MKP1 may be involved in the occurrence of depression by regulating hippocampal autophagy in rats.

BACKGROUND: Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in the hippocampus of patients with depression, while pharmacological inhibition of hippocampal MKP1 can mitigate depression-like behaviors in rodents. In addition, MAPK signaling regulates autophagy, and antidepressants were recently shown to target autophagic signaling pathways. We speculated that MKP1 contributes to depression by enhancing hippocampal autophagy through dephosphorylation of the MAPK isoform ERK1/2. METHODS: We established a rat depression model by exposure to chronic unpredictable mild stress (CUMS), and then examined depression-like behaviors in the sucrose preference test (SPT) and forced swimming test (FST) as well as expression changes in hippocampal MKP1, ERK1/2, phosphorylated ERK1/2, and autophagy-related proteins LC3II by Western blotting and immunostaining. These same measurements were repeated in rats exposed to CUMS following hippocampal infusion of a MKP1-targeted shRNA. Finally, the effects of MKP1 expression level on autophagy we examined in rat GMI-R1 microglia. RESULTS: CUMS-exposed rats demonstrated anhedonia in the SPT and helplessness in the FST, two core depression-like behaviors. Expression levels of MKP1 and LC3II were upregulated in the hippocampus of CUMS rats, suggesting enhanced autophagy, while pERK/ERK was downregulated. Knockdown of hippocampal MKP1 mitigated depression-like behaviors, downregulated hippocampal LC3II expression, and upregulated hippocampal pERK/ERK. Similarly, MKP1 knockdown in GMI-R1 cells upregulated pERK/ERK and reduced the number of LC3II autophagosomes, while MKP1 overexpression had the opposite effects. CONCLUSION: Enhanced hippocampal autophagy via MKP1-mediated ERK dephosphorylation may contribute to the development of depression.

Platinum-based neoadjuvant chemotherapy upregulates STING/IFN pathway expression and promotes TILs infiltration in NSCLC.

Objectives: To evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival. Materials and methods: A total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-ß, and the infiltration density of CD3+ TILs and CD8+TILs. The correlation between the expression of STING, PD-L1, IFN-ß and the infiltration density of CD3+ TILs and CD8+ TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed. Results: NACT increased the expression of STING, IFN-ß and PD-L1 in tumor cells, and the infiltration of CD3+ and CD8+ TILs. In addition, ypTNM stage, ypN stage, changes in CD3+ TILs and in PD-L1 were associated with DFS (disease-free survival). CD3+ TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3+ TILs changes were independent prognostic factors for DFS and OS. Conclusion: NACT stimulates STING/IFN-ß pathway, promotes infiltration of CD3+ and CD8+ TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3+TILs after NACT. Patients with ypN0 and elevated CD3+ TILs after NACT had better OS benefits.

The role of PD-1/PD-L1 axis in idiopathic pulmonary fibrosis: Friend or foe?

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with a bleak prognosis. Mounting evidence suggests that IPF shares bio-molecular similarities with lung cancer. Given the deep understanding of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in cancer immunity and the successful application of immune checkpoint inhibitors (ICIs) in lung cancer, recent studies have noticed the role of the PD-1/PD-L1 axis in IPF. However, the conclusions are ambiguous, and the latent mechanisms remain unclear. In this review, we will summarize the role of the PD-1/PD-L1 axis in IPF based on current murine models and clinical studies. We found that the PD-1/PD-L1 pathway plays a more predominant profibrotic role than its immunomodulatory role in IPF by interacting with multiple cell types and pathways. Most preclinical studies also indicated that blockade of the PD-1/PD-L1 pathway could attenuate the severity of pulmonary fibrosis in mice models. This review will bring significant insights into understanding the role of the PD-1/PD-L1 pathway in IPF and identifying new therapeutic targets.

Nanomedicines Targeting Metabolism in the Tumor Microenvironment.

