Impact of magnetic resonance imaging-derived skeletal muscle index in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the clinical implication of magnetic resonance imaging (MRI)-derived skeletal muscle index (SMI) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients undergoing induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and further to develop a nomogram for predicting survival prognosis. METHODS: SMI was determined through baseline MRI at the third cervical level. The nomogram was based on a training cohort involving 409 LANPC patients. We validated the prognostic accuracy of this prognostic model in an internal validation cohort (n = 204) and an external independent cohort (n = 272). RESULTS: SMI was an independent risk factor for OS. A prognostic model comprising age, TNM stage and SMI for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.686), predictive accuracy [time dependent area under the curve (tAUC) at 5 years: 0.70], and calibration, and was further validated in the internal and external validation datasets. A risk stratification derived from the model stratified these patients into three prognostic subgroups with significantly different survival. CONCLUSIONS: Low SMI accessed by MRI was significantly associated with poor overall survival in LANPC patients undergoing IC + CCRT. Moreover, we established and validated a novel nomogram involving age, TNM stage and SMI that could provide accurate prognostic stratification among this population.

Occurrence and fate of microplastics from a water source to two different drinking water treatment plants in a megacity in eastern China.

The widespread presence of microplastics (MPs) contamination in drinking water has raised concerns regarding water safety and public health. In this study, a micro-Raman spectrometer was used to trace the occurrence of MP transport from a water source to a drinking water treatment plant (DWTP)1 with an advanced treatment process and DWTP2 with a conventional treatment process and the contributions of different processes to the risk reduction of MPs were explored. Six types of MPs were detected: polyethylene terephthalate, polyethylene, polypropylene, polystyrene, polyamide, and polyvinyl chloride. 2-5 µm (35.8-41.2%) and polyethylene terephthalate (27.1-29.9%) were the most frequently detected MP sizes and types of water source samples, respectively. The abundance of MPs in treated water decreased by 72.7-83.0% compared to raw water. Ozonation and granular activated carbon (52.7%), and sand filtration (47.5%) were the most effective processes for removing MPs from DWTP1 and DWTP2, respectively. Both DWTPs showed significant removal effects on polyethylene terephthalate, with 80.0-88.1% removal rates. The concentrations of polystyrene increase by 30.0-53.4% after chlorination. The dominant components in the treated water of DWTP1 and DWTP2 were polypropylene (24.7%) and polyethylene 27.7%, respectively, and MPs of 2-5 µm had the highest proportion (55.3-64.3%). Pollution load index and potential ecological risk index of raw water treated by DWTPs were reduced by 48.0-58.7% and 94.5-94.7%, respectively. The estimated daily intake of MPs in treated water for infants was 45.5-75.0 items/kg/d, respectively, approximately twice that of adults. This study contributes to the knowledge gap regarding MP pollution in drinking water systems.

Radiation-Induced Surface Modification of MXene with Ionic Liquid to Improve Electrochemical Properties and Chemical Stability.

For the first time, an ionic liquid was grafted onto Ti3C2Tx MXene interlayers (MXene-g-IL) using a radiation technique. The IL was tightly immobilized on the surface of MXene nanosheets via chemical linkage, which exhibited excellent specific capacitance (160 F g-1 at 5 mV s-1) and improved structural stability (maintaining the sheet-like structure for 180 days). The facile, efficient, and scalable synthetic strategy derived from the radiation technique can open a new avenue for covalent functionalization of MXene-based materials and promote their further application.

Prognostic significance of cervical radiologic carotid artery invasion by lymph node on magnetic resonance imaging in nasopharyngeal carcinoma.

