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Background: An increasing number of studies in recent years have identified mean platelet volume (MPV) as a predictive marker for neonatal sepsis. However, most of these studies focused on single regions, and therefore, the findings remain inconclusive. We, in this study, aimed to evaluate the potential of MPV as a biological indicator of neonatal sepsis through a systematic review and meta-analysis., Methods: We searched PubMed, the Cochrane Library, Embase, and WanFang database for articles on MPV and neonatal sepsis, published from January 1, 1990 to December 31, 2018. We included 11 studies on 932 neonates with sepsis in this meta-analysis., Results: The overall meta-analysis showed that MPV was significantly higher in patients with neonatal sepsis compared with healthy controls. Subgroup analysis revealed that the type of diagnostic criteria, analyzer, analyte, and controls used in the studies affected the difference in MPV between patients and healthy controls., Conclusion: MPV was significantly higher in the neonatal sepsis group compared to the control group. Therefore, in clinical practice, MPV could be used as an indicator for the early diagnosis of neonatal sepsis.

Background: Primary tumors located in the right and left side have distinctive prognoses, but the details have not been fully identified in non-small cell lung cancer (NSCLC). This study investigated the impact of primary tumor side on long-term survival in NSCLC patients., Methods: Data of 90 407 patients from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. To avoid bias between groups, we used innovative propensity score matching (PSM) analysis., Results: There was no significant distinction in overall survival (OS) between right (n = 53 496) and left (n = 36 911) side tumors (hazard ratio [HR] 0.993, 95% confidence interval [CI] 0.9756-1.011; P = 0.432). Left side was associated with superior five-year cancer-specific survival (CSS) compared to right side NSCLC (HR 0.977, 95% CI 0.9574-0.9969; P = 0.024). No significant difference was observed in OS (P = 0.689) or CSS (P = 0.288) after PSM analysis. In the 51 319 patients who underwent surgery, left side (n = 21 245) was associated with poor OS compared to right side (n = 30 074) NSCLC (HR 1.039, 95% CI 1.011-1.067; P = 0.006), while CSS was similar (HR 1.031, 95% CI 0.997-1.065; P = 0.069). In patients who underwent surgery, there was also no significant difference in OS (P = 0.986) or CSS (P = 0.979) after PSM analysis., Conclusion: The prognosis between right and left side NSCLC in stage I-IIIA was similar regardless of whether patients underwent surgery. Primary tumor side cannot be considered a prognostic factor when choosing appropriate treatment., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Commonly, the thyroid gland is regarded as an organ with fewer metastatic diseases, and colorectal metastasis to the thyroid (CMT) is rarely reported, especially, with that the clinical sign of thyroid metastasis nidus is the chief complaint. The CMT occurs in advanced colorectal cancer and is associated with poor prognosis and short survival. Case Report: In this case, we reported a patient with the sign of neck mass as the first manifestation of CMT. The patient underwent a partial thyroidectomy in June 2019, immunohistochemical findings of thyroid carcinoma suggested the possibility of adenocarcinoma of gastrointestinal tract. The patient underwent a colonoscopy in July 2019 and a colonic mass was found. Pathological examination diagnosed rectal adenocarcinoma. The patient underwent neoadjuvant chemotherapy, surgical treatment, postoperative adjuvant chemotherapy and targeted therapy. The patient died in June 2022. Conclusion: The metastasis disease would not be ignored at all, when a patient complains at signs of neck mass. Further, the possibility of metastasis cancer should be considered once thyroid nodules occur in patients with colorectal cancer. Even though the biological characteristics and stage of the primary tumor have an important impact on the prognosis, positive standardized treatments can also be helpful. [ABSTRACT FROM AUTHOR]

Background: Membranous lupus nephritis (MLN) is a subepithelial immune deposition or its morphological sequelae with or without mesangial changes. Previous studies on the prognosis of MLN have shown relatively small sample sizes and short follow-up periods. Methods: Our study was a retrospective analysis of biopsy-proven MLN patients from January 2010 to January 2020 at Jinling Hospital in China. The clinical manifestations, pathological features, and renal outcomes of MLN patients were collected. The endpoint was defined as end-stage kidney disease (eGFR≤15 mL/min·1.73 m2 or need for renal replacement therapy) or a doubling of serum creatinine or an eGFR decline of more than 40%. We used Cox regression to analyze the risk factors for renal outcome and Kaplan–Meier curves were used to analyze renal survival rate. Results: In the total of 2884 lupus patients, we screened 535 MLN patients. 456 MLN patients were recruited with an average age of 34 ± 12 years, 87.8% for female patients and 62.1% patients of nephrotic syndrome with proteinuria of 2.67 g/24h. After follow-up of 78 (IQR, 47.3–113.0) months, 37 (8.1%) patients reached the renal endpoint. The 5-year and 10-year renal survival rates were 95.8% and 89.4%, respectively. 370 patients (81.1%) achieved complete remission, 43 patients (9.4%) had partial remission, and only 43 had no response. 34.4% MLN experienced a relapse. The Cox regression showed the risk factors that affect the renal prognosis include male, hypertension history, anemia, high uric acid, acute kidney injury, and interstitial fibrosis in the renal pathology. Conclusions: MLN mostly manifested as nephrotic syndrome, with few renal dysfunctions. Although MLN had a high relapse rate, most patients had a response to immunosuppressants and had a good renal outcome. [ABSTRACT FROM AUTHOR]

