Predictive biomarkers for immune-related adverse events in cancer patients treated with immune-checkpoint inhibitors.

PURPOSE: The objective of this study was to identify potential predictors of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitor therapy among serum indexes, case data, and liquid biopsy results. METHODS: We retrospectively analyzed 418 patients treated with anti-programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) inhibitors from January 2018 to May 2022 in our cancer center. We identified factors that correlated with the occurrence of irAEs and evaluated associations between irAEs and anti-PD-1/PD-L1 inhibitor responses. RESULTS: The incidence of irAEs was 42.1%, and pneumonitis (9.1%), thyroid toxicity (9.1%), cardiotoxicity (8.1%), and dermatologic toxicity (6.9%) were the four most common irAEs. Multivariate logistic analysis identified female sex, antibiotic use, higher post-treatment neutrophil-to-lymphocyte ratio (NLR), and higher baseline circulating tumor cell (CTC) level, as predictive biomarkers for the occurrence of irAEs. A lower baseline prognostic nutritional index (PNI), body mass index (BMI) ≥ 25 kg/m2, and higher post-treatment lactate dehydrogenase (LDH) level were predictive factors for more severe irAEs (higher severity grade). Patients without irAEs had better overall survival than those with irAEs. Specifically, pneumonitis and cardiotoxicity were found to be significant predictors of poor prognosis in the irAE subgroup with different organ-related irAEs. Low-dose steroid (dexamethasone 10 mg) treatment had no significant effect on outcomes. CONCLUSIONS: Gender, antibiotic use, post-treatment NLR, and baseline CTC level are potential predictive biomarkers of irAEs, while baseline PNI, BMI, and post-treatment LDH may predict the severity of irAEs. The predictive effect of irAE occurrence on survival benefit may depend on the type of irAE.

PLEK2 mediates metastasis and invasion via α5-nAChR activation in nicotine-induced lung adenocarcinoma.

Evidence has shown a strong relationship between smoking and epithelial mesenchymal transition (EMT). α5-nicotinic acetylcholine receptor (α5-nAChR) contributes to nicotine-induced lung cancer cell EMT. The cytoskeleton-associated protein PLEK2 is mainly involved in cytoskeletal protein recombination and cell stretch migration regulation, which is closely related to EMT. However, little is known about the link between nicotine/α5-nAChR and PLEK2 in lung adenocarcinoma (LUAD). Here, we identified a link between α5-nAChR and PLEK2 in LUAD. α5-nAChR expression was correlated with PLEK2 expression, smoking status and lower survival in vivo. α5-nAChR mediated nicotine-induced PLEK2 expression via STAT3. α5-nAChR/PLEK2 signaling is involved in LUAD cell migration, invasion and stemness. Moreover, PLEK2 was found to interact with CFL1 in nicotine-induced EMT in LUAD cells. Furthermore, the functional link among α5-nAChR, PLEK2 and CFL1 was confirmed in mouse xenograft tissues and human LUAD tissues. These findings reveal a novel α5-nAChR/PLEK2/CFL1 pathway involved in nicotine-induced LUAD progression.

α5-nAChR/STAT3/CD47 axis contributed to nicotine-related lung adenocarcinoma progression and immune escape.

