Identification of gemcitabine resistance-related AHNAK2 gene associated with prognosis and immune infiltration in pancreatic cancer.

Purpose: Gemcitabine is a basic chemotherapy drug for pancreatic cancer (PC), but resistance is common and causes tumor recurrence and metastasis. Therefore, it is significant to explore gemcitabine resistance-related molecules for individualized treatment and prognosis assessment of PC. Methods: In this study, transcriptome sequencing and TCGA database analysis were performed, and a differentiated gene AHNAK2 was screened. MEXPRESS database, tissue microarray analysis, and CIBERSORT and TIMER databases were used to correlate AHNAK2 expression with clinicopathological features and prognosis and immune infiltration of PC. Enrichment analysis was used to investigate the significant biological processes associated with AHNAK2. Results: AHNAK2 was highly expressed in gemcitabine-resistant cells. High expression of AHNAK2 increased the risk of poor overall survival (OS) and progression-free survival (PFS) in PC. Clinicopathologic analysis revealed that AHNAK2 correlated with KRAS, TP53 mutations, histologic type, short OS, N stage, and elevated CA199 levels in PC. Knockdown of AHNAK2 inhibited the ability of cell proliferation and colony formation and enhanced the toxic effect of gemcitabine in PC. Meanwhile, the knockdown of AHNAK2 expression enhanced cell-ECM adhesion, inhibited cell-cell adhesion, and downregulated the KRAS/p53 signaling pathway in PC. Furthermore, AHNAK2 was correlated with immune infiltration, especially B cells and macrophages. Conclusions: Our study unveils for the first time the pivotal role of AHNAK2 in PC, particularly its association with gemcitabine resistance, clinical prognosis, and immune infiltration. AHNAK2 not only drives the proliferation and drug resistance of PC cells by potentially activating the KRAS/p53 pathway but also significantly impacts cell-cell and cell- ECM adhesion. Additionally, AHNAK2 plays a crucial role in modulating the tumor immune microenvironment. These insights underscore AHNAK2's unique potential as a novel therapeutic target for overcoming gemcitabine resistance, offering new perspectives for PC treatment strategies.

Novel Ultrasound-Guided Radiofrequency Ablation of the Epicondylar Branch of the Posterior Cutaneous Nerve of the Forearm for Recalcitrant Lateral Epicondylosis.

This report describes a novel technique for the treatment of recalcitrant lateral epicondylosis (LE) by radiofrequency ablation (RFA) of the epicondylar branch of the posterior cutaneous nerve of the forearm (PCNF-BrEpi). Here, we describe two patients suffering from recalcitrant LE who were treated with ultrasound-guided RFA of the PCNF-BrEpi in the outpatient pain clinic setting. Patient follow-up was made at eight weeks, five months, and seven months. Numerical pain rating (NPR) for pain and Upper Extremity Functional Index-15 (UEFI-15) were obtained at baseline and at each of the follow-ups. Both patients reported significant improvement in their pain and function quickly. RFA may be a viable treatment option for recalcitrant LE. Larger comparative trials and further investigation are needed to establish results in comparison to conventional treatments and to validate RFA as a treatment option in recalcitrant LE.

Long-Term Pulmonary and Neurodevelopmental Outcomes of Meconium Aspiration Syndrome Affected Infants: A Retrospective National Population-Based Study in Taiwan.