PURPOSE: Carotid artery invasion (CAI) has been demonstrated to be an important prognosticator in some head and neck cancers. This study aimed to examine the prognostic value of radiologic CAI (rCAI) by cervical lymphadenopathy in nasopharyngeal carcinoma (NPC). METHODS: NPC patients treated between January 2013 and December 2016 were included. Pre-treatment MRIs were reviewed for cervical rCAI according to the radiologic criteria. Univariate and multivariate models were constructed to assess the association between cervical rCAI and clinical outcomes. A new N classification system was proposed and compared to the 8th AJCC system. RESULTS: The percentage of patients with MRI-positive lymph nodes was 84.7% (494/583), of whom cervical rCAI cases accounted for 42.3% (209/494). Cervical rCAI was associated with significantly poorer OS, DFS, DFFS and RFFS compared to non-rCAI (P < 0.05). Multivariate analyses confirmed that cervical rCAI was an independent prognosticator for DFS and DFFS, surpassing other nodal features, such as laterality, size, cervical node necrosis (CNN) and radiologic extranodal extension (rENE), while location of positive LNs remained independently associated with OS, DFS and DFFS. We propose a refined N classification: New_N1: upper neck LNs only without cervical rCAI; New_N2: upper neck LNs only with cervical rCAI; New_N3: upper and lower LNs. The proposed classification broadened the differences in OS, DFS and DFFS between N1 and N2 disease, and achieved a higher c-index for DFS and DFFS. CONCLUSIONS: Cervical rCAI was an independent unfavorable indicator of NPC. Compared to the AJCC system, the proposed N category showed satisfactory stratification between N1 and N2 disease, and better prediction of distant metastasis and disease failure.

Volatile Versus Total Intravenous Anesthesia on Postoperative Delirium in Adult Patients Undergoing Cardiac Valve Surgery: A Randomized Clinical Trial.

BACKGROUND: The effect of anesthesia regimens on postoperative delirium after on-pump cardiac valve surgery is yet undetermined. This study aimed to evaluate the effect of volatile anesthesia compared with propofol-based total intravenous anesthesia (TIVA) on the occurrence of delirium after on-pump cardiac valve surgery. METHODS: This randomized clinical trial was conducted at a university academic hospital in China, from February 2019 to January 2021. Patients scheduled for on-pump cardiac valve surgery or combined valve with coronary artery bypass grafting (CABG) surgeries were randomly assigned to receive anesthesia maintenance with either a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was the incidence of delirium during the first 7 days after surgery, assessed using the confusion assessment method for the intensive care unit (ICU). The secondary outcomes included duration of delirium, subtypes of delirium, 30-day mortality, pain score, major morbidity (including cerebral infarction, respiratory failure, and pneumonia), duration of mechanical ventilation, and lengths of ICU and hospital stay. The statistical analysis of the primary outcome variable was by Pearson's χ 2 test. RESULTS: Among the 684 patients analyzed (mean age, 53.8 years; 381 [55.7%] women), 676 were assessed for the primary outcome. Postoperative delirium occurred in 63 of 337 (18.7%) patients receiving volatile anesthesia versus 76 of 339 (22.4%) patients receiving propofol-based TIVA (relative risk, 0.80; 95% confidence interval [CI], 0.55-1.16; P = .231). There were no significant differences between the groups in any of the secondary outcomes. CONCLUSIONS: Among patients undergoing on-pump cardiac valve surgery, anesthesia maintenance with a volatile agent did not result in significantly fewer occurrences of postoperative delirium than propofol-based TIVA.

Pirfenidone inhibits stromal collagen deposition and improves intra-tumoral delivery and antitumor efficacy of Pegylated liposomal doxorubicin.

The effectiveness of cancer nanotherapeutics is greatly restricted by the dense collagen network in solid tumors. Pirfenidone (PFD) is a clinically approved oral antifibrotic agent widely used to treat idiopathic pulmonary fibrosis. To investigate whether PFD can enhance the penetration and tumor delivery efficiency of Pegylated liposomal doxorubicin (PLD), colorectal cancer xenograft mice were administered PFD, PLD, or combined regimens. As expected, high-dose PFD (H-PFD, 270 mg/kg/day) combined with PLD (H-PFD + PLD) exhibited a significantly higher tumor inhibition rate than PLD monotherapy (75.09% vs. 60.87%). Similarly, the intra-tumoral doxorubicin level was markedly elevated using H-PFD pretreatment, which induced over 34% elevation compared to PLD treatment alone (3.37 ± 0.41 vs. 2.51 ± 0.19 µg/mL). Additionally, Masson's trichrome staining and immunohistochemistry results of the H-PFD + PLD group revealed an attenuation of collagen deposition in vivo, and the in vitro TGF-ß1, α-SMA, and collagen protein expression were inhibited using PFD treatment. In contrast, although low-dose PFD (60 mg/kg/day) did not present superior benefits in promoting PLD penetration into tumors, it did downregulate collagen expression in vivo. This study provides a new strategy for PFD combined with chemotherapeutic drugs to improve the antitumor efficacy of nanomedicines.

