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Abstract The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.

Summary: Background: The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape. Methods: This retrospective multicenter study enrolled 6315 patients with nonmetastatic NPC from nonendemic and endemic regions of China from 2007 to 2020. We applied mixture and nonmixture cure models to estimate the cure probabilities and cure times by incorporating background mortality for the general population, matching by gender, age, and diagnosed year. Findings: With death as the uncured event, the probability of patients with NPC achieving a life expectancy at par with the general population was 78.1%. Considering progression as the uncured event, the likelihood of patients attaining a life expectancy without progression equivalent to that of the general population was 72.4%. For individuals, the probabilities of achieving cure were conditional and time-dependent, requiring approximately 7.1 and 4.7 years with 95% certainty, respectively. The corresponding cure times for uncured patients were 8.9 and 6.8 years, respectively. The cure probability was correlated with age, Eastern Cooperative Oncology Group score, TNM staging, Epstein–Barr virus DNA copies, and lactate dehydrogenase. The correlation was excellent between 5-year overall survival/progression-free survival and cure fractions. Interpretation: Statistical cure is potentially achievable among patients with NPC undergoing contemporary treatment modalities. The results hold significant potential implications for both clinical practice and patient perspectives. Funding: National High Level Hospital Clinical Research Funding; Beijing Xisike Clinical Oncology Research Foundation; Beijing hope run fund.

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron‐dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron‐induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Abstract Purpose To explore the feasibility of individualized elective prophylactic neck irradiation (iEPNI) for optimizing current approach by investigating metastatic lymph nodes (LNs) distribution in nasopharyngeal carcinoma (NPC). Materials and Methods Records of 870 NPC patients without distant metastasis in Hunan Cancer Hospital from January 2019 to December 2019 were reviewed. LNs' locations were identified based on the 2013 guidelines. The intra‐regional lymphatic drainage (IRLD) areas included Station 1st (level VIIa and II), Station 2nd (level III and Va), and Station 3rd (level IV, Vb, and Vc). Other levels were categorized as extra‐regional areas. Results Among the 870 patients, 94.5% cases exhibited LNs metastasis, including unilateral metastasis in 198 patients and bilateral metastasis in 624 patients. In the whole cohort, the most common involved IRLD areas were level IIb (87.1%), VIIa (80.0%), IIa (61.8%), Va (30.6%), IV (21.4%), Vb (8.9%), and Vc (1.1%). Besides, rates of LNs metastasis in Station 1st, 2nd, and 3rd were 94.3%, 61.1%, and 22.9%, respectively. Only four patients (4, 0.5%) revealed skipping metastasis among the three stations. Conclusions Lymph node metastasis follows an organized pattern from Station 1st to 3rd with scarce skipping metastasis. A potential iEPNI strategy of prophylactic neck irradiation to the ipsilateral latter node‐negative station appears promising in NPC patients. Further prospective investigations are warranted to validate the approach.

Abstract Background Current radiotherapy guidelines and consensus statements uniformly recommend elective region irradiation (ERI) as the standard strategy for nasopharyngeal carcinoma (NPC). However, given the scarcity of skip-metastasis, the improved assessment accuracy of nodal involvement, and the striking advancements in chemotherapy for NPC, a one-fits-all delineation scheme for clinical target volumes of the nodal region (CTVn) may not be appropriate anymore, and modifications of the CTVn delineation strategy may be warranted. Involved site irradiation (ISI) covering merely the initially involved nodal site and potential extranodal extension has been confirmed to be as effective as ERI with decreased radiation-related toxicities in some malignancies, but has not yet been investigated in NPC. This study aims to compare the regional control, survival outcomes, radiation-related toxicities, and quality of life (QoL) of ISI with conventional ERI in NPC patients with a limited nodal burden. Methods ISRT-NPC is a prospective, multicenter, open-label, noninferiority, phase III randomized controlled trial. A total of 414 patients will be randomly assigned in a 1:1 ratio to receive ISI or ERI. Randomization will be stratified by institution scale and N stage. Generally, in the ISI group, the high-risk CTV1 (dose: 60 Gy) includes a 1-cm expansion of the positive LN as well as the VIIa and the retrostyloid space above the bilateral transverse process of the atlantoaxial spine (C1), regardless of N status. The low-risk CTV2 (dose: 50 Gy) covers the cervical nodal region with a 3-cm caudal expansion below the transverse process of C1 for N0 disease and a 3-cm expansion below the positive LN for positive LNs. Discussion The results of this trial are expected to confirm that ISI is a non-inferior strategy to ERI in stage I-III patients with low LN burden, enabling the minimization of treatment-related toxicity and improvement of long-term QoL without compromising regional control. Trial registration ClinicalTrails.gov, NCT05145660. Registered December 6, 2021.