Background: The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches. Methods: Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated. Results: A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3. Conclusions: PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC. [ABSTRACT FROM AUTHOR]

Background: Despite progress in the diagnosis and treatment of proliferative lupus nephritis (PLN), the prognosis remains unfavorable. Previous investigations have suggested that the deficiency of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). But the prognostic value of Tregs in PLN remains controversial. This study aimed to investigate the association of Tregs with renal outcomes in patients with PLN. Methods: The baseline and follow-up data of patients with biopsy-proven PLN were collected in this study. All patients were divided into two groups according to whether the renal endpoint event occurred. Clinicopathologic features and therapeutic responses were compared between the two groups. Cox regression analyses curve fitting and threshold effect analysis were implemented to investigate the relationship between Tregs level and the long-term renal outcomes. The renal endpoint was defined as end-stage kidney disease (ESKD) or doubling the SCr value. Results: A total of 405 PLN patients were included. After a follow-up of 71.53 (53.13–97.47) months, 42 (10.4%) patients reached the renal endpoint. The Treg cell counts (16/μL) in the renal endpoint group were significantly decreased than that in the non-renal endpoint group (p < 0.001). Univariate and multivariate Cox regression analyses showed that the high level of Tregs was an independent protective factor for the long-term renal prognosis of PLN. Smooth curve fitting of the generalized additive mixed model analysis indicated that the risk of renal endpoint first decreased with Tregs and then slightly increased along with Treg cell levels. The segmented linear model revealed that when Treg cell counts <46/μL, the risk of renal endpoint decreased by 6.8% for every 1 μL increase in Treg levels (p = 0.0029). Conclusion: Treg cell counts are closely related to the long-term renal outcomes of patients with PLN, and increasing Treg cell levels may play an important role in improving the prognosis of the kidney, but there may be a turning point (i.e., threshold effect) at the Treg cell counts that leads to directional changes in the renal outcomes. [ABSTRACT FROM AUTHOR]

Background: As a cancer stem cells (CSCs) surface marker, Lgr5 plays an important role in the signal transduction of cancer cells and is a potential biomarker for cancer diagnosis and prognosis. However, the expression and prognostic value of Lgr5 in recurrent nasopharyngeal carcinoma (rNPC) remains ambiguous. Materials: We used RNA sequencing to screen differentially expressed mRNAs in eleven specimens of rNPC tissues and five fresh adjacent normal tissue samples and the CSC marker, Lgr5, was identified. The expression level of Lgr5 in rNPC samples was also detected by immunohistochemistry and Western blot assay. The chi-square test was used to analyze the relationship between the clinicopathological variables and the immunostaining of Lgr5. The Log-rank method was used for prognosis analysis. The Cox regression model was used for univariate and multivariate analysis. Results: Significantly elevated expression of Lgr5 in the rNPC tissues was observed compared to the normal tissues using RNA sequencing, Western blot and immunohistochemistry. The expression of Lgr5 was significantly correlated with the T stage (P=0.014). High Lgr5 expression (P=0.007), tumor necrosis (P=0.013) and WHO type II (P=0.043) in rNPC patients exhibited worse overall survival (OS). Lgr5 expression was proved to be an independent risk factor for OS (P=0.035) in multivariate analyses, and had promising predictive value for survival and recurrence in rNPC patients (area under the ROC curve: 0.711 and 0.665, P=0.017 and 0.028, respectively). Conclusion: Lgr5 as a CSC marker is a promising therapeutic target and could be employed to predict the survival prognosis of rNPC patients. [ABSTRACT FROM AUTHOR]