Bibliometric analysis of traditional Chinese medicine for smoking cessation.

INTRODUCTION: Smoking cessation is an efficient approach to reducing disease burden. Traditional Chinese Medicine (TCM) therapies such as acupuncture, acupressure, and herbal drugs are often used to help quit smoking. However, there is a lack of overarching bibliometric analysis of the clinical research on smoking cessation focusing on TCM. The aim of our study is to explore the current patterns and trends of TCM therapy for smoking cessation through bibliometric methods with visual presentation. METHODS: This study is an assessment of academic publications retrieved from the Scopus database on smoking cessation using TCM therapy published in the period 2005-2021. Sankey diagram, word-cloud, network analysis, thematic maps, tree-maps, and the collaborative work of authors, institutions and countries, were used to identify research trends on TCM therapy for smoking cessation. The total cited index and H-index (for journals, authors, countries, organizations) were used to identify the trends of worldwide development by R Package and Excel 2016. RESULTS: There was an upward trend, with some fluctuations, of 1908 articles from 2005 to 2021. The most productive country was China. The top institution in this field was Beijing University. The dominant author that contributed to TCM therapy for smoking cessation was Wang Y, who has the highest H-Index. The most productive cited journals were Evidence-Based Complementary and Alternative Medicines and the Chinese Journal of Clinical Rehabilitation. Liu L, (2011, STROKE) had the highest centrality. The keywords 'acupuncture', 'traditional Chinese medicine', 'colitis', 'hypertension', 'chronic obstructive pulmonary disease', 'risk factors' and 'alternative medicine' ranked highest in frequency. The diseases of healthy people concerned mainly cardiovascular, cancer, diabetes, hypertension and pregnancy. The diseases of the patients concerned mainly cancer, diabetes, hematopathy, stroke, cardiovascular, diabetes, lung disease, and hypertension. Treatment methods were mainly traditional Chinese medicine and acupuncture. The research methods mainly included randomized controlled trials that were multi-center and double-blind. CONCLUSIONS: A substantial number of articles on TCM therapy for smoking cessation, mainly focusing on TCM and acupuncture were identified. It is worth noting that research that focused on TCM therapy for smoking cessation also was related to COVID-19.

A multifunctional theranostics nanosystem featuring self-assembly of alcohol-abuse drug and photosensitizers for synergistic cancer therapy.

Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect in vitro and possessed precise spatial delivery to HepG2 cells with the dual-targeting nanocarrier. Intriguingly, a robust anticancer response of chemo-phototherapy was achieved; chemotherapy combined with the efficacy of phototherapy to cause cellular apoptosis of HepG2 cells (>35%) and inhibit the regrowth of damaged cells. Furthermore, the theranostic nanosystem displayed fluorescence imaging in vivo, attributed to its splendid accumulation in the tumor site, and it provided exceptional tumor inhibition rate against liver cancer cells (>76%). Overall, our research presents a promising multifunctional theranostic nanoplatform for the development of synergistic therapeutics for tumors in further applications.