OBJECTIVES: The CHRNΑ5 gene, which encodes the α5-nicotinic acetylcholine receptor (α5-nAChR), is related to lung cancer and nicotine addiction. Smoking is closely related to the immunosuppressive effect of macrophages. CD47, a phagocytosis checkpoint in macrophages, is a therapeutic target in various cancer types. Nevertheless, the relationship between α5-nAChR and CD47 in lung cancer is still unclear. METHODS AND RESULTS: The present study showed that α5-nAChR-mediated CD47 expression via STAT3 signaling, consequently leading to tumor progression and immune suppression in lung adenocarcinoma (LUAD). α5-nAChR expression was correlated with STAT3 expression, CD47 expression, smoking status and poor prognosis of LUAD in vivo. In vitro, α5-nAChR expression mediated the phosphorylation of STAT3, and phosphorylated STAT3 bound to the CD47 promoter and mediated CD47 expression. Downregulation of α5-nAChR and/or CD47 significantly reduced cell proliferation, migration, invasion, stemness and IL-10 expression, but increased TNF-α expression and phagocytosis of macrophages in LUAD. Furthermore, α5-nAChR/CD47 signaling contributed to the growth of subcutaneous xenograft tumors and liver metastasis of tumors in mice. CONCLUSION: The α5-nAChR/STAT3/CD47 axis contributed to the progression and immune escape of lung cancer and may be a potential target for LUAD immunotherapy.

Construction and external validation of a nomogram model for predicting the risk of esophageal stricture after endoscopic submucosal dissection: a multicenter case-control study.

Esophageal stricture is a common complication after endoscopic submucosal dissection (ESD) for superficial esophageal cancer and precancerous lesions, we intend to investigate the independent risk factors of esophageal stricture after ESD by adding the data of included living habits, established a nomogram model to predict the risk of esophageal stricture, and verified it by external data. The clinical data and living habits of patients with early esophageal cancer and precancerous lesions who underwent ESD in the Affiliated Hospital of North Sichuan Medical College and Langzhong People's Hospital from March 2017 to August 2021 were retrospectively collected. The data collected from the two hospitals were used as the development group (n = 256) and the validation group (n = 105), respectively. Univariate and multivariate logistic regression analyses were used to determine independent risk factors for esophageal stricture after ESD and establish a nomogram model for the development group. The prediction performance of the nomogram model is internally and externally verified by calculating C-Index and plotting the receiver operating characteristic curve (ROC) and calibration curve, respectively. The results showed that Age, drinking water temperature, neutrophil-lymphocyte ratio, the extent of esophageal mucosal defect, longitudinal diameter of resected mucosa, and depth of tissue invasion (P < 0.05) were independent risk factors for esophageal stricture after ESD. The C-Index of the development group and validation group was 0.925 and 0.861, respectively. The ROC curve and area under the curve (AUC) of the two groups suggested that the discrimination and prediction performance of the model were good. The two groups of calibration curves are consistent and almost overlap with the ideal calibration curve, indicating that the predicted results of this model are in good agreement with the actual observed results. In conclusion, this nomogram model has a high accuracy for predicting the risk of esophageal stricture after ESD, providing a theoretical basis for reducing or avoiding esophageal stricture and guiding clinical practice.

Effect of erector spinae plane block with different doses of dexmedetomidine as adjuvant for ropivacaine on the postoperative quality of recovery after video-assisted thoracoscopic lobectomy surgery: a randomized controlled trial.