Cancer cells reprogram their metabolism to meet their growing demand for bioenergy and biosynthesis. The metabolic profile of cancer cells usually includes dysregulation of main nutritional metabolic pathways and the production of metabolites, which leads to a tumor microenvironment (TME) having the characteristics of acidity, hypoxic, and/or nutrient depletion. Therapies targeting metabolism have become an active and revolutionary research topic for anti-cancer drug development. The differential metabolic vulnerabilities between tumor cells and other cells within TME provide nanotechnology a therapeutic window of anti-cancer. In this review, we present the metabolic characteristics of intrinsic cancer cells and TME and summarize representative strategies of nanoparticles in metabolism-regulating anti-cancer therapy. Then, we put forward the challenges and opportunities of using nanoparticles in this emerging field.

Atrial Cardiomyopathy Predicts Worse Outcome in Patients With Lung Cancer.

Background: Reports of the clinical outcomes associated with the co-occurrence of atrial cardiomyopathy (ACM) and lung cancer (LC) are limited. Objectives: This study aims to investigate the influence of ACM on the prognosis of LC patients and related clinical determinants. Methods: Newly diagnosed LC patients from January 1st, 2015, to December 31st, 2020, were retrospectively enrolled at the First Affiliated Hospital of Xi'an Jiaotong University. The demographics and overall survival (OS) of the patients with or without ACM were compared. The survival rate was analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. Binary logistic regression analysis was used to determine the risk factors for ACM. Results: A total of 306 patients (65.04 ± 10.30 years of age, 72.88% male) were analyzed. The prevalence of ACM in the non-small cell lung cancer (241, 78.76%) and small cell lung cancer (65, 21.24%) population was not statistically different. Overall, 53 (17.32%) LC patients had coexisting ACM. ACM patients were older (69 vs. 64, p = 0.0013) and had higher D-dimer levels (1.0 vs. 0.6, p = 0.001), lower serum calcium levels (2.23 vs. 2.31, p = 0.001), lower left ventricular ejection fraction (LVEF) values (67% vs. 69%, p = 0.036) and had more frequent coronary comorbidity disease (16.98% vs. 8.82%, p = 0.031). The median OS for patients with or without ACM was 15 months and 25 months, respectively (p = 0.018). Coexisting ACM compared to non-ACM was associated with worse OS in patients with LC (HR = 1.543, 95% CI: 1.042-2.283, p = 0.030). Conclusion: Coexisting ACM is associated with undesirable survival outcomes in patients with LC. These findings could help us to better understand the cardiac burden in these patients and provide additional risk stratification for them.

Establishment and validation of a nomogram to predict the in-hospital death risk of nosocomial infections in cancer patients.

BACKGROUND: Attributed to the immunosuppression caused by malignancy itself and its treatments, cancer patients are vulnerable to developing nosocomial infections. This study aimed to develop a nomogram to predict the in-hospital death risk of these patients. METHODS: This retrospective study was conducted at a medical center in Northwestern China. The univariate and multivariate logistic regression analyses were adopted to identify predictive factors for in-hospital mortality of nosocomial infections in cancer patients. A nomogram was developed to predict the in-hospital mortality of each patient, with receiver operating characteristic curves and calibration curves being generated to assess its predictive ability. Furthermore, decision curve analysis (DCA) was also performed to estimate the clinical utility of the nomogram. RESULTS: A total of 1,008 nosocomial infection episodes were recognized from 14,695 cancer patients. Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (15.5%) was the most predominant causative pathogen. Besides, multidrug-resistant strains were discovered in 25.5% of cases. The multivariate analysis indicated that Eastern Cooperative Oncology Group Performance Status 3-4, mechanical ventilation, septic shock, hypoproteinemia, and length of antimicrobial treatment < 7 days were correlated with higher in-hospital mortality. Patients who received curative surgery were correlated with favorable survival outcomes. Ultimately, a nomogram was constructed to predict the in-hospital mortality of nosocomial infections in cancer patients. The area under the curve values of the nomogram were 0.811 and 0.795 in the training and validation cohorts. The calibration curve showed high consistency between the actual and predicted in-hospital mortality. DCA indicated that the nomogram was of good clinical utility and more credible net clinical benefits in predicting in-hospital mortality. CONCLUSIONS: Nosocomial infections stay conjoint in cancer patients, with gram-negative bacteria being the most frequent causative pathogens. We developed and verified a nomogram that could effectively predict the in-hospital death risk of nosocomial infections among these patients. Precise management of high-risk patients, early recognition of septic shock, rapid and adequate antimicrobial treatment, and dynamic monitoring of serum albumin levels may improve the prognosis of these individuals.