INTRODUCTION: Meconium aspiration syndrome (MAS) may cause severe pulmonary and neurologic injuries in affected infants after birth, leading to long-term adverse pulmonary or neurodevelopmental outcomes. METHODS: This retrospective population-based cohort study enrolled 1,554,069 mother-child pairs between 2004 and 2014. A total of 8,049 infants were in the MAS-affected group, whereas 1,546,020 were in the healthy control group. Children were followed up for at least 3 years. According to respiratory support, MAS was classified as mild, moderate, and severe. With the healthy control group as the reference, the associations between MAS severity and adverse pulmonary outcomes (hospital admission, intensive care unit (ICU) admission, length of hospital stay, or invasive ventilator support during admission related to pulmonary problem) or adverse neurodevelopmental outcomes (cerebral palsy, needs for rehabilitation, visual impairment, or hearing impairment) were accessed. RESULTS: MAS-affected infants had a higher risk of hospital and ICU admission and longer length of hospital stay, regardless of severity. Infants with severe MAS had a higher risk of invasive ventilator support during re-admission (odds ratio: 17.50, 95% confidence interval [CI]: 7.70-39.75, p < 0.001). Moderate (hazard ratio [HR]: 1.66, 95% CI: 1.30-2.13, p < 0.001) and severe (HR: 4.94, 95% CI: 4.94-7.11, p < 0.001) MAS groups had a higher risk of adverse neurodevelopmental outcome, and the statistical significance remained remarkable in severe MAS group after adjusting for covariates (adjusted HR: 2.28, 95% CI: 1.54-3.38, p < 0.001) Conclusions: Adverse pulmonary or neurodevelopmental outcomes could occur in MAS-affected infants at birth. Close monitoring and follow-up of MAS-affected infants are warranted.

Trichoplusia ni Transcriptomic Responses to the Phytosaponin Aglycone Hederagenin: Sex-Related Differences.

Many plant species, particularly legumes, protect themselves with saponins. Previously, a correlation was observed between levels of oleanolic acid-derived saponins, such as hederagenin-derived compounds, in the legume Medicago truncatula and caterpillar deterrence. Using concentrations that reflect the foliar levels of hederagenin-type saponins, the sapogenin hederagenin was not toxic to 4th instar caterpillars of the cabbage looper Trichoplusia ni nor did it act as a feeding deterrent. Female caterpillars consumed more diet than males, presumably to obtain the additional nutrients required for oogenesis, and are, thus, exposed to higher hederagenin levels. When fed the hederagenin diet, male caterpillars expressed genes encoding trypsin-like proteins (LOC113500509, LOC113501951, LOC113501953, LOC113501966, LOC113501965, LOC113499659, LOC113501950, LOC113501948, LOC113501957, LOC113501962, LOC113497819, LOC113501946, LOC113503910) as well as stress-responsive (LOC113503484, LOC113505107) proteins and cytochrome P450 6B2-like (LOC113493761) at higher levels than females. In comparison, female caterpillars expressed higher levels of cytochrome P450 6B7-like (LOC113492289). Bioinformatic tools predict that cytochrome P450s could catalyze the oxygenation of hederagenin which would increase the hydrophilicity of the compound. Expression of a Major Facilitator Subfamily (MFS) transporter (LOC113492899) showed a hederagenin dose-dependent increase in gene expression suggesting that this transporter may be involved in sapogenin efflux. These sex-related differences in feeding and detoxification should be taken into consideration in insecticide evaluations to minimize pesticide resistance.

Effect of sublethal concentrations of the bioinsecticide spinosyn treatment of Trichoplusia ni eggs on the caterpillar and its parasitoid, Trichogramma brassicae.

BACKGROUND: Integrated Pest Management (IPM) seeks to combine multiple management strategies for optimal pest control. One method that is successfully employed in IPM is the use of beneficial organisms. However, in severe circumstances when pest insects exceed threshold limits, insecticides may still need to be implemented. Thus, understanding the effects of insecticides on biocontrol agents, such as parasitoid wasps, is paramount to ensure sustainable agroecosystems. Sublethal effects of the bioinsecticide spinosyn, a mixture of the bacterial Saccharopolyspora spinosa (Mertz and Yao) fermentation products spinosyn A and D, on eggs of Trichoplusia ni (Hübner), a cruciferous crop pest, and its egg parasitoid Trichogramma brassicae (Bezdenko) was investigated. RESULTS: The LC50 for spinosyn A and D (dissolved in ethanol) on T. ni eggs is 54 ng mL-1. Transcriptomics on caterpillars (1st and 3rd instars) that hatched from eggs treated with sublethal concentrations of spinosyn identified the upregulation of several genes encoding proteins that may be involved in insecticide resistance including detoxification enzymes, such as cytochrome P450s, glutathione S-transferases and esterases. Sublethal T. ni egg treatments did not affect parasitoid emergence, however, there was a marked increase in the size of T. brassicae hind tibia and wings that emerged from spinosyn-treated eggs. CONCLUSIONS: For the caterpillar, treatment of eggs with sublethal concentrations of spinosyn may induce insecticide resistance mechanisms. For the parasitoids, their increased size when reared in spinosyn-treated eggs suggests that the emerged wasps may have higher performance. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Prognostic value of RRM1 and its effect on chemoresistance in pancreatic cancer.