BACKGROUND: Erector spinae plane block (ESPB) improves postoperative analgesia and significantly enhances the quality of recovery (QoR) after video-assisted thoracoscopic lobectomy surgery (VATLS). However, it is not known whether the use of dexmedetomidine (Dex) as an adjunct for ropivacaine to ESPB affects the QoR after VATLS. The purpose of this study was to explore the effects of different Dex dosages as an adjunct for ropivacaine in combination with ultrasound-guided ESPB on the quality of postoperative recovery in patients with VATLS. METHODS: In this single-center, double-blind, randomized study, 120 patients between the ages of 18 and 65 who were scheduled for VATLS from december 2021 and october 2022 in our hospital under general anesthesia were randomly divided into three groups: ultrasound-guided ESPB with 30 mL of 0.5% ropivacaine (Group R), ultrasound-guided ESPB 0.5% ropivacaine plus 0.5 µg/kg Dex (Group RD1), and ultrasound-guided ESPB 0.5% ropivacaine plus 1.0 µg/kg Dex (Group RD2), ultrasound-guided ESPB was administrated at the T5 vertebral level before surgery. The primary outcome was the QoR-15 score 24 h after the surgery. The secondary outcomes included the QoR-15 scores at 12 h, 48 h, and 72 h after the operation, visual analogue scale (VAS) scores at 8 h, 12 h, 24 h, and 48 h after surgery, cumulative flurbiprofen consumption, postoperative nausea and vomiting (PONV), postoperative bradycardia, and hypotension. RESULTS: The QoR-15 scores were higher in group RD2 than the R and RD1 groups on postoperative day 1 (P < 0.05), in addition, no significant difference was found in the QoR-15 scores between groups R and RD1 on postoperative day 1. The VAS scores were significantly lower in group RD2 than in groups RD1 and group R 12-24 h after surgery (P < 0.05). No significant differences were observed in the QoR-15 and VAS scores at 48 and 72 h after surgery between the three groups. The cumulative flurbiprofen consumption was markedly reduced during the 72 h after surgery in the RD2 group (P < 0.05). The incidence of postoperative nausea and vomiting was lower in the RD2 group (P < 0.05). CONCLUSIONS: The combination of 1 µg/kg dexmedetomidine as an adjunct with 0.5% ropivacaine 30 ml for erector spinae plane block significantly improved the postoperative quality of recovery and provided better postoperative analgesia on postoperative day 1 in patients undergoing Video-assisted thoracoscopic lobectomy surgery. However, dexmedetomidine (1 µg/kg) as an adjunct for ropivacaine combined with erector spinae plane block did not enhance the postoperative quality of recovery at 48 and 72 h postoperatively. TRIAL REGISTRY NUMBER: The number of this clinical trial registry is ChiCTR2100053230, date of registration: 16/11/ 2021).

Molecular Mechanism of Action of Cycloxaprid, An Oxabridged cis-Nitromethylene Neonicotinoid.

Cycloxaprid, an oxabridged cis-nitromethylene neonicotinoid, showed high insecticidal activity in Hemipteran insect pests. In this study, the action of cycloxaprid was characterized by recombinant receptor Nlα1/rß2 and cockroach neurons. On Nlα1/ß2 in Xenopus oocytes, cycloxaprid acted as a full agonist. The imidacloprid resistance-associated mutation Y151S reduced the Imax of cycloxaprid by 37.0% and increased EC50 values by 1.9-fold, while the Imax of imidacloprid was reduced by 72.0%, and EC50 values increased by 2.3-fold. On cockroach neurons, the maximum currents elicited by cycloxaprid were only 55% of that of acetylcholine, a full agonist, but with close EC50 values of that of trans-neonicotinoids. In addition, cycloxaprid inhibited acetylcholine-evoked currents on insect neurons in a concentration-dependent manner when co-applied with acetylcholine. Cycloxaprid at low concentrations significantly inhibited the activation of nAChRs by acetylcholine, and its inhibition potency at 1 µM was higher than its activation potency on insect neurons. Two action potencies, activation, and inhibition, by cycloxaprid on insect neurons provided an explanation for its high toxicity to insect pests. In summary, as a cis-nitromethylene neonicotinoid, cycloxaprid showed high potency on both recombinant nAChR Nlα1/ß2 and cockroach neurons, which guaranteed its high control effects on a variety of insect pests.

Nocardia infection following ocular surface surgery.