Effect of Volatile Anesthesia Versus Total Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

OBJECTIVES: The purpose of this study was to evaluate the effect of volatile anesthesia and propofol-based total intravenous anesthesia (TIVA) on postoperative pulmonary complications (PPCs) among patients undergoing cardiac surgery. DESIGN: Parallel-group, randomized controlled trial. SETTING: Single-center tertiary care hospital. PARTICIPANTS: Five hundred twenty-four patients undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: The patients were assigned randomly (1:1) to receive anesthesia maintenance with a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days. The PPCs occurred in 118 of 262 patients (45.0%) in the volatile anesthesia group compared with 105 of 262 patients (40.1%) in the propofol-based intravenous anesthesia group (relative risk: 1.17 [95% CI 0.96-1.42], p = 0.123). There were no significant differences in the severity of PPCs within 7 days postoperatively, the occurrence and severity grade of PPCs within 30 days, the incidence of hypoxia, and 30-day mortality. CONCLUSIONS: In adult patients undergoing cardiac surgery with cardiopulmonary bypass, general anesthesia with a volatile anesthetic compared with propofol-based TIVA had not reduced pulmonary complications within the first 7 days after surgery.

Protective Effects and Therapeutics of Ginsenosides for Improving Endothelial Dysfunction: From Therapeutic Potentials, Pharmaceutical Developments to Clinical Trials.

The endothelium covers the internal lumen of the entire circulatory system and plays an important modulatory role in vascular homeostasis. Endothelium dysfunction, characterized by a vasoconstrictive, pro-inflammatory, and pro-coagulant state, usually manifests as a significant pathological process of vascular diseases, including hypertension, atherosclerosis (AS), stroke, diabetes mellitus, coronary artery disease, and cancer. Therefore, there is an urgent necessity to seek promising therapeutic drugs or remedies to ameliorate endothelial dysfunction-induced vascular ailments and complications. Recently, much attention has been attached to ginsenosides, the most significant active components of ginseng, which have always been referred to as "all-healing" and widely used for its extensively medicinal value. Surprisingly, ginsenosides have diverse biological activity which might be related to inflammation, apoptosis, oxidative stress, and angiogenesis. In this review, a brief introduction about endothelial dysfunction and ginsenosides was demonstrated, and the emphasis was put on summarizing multi-faceted pharmacological effects and underlying molecular mechanisms of ginsenosides on the endothelium, including vasorelaxation, anti-oxidation, anti-inflammation, and angio-modulation. Beyond that, nanotechnology to improve efficacy and the existing clinical trials of ginsenosides were concluded. Hopefully, our work will give suggestions for promoting clinical application of traditional Chinese medicine, e.g., hypertension, AS, diabetes, ischemic stroke, and cancer. This review provides a comprehensive base of knowledge for ginsenosides to prevention and treatment of vascular injury- related diseases with clinical significance.

Prognostic impact of pretreatment serum superoxide dismutase activity in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the prognostic effect of pretreatment serum superoxide dismutase (SOD) activity in locoregionally advanced nasopharyngeal carcinoma. METHODS: A total of 498 patients diagnosed with stage III-IVA nasopharyngeal carcinoma between January 2013 and December 2016 were involved in this study. The X-tile program was used to determine the cut-off value of pretreatment serum SOD activity based on disease-free survival. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the impact of serum SOD levels on survival outcomes. The receiver operating characteristic (ROC) curve analysis was used to compare the prognostic value of clinical stage, pretreatment serum SOD level, and the combination of them regarding disease-free survival. RESULTS: Based on the X-tile plot, the optimal cutoff value of pretreatment serum SOD activity for disease-free survival was 146.0U/mL. As a dichotomous variable, SOD was significantly higher in non-keratinizing differentiated disease (P = 0.027) and early T stage (P = 0.011). Compared with the lower subset, higher SOD activity predicted an inferior 3-year rates of overall survival (84.6 vs. 94.7%, P < 0.001), distant metastasis-free survival (78.3 vs. 92.8%, P < 0.001) and disease-free survival (78.2 vs. 92.8%, P < 0.001). Multivariate analysis verified that the SOD activity was an independent prognostic indicator to predict distant metastasis, disease progression, and death. The area under the ROC curve (AUC) of the combination was superior to that of clinical stage or SOD alone for disease-free survival (both P < 0.01). CONCLUSION: Serological SOD activity before treatment is an important prognostic indicator for patients with stage III-IV non-metastatic nasopharyngeal carcinoma undergoing chemoradiation therapy.