Construction and Validation of a Novel Nomogram to Predict the Overall Survival of Patients With Combined Small Cell Lung Cancer: A Surveillance, Epidemiology, and End Results Population-Based Study.

INTRODUCTION: Combined small cell lung cancer (C-SCLC) represents a rare subtype of all small cell lung cancer cases, with limited studies investigated its prognostic factors. The aim of this study was to construct a novel nomogram to predict the overall survival (OS) of patients with C-SCLC. METHODS: In this retrospective study, a total of 588 C-SCLC patients were selected from the Surveillance, Epidemiology, and End Results database. The univariate and multivariate Cox analyses were performed to identify optimal prognostic variables and construct the nomogram, with concordance index (C-index), receiver operating characteristic curves, and calibration curves being used to evaluate its discrimination and calibration abilities. Furthermore, decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) were also adopted to assess its clinical utility and predictive ability compared with the classic TNM staging system. RESULTS: Seven independent predictive factors were identified to construct the nomogram, including T stage, N stage, M stage, brain metastasis, liver metastasis, surgery, and chemotherapy. We observed a higher C-index in both the training (.751) and validation cohorts (.736). The nomogram has higher area under the curve in predicting 6-, 12-, 18-, 24-, and 36-month survival probability of patients with C-SCLC. Meanwhile, the calibration curves also revealed high consistencies between the actual and predicted OS. DCA revealed that the nomogram could provide greater clinical net benefits to these patients. We found that the NRI for 6- and 12-month OS were .196 and .225, and the IDI for 6- and 12-month OS were .217 and .156 in the training group, suggesting that the nomogram can predict a more accurate survival probability. Similar results were also observed in the validation cohort. CONCLUSION: We developed and verified a novel nomogram that can help clinicians recognize high-risk patients with C-SCLC and predict their OS.

Identification and validation of an autophagy-related long non-coding RNA signature as a prognostic biomarker for patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most predominant pathological subtype of lung cancer, accounting for 40-70% of all lung cancer cases. Although significant improvements have been made in the screening, diagnosis, and precise management in recent years, the prognosis of LUAD remains bleak. This study aimed to investigate the prognostic significance of autophagy-related long non-coding RNAs (lncRNAs) and construct an autophagy-related lncRNA prognostic model in LUAD. METHODS: The gene expression data of LUAD patients were obtained from The Cancer Genome Atlas (TCGA) database. All autophagy-related genes were downloaded from the Human Autophagy Database (HADb). Spearman's correlation test was exploited to identify potential autophagy-related lncRNAs. The multivariate Cox regression analysis was used to construct the prognostic signature, which divided LUAD patients into high-risk and low-risk groups. Subsequently, the receiver operating characteristic (ROC) curves were generated to assess the predictive ability of this prognostic model for overall survival (OS) in these individuals. Then, the Gene set enrichment analysis (GSEA) was conducted to execute pathway enrichment analysis. Finally, a multidimensional validation was exploited to verify our findings. RESULTS: A total of 1,144 autophagy-related lncRNAs were identified to construct the co-expression network via Spearman's correlation test (|R2| >0.4 and P≤0.001). Ultimately, a 16 autophagy-related lncRNAs prognostic model was constructed, and the area under the ROC curve (AUC) was 0.775. The results of GSEA enrichment analysis showed that the genes in the high-risk group were mainly enriched in cell cycle and p53 signaling pathways. The results of the multidimensional database validation indicated that the expression level of BIRC5 was significantly correlated with the expression level of TMPO-AS1. Furthermore, both TMPO-AS1 and BIRC5 had a higher expression level in LUAD samples. LUAD patients with high expression levels of TMPO-AS1 and BIRC5 were correlated with advanced disease stage and poor OS. CONCLUSIONS: In summary, our results suggested that the prognostic signature of the 16 autophagy-related lncRNAs has significant prognostic value for LUAD patients. Furthermore, TMPO-AS1 and BIRC5 are potential predictors and therapeutic targets in these individuals.

Efficacy Analysis of Adjuvant Chemotherapy with Gemcitabine Plus Platinum or S-1 in Biliary Tract Carcinoma: A Multi-Center Retrospective Study.