• The sequence type 5 (ST5) lineage caused a significant burden on HIV-negative hosts in East Asia. • The high ST5 lineage infection rate was not due to environmental abundance. • Seven factors predicted acute death in patients without HIV who were infected with ST5 lineage. • We provided an understanding of the ST5 lineage associated with cryptococcosis. Cryptococcus neoformans sequence type 5 (ST5) lineage could infect immunocompetent hosts and cause a significant medical burden. We sought to identify characteristics and prognostic risk factors of ST5 lineage-associated cryptococcosis. Multilocus sequence typing and antifungal susceptibility testing were conducted for Cryptococcus isolates. The clinical and laboratory characteristics of cryptococcosis patients were investigated. The multivariable logistic regression identified variables independently associated with 30-day mortality in patients with ST5 lineage-associated cryptococcosis without HIV. The infection rate of the ST5 isolates was 89.4% (370/414) in China. The proportion of ST5 isolates with nonwild-type minimum inhibitory concentrations to amphotericin B, 5-flucytosine, voriconazole, posaconazole, itraconazole, and fluconazole were 0%, 5.4%, 0.3%, 1.4%, 0.3%, and 8.1%, respectively. The ST5 lineage-infected group exhibited significantly higher blood platelet count, lower blood cryptococcal antigen (CrAg) titer, lower cerebrospinal fluid (CSF) CrAg titer than the non-ST5 lineage-infected group, and lower hemoglobin and lower CSF CrAg titer than the Cryptococcus gattii isolates-infected group. Seven baseline parameters, including underlying disease, dyskinesia, anemia, high peripheral blood neutrophils, low platelet count, high CSF fungal burden, and high CSF opening pressure, were associated independently with the 30-day mortality of patients with ST5 lineage-associated cryptococcosis without HIV. Our study has provided an understanding of the ST5 lineage associated with cryptococcosis. [ABSTRACT FROM AUTHOR]

ABO blood group antigens exhibit alternative phenotypes and genetically derived structures that are located on the red cell surface. The role of ABO blood group in cancer biology has been intensely reported by several studies, and it is now widely recognized that ABO antigens are associated with the risk and prognosis of several types of tumors, namely gastric cancer and pancreatic cancer. However, there have been contentious limited issues with the association between the ABO blood group and lymphoma. In this narrative review, based on literature data, we discuss the role of ABO blood group in the risk and prognosis of lymphoma and summarize the current knowledge of the underlying pathogenic mechanisms of the association. The possible association of ABO blood group with racial disparities and pathological classification in lymphoma patients is also discussed. [ABSTRACT FROM AUTHOR]

Background: American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) rT staging have great clinical impracticality. The aim of the present study was to establish a new rT staging to guide endoscopic surgery for the treatment of recurrent nasopharyngeal carcinoma (rNPC). Methods: This surgical rT staging (named Fudan rT staging) was constructed using two significant risk factors: the distance from the tumor margin to the internal carotid artery, and dural invasion. Log‐rank and receiver operating characteristic (ROC) curve analyses were used to evaluate its effectiveness. Results: Fudan rT staging can effectively separate the overall survival (OS) and progression‐free survival (PFS) of patients with rNPC according to the different rT stages (p < 0.05). In addition, ROC analysis showed that the Fudan rT staging exhibited enhanced prognostic value for OS and PFS compared with the AJCC/UICC rT staging. Conclusions: The innovative Fudan rT staging has a better predictive value for the survival of patients with rNPC than AJCC/UICC rT staging. [ABSTRACT FROM AUTHOR]

Background: NF‐κB signaling is widely linked to the pathogenesis and treatment resistance in cancers. Increasing attention has been paid to its anti‐oncogenic roles, due to its key functions in cellular senescence and the senescence‐associated secretory phenotype (SASP). Therefore, thoroughly understanding the function and regulation of NF‐κB in cancers is necessary prior to the application of NF‐κB inhibitors. Methods: We established glioblastoma (GBM) cell lines expressing ectopic TCF4N, an isoform of the β‐catenin interacting transcription factor TCF7L2, and evaluated its functions in GBM tumorigenesis and chemotherapy in vitro and in vivo. In p65 knock‐out or phosphorylation mimic (S536D) cell lines, the dual role and correlation of TCF4N and NF‐κB signaling in promoting tumorigenesis and chemosensitivity was investigated by in vitro and in vivo functional experiments. RNA‐seq and computational analysis, immunoprecipitation and ubiquitination assay, minigene splicing assay and luciferase reporter assay were performed to identify the underlying mechanism of positive feedback regulation loop between TCF4N and the p65 subunit of NF‐κB. A eukaryotic cell‐penetrating peptide targeting TCF4N, 4N, was used to confirm the therapeutic significance. Results: Our results indicated that p65 subunit phosphorylation at Ser 536 (S536) and nuclear accumulation was a promising prognostic marker for GBM, and endowed the dual functions of NF‐κB in promoting tumorigenesis and chemosensitivity. p65 S536 phosphorylation and nuclear stability in GBM was regulated by TCF4N. TCF4N bound p65, induced p65 phosphorylation and nuclear translocation, inhibited its ubiquitination/degradation, and subsequently promoted NF‐κB activity. p65 S536 phosphorylation was essential for TCF4N‐led senescence‐independent SASP, GBM tumorigenesis, tumor stem‐like cell differentiation and chemosensitivity. Activation of p65 was closely connected to alterative splicing of TCF4N, a likely positive feedback regulation loop between TCF4N and p65 in GBM. 4N increased chemosensitivity, highlighting a novel anti‐cancer strategy. Conclusion: Our study defined key roles of TCF4N as a novel regulator of NF‐κB through mutual regulation with p65 and provided a new avenue for GBM inhibition. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) remains a lethal disease worldwide, with numerous studies exploring its potential prognostic markers using traditional RNA sequencing (RNA- seq) data. However, it cannot detect the exact cellular and molecular changes in tumor cells. This study aimed to construct a prognostic model for LUAD using single-cell RNA- seq (scRNA- seq) and traditional RNA- seq data. Methods: Bulk RNA- seq data were downloaded from The Cancer Genome Atlas (TCGA) database. LUAD scRNA- seq data were acquired from Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) was used for dimensionality reduction and cluster identification. Weighted Gene Correlation Network Analysis (WGCNA) was utilized to identify key modules and differentially expressed genes (DEGs). The non-negative Matrix Factorization (NMF) algorithm was used to identify different subtypes based on DEGs. The Cox regression analysis was used to develop the prognostic model. The characteristics of mutation landscape, immune status, and immune checkpoint inhibitors (ICIs) related genes between different risk groups were also investigated. Results: scRNA- seq data of four samples were integrated to identify 13 clusters and 9cell types. After applying differential analysis, NK cells, bladder epithelial cells, and bronchial epithelial cells were identified as significant cell types. Overall, 329 DEGs were selected for prognostic model construction through differential analysis and WGCNA. Besides, NMF identified two clusters based on DEGs in the TCGA cohort, with distinct prognosis and immune characteristics being observed. We developed a prognostic model based on the expression levels of six DEGs. A higher risk score was significantly correlated with poor survival outcomes but was associated with a more frequent TP53 mutation rate, higher tumor mutation burden (TMB), and up-regulation of PD-L1. Two independent external validation cohorts were also adopted to verify our results, with consistent results observed in them. Conclusion: This study constructed and validated a prognostic model for LUAD by integrating 10× scRNA- seq and bulk RNA- seq data. Besides, we observed two distinct subtypes in this population, with different prognosis and immune characteristics. [ABSTRACT FROM AUTHOR]