PURPOSE: Pancreatic cancer (PC) remains a lethal disease, and gemcitabine resistance is prevalent. However, the biomarkers suggestive of gemcitabine resistance remain unclear. METHODS: Bioinformatic tools identified ribonucleotide reductase catalytic subunit M1 (RRM1) in gemcitabine-related datasets. A cox regression model revealed the predictive value of RRM1 with clinical features. An external clinical cohort confirmed the prognostic value of RRM1. RRM1 expression was validated in gemcitabine-resistant cells in vitro and in orthotopic PC model. CCK8, flow cytometry, transwell migration, and invasion assays were used to explore the effect of RRM1 on gemcitabine-resistant cells. The CIBERSORT algorithm investigated the impact of RRM1 on immune infiltration. RESULTS: The constructed nomogram based on RRM1 effectively predicted prognosis and was further validated. Moreover, patients with higher RRM1 had shorter overall survival. RRM1 expression was significantly higher in PC tissue and gemcitabine-resistant cells in vitro and in vivo. RRM1 knockdown reversed gemcitabine resistance, inhibited migration and invasion. The infiltration levels of CD4 + T cells, CD8 + T cells, neutrophils, and plasma cells correlated markedly with RRM1 expression, and communication between tumor and immune cells probably depends on NF-κB/mTOR signaling. CONCLUSION: RRM1 may be a potential marker for prognosis and a target marker for gemcitabine resistance in PC.

Predictors of bacteremia in febrile infants under 3 months old in the pediatric emergency department.

INTRODUCTION: Fever may serve as the primary indicator of underlying infection in children admitted to the pediatric emergency department (PED), especially in high-risk young infants. This study aimed to identify early clinical factors that could help predict bacteremia in young febrile infants. METHODS: The study included infants under 90 days of age who were admitted to the PED due to fever. Patients were divided into two groups based on the presence or absence of bacteremia and further divided into three age groups: (1) less than 30 days, (2) 30 to 59 days, and (3) 60 to 90 days. Several clinical and laboratory variables were analyzed, and logistic regression and receiver operating characteristic (ROC) analyses were used to identify potential risk factors associated with bacteremia in young febrile infants. RESULTS: A total of 498 febrile infants were included, of whom 6.4% were diagnosed with bacteremia. The bacteremia group had a higher body temperature (BT) at triage, especially in neonates, higher pulse rates at triage, longer fever subsidence time, longer hospital stays, higher neutrophil counts, and higher C-reactive protein (CRP) levels than those of the non-bacteremia group. ROC analysis showed that the best cut-off values for predicting bacteremia in infants with pyrexia were a BT of 38.7 °C, neutrophil count of 57.9%, and CRP concentration of 53.8 mg/L. CONCLUSIONS: A higher BT at triage, increased total neutrophil count, and elevated CRP levels may be useful for identifying bacteremia in young febrile infants admitted to the PED.

Arsenic trioxide sensitizes pancreatic cancer cells to gemcitabine through downregulation of the TIMP1/PI3K/AKT/mTOR axis.