OBJECTIVE: To investigate the clinical characteristics and treatment outcomes of Nocardia infection after ocular surface surgery. METHODS: This is a retrospective study. Eight cases of culture-proven Nocardia infection, which developed within 1 month after ocular surface surgery were included. Demographics and clinical history of patients were investigated. RESULTS: There were 8 eyes (2 left and 6 right) of 8 patients (5 males and 3 females), aged 27-65, with a median age of 52.9 years. Three cases underwent pterygium excision, three were subjected to conjunctival flap covering, and two were treated with lamellar corneal transplantation. The time interval between previous surgery and the onset of symptoms varied from 7 to 28 days (mean = 20.5 ± 7.13 days). All the cases presented grey-white infiltrates at the surgical incision site while appearing with six corneal ulcers and two conjunctival ulcers. Filaments of Nocardia were founded by confocal microscopy in two of the five cases. All responded poorly to medical therapy. Seven of the eight cases were treated with reoperation. Nocardia infection recurred in three cases after reoperation, and one was eviscerated. CONCLUSIONS: Surgical trauma is a risk factor for ocular Nocardia infection. Nocardia infection should be suspected when secondary infection occurs in a surgical incision with an atypical clinical presentation. The use of corticosteroids may influence the efficacy of drugs. Complete removal of lesions may lower the recurrence of Nocardia infection with poor drug treatment effects.

ALKBH5-mediated m6A modification of lncRNA KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9.

It has been shown that N6-methyladenosine (m6A) modification is involved in the development of complex human diseases, especially in the development of cancer. Our research investigated the role and mechanism of the m6A modification of lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) in Laryngeal squamous cell carcinoma (LSCC) progression. Microarray analysis was used to quantitatively detect the m6A apparent transcriptional modification level of lncRNA in LSCC tissue. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), in situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR) were used to examine the m6A modification and expression of KCNQ1OT1. In addition, in vivo and in vitro experiments have tested the effects of KCNQ1OT1 knockdown on the proliferation, invasion and metastasis of LSCC. Mechanically, we found the N6-methyladenosine (m6A) demethylase ALKBH5 mediates KCNQ1OT1 expression via an m6A-YTHDF2-dependent manner and KCNQ1OT1 could directly bind to HOXA9 to further regulate the proliferation, invasion and metastasis of LSCC cells. In general, our research indicates that ALKBH5-mediated m6A modification of KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9.

Exosomal lncRNA HOTAIR induce macrophages to M2 polarization via PI3K/ p-AKT /AKT pathway and promote EMT and metastasis in laryngeal squamous cell carcinoma.

Exosomes are a new way of the communication between the tumor cell and macrophage in the micro-environment. The macrophage can be induced to different phenotypes according to the different tumors. In the present study, long-chain noncoding RNA HOTAIR (lncRNA HOTAIR) was highly expressed in LSCC and exosomes. The pathway of exosomal lncRNA HOTAIR inducing macrophage to M2 polarization in the LSCC was investigated. The carcinoma tissues and adjacent tissues were collected from 104 LSCC cases, and the positive relationship between CD163-/CD206-M2 macrophage infiltration and clinical phase, lymph node spreading and pathological phase in LSCC was observed. To examine the role of exosomal lncRNA HOTAIR, macrophages were co-cultured with LSCC-exosomes of high lncRNA HOTAIR expression or transferred with HOTAIR mimics. It was suggested that exosomal lncRNA HOTAIR can induce macrophages to M2 polarization by PI3K/p-AKT/AKT signaling pathway. Furthermore, exo-treated M2 macrophages facilitate the migration, proliferation, and EMT of LSCC.

A novel electrochemical sensor based on autotropic and heterotrophic nitrifying biofilm for trichloroacetic acid toxicity monitoring.

Trichloroacetic acid (TCA), a toxic substance produced in the disinfection process of wastewater treatment plants, will accumulate in the receiving water. The detection of TCA in the water can achieve the purpose of early warning. However, currently there are few reports on microbial sensors used for TCA detection, and the characteristics of their microbial communities are still unclear. In this work, a toxicity monitoring microbial system (TMMS) with nitrifying biofilm as a sensing element and cathode oxygen reduction as a current signal was successfully constructed for TCA detection. The current and nitrification rate showed a linear relationship with low TCA concentration from 0 to 50 µg/L (R2current = 0.9892, R2nitrification = 0.9860), and high concentration range from 50 to 5000 µg/L (R2current = 0.9883, R2nitrification = 0.9721). High-throughput sequencing revealed that the TMMS was composed of autotrophic/heterotrophic nitrifying and denitrifying microorganisms. Further analysis via symbiotic relationship network demonstrated that Arenimonas and Hyphomicrobium were the core nodes for maintaining interaction between autotropic and heterotrophic nitrifying bacteria. Kyoto Encyclopedia of Genes and Genomes analysis showed that after adding TCA to TMMS, the carbon metabolism and the abundance of the tricarboxylic acid cycle pathway were reduced, and the activity of microorganisms was inhibited. TCA stress caused a low abundance of nitrifying and denitrifying functional enzymes, resulting in low oxygen consumption in the nitrification process, but more oxygen supply for cathode oxygen reduction. This work explored a novel sensor combined with electrochemistry and autotrophic/heterotrophic nitrification, which provided a new insight into the development of microbial monitoring of toxic substances.