Retinoid-related orphan receptor alpha (RORα) and nuclear receptor subfamily 1 group D member 1 (REV-ERBα) play critical roles in many human cancers. Whether RORα and REV-ERBα expression levels are associated with clinical characteristics are poorly understood, and they may be independent predictors of overall survival (OS) and progression-free survival (PFS) in gastric cancer (GC). This study aimed to investigate the correlation of RORα and REV-ERBα expression levels with clinicopathological parameters, OS, and PFS in GC. Immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were employed to assess the expression levels of RORα and REV-ERBα, which were downregulated in GC tissues compared with normal gastric tissues (P <.001; P <.001) and were associated with several clinicopathological parameters, including histological grade (P =.032; P <.001), preoperative carcinoembryonic antigen (CEA) levels (P =.004; P <.001), and tumor-node-metastasis (TNM) stage (P =.015; P <.001). Additionally, low RORα and REV-ERBα expression levels were associated with poor OS and PFS in GC patients, respectively (P <.001; P =.001). Furthermore, univariate Cox regression model analysis showed that histological grade (P <.001; P <.001), preoperative CEA levels (P <.001; P =.001), TNM stage (P <.001; P <.001), lymph node metastasis (P =.002; P =.002), RORα expression levels (P =.001; P <.001), and REV-ERBα expression levels (P <.001; P =.001) were associated with OS and PFS in GC. Multivariate Cox regression model analysis indicated that RORα expression levels and REV-ERBα expression levels are independent factors of OS and PFS in GC. Besides, RORα and REV-ERBα expression may be positively correlated (χ2 = 6.835; P =.009), and GC patients with both high RORα and REV-ERBα expression levels had the best prognosis. In conclusion, RORα and REV-ERBα may coparticipate in tumor activities and show potential to estimate the prognosis of GC. [ABSTRACT FROM AUTHOR]