Clinical and molecular characteristics of Wiskott-Aldrich Syndrome in five unrelated Chinese families.

Wiskott-Aldrich syndrome (WAS) also called the eczema-thrombocytopenia-immunodeficiency syndrome is a primary immunodeficiency disease with X-linked recessive inheritance caused by mutations in the WAS protein (WASp) gene and characterized by thrombocytopenia with reduced platelet volume, eczema, immunodeficiency, and increased risk of malignant tumours. The mutations will lead to separate WAS severity which can be typical severe 'classical' WAS or less severe 'non-classical' WAS. This article will review and analyse clinical and immune characteristics of five unrelated Chinese families harbouring classical and non-classical WAS. The expression of WASp was detected in the peripheral blood monocytes (PBMC) by flow cytometry, and five mutations were found by WAS gene sequencing, one of which had not been reported in the literature, namely frameshift mutation c.1240_1247delCCACTCCC (p. P414Sfs*41).

ATP-dependent activation of NLRP3 inflammasome in primary murine macrophages infected by pseudorabies virus.

Pseudorabies virus (PRV), an alphaherpesvirus, causes respiratory and reproductive diseases in pigs and severe nervous symptom in other susceptible hosts. Previous studies showed that PRV infection induced a systemic inflammatory response in mice, indicating that pro-inflammatory cytokines participated in viral neuropathy in mice. The pro-inflammatory cytokine IL-1ß is a key mediator of the inflammatory response and plays an important role in host-response to pathogens. However, the secretion of IL-1ß and its relationship with inflammasome activation during PRV infection remains poorly understood. In this study, we found that PRV infection caused significant secretion of several pro-inflammatory cytokines in macrophages and promoted IL-1ß secretion in an ATP-dependent manner. Furthermore, the expression of IL-1ß can be induced by only PRV infection and depended on NF-κB pathway activation, while the subsequent secretion of IL-1ß was mediated by ATP-induced P2 × 7R activation, loss of intracellular K+, and the subsequent NLRP3 inflammasome activation. By using a mouse infection model, we also found that ATP exacerbated clinical signs and death of mice infected by PRV in a NLRP3-dependent manner. These results indicate that ATP facilitates activation of NLRP3 inflammasome and enhances the pathogenicity of PRV in mice during its acute infection.

ATP Facilitates Staphylococcal Enterotoxin O Induced Neutrophil IL-1ß Secretion via NLRP3 Inflammasome Dependent Pathways.

Staphylococcus aureus (S. aureus) is an important zoonotic food-borne pathogen causing severe invasive infections, such as sepsis, pneumonia, food poisoning, toxic shock syndrome and autoimmune diseases. Staphylococcal enterotoxin O (SEO) is a new type of enterotoxins of S. aureus with superantigenic and emetic activity. However, it is still unclear about SEO-induced host inflammatory response. Therefore, the mechanism of SEO-induced interleukin-1ß (IL-1ß) secretion in mouse neutrophils was investigated in this study. Our results showed that recombinant SEO had superantigenic activity with high level of gamma interferon (IFN-γ) production in mouse spleen cells and induced inflammatory cytokines expression including IL-1α, IL-1ß, IL-6 and TNF-α in neutrophils under the action of ATP. In addition, SEO-induced IL-1ß secretion was dependent on activation of Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways. However, SEO-induced IL-1ß secretion was abolished in the neutrophils of NLRP3-/- mice compared with those of wild type mice, indicating that activation of NLRP3 inflammasome mediated IL-1ß secretion during neutrophils stimulation with SEO under the action of ATP. Moreover, this process of SEO+ATP-induced IL-1ß secretion was dependent on potassium (K+) efflux. Taken together, our study suggests that activation of TLR4/JNK/NLRP3 inflammasome signaling pathway mediate maturation and secretion of IL-1ß and provides a new insight on S. aureus virulence factor-induced host immune response.