Absolute eosinophil count may be an optimal peripheral blood marker to identify the risk of immune-related adverse events in advanced malignant tumors treated with PD-1/PD-L1 inhibitors: a retrospective analysis.

BACKGROUND: This study aimed to investigate the predictive values of serum biomarkers including absolute eosinophil count (AEC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) with respect to immune-related adverse events (irAEs) during anti-PD-1/PD-L1 inhibitor treatment in patients with advanced malignant tumors. METHODS: We retrospectively analyzed 95 patients with advanced cancer who were treated with anti-PD-1/PD-L1 inhibitors from January 1, 2017, to May 1, 2020, in our cancer center. We then analyzed associations between irAEs and anti-PD-1/PD-L1 inhibitor responses and evaluated the predictive values of serum biomarkers with respect to the risk of irAEs. RESULTS: The incidence of irAEs was 55.8%. There were no statistically significant differences between the irAEs and no-irAEs groups in an objective response rate (ORR) or disease control rate (DCR). However, landmark analysis showed that the irAEs group had better survival after 120 days following the initiation of anti-PD-1/PD-L1 inhibitor treatment, compared with the no-irAEs group. The incidences of irAEs were greater in the high-AEC and low-NLR groups than in the low-AEC and high-NLR groups. Univariate logistic analysis showed that low NLR, ECOG performance status (0-1), and high AEC were risk factors for irAEs. Multivariate logistic analysis showed that high AEC and good ECOG performance status were independent predictors for irAEs. CONCLUSIONS: irAEs may be associated with a survival benefit. Baseline AEC is a strong predictor of irAEs in patients undergoing treatment with anti-PD-1/PD-L1 inhibitors.

Role of long non-coding RNA H19 in therapy resistance of digestive system cancers.

Digestive system cancers are associated with high morbidity and mortality. Chemotherapy and radiotherapy are the main treatment modalities for these cancers. However, the development of therapy resistance leads to high rates of tumor recurrence and metastasis, resulting in dismal prognosis. Long non-coding RNA (LncRNA) H19, one of the most intriguing non-coding RNAs, has been shown to play a key role in the development and therapy resistance of various digestive system cancers (including hepatocellular carcinoma, colorectal cancer, pancreatic ductal adenocarcinoma, esophageal carcinoma, gastric cancer, and biliary system cancer) by regulating the abnormal expression of genes. In this review, we discuss the potential mechanisms of LncRNA H19 related therapy resistance in the context of digestive system cancers. LncRNA H19 is a potential novel therapeutic target for amelioration of cancer therapy resistance.

Introduced ecological engineers drive behavioral changes of grasshoppers, consequently linking to its abundance in two grassland plant communities.