Background: Cutaneous melanoma is a highly malignant skin tumor, and most patients have a poor prognosis. In recent years, immunotherapy has assumed an important role in the treatment of advanced cutaneous melanoma, but only a small percentage of patients benefit from immunotherapy. A growing number of studies have demonstrated that the prognosis of patients with cutaneous melanoma is closely related to long non-coding RNA and the tumor immune microenvironment. Methods: We downloaded RNA expression data and immune-related gene lists of cutaneous melanoma patients separately from The Cancer Genome Atlas database and ImmPort website and identified immune-related lncRNAs by co-expression analysis. The prognostic model was constructed by applying least absolute shrinkage and selection operator regression, and all patients were classified into high- and low-risk groups according to the risk score of the model. We evaluated the differences between the two groups in terms of survival outcomes, immune infiltration, pathway enrichment, chemotherapeutic drug sensitivity and immune checkpoint gene expression to verify the impact of lncRNA signature on clinical prognosis and immunotherapy efficacy. Results: By correlation analysis and LASSO regression analysis, we constructed an immune-related lncRNA prognostic model based on five lncRNA: HLA-DQB1-AS1, MIR205HG, RP11-643G5.6, USP30-AS1 and RP11-415F23.4. Based on this model, we plotted Kaplan–Meier survival curves and time-dependent ROC curves and analyzed its ability as an independent prognostic factor for cutaneous melanoma in combination with clinicopathological features. The results showed that these lncRNA signature was an independent prognostic factor of cutaneous melanoma with favorable prognostic ability. Our results also show a higher degree of immune infiltration, higher expression of immune checkpoint-associated genes, and better outcome of immunotherapy in the low-risk group of the lncRNA signature. Conclusion: The 5 immune-related lncRNA signatures constructed in our study can predict the prognosis of cutaneous melanoma and contribute to the selection of immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: The optimal treatment strategy of combining systemic chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC) is controversial. This study aimed to compare the efficacy and toxicities of induction chemotherapy followed by intensity‐modulated radiotherapy (IC‐RT) versus concurrent chemoradiotherapy (CCRT) in NPC. Methods: Of 448 stage II‐IVb NPC patients treated with IC‐RT or CCRT were retrospectively analysed. The primary outcome was overall survival, which was analysed by using Kaplan‐Meier curves and log‐rank (Mantel‐Cox) test. Results: The median follow‐up was 66 months (interquartile range, 46‐84 months). There was no statistically significant difference in the estimated 5‐year overall survival (OS), progression‐free survival (PFS), distance metastasis‐free survival (DMFS) and locoregional relapse‐free survival (LRFS) between IC‐RT group and CCRT group (OS: 89.5% vs 91.7%, P =.568; PFS: 85.2% vs 87.5%, P =.615; DMFS: 90.9% vs 91.7%, P =.847; LRFS: 92.0% vs 96.9%, P =.104). In the multivariate analysis, the treatment group (IC‐RT vs CCRT) was not an independent prognostic factor for OS, PFS, DMFS and LRFS. Less advanced tumour stage and lymph node stage were predictive of higher OS. EBV‐DNA level was an independent prognostic factor that was only significantly associated with LRFS. Conclusions: IC‐RT achieves similar survival outcomes and treatment‐related toxicities as CCRT in OS, PFS, DMFS and LRFS for patients with NPC. We need multicentre randomised controlled trials to reconfirm our data. [ABSTRACT FROM AUTHOR]

Acute liver injury (ALI) refers to abnormalities in liver function caused by various causes and accompanied by poor prognosis and high mortality. Common predisposing factors for the disease are viral hepatitis, bacteria, alcohol, and certain hepatotoxic drugs. Inflammatory response and oxidative stress are critical for the pathogenesis of ALI. Pterostilbene (Pte), a natural polyphenol product extracted from blueberries and grapes, has been reported that exerted multiple biological activities, including antioxidative, anti-inflammatory, anti-carcinogenic, and anti-apoptotic properties. However, there is very little data showing the hepatoprotective effect of Pte on lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced ALI in mice. In this study, the possible protective effect and potential mechanisms of Pte on ALI are being investigated. It has been found that Pte markedly ameliorates LPS/D-Gal-induced inflammatory infiltration, hemorrhage, and dissociation of the hepatic cord, reducing the myeloperoxidase (MPO) activity in liver tissues and serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in ALI. Pte also inhibits LPS/D-Gal-induced secretion of pro-inflammatory cytokine tumor necrosis factor-a (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β) in liver tissues. Furthermore, the western blot analysis reveals that LPS/D-Gal-activated nuclear factor-kappa B (NF-κB) is significantly inhibited by Pte, and nuclear factor (erythroid-derived 2)–like 2 (Nrf2) and heme oxygenase-1 (HO-1) are upregulated by Pte. In conclusion, our results suggest that Pte exerts anti-inflammatory and antioxidative effects, which might contribute to ameliorating LPS/D-Gal-induced ALI in mice. Pte has the potential to be a preventive hepatoprotective agent. [ABSTRACT FROM AUTHOR]