Gemcitabine (GEM) is the first-line medication for pancreatic ductal adenocarcinoma (PDAC). However, over some treatment cycles, GEM sensitivity declines and chemotherapeutic resistance develops, resulting in tumor recurrence and metastasis. Therefore, it is critical to elucidate the mechanism of GEM chemoresistance. And a specific drug that is closely related to the mechanism is urgently required to sensitize GEM. Here, tissue inhibitor of matrix metalloproteinases 1 (TIMP1) and phosphorylated mammalian target of rapamycin (p-mTOR) were found to be substantially elevated in PDAC patients and were associated with worse overall survival. The TIMP1/PI3K/AKT/mTOR pathway was found in GEM-resistant PDAC cells and was revealed to be involved in epithelial-mesenchymal transition (EMT) and apoptosis. Furthermore, arsenic trioxide (ATO), a basic therapeutic drug for acute promyelocytic leukemia, mediated TIMP1 reduction by inducing reactive oxygen species generation and hampered the subsequent PI3K/AKT/mTOR axis. Moreover, the combination of ATO and GEM cooperatively suppressed the TIMP1/PI3K/AKT/mTOR pathway, synergistically inhibited EMT and promoted apoptosis. In vitro and in vivo, ATO combined with GEM has a collaborative anticancer effect, inhibiting cancer cell proliferation, migration, invasion, and suppressing tumor growth both in PDAC parental and GEM-resistant cells. Overall, the TIMP1/PI3K/AKT/mTOR pathway is present in PDAC and linked to GEM resistance. ATO suppresses the axis to sensitize GEM and reverse GEM resistance, suggesting a promising treatment for the disease.

Novel Ultrasound-Guided Radiofrequency Ablation of the Medial Epicondylar Sensory Nerve for Recalcitrant Medial Epicondylosis: A Case-Based Technical Report.

Recalcitrant medial epicondylosis (ME) is a chronic tendinopathy affecting the common flexor-pronator tendon origin which causes significant pain and functional limitations. Recalcitrant ME is difficult to manage with non-surgical treatment options. The medial epicondylar sensory nerve (MEsn) is a small sensory nerve that travels within the medial intermuscular septum to innervate the osseous-tendinous structures of the medial epicondyle. In this report, we describe a novel technique for the treatment of recalcitrant ME via radiofrequency ablation (RFA) of the MEsn under ultrasound guidance. The MEsn is localized under ultrasound in the medial distal arm, just proximal to the medial epicondyle. Patients with a positive prognostic block of the MEsn subsequently underwent RFA of the MEsn. We have performed this procedure on two patients who have demonstrated improvement in pain and function for up to nearly one year after the procedure. The relief from pain and improvement in function of these patients warrants further investigation and comparative trials with respect to conventional treatment options, as MEsn RFA may be a viable treatment option for recalcitrant ME.

Adjuvant probiotic Bifidobacterium animalis subsp. lactis CP-9 improve phototherapeutic treatment outcomes in neonatal jaundice among full-term newborns: A randomized double-blind clinical study.

BACKGROUND: Probiotics had been used to decreased bilirubin level in neonatal jaundice (NJ) without being further studied mechanism and stratification. The intestinal pathogen Escherichia coli produced ß-glucuronidase would increase enterohepatic circulation and elevate serum bilirubin levels (SBLs) which might worsen the disease process of NJ. STUDY OBJECTIVE: We hypothesized that some probiotics could decrease bilirubin level through inhibiting the growth of E. coli. It's assumed that adjuvant probiotic intervention might accelerate the phototherapy for NJ and alleviate the severity of the NJ. Besides, it's further study the efficacy of the probiotic intervention in NJ among the full-term and preterm newborns. MATERIALS AND METHODS: Firstly, the Bifidobacterium animalis subsp. lactis CP-9 was screened for its anti-E. coli activity. Then, it was orally administered to newborns with NJ in combination with conventional phototherapy (wavelength 425-457 nm) to determine its efficacy. 83 neonatal patients whose serum bilirubinemia was at a concentration of ≥ 15 mg/dL were participated the double-blind randomized trial and conducted in the neonatal ward of China Medical University Children's Hospital (CMUCH, Taichung, Taiwan). The test was conducted in 2 groups: experimental group: phototherapy + B. animalis subsp. lactis CP-9 (n = 43; 5 × 109 CFU/capsule) and control group: phototherapy + placebo (n = 40). The SBL and total phototherapy duration were measured. RESULTS: The experimental group showed improved serum bilirubin decline rate (-0.16 ±â€…0.02 mg/dL/h; P = .009, 95% CI -0.12 to -0.2), particularly in the first 24 hour of in-hospital care, and reduced total phototherapy duration (44.82 ±â€…3.23 h; P = .011, 95% CI: 51.3-38.2) compared with the control group. Especially, probiotics had a significant therapeutic effect (serum bilirubin decline rate: -0.18 ±â€…0.02 mg/dL/h, 95% CI -0.12 to -0.23, P = .014; phototherapy duration: 43.17 ±â€…22.72 h, 95% CI 51.9-34.3, P = .019) in the low-risk subgroup (full-term newborns). CONCLUSIONS: In conclusion, B. animalis subsp. lactis CP-9 synergistically improves treatment outcomes of NJ during in-hospital phototherapy including reduced total phototherapy duration and improved serum bilirubin decline rate, particularly in full-term newborns.