PURPOSE: Biliary tract cancers (BTCs) have a poor overall prognosis, as patients who underwent curative surgery frequently experience disease recurrence. At present, there is a paucity of well-documented adjuvant chemotherapy regimen. This study aimed to assess whether gemcitabine plus platinum or S-1 adjuvant chemotherapy have different impact on relapse-free survival (RFS). PATIENTS AND METHODS: We selected patients undergoing radical biliary tract cancer surgery, pathologically confirmed adenocarcinoma and received gemcitabine plus platinum (cisplatin or oxaliplatin) or S-1 adjuvant chemotherapy from September 2013 to May 2020. The primary study endpoint was RFS. The secondary endpoint was safety. RESULTS: Overall 136 patients were enrolled. The median follow-up was 32.3 months and the median RFS was 17.0 months (95% CI 8.9-25.1). The median RFS was 14.1 months (95% CI 6.7-21.5) in gemcitabine plus platinum group and 33.0 months (95% CI 9.3-56.7) in gemcitabine plus S-1 (GS) group, a non-significant difference both in univariate (P=0.092) and in multivariate analysis (P=0.058). Lymph node status (N- vs N+: HR=0.477, 95% CI 0.285-0.799; P=0.005) and chemotherapy cycles (<6 vs 6-8: HR=1.828, 95% CI 1.117-2.993; P=0.016) were independent impact factors for RFS. GS group had lower incidence of adverse reactions. CONCLUSION: Compared with gemcitabine plus platinum, GS regimen has a tendency to obtain longer RFS (although there is no statistically significant difference) and less toxic. GS regimen has the potential to be investigated as a standard regimen for adjuvant chemotherapy.

Atrial Cardiomyopathy and Atrial Fibrillation in Cancer.

The number of patients with oncologic and cardiologic comorbidities is increasing. A growing number of evidence shows an inextricable link between cancer, atrial fibrillation, and atrial cardiomyopathy. Cancer itself and resultant inflammation, anticancer treatment, and other comorbidities lead to atrial remodeling and fibrosis, which increases the tendency to develop atrial cardiomyopathy and atrial fibrillation. The scarcity of current literature and ambiguous results make its relationship difficult to fully understand. In this review, we will summarize existing evidence of the relationships and interactions among cancer, atrial cardiomyopathy, and atrial fibrillation and discuss the underlying mechanisms, and provide better information for the management of these patients.

Tumor Mutation Burden, Immune Cell Infiltration, and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.

The prognostic value of pretreatment prognostic nutritional index in patients with small cell lung cancer and it's influencing factors: a meta-analysis of observational studies.

BACKGROUND: Numerous studies identified that pretreatment prognostic nutritional index (PNI) was significantly associated with the prognosis in various kinds of malignant tumors. However, the prognostic value of PNI in small cell lung cancer (SCLC) remains controversial. We performed the present meta-analysis to estimate the prognostic value of PNI in SCLC and to explore the relationship between PNI and clinical characteristics. METHODS: We systematically and comprehensively searched PubMed, EMBASE, and Web of Science for available studies until April 17, 2020. Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to evaluate the correlation between PNI and overall survival (OS) and progression-free survival (PFS) in SCLC. Odds ratios (ORs) and 95% CIs were applied to evaluate the relationship between clinical features and PNI in SCLC. RESULTS: A total of nine studies with 4,164 SCLC patients were included in the meta-analysis. The pooled data elucidated that lower PNI status was an independent risk factor for worse OS in SCLC (HR =1.43; 95% CI: 1.24-1.64; P<0.001), while there was no significant correlation between PNI status and PFS (HR =1.44; 95% CI: 0.89-2.31; P=0.134). We also found that Eastern Cooperative Oncology Group (ECOG) performance status ≥2 (OR =2.72; 95% CI: 1.63-4.53; P<0.001) and extensive-stage (ES) disease (OR =1.93; 95% CI: 1.62-2.30; P<0.001) were risk factors for low PNI, while prophylactic cranial irradiation (PCI) (OR =0.53; 95% CI: 0.40-0.69; P<0.001) was a protective factor for low PNI. CONCLUSIONS: Our findings suggested that low PNI status was closely correlated with the decreased OS in SCLC. Surveillance on PNI, amelioration of nutritional and immune status, and timely initiation of PCI may improve the prognosis of SCLC.