Background: Cumulating evidence indicates that the systemic inflammatory response (SIR) plays a crucial role in the prognosis of various cancers. We aimed to generate a preoperative risk grade (PRG) by integrating SIR markers to preoperatively predict the long-term prognosis of intrahepatic cholangiocarcinoma (ICC).Methods: 468 consecutive ICC patients who underwent hepatectomy between 2010 and 2017 were enrolled. The PRG and a nomogram were generated and their predictive accuracy was evaluated.Results: The PRG consisted of two non-tumor-specific SIR markers platelet-to-lymphocyte ratio (PLR) and albumin (ALB), which were both the independent predictors of overall survival (OS). Multivariate analysis showed that the PRG was significantly associated with OS (PRG = 1: hazard ratio (HR) = 3.800, p < 0.001; PRG = 2: HR = 7.585, p < 0.001). The C-index of the PRG for predicting survival was 0.685 (95% CI 0.655 to 0.716), which was statistically higher than that of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (C-index 0.645), Liver Cancer Study Group of Japan (LCSGJ) (C-index 0.644) and Okabayashi (C-index 0.633) (p < 0.05). Besides, the C-index of the nomogram only consisting of the tumor-specific factors (serum carcinoembryonic antigen, carbohydrate antigen 19-9, tumor number) could be improved to 0.737 (95% CI 0.062-0.768) from 0.625 (95% CI 0.585-0.665) when the PRG was incorporated (p < 0.001).Conclusions: The PRG integrating two non-tumor-specific SIR markers PLR and ALB was a novel method to preoperative predicting the prognosis of ICC. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma (ACC) is a relatively uncommon tumor. The existing prediction model is limited to the head and neck. We aim to construct a prognostic nomogram combined with the clinical features and treatment options of ACC to predict the disease‐specific survival (DSS) of patients diagnosed with ACC in different anatomic sites. Methods: A novel predictive model was constructed using 1285 patients with ACC from the Surveillance, Epidemiology, and End Results (SEER) registry between 2010 and 2015. The performance of this model was externally validated using 118 patients with ACC in the West China Hospital, Sichuan University between 2010 and 2017. Results: The prognostic model demonstrated that age, primary site, lymph node metastasis, distant metastasis, radiotherapy and surgery were independent factors for DSS. The validation of the model using an external cohort proved its reliability. Conclusion: The developed novel predictive model is shown to provide accurate and efficient predictive information for patients with ACC for different anatomic sites. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BLCA) is the 11th most common malignancy worldwide. Although significant improvements have been made in screening, diagnosis, and precise management in recent years, the prognosis of BLCA remains bleak. Objectives: This study aimed to investigate the prognostic significance of tumor-infiltrating immune cells and construct ceRNA networks in BLCA patients. Methods: The expression data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. A competing endogenous RNA (ceRNA) network was constructed to identify the hub genes involved in the prognosis of BLCA. The CIBERSORT algorithm was utilized to investigate the infiltration levels of 22 subsets of immune cells. Ultimately, the nomogram was generated to visualize the survival probability of each patient, with the calibration curve being performed to assess its performance. Furthermore, the Pearson correlation test was used to explore the correlation between the identified hub genes in the ceRNA network and the prognostic-related immune cells. Results: A total of eight elements in the ceRNA network were considered as key members and correlated with the prognosis of BLCA, including ELN , SREBF1 , DSC2 , TTLL7 , DIP2C , SATB1 , hsa-miR-20a-5p , and hsa-miR-29c-3p. T cells CD8, T cells follicular helper (Tfh), and neutrophils were identified as independent prognostic factors in BLCA. The co-expression analysis showed that there was a significant correlation between the identified hub genes and immune cells. Conclusion: Our results suggest that the mechanism of hsa-miR-29c-3p regulates the expression of ELN and DSC2 , and the infiltration of Tfh and neutrophils might play pivotal roles in the progression of BLCA. [ABSTRACT FROM AUTHOR]

Objective: The prognostic value of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IIIC staging in endometrioid carcinoma patients remains debatable. The current study aimed to compare the prognosis between IIIC1 and IIIC2 patients with endometrioid carcinoma and attempt to conduct a new subdivision. Methods: By using the Surveillance, Epidemiology, and End Results (SEER) database, patients with endometrioid-type endometrial cancer diagnosed from 2004 to 2015 were identified and randomly divided into training and validation sets. We developed a Fine–Gray competing risk model to compare the cancer-specific mortality (CSM). The IIIC subdivision system was built based on the independent prognostic factors. The cumulative incidence curves were compared using Gray's test or log-rank test. Nomogram for predicting 3- or 5-years CSM was constructed and subsequently validated internally and externally. Results: The IIIC subdivision defined by FIGO staging, including IIIC1 and IIIC2, exhibited no association with CSM in multivariate analysis [subdistribution hazard ratio [SHR] = 1.03, 95% CI [0.85–1.26], P = 0.760]. The IIIC category was subdivided into three subcategories based on the tumor (T) and nodes (N) stage, including IIICa (T1N1 and T1N2), IIICb (T2N1 and T2N2), and IIICc (T2N1 and T2N2). The prognosis across new IIIC subcategories with CSM remained significant [IIICb vs. IIICa: SHR = 1.53, 95% CI [1.18–1.98], P = 0.001; IIICc vs. IIICa: SHR = 2.64, 95% CI [2.13–3.28], P < 0.001]. Postoperative adjuvant chemotherapy or radiotherapy alone did not improve survival for patients categorized as IIICa or IIICb, and all IIIC patients benefited most from combination of postoperative chemotherapy and radiotherapy [IIICa: SHR = 0.59, 95% CI [0.43–0.82], P = 0.001; IIICb: SHR = 0.66, 95% CI [0.45–0.97], P = 0.036; IIICc: SHR = 0.44, 95% CI [0.34–0.58], P < 0.001]. A nomogram based on competing risk model was built to predict the long-term survival of IIIC patients, with a concordance index above 0.70 both in training and validation set. Conclusion: There was no prognostic difference between FIGO IIIC1 and IIIC2 patients with endometrioid-type endometrial cancer. A new subdivision of IIIC category facilitates prognosis prediction and treatment modalities. A combination of postoperative chemotherapy and radiotherapy exerted as the optimal choice for endometrioid cancer patients with IIIC stage. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates from the pleura and has a poor prognosis. Eligible patients can benefit from surgery, but their survival is affected by many factors. Therefore, we created a graphic model that could predict the prognosis of surgically treated patients. Methods: We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results database from 2004 to 2014 to identify the key factors affecting the prognosis of surgically treated MPM patients. On this basis we built a nomogram to predict survival. We then evaluated the performance of the nomogram in a validation cohort. Results: In a training cohort of 828 cases, independent prognostic factors, including age, gender, histological type, differentiation, N stage, chemotherapy, type of surgery, and lymph node dissection, were identified. We then developed a nomogram to evaluate individual patient survival. In Kaplan–Meier analysis, a higher score in the nomogram was associated with a worse prognosis. We also used a validation cohort consisting of 312 patients to evaluate the performance of the nomogram, which was well calibrated and had good discrimination ability, with concordance indices of 0.715 and 0.656 for the training and validation cohorts, respectively. Conclusion: This study has improved our understanding of resected MPM and shown that key factors, including age and histological type, are associated with overall survival. The nomogram is a reliable tool that can help clinicians turn individualized prediction into reality and maximize patient benefit by identifying the most beneficial treatment approach. [ABSTRACT FROM AUTHOR]