Reducing intraventricular hemorrhage following the implementation of a prevention bundle for neonatal hypothermia.

INTRODUCTION: In very low birth weight (VLBW) infants, hypothermia immediately following birth is common even in countries rich in medical resources. The purpose of this study is to design a standard prevention bundle that decreases the rate of hypothermia among infants after birth and to investigate efficacy of the bundle and short-term outcomes for VLBW infants. METHODS: This quality improvement project was conducted from February 2017 to July 2018 on all VLBW preterm infants admitted at a single referral level III neonatal intensive care unit. The infants were classified into the pre-intervention (February to September 2017) and post-intervention (October 2017 to July 2018) groups according to the time periods when they were recruited. During the pre-intervention period, we analyzed the primary causes of hypothermia, developed solutions corresponding to each cause, integrated all solutions into a prevention bundle, and applied the bundle during the post-intervention period. Afterwards, the incidence of neonatal hypothermia and short-term outcomes, such as intraventricular hemorrhage (IVH), acidosis, and shock requiring inotropic agents, in each group were compared. RESULTS: A total of 95 VLBW infants were enrolled in the study, including 37 pre-intervention, and 58 post-intervention cases. The incidence of hypothermia in preterm infants decreased significantly upon the implementation of our prevention bundle, both in the delivery room (from 45.9% to 8.6%) and on admission (59.5% to 15.5%). In addition, the short-term outcomes of VLBW infants improved significantly, especially with the decreased incidence of IVH (from 21.6% to 5.2%, P = 0.015). CONCLUSIONS: Our standardized prevention bundle for preventing hypothermia in VLBW infants is effective and decreased the IVH rate in VLBW infants. We strongly believe that this prevention bundle is a simple, low-cost, replicable, and effective tool that hospitals can adopt to improve VLBW infant outcomes.

TIMP1 derived from pancreatic cancer cells stimulates Schwann cells and promotes the occurrence of perineural invasion.

Perineural invasion (PNI) occurs in most pancreatic ductal adenocarcinomas (PDACs). The relationship between cancer cells and peripheral nerves, however, is unknown. Therefore, we focused on the cooperation of PDAC cells and peripheral nerve astrocytes, Schwann cells (SCs), in PNI. The mutual tumor-supportive secretory cytokines between SCs (sNF96.2) and PDAC cells (PANC-1, BxPC-3) were screened by human cytokine arrays and verified. The prognostic value of selected cytokines and SC-associated markers was confirmed in PDAC patients. TIMP1 and CCL7 were found to form a paracrine feedback loop between PDAC cells and SCs. PDAC cell-derived TIMP1 promotes SCs proliferation and migration via CD63/PI3K/AKT signaling. CCL7 secreted from SCs enhances PDAC cell migration, invasion and expression of TIMP1 via CCR2/STAT3. PDAC cell-SC cooperation in PNI was blocked when TIMP1 knockdown in vitro and in vivo. Finally, TIMP1, CCL7 and SC-associated markers were correlated with PNI and prognosis in PDAC patients. In conclusion, SCs collaborate with PDAC cells through the TIMP1-CCL7 paracrine feedback loop to promote PNI. TIMP1 knockdown in PDAC cells suppresses PNI. Strategies to disrupt the TIMP1-CCL7 feedback loop might be developed to inhibit PNI in PDAC.

Overcoming resistance to oncolytic virus M1 by targeting PI3K-γ in tumor-associated myeloid cells.