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

Abstract Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

Abstract Prohibitins (PHBs) are a class of highly evolutionarily conserved proteins that widely distribute in prokaryotes and eukaryotes. PHBs function in cell growth and proliferation or differentiation, regulating metabolism and signaling pathways. PHBs have different subcellular localization in eukaryotes, but they are mainly located in mitochondria. In the mitochondria, PHBs stabilize the structure of the mitochondrial membrane and regulate mitochondrial autophagy, mitochondrial dynamics, mitochondrial biogenesis and quality control, and mitochondrial unfolded protein response. PHBs has shown to be associated with many diseases, such as mitochondria diseases, cancers, infectious diseases, and so on. Some molecule targets of PHBs can interfere with the occurrence and development of diseases. Therefore, this review clarifies the functions of PHBs in mitochondria, and provides a summary of the potential values in clinics.

Organoids are a class of multicellular structures with the capability of self-organizing and the characteristic of original tissues, they are generated from stem cells in 3D culture in vitro. Organoids can mimic the occurrence and progression of original tissues and widely used in disease models in recent years. The ability of tumor organoids to retain characteristic of original tumors make them unique for tumorigenesis and cancer therapy. However, the history of organoid development and the application of organoid technology in cancer therapy are not well understood. In this paper, we reviewed the history of organoids development, the culture methods of tumor organoids establishing and the applications of organoids in cancer research for better understanding the process of tumor development and providing better strategies for cancer therapy. The standardization of organoids cultivation facilitated the large-scale production of tumor organoids. Moreover, it was found that combination of tumor organoids and other cells such as immune cells, fibroblasts and nervous cells would better mimic the microenvironment of tumor progression. This might be important developing directions for tumor organoids in the future.

The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3′ UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.

Abstract Background To summarize the characteristics of local invasion and distribution of metastatic lymph nodes in unilateral nasopharyngeal carcinoma (NPC) by magnetic resonance imaging (MRI) to provide references for the optimization of clinical target volume. Methods MRI and clinical data of 176 cases of unilateral NPC admitted to the Hunan Cancer Hospital from January 2019 to December 2019 were collected. Unilateral NPC was defined as a lesion confined to the one side of the nasopharynx and had not exceeded the midline as judged by MRI. Results Ipsilateral levator veli muscle (63.1%, 111/176), tensor veli palatini muscle (55.7%, 98/176), parapharyngeal space (50.0%, 88/176), and prevertebral muscle (43.7%, 77/176) were more likely to be invaded. Contralateral parapharyngeal space and skull base foramina were not invaded. All local invasions presented as continuous invasion from gross lesions and discontinuous invasions were not observed. The overall lymph node metastatic rate was 89.8% (158/176), of which bilateral metastasis accounted for 56.3% (89/158), and ipsilateral metastasis accounted for 88.1% (155/176), which was higher than the contralateral metastatic rate (55.4%, 94/176) (P

Abstract Background Postpartum depression (PPD) is a common complication of cesarean section. S-ketamine given intravenously during surgery can help prevent PPD. However, whether S-ketamine in patient-controlled intravenous analgesia (PCIA) can reduce the incidence of PPD is unknown. This study assessed the effect of S-ketamine as an adjuvant in PCIA for preventing PPD in women undergoing cesarean delivery. Methods A total of 375 parturients scheduled to undergo cesarean section and then receive PCIA were recruited from a single center and were randomly assigned to control (C) group (sufentanil 2 μg/kg + tropisetron 10 mg) or S-ketamine (S) group (S-ketamine 0.5 mg/kg + sufentanil 2 μg/kg + tropisetron 10 mg). The primary outcome was the incidence of PPD measured by the Edinburgh postnatal depression scale (EPDS) after surgery. The secondary outcomes were EPDS scores, visual analog scale (VAS) scores, Ramsay sedation scale (RSS) scores, and the rate of adverse events, including headache, nausea, dizziness, drowsiness, and vomit. Results A total of 275 puerperal women were included in the study. The rate of depression in parturient on postoperative days 3, 14, 28 in the C group and S group were 17.6 and 8.2% (p