High rate of recurrence impaired the prognosis of hepatocellular carcinoma (HCC) after surgery. We aimed to explore the safety and efficacy of neoadjuvant drug-eluting bead transarterial chemoembolization (D-TACE) and tislelizumab therapy for resectable or borderline resectable HCC. 41 HCC patients received neoadjuvant therapy and surgery were respectively enrolled. The safety and efficacy of the neoadjuvant therapy were assessed. The prognosis was evaluated and compared with that of 41 matched HCC patients who received surgery alone. 36 (87.8%) patients had adverse events (AEs) and only one patient had a grade 3/4 of ALT elevated. All patients performed surgery successfully and no severe postoperative complications occurred. The objective response rate (ORR) was 56.1% and 87.8% based on RECIST 1.1 and mRECIST, respectively. 15 (36.6%) patients had radiological complete tumor necrosis and the disease control rate (DCR) was 100%. The pathological complete response (pCR) and major pathological response (MPR) was 13 (31.7%) and 18 (43.9%), respectively. The incidence of microvascular invasion (MVI) was 4.9% in neoadjuvant therapy patients, compared with 64.9% before propensity score matching (PSM) and 60.9% after PSM for surgery alone patients. Neoadjuvant therapy patients had a significant better prognosis than surgery alone patients (recurrence-free survival p = 0.041, overall survival p = 0.006). Our preliminary results suggest the neoadjuvant D-TACE and tislelizumab therapy is safe and benefit to the pathological results and prognosis for patients with resectable or borderline resectable HCC. [ABSTRACT FROM AUTHOR]

Background: Gemcitabine plus cisplatin (GP) is commonly used to treat lung squamous cell carcinoma (SCC); however, it is not clear which subgroup of lung SCC patients could benefit most from GP treatment. We explored the predictive factors in lung SCC patient cohorts. Methods: Seventy‐eight lung SCC patients treated with a first‐line GP regimen were enrolled in this retrospective cohort study. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Classification tree models were used to explore the risk factors for PFS and OS in these patients. Results: The median PFS and OS in SCC patients treated with a GP regimen were 6.0 and 13.6 months, respectively. Three terminal subgroups were formed for both PFS and OS. The subgroup with a body mass index (BMI) > 23.94 kg/m2 and aged ≤ 54.5 had the longest PFS (9.0 months); the subgroup with a BMI < 23.94  kg/m2 and aged ≤ 54.5 had the shortest PFS (4.05 months). Patients with an objective response (partial or complete response) to treatment had the longest OS (20.0 months), while patients with a BMI ≤ 26.92 kg/m2 and stable or progressive disease as the best response had the shortest OS (11.2 months). Conclusions: BMI and age may be predictors of PFS in lung SCC patients who receive GP treatment. BMI and best response to GP treatment predicts OS in such patients. Patients’ clinical pathological characteristics may be used to predict the therapeutic efficacy of chemotherapy and survival. [ABSTRACT FROM AUTHOR]