Oncolytic viruses (OVs) have become a category of promising anticancer immunotherapeutic agents over the last decade. However, the fact that many individuals fail to respond to OVs highlights the importance of defining the barely known immunosuppressive mechanisms that lead to treatment resistance. Here we found that the immunosuppression mediated by tumor-associated myeloid cells (TAMCs) directly quenches the antitumor effect of oncolytic virus M1 (OVM). OVM induces myeloid cells to migrate into tumors and strengthens their immunosuppressive phenotypes. Mechanically, tumor cells treated with OVM secrete interleukin-6 (IL-6) to activate the phosphatidylinositol 3-kinase (PI3K)-γ/Akt axis in TAMCs, promoting infiltration of TAMCs and aggravating their inhibition on cytotoxic CD8+ T lymphocytes. Pharmacologically targeting PI3K-γ relieves TAMC-mediated immunosuppression and enhances the efficacy of OVM. Additional treatment with immune checkpoint antibodies eradicates multiple refractory solid tumors and induces potent long-term antitumor immune memory. Our findings indicate that OVM functions as a double-edged sword in antitumor immunity and provide insights into the rationale for liberating T cell-mediated antitumor activity by abolishing TAMC-mediated immunosuppression.

Epidemiological evolution of early-onset neonatal sepsis over 12 years: A single center, population-based study in central Taiwan.

BACKGROUND: We aimed to explore the epidemiology and evolution of pathogens, antibiotic susceptibility, and mortality rate in cases of neonatal early-onset sepsis (EOS) reported over a period of 12 years in a level III neonatal center in Central Taiwan. METHODS: Patients' medical records in a neonatal center from 2007 to 2018 were reviewed to obtain information on infants with culture-proven EOS, which included pathogens found in the blood or cerebrospinal fluid cultures. RESULTS: The incidence of neonatal EOS during this period was 2.11 cases/1,000 admissions. Group B streptococcal (GBS) and Escherichia coli were the most common pathogens. The overall rates of GBS and E. coli infections were 0.68/1,000 and 0.77/1,000 live births, respectively. The incidence of EOS in infants with a birth weight ≥1,500 g decreased significantly with decreasing incidence of GBS-related sepsis. The incidence of EOS remained high in very-low-birth-weight (VLBW) infants and increased over time. There was an increasing trend in of E. coli infection and emergence of drug-resistant strains. In addition, E. coli sepsis had high mortality in VLBW infants. CONCLUSION: Novel screening and prevention strategies against E. coli and reserving broad-spectrum antibiotics for the most critically ill or VLBW patients with maternal chorioamnionitis might help in early diagnosis and further improve the outcomes of EOS.

A Novel Treatment Approach of Ultrasound-Guided Radiofrequency Ablation of the Greater Trochanteric Sensory Nerve for Recalcitrant Greater Trochanteric Pain Syndrome.

This report describes a novel technique for the treatment of recalcitrant greater trochanteric pain syndrome (GPTS) by radiofrequency ablation (RFA) of the greater trochanteric sensory nerve (GTsn). Here, we describe one patient suffering from recalcitrant GTPS treated with RFA of the GTsn in the outpatient pain clinic setting. Over the eight months subsequent to treatment, the patient was monitored for changes in the Numerical Pain Rating (NPR) and Lower Extremity Functional Score (LEFS). The patient demonstrated meaningful symptomatic and functional improvement as measured by both NPR and LEFS. GTsn RFA may be a viable treatment option for recalcitrant GTPS. Larger comparative trials are needed to establish improved results over conventional treatments.

Case Report: Factor VII Deficiency Presented With Cephalohematoma After Birth.