Expanding the codes: The development of density-encoded hydrogel microcarriers for suspension arrays.

Although suspension array technology (SAT), which uses encoded microspheres, provides high-quality results with versatile applicability for information-intensive bioanalytic applications, current encoding strategies limit the number of codes that can be distinguished. In this paper, we introduce density-encoded hydrogel microcarriers (DMs), which employ the intrinsic density property of biomaterials as a high-capacity coding dimension. Two hydrogel monomers were employed at different ratios to synthesize microgels with distinctive densities. DMs not only can be simultaneously decoded and separated using density gradient centrifugation, but also are compatible with flow cytometry detection. The size and color of DMs have been used as extra coding parameters, to construct an 8 × 2 × 4 (density × size × color) three-dimensionally encoded hydrogel microcarrier library. With aptamer-functionalized DMs (ADMs), we developed a 4-plex protein quantification method for the label-free detection of plasma biomarkers with sub-nanomolar detection limits and good linearities. Moreover, ADMs can be used for label-free naked-eye detection of tumor-derived exosomes. We believe that the simplicity and functionality of DMs will advance the field of suspension arrays and inspire the development of DM-based diagnostic applications.

A smart dual-drug nanosystem based on co-assembly of plant and food-derived natural products for synergistic HCC immunotherapy.

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel "core‒shell" co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and "green" method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells in vitro, good biosafety of organic tissues and efficient tumor accumulation in vivo. Importantly, UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic effect. The research could provide new ideas for the research and development of self-assembly delivery system in the future, and offer effective intervention strategies for clinical HCC treatment.

Insight on structure-property relationships of carrageenan from marine red algal: A review.

Carrageenan (CRG) is a kind of linear sulfated polysaccharide that emerging as a promising substituent in food, pharmaceutics, and cosmetics. In recent years, biological properties of CRG polysaccharides such as antiviral, immunomodulatory, anticoagulant, antioxidant, and anticancer have been broadly studied, however, systematical summary of their structure-property relationships is scarce. Moreover, chemical modification is of great significance to explore biological and physiochemical properties of CRG polysaccharides which should be focused on. Chemical modification of CRG polysaccharides, e.g., carboxymethylation, thiolation, acetylation, phosphorylation, oversulfation, oxidization, and cationic or other derivatives, can improve their bioactivities and facilitate their applications in different biological systems. Hence, this review aims to elucidate structure-property relationships of CRG and its chemically modified derivatives with different structures and bioactivities, so as toxicity of CRG as food additive for the guidance of its clinical application.

Toxic Shock Syndrome Toxin 1 Induces Immune Response via the Activation of NLRP3 Inflammasome.

Staphylococcus aureus is a Gram-positive opportunistic pathogen which causes infections in a variety of vertebrates. Virulence factors are the main pathogenesis of S. aureus as a pathogen, which induce the host's innate and adaptive immune responses. Toxic shock syndrome toxin 1 (TSST-1) is one of the most important virulence factors of S. aureus. However, the role of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) in TSST-1-induced innate immune response is still unclear. Here, purified recombinant TSST-1 (rTSST-1) was prepared and used to stimulate mouse peritoneal macrophages. The results showed that under the action of adenosine-triphosphate (ATP), rTSST-1 significantly induced interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) production in mouse macrophages and the production was dose-dependent. In addition, rTSST-1+ATP-stimulated cytokine production in macrophage depends on the activation of toll like receptor 4 (TLR4), but not TLR2 on the cells. Furthermore, the macrophages of NLRP3-/- mice stimulated with rTSST-1+ATP showed significantly low levels of IL-1ß production compared to that of wild-type mice. These results demonstrated that TSST-1 can induce the expression of inflammatory cytokines in macrophages via the activation of the TLR4 and NLRP3 signaling pathways. Our study provides new information about the mechanism of the TSST-1-inducing host's innate immune responses.