Background: KIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features.Methods: Total RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients.Results: The two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6% (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4% (135/143) HCC samples and the mean H-score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p=0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival.Conclusion: In this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) act as competing endogenous RNAs, which are involved in the regulation of many types of cancers. They primarily function by sponging microRNAs (miRNAs) and influencing the expression of miRNA by target messenger RNA. However, the role of circRNAs in the progression of nasopharyngeal carcinoma (NPC) remains largely unclear. In this study, differentially expressed miRNAs associated with NPC were screened using microarray analyses, from which miR-107 was identified. Increased miR-107 expression was associated with poor prognosis in NPC, and miR-107 promoted the proliferation and migration of NPC cells. TGFBR2 was identified as the direct target of miR-107, which could reverse its effect on NPC cells. Furthermore, the expression of circTGFBR2 was downregulated in NPC tissue samples, while circTGFBR2 overexpression correlated with favorable prognosis in NPC. Functionally, circTGFBR2 overexpression inhibited the proliferation and migration of NPC cells both in vitro and in vivo. Further analysis showed that circTGFBR2 sponged miR-107, leading to the upregulation of TGFBR2 expression and suppression of NPC progression. Therefore, circTGFBR2 may serve as a novel tumor suppressive factor and potential target for new therapies in NPC patients. [ABSTRACT FROM AUTHOR]

Background: Juvenile nasopharyngeal angiofibroma (JNA) has a high recurrence rate after surgery. Cofilin overexpression is associated with increased tumor cell metastasis, and progression of various human cancers. However, studies on cofilin expression in JNA are rare. The purpose of this study was to investigate the expression and localization of cofilin in a tissue microarray (TMA) of JNA specimens. In addition, we also analyzed its correlation with clinicopathological features and recurrence. Methods: Immunohistochemistry was performed to detect cofilin expression in a TMA of samples from 70 JNA patients and 10 control subjects. The association between clinicopathological variables and cofilin immunostaining was analyzed using Pearson's chi‐square test. Kaplan‐Meier survival analysis was used to calculate the disease‐free survival rate, and investigate the effect of cofilin expression on time to recurrence (TTR) in JNA patients. The Cox regression model was used for multivariate survival analysis. Results: Cofilin was detected in irregular smooth muscle cells, pericytes, less differentiated stromal cells, and plump cells, but not in inactive fibroblasts and mature vascular endothelial cells of JNA specimens. The presence of cofilin in JNA was correlated with tumor stage (p = 0.012) and volume of intraoperative hemorrhage (p < 0.001). JNA patients with high cofilin expression had a higher recurrence rate than those with low cofilin expression (p = 0.012). Cofilin expression and patient's age were significant predictors of TTR, and cofilin was a better predictor for disease recurrence (area under the receiver operating curve [AUROC; 0.711; p = 0.005) than other clinicopathological features. Conclusion: Cofilin is an independent prognostic marker for JNA patients who have undergone surgical treatment and may represent a novel therapeutic target for extensive JNA. [ABSTRACT FROM AUTHOR]

The ubiquitin ligase family member triplex motif protein 21 (TRIM21), which is involved in the proliferation, metastasis, and selective death of tumor cells, is crucial in the ubiquitination of a number of tumor marker proteins. As research progresses, more studies demonstrate that TRIM21 expression levels can be used to predict cancer prognosis. However, it is unclear how exactly TRIM21 contributes to cervical squamous carcinoma. Immunohistochemistry, Western Blot, and q-PCR were utilized to determine the expression level of TRIM21 in 113 patients with CESC removed by stage I surgery at Xijing Hospital from 2018 to 2023 using paraffin-embedded tumor tissues and 12 pairs of fresh tumor tissues and their paracancerous tissues. Log-rank analysis using SPSS 23.0 was performed for prognosis and survival analysis using univariate/multifactorial analysis. CCK-8, wound-healing and Scratch assay verified that TRIM21 promoted cell proliferation, migration and invasion. The effect of overexpression and knockdown of TRIM21 on tumor stemness was examined using sphere-forming assay and Western Blot. Finally, we constructed a xenograft model to observe the effect of TRIM21 on tumorigenesis in Si Ha cell lines in vivo. TRIM21 expression is greater in CESC tissues than in paracancerous tissues, according to immunohistochemical data. Similarly, at the protein and mRNA levels, we verified this conclusion using Western-Blotting and q-PCR. Prognostic and OS analysis showed that TRIM21 expression levels are associated with individual prognostic factors. CCK-8, Wound healing, Transwell, and Sphere-forming tests all demonstrated that TRIM21 overexpression enhances Ca Ski cell proliferation, migration, invasion, and stemness. TRIM21 knockdown in Si Ha inhibited tumor cell proliferation, migration, invasion, and stemness. The experimental results of xenograft models demonstrated that TRIM21 knockdown in Si Ha cells inhibited tumor development. TRIM21 is a poor predictor of prognosis for cervical squamous cell carcinoma and might open up new avenues for investigation into therapeutic targets. [ABSTRACT FROM AUTHOR]