting.

Prognostic Value of Nevus-Associated Melanoma in Patients with Melanoma.

Although most melanomas develop de novo, about 30% are nevus-associated melanomas, where the prognostic value is unclear. Our study aimed to determine whether nevus-associated melanoma is associated with sentinel lymph node (SLN) status and prognosis in patients with melanoma. The Sentinel Lymph Node Working Group database, which includes comprehensive clinicopathological and outcome data, was utilized to investigate the association of nevus-associated melanoma with SLN status as well as relapse-free (RFS), melanoma-specific (MSS), and overall survival (OS) using multivariable logistic regression and Cox regression modeling. A total of 3447 adult patients with a median follow-up of 2.6 years (interquartile range 0.9-6.9) were evaluable. Compared with de novo melanomas, nevus-associated melanomas showed a significant correlation with younger age as well as favorable histological features. The presence of a nevus-associated melanoma was not identified as an independent factor for SLN status (odds ratio 1.06, 95% confidence interval [CI] 0.80-1.41; p=0.68). Compared with de novo melanomas, nevus-associated melanomas provided independent prognostic information for a favorable RFS (hazard ratio [HR] 0.67, 95% CI 0.53-0.84; p<0.001), MSS (HR 0.54, 95% CI 0.34-0.85; p=0.008), and OS (HR 0.42, 95% CI 0.30-0.57; p<0.001). Melanomas associated with pre-existing nevi appear to be an independent favorable prognostic factor for recurrence and survival and may potentially be used as a clinical parameter for identifying patients with lower risk of recurrence.

Impact of text message reminders on immunosuppressive medication adherence among kidney transplant recipients: A randomized controlled study.

One of the most common problems encountered in transplant patients is nonadherence with immunosuppressive drugs, one of the most important reasons for graft rejection. The study aimed to assess the impact of text message reminders on medication adherence among kidney transplant recipients. A randomized controlled trial. The study was conducted from January to October 2021. This study included a total of 100 patients receiving a kidney transplant, 50 in the intervention group and 50 in the control group. Patients in the intervention group were sent text message reminders four times a day during the 6th-9th months after transplantation. Control patients received no such intervention. Tacrolimus concentrations in the bloodstream were monitored for all participants through measurements taken at Months 7, 8 and 9. Data collection tools included Sociodemographic Form and Immunosuppressive Medication Adherence Scale. Patients were homogeneously distributed among the groups. Sending daily text message reminders to transplant recipients caused an independent positive effect on medication adherence scale scores at the end of the study. Mean pretest medication adherence score of all patients was 45.18 ± 4.22 and posttest score was 47.4 ± 3.6. The intervention group exhibited a significantly higher mean posttest adherence score compared to controls, with values of 48.68 ± 2.58 and 45.62 ± 4.42, respectively (p < 0.001). Findings demonstrated a substantial improvement in the final medication adherence scores of transplant patients when they received daily Short Message Service reminders, acting as an independent factor (β = 0.356, p < 0.001). Sending text message reminders to kidney transplant recipients is a statistically and clinically effective intervention to improve immunosuppressive medication adherence.

Regorafenib combined with immunotherapy and prognosis of unresectable hepatocellular carcinoma.

541 Background: To investigate the prognosis and influencing factors of patients with unresectable hepatocellular carcinoma (uHCC) receiving regorafenib in different treatment modes. Methods: A total of 227 patients with uHCC who received at least 2 cycles of regorafenib treatment in the Affiliated Hospital of Qingdao University between June 2018 and August 2022 were retrospectively collected through the Hospital Information System (HIS). 204 patients were finally enrolled by inclusion and exclusion criteria after screening. Results: The median follow-up was 25.9 (4.5-69.7) months. The median overall survival (OS) of 204 patients with uHCC was 27.7 (95%CI 21.98-33.42) months. The 1, 2, 3 and 5-year OS were 80.9%, 55.9%, 41.4% and 26.7%, respectively. Univariate analysis showed that combination with immune checkpoint inhibitor (ICI) and metabolic-associated complications were independent factors for survival benefit of regorafenib, while the Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) scale = 2, undecreased Alpha-fetoprotein (AFP), macrovascular invasion and extrahepatic metastasis were independent risk factors for poor prognosis (P&lt;0.05). Compared with 60 patients receiving regorafenib alone, 144 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 16.9 vs. 31.5 months, respectively, P=0.006). The median OS of 153 patients receiving second-line therapy with regorafenib was 30.3 months. Among 51 patients receiving third or more lines of therapy with regorafenib, compared with 4 patients receiving regorafenib alone, 47 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 9.4 vs. 24.1 months, respectively, P=0.000). Among 148 patients receiving local treatment, the median OS of patients with regorafenib combined with ICI (n=115) or without ICI (n=33) was 33.2 and 16.5 months, respectively (P=0.005). Conclusions: Regorafenib has a good prognosis in second-line treatment of uHCC. The OS of patients with regorafenib combined with ICI were significantly better than that of patients without ICI. The OS benefit of regorafenib combined with ICI was also equivalent in patients with third or more lines. The benefit of regorafenib combined with ICI was better for patients receiving local treatment.