Introduced ecosystem engineers are expected to have extensive ecological impacts on a broad range of resident biota by altering the physical-chemical structure of ecosystems. Livestock that are potentially important introduced ecosystem engineers in grassland systems could create and/or modify habitats for native plant-dwelling insects. Yet, there is little knowledge of how insects respond to engineering effects of introduced livestock. To bridge this gap, we tested how domestic sheep affects the behavior and abundance of a native grasshopper Euchorthippus unicolor at both low (11.8 ± 0.4 plant species per plot) and high (19.8 ± 0.5 plant species per plot) diversity sites. Results found grasshoppers shifted their resting and feeding locations from the upper to the intermediate or low layers of vegetation, and fed on more plants species following livestock engineering effects. In the low plant diversity habitats, grazing caused grasshoppers to increase switching frequency, spend more time searching for host plants, and reduce time spent feeding, but had opposite effects on all the three behaviors in the high-diversity habitats. Moreover, grazing engineering effects on behavioral changes of grasshoppers were potentially related to their abundance. Overall, this study highlights native insect species' behavior and abundance in responses to introduced ecological engineers, and suggests that ecosystem engineers of non-native species have strong and important impacts extending beyond their often most obvious and frequently documented direct ecological effects.

Hypoxemia and pulmonary hypertension in patients with concomitant restrictive ventilatory defect and sleep apnea: the overlap syndrome.

BACKGROUND: To investigate the severity of hypoxemia and prevalence of pulmonary hypertension (PHTN) in patients with the overlap syndrome (OS) of restrictive ventilatory defect (RVD) and sleep apnea (SA). METHODS: Patients referred for both sleep test and spirometry for suspected SA and ventilatory disorders were recruited prospectively from January 2019 to January 2020. SA was determined by an apnea-hypopnea index ≥ 5/h; average oxygen saturation during sleep (meanSaO2) and percentage of total sleep time with saturation < 90% (T90) were calculated. RVD was diagnosed in the presence of forced expiratory volume in the first second/forced vital capacity (FVC) > 0.7 and FVC < 80% predicted value. PHTN was defined by tricuspid regurgitation peak velocity ≥ 3.4 m/s, documented by noninvasive transthoracic echocardiography. RESULTS: Patients with OS had significantly lower meanSaO2 but higher T90 than subjects with isolated SA and isolated RVD. Patients with OS vs. those with isolated SA had higher odds of PHTN in multivariable analysis with age, sex, and body mass index adjusted for (OR 2.96, 95%CI 1.05-8.91, p = 0.040). Patients with meanSaO2 < 92% vs. meanSaO2 ≥ 92% had significantly higher odds of being diagnosed with PHTN (OR 5.40, 95%CI 2.01-15.7, p < 0.001). Similarly, T90 (≥ 4.5% versus < 4.5%) was also independently associated with the prevalence of PHTN (OR 7.21, 95%CI 2.54-23.67, p < 0.001). CONCLUSION: Patients with OS of RVD and SA had severe hypoxemia, which is associated with the prevalence of PHTN. Further investigation is needed to discern whether therapeutic strategies toward OS might mitigate PHTN in this cohort. TRIAL REGISTRATION: Clinical Trial Registration No. ChiCTR1900027294 on 1 October 2019.

Physical activity in the context of advanced breast cancer: An integrative review.

AIMS: To describe and synthesize diverse empirical evidence regarding physical activity (PA) in the context of advanced breast cancer (ABC). DESIGN: Integrative review guided by the work of Whittemore and Knafl (2005). DATA SOURCES: Six electronic databases were systematically searched to identify relevant literature published between January 2007-June 2019. REVIEW METHODS: Abstracts of papers that met the inclusion criteria were reviewed by two researchers and full texts of eligible papers were assessed. Data were extracted by two independent researchers and inter-rater reliability of data extraction established. Quality of papers was evaluated using the Mixed Methods Appraisal Tool. Data were organized according to comprehensive thematic analysis and the biobehavioural model for the study of exercise interventions. RESULTS: Of the 532 abstracts, 18 studies met the inclusion criteria which included six randomized controlled trials, one quantitative non-randomized study, seven quantitative descriptive studies, three mixed method studies and one qualitative study. Results from studies enrolled fell into four domains: PA performance and its influence on survival; barriers and preferences for PA; interventions to enhance PA; perceived benefits of PA from qualitative feedback. CONCLUSION: Evidence suggests that ABC patients are physically inactive. Main barriers of PA are less aerobic fitness and heavy symptom burden. Simple, tailored and specialist-supervised PA is preferred by ABC patients. Form of joint self-instructed and group accompanying is advocated as well. PA intervention programmes identified in this review vary on type, intensity, duration and frequency, while generally, are found to be feasible, safe and beneficial to patients' physical and psychosocial well-being. IMPACT: The results propose tailored, supervised, group-based PA programmes are in urgent need for ABC patients. Clinical professionals should manage more feasible and safer PA interventions to help improve patients' overall health. More research with rigorous methodology design is warranted to explore PA's effect on long-term health outcomes.