For artificial snowfall, snow particle size can have a direct impact on snow quality. The operating conditions of the snow-makers and environmental factors will influence the atomization and crystallization processes of artificial snow making, which consequently affect snow particle size. This paper investigates the size distribution of snow particles during artificial snow making under different operating conditions and environmental parameters. For this purpose, an environmental chamber is designed and structured. The laser scattering method was used to measure the size distribution of snow under different parameters in the room. The results show that the distribution of snow crystal particle size aligns closely with the Rosin–Rammler (R-R) distribution. The higher the height of the snowfall, the longer the snow crystals grow and the larger the snow crystal particle size. It has been found that a higher air pressure favors atomization, while the opposite is true for water pressure, which results in a higher air–water pressure ratio, producing smaller snow particle sizes. Additionally, an ambient temperature in the range of −5 °C to −15 °C contributes to the snow crystal form transforming from plates to columns and then back to plates; the snow particle size first decreases and then increases. Snow crystal particles at −10 °C have the smallest size. Outdoor snow-makers should be operated at the highest possible air–water pressure ratio and snow height, and at a suitable ambient temperature.

Tripartite motif-containing 28 (TRIM28) belongs to tripartite motif (TRIM) family. TRIM28 not only binds and degrades its downstream target, but also acts as a transcription co-factor to inhibit gene expression. More and more studies have shown that TRIM28 plays a vital role in tumor genesis and progression. Here, we reviewed the role of TRIM28 in tumor proliferation, migration, invasion and cell death. Moreover, we also summarized the important role of TRIM28 in tumor stemness sustainability and immune regulation. Because of the importance of TRIM28 in tumors, TIRM28 may be a candidate target for anti-tumor therapy and play an important role in tumor diagnosis and treatment in the future.

Background: Ferroptosis is a newly proposed concept of programmed cell death and has been widely studied in many diseases during the past decade. However, a bibliometric study that concentrates on publication outputs and research trends of ferroptosis related to the brain is lacking.Methods: We retrieved publication data in the field of ferroptosis in the brain from the Web of Science Core Collection on 31 December 2021. A bibliometric analysis was performed using VOSviewer and CiteSpace software.Results: Six hundred fifty-six documents focusing on ferroptosis in the brain were published from 2012 to 2021. The number of publications in this field has shown a steady increase in recent years. Most publications were from China (338) and the United States (166), while the most productive organizations were at the University of Melbourne (34) and University of Pittsburgh (23). Ashley I. Bush was the most productive author, while Scott J Dixon was the most co-cited author. The journal Free Radical Biology and Medicine published the most articles in this field, while Cell was the most cited journal. Among 656 publications, top 10 cited documents were cited at least 300 times. Among the top 20 references with the strongest citation bursts, half of the papers had a burst until 2021. The keywords analysis suggests that the top 20 keywords appeared at least 40 times. Additionally, “amyloid precursor protein” was the keyword with strongest bursts.Conclusion: Research on ferroptosis in the brain will continue to be highly regarded. This study analyzed the research landscape of ferroptosis in the brain and offers a new reference for researchers in this field.