Development of a modified nutritional index model based on nutritional status and sarcopenia to predict long-term survival and chemotherapy benefits in elderly patients with advanced gastric cancer

BackgroundElderly patients with advanced gastric cancer have poor prognoses. This study aims to develop a prediction model for long-term survival after radical surgery and to identify patients who may benefit from chemotherapy. MethodsData from 555 elderly patients with advanced gastric cancer admitted to two medical centers from 2009 to 2018 were retrospectively analyzed. Sarcopenia was combined with the Controlling Nutritional Status (CONUT) score to create a modified nutritional index (mCONUT). Cox regression analyses were used to develop a novel nomogram prediction model (mCNS) that combined mCONUT, pN, and tumor size, and its performance was further verified both internally and externally. ResultsMultivariate Cox analysis revealed that tumor size, pN, and mCONUT were independent prognostic risk factors for overall survival (OS). The mCNS model showed good fit and high predictive value (AUC: training set 0.711; validation set 0.707), outperforming the pTNM model (p<0.05). To further investigate the association between the model and adjuvant chemotherapy, we categorized the model into two risk groups : a high-risk group and a low-risk group. Further analysis revealed that, in the low-risk group, the OS and recurrence-free survival(RFS) for patients receiving adjuvant chemotherapy was significantly better than that of those who did not receive chemotherapy (p=0.047,p=0.019). In the high-risk group, this result was not observed (p=0.120, p=0.053). ConclusionThe mCNS model has high predictive value in predicting long-term survival of elderly patients with advanced gastric cancer. Patients with mCNS-L were able to benefit from chemotherapy after laparoscopic radical gastrectomy.

M6A-related genes ALKBH5 and RBMX as prognostic and progression biomarkers in Chinese oral squamous cell carcinoma patients

ObjectiveN6-methyladenosine (m6A) RNA dysregulation is crucial for cancer development. The study aimed to explore the effects of m6A modification in oral squamous cell carcinoma (OSCC) and its potential as a biomarker and therapeutic target. DesignWe first analyzed m6A-related gene expression and its impact on OSCC prognosis and progression using the TCGA database. Subsequently, a Chinese cohort of 134 samples was used for validation. Bioinformatics analysis was conducted with TCGA data, and m6A levels were measured in the validation cohort using a quantification kit. Survival analysis was performed to study the relationship between m6A-related genes and OSCC prognosis in the Chinese population. The expression of m6A-related genes was assessed by using quantitative real-time PCR, Western blot analysis, and immunohistochemistry. ResultsIn the TCGA database, we found dysregulated expressions of METTL14, ALKBH5, YTHDF2, HNRNPC, LRPPRC, HNRNPA2B1, IGF2BP2, and RBMX in OSCC. Based on this, we observed significantly elevated total m6A content in OSCC tissues compared to normal controls in the validation cohort. Among the m6A candidate genes, only ALKBH5 and RBMX upregulation were found to be independent prognostic risk factors for poor OSCC survival in the Chinese population. And the inclusion of these two genes had a higher area under the curve for 3-year (0.705, 0.826), and 5-year (0.715, 0.788) overall survival compared to the model that only considered clinical parameters. ConclusionsWe found the upregulation of m6A status in OSCC, of which, ALKBH5 and RBMX may serve as promising diagnostic and prognostic biomarkers for Chinese patients with OSCC.

High expression of ARPC1B promotes the proliferation and apoptosis of clear cell renal cell carcinoma cells, leading to a poor prognosis.