Long Noncoding RNA NEAT1: A Potential Biomarker in the Progression of Laryngeal Squamous Cell Carcinoma.

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is diverse in its natural history and responsiveness to treatments. There is an urgent need to generate candidate biomarkers for the stratification and individualization of treatment to avoid overtreatment or inadequate treatment. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been identified as an oncogenic gene in multiple human tumors entitles, and dysregulation of NEAT1 was tightly linked to carcinogenesis and cancer progression. METHODS: One hundred two paraffin samples of LSCC patients were collected. Furthermore, in situ hybridization (ISH), Kaplan-Meier, and MTT were used to analyze the relationship between NEAT1 and the progress of LSCC. RESULTS: In this study, ISH revealed that NEAT1 was strongly expressed in the nucleus. The increased expression of NEAT1 was correlated with T grade, neck nodal metastasis, clinical stage, drinking history, or smoking history of LSCC. The Kaplan-Meier analysis indicated that patients with higher NEAT1 expression had a worse overall survival in LSCC patients. In addition, NEAT1 knockdown significantly inhibited the growth of LSCC cells. CONCLUSION: Together, these results suggested that NEAT1 involved in the progress of LSCC and might act as a tumor oncogenic gene. This study provides a potential new marker and target for gene therapy in the treatment of LSCC.

Salmonella enterica Serovar Typhi Induces Host Metabolic Reprogramming to Increase Glucose Availability for Intracellular Replication.

Salmonella enterica serovar Typhi (S. Typhi) is a human-limited intracellular pathogen and the cause of typhoid fever, a severe systemic disease. Pathogen-host interaction at the metabolic level affects the pathogenicity of intracellular pathogens, but it remains unclear how S. Typhi infection influences host metabolism for its own benefit. Herein, using metabolomics and transcriptomics analyses, combined with in vitro and in vivo infection assays, we investigated metabolic responses in human macrophages during S. Typhi infection, and the impact of these responses on S. Typhi intracellular replication and systemic pathogenicity. We observed increased glucose content, higher rates of glucose uptake and glycolysis, and decreased oxidative phosphorylation in S. Typhi-infected human primary macrophages. Replication in human macrophages and the bacterial burden in systemic organs of humanized mice were reduced by either the inhibition of host glucose uptake or a mutation of the bacterial glucose uptake system, indicating that S. Typhi utilizes host-derived glucose to enhance intracellular replication and virulence. Thus, S. Typhi promotes its pathogenicity by inducing metabolic changes in host macrophages and utilizing the glucose that subsequently accumulates as a nutrient for intracellular replication. Our findings provide the first metabolic signature of S. Typhi-infected host cells and identifies a new strategy utilized by S. Typhi for intracellular replication.

Interaction of aflatoxin G1 with free DNA in vitro and possibility of its application in removing aflatoxin G1.