Introduction: Factor VII deficiency is a rare inherited autosomal recessive bleeding disorder with a global prevalence of 1/500,000. Most cases remain asymptomatic, and cases with severe clinical presentation are rarely reported. Case Presentation: A newborn male with no relevant maternal antenatal history, delivered via vacuum-assisted cesarean section, presented with a large cephalohematoma after delivery. Poor appetite, pale appearance, and bulging fontanelles were observed 2 days later, progressing to hypovolemic shock. Further imaging examination revealed a large intracranial hemorrhage. Serial laboratory examination revealed remarkable coagulopathy with prolonged prothrombin time and factor VII deficiency (<1%, severe type). The patient was genetically confirmed to have the FVII:c 681+1 G>T homozygous mutation. Brain hemorrhage was resolved with high-dose factor VII replacement therapy with recombinant activated factor VII. However, repeated hemothorax and intracranial hemorrhage were detected. Therefore, the patient was under regular factor VII supplementation with a rehabilitation program for cerebral palsy. Conclusions: A case of factor VII deficiency with large cephalohematoma and intracranial hemorrhage after birth is described herein, which was treated with high-dose replacement therapy. Variants of the FVII:c 681+1 G>T (IVS6+1G>T) homozygous genotype may present with a severe phenotype at the neonatal stage. We aim to share a unique neonatal presentation with a certain genotype and treatment experience with initial replacement therapy, followed by regular prophylactic dosage.

Bioinformatics-Based Identification of Tumor Microenvironment-Related Prognostic Genes in Pancreatic Cancer.

OBJECTIVE: Growing evidence has highlighted that the immune and stromal cells that infiltrate in pancreatic cancer microenvironment significantly influence tumor progression. However, reliable microenvironment-related prognostic gene signatures are yet to be established. The present study aimed to elucidate tumor microenvironment-related prognostic genes in pancreatic cancer. METHODS: We applied the ESTIMATE algorithm to categorize patients with pancreatic cancer from TCGA dataset into high and low immune/stromal score groups and determined their differentially expressed genes. Then, univariate and LASSO Cox regression was performed to identify overall survival-related differentially expressed genes (DEGs). And multivariate Cox regression analysis was used to screen independent prognostic genes and construct a risk score model. Finally, the performance of the risk score model was evaluated by Kaplan-Meier curve, time-dependent receiver operating characteristic and Harrell's concordance index. RESULTS: The overall survival analysis demonstrated that high immune/stromal score groups were closely associated with poor prognosis. The multivariate Cox regression analysis indicated that the signatures of four genes, including TRPC7, CXCL10, CUX2, and COL2A1, were independent prognostic factors. Subsequently, the risk prediction model constructed by those genes was superior to AJCC staging as evaluated by time-dependent receiver operating characteristic and Harrell's concordance index, and both KRAS and TP53 mutations were closely associated with high risk scores. In addition, CXCL10 was predominantly expressed by tumor associated macrophages and its receptor CXCR3 was highly expressed in T cells at the single-cell level. CONCLUSIONS: This study comprehensively investigated the tumor microenvironment and verified immune/stromal-related biomarkers for pancreatic cancer.

Severe bacterial infection in young infants with pyrexia admitted to the emergency department.

ABSTRACT: The objectives of this study were to understand the clinical presentations of febrile young infants with severe bacterial infection (SBI), and to investigate the pathogen variations throughout the vaccine era and after antenatal group B Streptococcus (GBS) screening.All infants < 90 days old with a body temperature of ≥38.0°C and admitted to the emergency department were retrospectively enrolled in our study. SBI was defined as a positive culture of urine, blood, or cerebrospinal fluid. All clinical variables were analyzed and compared between the SBI group and the non-SBI group, to identify the relevant risk factors for SBI in infants with pyrexia.A total of 498 infants were studied, 279 of whom (56%) had SBI. The body temperature at triage was higher in the SBI group, and the difference was highly obvious in the neonatal group. White blood cell count and C-reactive protein levels were both significantly higher in the SBI group (P < .05), whereas neutrophil percentage and band percentage demonstrated no significant differences. Escherichia coli was the most common pathogen and plasmid-mediated extended-spectrum lactamases were detected in up to 9.1%. GBS was detected in 16 cases of bacteremia (6 cases with concurrent meningitis).The body temperature at triage may provide a clue for differentiating sick babies, especially in the neonatal group. Complete serum analysis is required for infection survey, especially white blood cell and C-reactive protein. Escherichia coli is the most common pathogen, and clinician should raise awareness of drug resistance in some patients. The prevalence of GBS infection in the young infant group remains high after routine antenatal GBS screening.