ARPC1B has been identified as a key regulator of malignant biological behavior in various tumors. However, its specific role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. This study aims to evaluate the influence of ARPC1B on the prognosis and disease progression in ccRCC patients. Multi-omics data and clinical information from public databases were analyzed to determine the associations between ARPC1B and prognosis, clinical features, immune microenvironment, and drug sensitivity in ccRCC. Co-expression and gene set enrichment analyses were conducted to elucidate the potential role of ARPC1B in ccRCC pathogenesis. Functional assays, including RT-qPCR, CCK8 assays, colony formation assays, immunofluorescence, immunohistochemistry, and xenograft tumor formation in nude mice, were performed to assess ARPC1B's impact on cell proliferation and apoptosis. Flow cytometry and Western blotting were further employed to investigate the underlying molecular mechanisms of ARPC1B in ccRCC. ARPC1B expression was significantly elevated in ccRCC and associated with an unfavorable prognosis. Both independent and meta-analyses confirmed that ARPC1B is an independent prognostic risk factor in ccRCC. Furthermore, ARPC1B expression significantly correlated with the immune microenvironment and drug sensitivity. In vitro, experiments demonstrated that ARPC1B knockdown suppressed ccRCC cell proliferation and induced apoptosis through the BAX-Bcl-2/c-caspase3/c-PARP axis, which was further validated by in vivo studies. ARPC1B overexpression is associated with poor prognosis, altered immune status, and drug sensitivity in ccRCC. Furthermore, ARPC1B promotes the malignant behavior of ccRCC cells and holds potential as a prognostic biomarker and therapeutic target for ccRCC.

Prognostic prediction for inflammatory breast cancer patients using random survival forest modeling.

Inflammatory breast cancer (IBC) is an aggressive and rare phenotype of breast cancer, which has a poor prognosis. Thus, it is necessary to establish a novel predictive model of high accuracy for the prognosis of IBC patients. Clinical information of 1,230 IBC patients from 2010 to 2020 was extracted from the Surveillance, Epidemiology and End Results (SEER) database. Cox analysis was applied to identify clinicopathological characteristics associated with the overall survival (OS) of IBC patients. Random survival forest (RSF) algorithm was adopted to construct an accurate prognostic prediction model for IBC patients. Kaplan-Meier analysis was performed for survival analyses. Race, N stage, M stage, molecular subtype, history of chemotherapy and surgery, and response to neoadjuvant therapy were identified as independent predictive factors for the OS of IBC patients. The top five significant variables included surgery, response to neoadjuvant therapy, chemotherapy, breast cancer molecular subtypes, and M stage. The C-index of RSF model was 0.7704 and the area under curve (AUC) values for 1, 3, 5 years in training and validation datasets were 0.879-0.955, suggesting the excellent predictive performance of RSF model. IBC patients were divided into high-risk group and low-risk group according the risk score of RSF model, and the OS of patients in the low-risk group was significantly longer than those in the high-risk group. In this study, we constructed a prognosis prediction model for IBC patients through RSF algorithm, which may potentially serve as a useful tool during clinical decision-making.

Computed tomography-based absolute delta radiomics nomogram for predicting perineural invasion in hypopharyngeal squamous cell carcinoma.

To assess the efficacy of computed tomography (CT)-based radiomics nomogram in predicting perineural invasion (PNI) in patients with hypopharyngeal squamous cell carcinoma (HPSCC). Overall, 146 patients were retrospectively recruited and divided into training and test cohorts at a 7:3 ratio. Radiomics features were extracted and delta and absolute delta radiomics features were calculated. Feature selection was performed using maximum relevance minimum redundancy and least absolute shrinkage and selection operator methods. Preliminary models were built using logistic regression, and the optimal one was selected as the radiomics signature. A nomogram was constructed by combining independent clinical factors and the radiomics signature. Its performance was evaluated using the area under the curve (AUC) values of receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves. The radiomics signature comprised 14 absolute delta radiomics features. The nomogram, incorporating tumor thickness and radiomics signature, outperformed the other models (AUC=0.79 and 0.78, training and test cohorts, respectively). The Delong test demonstrated that the nomogram's predictive performance was significantly higher than that of the clinical model (p<0.05) in both cohorts. Calibration curves indicated good calibration, and the Hosmer-Lemeshow test confirmed a good fit (p=0.969 and 0.429, training and test cohorts, respectively). DCA highlighted the nomogram's considerable clinical usefulness. The CT-based absolute delta radiomics nomogram can noninvasively and preoperatively predict PNI status in patients with HPSCC, providing a valuable tool for clinical decision making and individualized treatment plans.