Gibberellins modulate local auxin biosynthesis and polar auxin transport by negatively affecting flavonoid biosynthesis in the root tips of rice.

As critical signalling molecules, both gibberellin (GA) and auxin play essential roles in regulating root elongation, and many studies have been shown that auxin influences GA biosynthesis and signalling. However, the mechanism by which GA affects auxin in root elongation is still unknown. In this study, root elongation and DR5-GUS activity were analyzed in rice seedlings. Paclobutrazol-induced short root phenotypes could be partially reversed by co-treatment with IAA, and the inhibition of root elongation caused by naphthylphthalamic acid could be partially reversed when plants were co-treated with GA. DR5-GUS activity was increased in the presence of GA and was reduced at the root tip of paclobutrazol-treated seedlings, indicating that GA could regulate local auxin biosynthesis and polar auxin transport (PAT) in rice root tips. Our RNA-seq analysis showed that GA was involved in the regulation of flavonoid biosynthesis. Flavonoid accumulation level in ks1 root tips was significantly increased and negatively correlated with GA content in GA- and PAC-treated seedlings. GA also rescued the decreased DR5-GUS activity induced by quercetin in rice root tips, confirming that flavonoids act as an intermediary in GA-mediated auxin biosynthesis and PAT. Based on RNA-seq and qPCR analyses, we determined that GA regulates local auxin biosynthesis and polar auxin transport by modulating the expression of OsYUCCA6 and PIN. Our findings provide valuable new insights into the interactions between GA and auxin in the root tips of rice.

Nosocomial Infections in Gastrointestinal Cancer Patients: Bacterial Profile, Antibiotic Resistance Pattern, and Prognostic Factors.

BACKGROUND: Cancers of the gastrointestinal (GI) tract and its associated excretory glands are one of the most common causes of cancer-related death worldwide, and these patients are more likely to developing nosocomial infections due to immunodeficiency. OBJECTIVE: To explore the bacterial profile, antibiotic resistance pattern, and prognostic factors of nosocomial infections in hospitalized GI cancer patients. METHODS: All electronic medical records of nosocomial infection episodes in hospitalized GI cancer patients were retrospectively reviewed. In-hospital mortality was used to evaluate the prognosis of patients. Mann-Whitney test, Chi-square test, and binary logistic regression analysis were used to identify potential risk factors for in-hospital mortality. P-values <0.05 were considered statistically significant. RESULTS: A total of 428 GI cancer patients developed nosocomial infections during hospitalization. Respiratory tract infections (44.2%), bloodstream infections (BSIs) (11.7%), and abdominal cavity infections (11.4%) were the most common infection sites. The predominant causative pathogens were extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (13.6%), ESBL-negative E. coli (11.9%), and Klebsiella pneumoniae (10.0%). Multidrug-resistant (MDR) strains were detected in 27.6% of isolates. Antimicrobial susceptibility analysis showed that the isolated Gram-negative bacteria (GNB) exhibited high sensitivity to amikacin, meropenem, imipenem, and piperacillin/tazobactam, while the isolated Gram-positive bacteria exhibited high sensitivity to tigecycline, linezolid, and vancomycin. The overall in-hospital mortality of all patients was 11.2% in the study. Multivariate analysis showed that ECOG performance status ≥two scores, length of antibiotic treatment <9.0 days, existence of septic shock, and hypoproteinemia were independent risk factors for in-hospital mortality. CONCLUSION: The burden of nosocomial infections in GI cancer patients is considerably high, with GNB being predominantly isolated causative pathogens. Surveillance on serum albumin level, adequate antibiotic treatment, early identification, and prompt treatment of septic shock could benefit the prognosis.

Nosocomial infections due to multidrug-resistant bacteria in cancer patients: a six-year retrospective study of an oncology Center in Western China.

BACKGROUND: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. METHODS: This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values < 0.05 were considered significant. RESULTS: One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. CONCLUSIONS: The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.

The Construction and Analysis of Tumor-Infiltrating Immune Cells and ceRNA Networks in Bladder Cancer.

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.