The present study sought to evaluate the interaction between aflatoxin G1 and free DNA in vitro through different analytical techniques. The UV-visible spectra results showed that the structure of DNA might be changed with a new aflatoxin G1-DNA complex forming, which indicated that the interacting mode between them was the intercalating mode. The DNA melting temperature increased by 12.80 °C, suggesting that the DNA double helix structure was more compact and stable through intercalation. The circular dichroism (CD) spectra results indicated that the interaction of aflatoxin G1 with DNA induced the DNA base stacking changes. The results of agarose gel electrophoresis and fluorescence microscope further verified that the interacting mode between aflatoxin G1 and DNA was intercalation mode. According to the fluorescence spectrum data, the binding constant was calculated 6.24 × 104 L·mol-1. The thermodynamic results demonstrated that the reaction of aflatoxin G1 intercalating to DNA was a spontaneous reaction. The elimination results suggested that aflatoxin G1 could be enriched and removed by DNA intercalation through magnetic beads separation, with the removal efficiency of 93.73%. The study results would provide a theoretical basis for establishing a new aflatoxin removal method based on DNA intercalation.

Differences in practice and preferences associated with truth-telling to cancer patients.

BACKGROUND: Doctors should disclose the diagnosis to patients according to the principle of autonomy. However, not disclosing the diagnosis and prognosis to cancer patients remains common in mainland China. OBJECTIVE: The study explored the experiences and attitudes of patients with cancer, family members, and the medical staff in truth-telling. RESEARCH DESIGN: A quantitative survey with three closed-ended questionnaires was conducted. PARTICIPANTS: In all, 137 patients with cancer, 134 family members caring for cancer cases, and 54 medical staff were surveyed. Descriptive statistics were used to summarize all characteristics, and the chi-square test was performed to analyze group differences in attitudes toward cancer disclosure. ETHICAL CONSIDERATIONS: This study was approved by the Committee on Ethics of Biomedicine Research, at the Second Military Medical University (HJEC-2018-YF-001). Informed consent was obtained from all participants prior to study commencement. FINDINGS: A total of 59.8% of patients were informed about their diagnosis within 1 week, and 19.7% inferred theirs. The medical staff preferred to prioritize family members in informing about patient diagnosis while 77.4% of patients preferred to be told the whole truth at the time of initial diagnosis. More patients than family members and medical staff wanted the patients to be informed about the diagnosis (p < 0.001). A significant difference was found between the patients and family members regarding who should tell the patients. DISCUSSION: The willingness of patients in knowing the truth was underestimated by their family members as well as the medical staff. Guessing the truth indirectly may exert negative effects on the patients, and not telling the truth is inappropriate in patients who want to be informed. CONCLUSION: Disclosure of a cancer diagnosis is a complex process involving medical practice, as well as a range of cultural, ethical, and legal factors. The medical staff should first assess each patient's willingness in truth-telling and inform about disease diagnosis with respect. Emotional support and comfort from family members are encouraged. Anyone in the patient's care team, especially nurses, could be integrated in the process of truth-telling.

SoxS is a positive regulator of key pathogenesis genes and promotes intracellular replication and virulence of Salmonella Typhimurium.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important intracellular pathogen, causing gastroenteritis or severe systemic infection in a variety of hosts. During infection, S. Typhimurium must survive and replicate in host macrophages, which produce abundant oxidative compounds. SoxRS regulon is a well-known regulator that is activated in response to oxidative stress and promotes bacterial tolerance to oxidants in E. coli. However, the global regulatory function of SoxS in S. Typhimurium remains poorly characterized. Here, we used an RNA sequencing-based approach to investigate the role of SoxS in the expression of S. Typhimurium virulence genes. Besides the downregulation of genes related to resistance to oxidative stress, we found that in a soxS deletion mutant the expression of Salmonella pathogenicity island (SPI)-2 genes, which are crucial for replication within macrophages, was significantly repressed. Moreover, immunofluorescence and mice infection experiments showed that soxS deletion inhibited replication in macrophages and decreased virulence upon intraperitoneal inoculation in mice, respectively. Collectively, our findings demonstrate that SoxS is a positive regulator of SPI-2 genes and, therefore, plays a crucial role in S. Typhimurium intracellular replication and virulence.