BackgroundHigh flow nasal cannula is gaining increasingly used in patients undergoing endoscopic procedures. We undertook this systematic review and meta-analysis to determine whether high flow nasal cannula (HFNC) could effectively minimize the risk of hypoxemia as compared with conventional oxygen therapy (COT).MethodsWe performed a comprehensive search of Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science. Studies involving the application of HFNC during endoscopic procedures were identified.ResultsWe included 15 randomized controlled trials (7 bronchoscopy, 8 gastrointestinal endoscopy). Patients receiving HFNC during endoscopic procedures had a significantly lower risk of hypoxemia (defined as SpO2

Abstract The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE2, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

ObjectiveThis study aims to identify clinically relevant diagnostic biomarkers in chronic obstructive pulmonary disease (COPD) while exploring how immune cell infiltration contributes towards COPD pathogenesis.MethodsThe GEO database provided two human COPD gene expression datasets (GSE38974 and GSE76925; n=134) along with the relevant controls (n=49) for differentially expressed gene (DEG) analyses. Candidate biomarkers were identified using the support vector machine recursive feature elimination (SVM-RFE) analysis and the LASSO regression model. The discriminatory ability was determined using the area under the receiver operating characteristic curve (AUC) values. These candidate biomarkers were characterized in the GSE106986 dataset (14 COPD patients and 5 controls) in terms of their respective diagnostic values and expression levels. The CIBERSORT program was used to estimate patterns of tissue infiltration of 22 types of immune cells. Furthermore, the in vivo and in vitro model of COPD was established using cigarette smoke extract (CSE) to validated the bioinformatics results.Results80 genes were identified via DEG analysis that were primarily involved in cellular amino acid and metabolic processes, regulation of telomerase activity and phagocytosis, antigen processing and MHC class I-mediated peptide antigen presentation, and other biological processes. LASSO and SVM-RFE were used to further characterize the candidate diagnostic markers for COPD, SLC27A3, and STAU1. SLC27A3 and STAU1 were found to be diagnostic markers of COPD in the metadata cohort (AUC=0.734, AUC=0.745). Their relevance in COPD were validated in the GSE106986 dataset (AUC=0.900 AUC=0.971). Subsequent analysis of immune cell infiltration discovered an association between SLC27A3 and STAU1 with resting NK cells, plasma cells, eosinophils, activated mast cells, memory B cells, CD8+, CD4+, and helper follicular T-cells. The expressions of SLC27A3 and STAU1 were upregulated in COPD models both in vivo and in vitro. Immune infiltration activation was observed in COPD models, accompanied by the enhanced expression of SLC27A3 and STAU1. Whereas, the knockdown of SLC27A3 or STAU1 attenuated the effect of CSE on BEAS-2B cells.ConclusionSTUA1 and SLC27A3 are valuable diagnostic biomarkers of COPD. COPD pathogenesis is heavily influenced by patterns of immune cell infiltration. This study provides a molecular biology insight into COPD occurrence and in exploring new therapeutic means useful in COPD.

Genomic selection in plants and animals has become a standard tool for breeding because of the advantages of high accuracy and short generation intervals. Implementation of this technology is hindered by the high cost of genotyping and other factors. The aim of this study was to determine an optional marker density panel and reference population size for using genomic selection of goats, with speculation on the number of QTLs that affect the important economic traits of goats. In addition, the effect of buck population size in the reference population on the accuracy of genomic estimated breeding value (GEBV) was discussed. Based on the previous genetic evaluation results of Inner Mongolia White Cashmere Goats, live body weight (LBW, h2 = 0.11) and fiber diameter (FD, h2 = 0.34) were chosen to perform genomic selection in this study. Reasonable genome parameters and generation transmission processes were set, and phenotypic and genotype data of the two traits were simulated. Then, different sizes of the reference population and validation population were selected from progeny. The GEBVs were obtained by six methods, including GBLUP (Genomic Best Linear Unbiased Prediction), ssGBLUP (Single Step Genomic Best Linear Unbiased Prediction), BayesA, BayesB, Bayesian ridge regression, and Bayesian LASSO. The correlation coefficient between the predicted and realized phenotypes from simulation was calculated and used as a measure of the accuracy of GEBV in each trait. The results showed that the medium marker density Panel (45 K) could be used for genomic selection in goats, which can ensure the accuracy of the GEBV. The reference population size of 1,500 can achieve greater genetic progress in genomic selection for fiber diameter and live body weight in goats by comparing with the population size below this level. The accuracy of the GEBV for live body weight and fiber diameter was better when the number of QTLs was 100 and 50, respectively. Additionally, the accuracy of GEBV was discovered to be good when the buck population size was up to 200. Meanwhile, the accuracy of the GEBV for medium heritability traits (FDs) was found to be higher than the accuracy of the GEBV for low heritability traits (LBWs). These findings will provide theoretical guidance for genomic selection in goats by using real data.