Serum Irisin as a Predictor for Peripheral arterial disease: Insights from a Clinical Study

ObjectiveThe purpose of this study was to investigate the correlation between serum irisin concentration and peripheral arterial disease (PAD), and to establish clinical prediction nomograms for PAD occurrence by comparing and analyzing clinical data from patients with PAD patients and healthy controls. MethodsA total of 112 patients with PAD and 90 healthy individuals were recruited for the study. Clinical data from both groups were collected and serum irisin concentration was measured using enzyme-linked immunosorbent assay (ELISA). Correlation analysis was conducted. Risk factors for PAD were identified through univariate and multivariate logistic regression. The clinical prediction nomograms were established and validated. ResultsA total of 202 patients were enrolled in this study, with an average age of 63.98 ± 10.40 years. Of these, 123 were male (60.9%) and 79 were female (39.1%). Hypertension was present in 104 patients (51.5%), diabetes in 59 patients (29.2%), dyslipidemia in 94 patients (46.5%), and 105 patients (52.0%) were smokers. Among them, 90 patients were assigned to the PAD group, which included 78 males (69.6%) and 34 females (30.4%), with an average age of 67.54 ± 10.31 years. In this group, 62 patients (55.4%) had hypertension, 53 (47.3%) had diabetes, 62 (55.4%) had dyslipidemia, and 78 (69.6%) were smokers. The Rutherford classification of these patients showed that 64 (57.1%) were at stage I, 25 (22.3%) at stage II, 16 (14.3%) at stage III, and 7 (6.3%) at stage IV. Serum irisin concentration in patients with PAD showed a significant positive correlation with serum high-density lipoprotein (HDL) (r=0.255) and a significant negative correlation with Rutherford classification (r=-0.374) and smoking status (r=-0.263). Univariate and multivariate logistic regression analyses identified irisin, age, diabetes, dyslipidemia, smoking, creatinine(CR), and neutrophil/lymphocyte ratio (NLR) as independent risk factors for the development of PAD ( P < 0.05). Based on these findings, a clinical prediction nomogram was established. Internal validation of the nomogram demonstrated strong discriminatory ability, with an area under the curve (AUC) of 0.942, indicating the model's excellent performance. Calibration curves and decision curve analyses further confirmed the model’s robust calibration and clinical applicability. ConclusionThis study concluded that serum irisin concentrations were significantly lower in the PAD group compared to the healthy control group, and that serum irisin concentrations in the PAD group were significantly correlated with serum HDL, Rutherford classification, and smoking status. Additionally, Irisin level, age, diabetes, dyslipidemia, smoking, CR, and NLR were identified as independent risk factors for PAD development. The clinical prediction nomogram based on these factors may aid in accurately predicting the risk of PAD development.

Peak-postoperative Serum Transaminases Correlate With Post-hepatectomy Liver Failure and Inflow Occlusion After Laparoscopic Liver Resection.

Peak-postoperative serum transaminases (PST) may indicate hepatocellular damage caused by liver resection and ischemia-reperfusion injuries induced by inflow occlusion. However, the potential of PST to predict postoperative outcomes and its correlation with the duration of inflow occlusion remains controversial. Moreover, there have been no reports regarding PST after laparoscopic liver resection (LLR). This study aimed to evaluate the efficacy of PST after LLR and the correlation between PST and the duration of inflow occlusion. A total of 313 consecutive patients who underwent LLR between 2012 and 2023 were included in this study. The area under the receiver-operating characteristic curve values of PST-AST and PST-ALT for predicting post-hepatectomy liver failure (PHLF) was 0.801 and 0.790, respectively. We defined PST-AST or PST-ALT ≥1,000 U/l as an exceptionally high PST. Multivariate analysis revealed that an exceptionally high PST was an independent risk factor for PHLF [p<0.001; odds ratio (OR)=25.50 (95% CI=5.35-121.00)]. PST-AST and PST-ALT correlated with the duration of inflow occlusion (Spearman's ϱ=0.5306 and 0.5632, p<0.001). Exceptionally high PST (≥1,000 U/l) is an independent risk factor for PHLF. The duration of inflow occlusion correlates with PST following LLR.