The Prognostic Impact of Combined Tumor-Infiltrating Lymphocytes and Pretreatment Blood Lymphocyte Percentage in Locally Advanced Nasopharyngeal Carcinoma.

PURPOSE: To explore the prognostic impact of combined tumor-infiltrating lymphocytes (TILs) and pretreatment peripheral lymphocyte percentage (LYM%) among patients with locally advanced nasopharyngeal carcinoma (LA-NPC). PATIENTS AND METHODS: TILs and pretreatment LYM% were retrospectively assessed in 253 LA-NPC patients who underwent chemoradiation therapy between January 2012 and December 2017. According to TILs and LYM% status, the patients were divided into three groups: high-risk group (HRG) (TILs-LYM% score = 0), middle-risk group (MRG) (TILs-LYM% score = 1), and low-risk group (LRG) (TILs-LYM% score = 2). The relationship between TILs level and LYM%, and also the associations of TILs-LYM% status with clinicopathological factors and survival, were evaluated. RESULTS: As a continuous variable, LYM% was significantly higher in TILs-high group. High TILs or high LYM% alone was significantly related to better 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS), respectively. Kaplan-Meier analysis and log-rank tests also revealed significant decreases in DFS, OS, DMFS, and LRRFS among LA-NPC patients with TILs-LYM% score of 0, 1, and 2 (all P <0.05). Further multivariate analyses showed that TILs-LYM% score was an independent factor affecting survival of the patients, and HRG (TILs-LYM% score = 0) had increased hazard ratios (HRs) for disease (HR = 6.89, P <0.001), death (HR = 8.08, P = 0.008), distant metastasis (HR = 7.66, P = 0.001), and local relapse (HR = 5.18, P = 0.013) compared with LRG (TILs-LYM% score = 2). In receiver operating characteristics (ROC) analyses, TILs-LYM% score had a higher area under the ROC curve (AUC) for the prediction of DFS than did TILs or LYM% alone. CONCLUSIONS: A positive correlation was found between TILs level and pretreatment blood lymphocyte percentage. Moreover, TILs-LYM% score can be considered as a novel independent prognostic indicator of survival outcome among patients with LA-NPC.

The Effect of Propofol Versus Volatile Anesthetics on Persistent Pain After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: Sternal incisions can generate persistent and intense post-sternotomy pain. Propofol has been shown to improve postoperative analgesia, but the preventive effect on persistent pain after cardiac surgery is unknown. The hypothesis of the present study was that intraoperative propofol-based anesthesia compared with volatile anesthesia could reduce the risk of chronic pain after cardiac surgery. DESIGN: A single-center, two-arm, patient-and-evaluator-blinded, randomized controlled trial. SETTING: A single major urban teaching and university hospital. PATIENTS: Five-hundred adult patients undergoing cardiac surgery via sternotomy randomly were assigned. With six withdrawals from the study and five from surgery, 244 in the total intravenous anesthesia group and 245 in the volatile group were included in the modified intention-to-treat analysis. INTERVENTIONS: Patients randomly were assigned to receive either propofol-based total intravenous anesthesia or volatile anesthesia during surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the incidence of pain at three, six, and 12 months after surgery defined as pain score >0 on the numeric rating scale. The secondary outcomes included acute pain, opioid use during the first 72 hours after surgery, and quality of life. The use of propofol did not significantly affect chronic pain at three months (55.4% v 52.9%, difference 2.5%, 95% confidence interval [CI] -6.6 to 11.6; p = 0.656), six months (35.5% v 37.5%, difference -2.0%, 95% CI -10.9 to 6.9; p = 0.657), or 12 months (18.2% v 20.7%, difference -2.5%, 95% CI -9.8 to 4.8; p = 0.495) compared with volatile anesthetics. Furthermore, there were no differences in acute pain score; morphine-equivalent consumption during the first 72 hours; and quality of life at three, six, and 12 months after surgery. CONCLUSIONS: Intraoperative administration of propofol did not reduce persistent pain after cardiac surgery compared with volatile anesthetics.