Abstract The correct folding is a key process for a protein to acquire its functional structure and conformation. Prefoldin is a well-known chaperone protein that regulates the correct folding of proteins. Prefoldin plays a crucial role in the pathogenesis of common neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). The important role of prefoldin in emerging fields (such as nanoparticles, biomaterials) and tumors has attracted widespread attention. Also, each of the prefoldin subunits has different and independent functions from the prefoldin complex. It has abnormal expression in different tumors and plays an important role in tumorigenesis and development, especially c-Myc binding protein MM-1. MM-1 can inhibit the activity of c-Myc through various mechanisms to regulate tumor growth. Therefore, an in-depth analysis of the complex functions of prefoldin and their subunits is helpful to understand the mechanisms of protein misfolding and the pathogenesis of diseases caused by misfolded aggregation.

Abstract Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

IntroductionAn optimal approach to define tumor volume in locoregionally advanced nasopharyngeal carcinoma (NPC) using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) remains unclear. This retrospective study aimed at comparing the outcomes and toxicities of different FDG-PET/CT-guided techniques for primary tumor volume delineation in locoregionally advanced NPC.MethodsFrom August 2015 to February 2018, 292 patients with stage III-IVB NPC received FDG-PET/CT-guided IMRT. Three PET/CT-based techniques were used to determine the gross tumor volume (GTV) as follows: visual criteria (group A; n = 98), a standard uptake value (SUV) threshold of 2.5 (group B; n = 95), and a threshold of 50% maximal intensity (group C, n = 99) combined with a dose-painting technique.ResultsIn groups A, B, and C, the 5-year LRFS rates were 89.4%, 90.0%, and 97.8%, respectively (p = 0.043). The 5-year DMFS rates were 75.1%, 76.0%, and 87.7%, respectively (p = 0.043). The 5-year DFS rates were 70.9%, 70.3%, and 82.2%, respectively (p = 0.048). The 5-year OS rates were 73.5%, 73.9%, and 84.9%, respectively (p = 0.038). Group C showed significantly higher 5-year LRFS, LRRFS, DMFS, DFS, and OS than those in groups A and B (p < 0.05). No statistically significant differences were observed between the three study groups in the cumulative incidences of grade 3-4 acute and late toxicities. Multivariate analyses showed that the PET/CT-guided technique for target volume delineation was an independent prognostic factor for 5-year LRFS, DFS, DMFS, and OS (p = 0.039, p = 0.030, p = 0.035 and p = 0.028, respectively), and was marginally significant in predicting LRRFS (p = 0.080).ConclusionsThe 50% SUVmax threshold regimen for GTV delineation with dose-painting appeared to be superior to the visual criteria or SUV2.5 threshold in locoregionally advanced NPC, and there was no increased toxicity.

Background: Emergence delirium (ED) usually occurs in children after surgery with an incidence of 10−80%. Though ED is mostly self-limited, its potential injuries cannot be ignored. Whether electroencephalography (EEG)-parameter-guided anesthesia could reduce the incidence of ED in pediatric surgery has not been fully discussed to date. Methods: Fifty-four boys aged 2–12 years undergoing elective hypospadias surgery under sevoflurane anesthesia were selected. In the EEG-parameter-guided group (E group), sevoflurane was used for anesthesia induction and was maintained by titrating the spectral edge frequency (SEF) to 10–15 and combining the monitoring of density spectral array (DSA) power spectra and raw EEG. While in the control group (C group), anesthesiologists were blinded to the SedLine screen (including SEF, DSA, and raw EEG) and adjusted the intraoperative drug usage according to their experience. Patients with a Pediatric Anesthesia Emergence Delirium (PAED) score > 10 were diagnosed with ED, while patients with a PAED score > 2 were diagnosed with emergence agitation (EA). Results: Finally, a total of 37 patients were included in this trial. The incidence of ED in the E group was lower than in the C group (5.6% vs. 36.8%; p = 0.04), while the incidence of EA was similar in the two groups (61% vs. 78.9%; p = 0.48). Intraoperative parameters including remifentanil dosage and the decrease in mean arterial pressure (MAP) were not different between the two groups (p > 0.05), but the mean end-tidal sevoflurane concentration (EtSevo) was lower in the E group than in the C group (p > 0.05). Moreover, during PACU stay, the extubation time and discharge time of the groups were similar, while the PAED scores within 5 min from extubation and the Face, Legs, Activity, Cry, and Consolability (FLACC) scores within 30 min from extubation were lower in the E group than in the C group. Conclusion: EEG-parameter-guided anesthesia management reduced the incidence of ED in children. Studies with larger sample sizes are needed to obtain more convincing results.

RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

Abstract Reprogramming of cancer metabolism is a newly recognized hallmark of malignancy. The aberrant glucose metabolism is associated with dramatically increased bioenergetics, biosynthetic, and redox demands, which is vital to maintain rapid cell proliferation, tumor progression, and resistance to chemotherapy and radiation. When the glucose metabolism of cancer is rewiring, the characters of cancer will also occur corresponding changes to regulate the chemo- and radio-resistance of cancer. The procedure is involved in the alteration of many activities, such as the aberrant DNA repairing, enhanced autophagy, oxygen-deficient environment, and increasing exosomes secretions, etc. Targeting altered metabolic pathways related with the glucose metabolism has become a promising anti-cancer strategy. This review summarizes recent progress in our understanding of glucose metabolism in chemo- and radio-resistance malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.

Micro/nanorobots are functional devices in microns, at nanoscale, which enable efficient propulsion through chemical reactions or external physical field, including ultrasonic, optical, magnetic, and other external fields, as well as microorganisms. Compared with traditional robots, micro/nanorobots can perform various tasks on the micro/nanoscale, which has the advantages of high precision, strong flexibility, and wide adaptability. In addition, such robots can also perform tasks in a cluster manner. The design and development of micro/nanorobots and the integration of surface functionalization, remote drive system, and imaging tracking technology will become a key step for their medical applications in organisms. Thus, micro/nanorobots are expected to achieve more efficient and accurate local diagnosis and treatment, and they have broad application prospects in the biomedical field. This paper aims to introduce relevant driving methods of micro/nanorobots preparation in detail, summarizes the progress of research in medical applications, and discusses the challenges it faces in clinical applications and the future direction of development.

A cost-effective, simple, flexible, reproducible electrochemiluminescence (ECL) sensor is a prerequisite for the development of possible foldable sensing devices. Herein, a three-dimensional (3D) flexible electrochemiluminescence (ECL) sensor was fabricated based on a porous graphene paper electrode (GPE) with high specific surface area, excellent conductivity and a wide electrochemical potential window. The 3D GPE was fabricated by a simple tape stripping method. It keeps its original appearance after stripping five times, and retains good electrochemical characteristics after folding 200 times. Tripropylamine was used as a representative ECL coreactant to evaluate the proposed sensor, which showed a linear relationship in the concentration range between 5 nM and 1 mM and a low detection limit of 2.8 nM (S/N ≥ 3). It also exhibited excellent reproducibility and long-term stability. Importantly, this electrode could also be used for analysis of the drug lidocaine in human serum, achieving a wide detection range of 10 nM–10 mM and a low detection limit of 7.8 nM (S/N ≥ 3). The proposed 3D GPE was thus shown to be advantageous in terms of simple operation, foldability, and applicability compared with most previous ECL sensors.

Radiation therapy is a common and acceptable approach for lung cancer. Although the benefit of ionizing radiation (IR) is well-established, cancer cells can still survive via pro-survival and metastasis signaling pathways. Ras related C3 botulinum toxin substrate1 (RAC1), a member of Rho family GTPases, plays important roles in cell migration and survival. In the present study, we investigated the effects of RAC1 on the survival of lung cancer cells treated with irradiation. The results showed RAC1 is overexpressed in lung cancer cells and promoted cell proliferation and survival. Furthermore, IR induced RAC1 expression and activity via the activation of PI3K/AKT signaling pathway, and then enhancing cell proliferation, survival, migration and metastasis and increasing levels of epithelial-to-mesenchymal transition (EMT) markers, which facilitated the cell survival and invasive phenotypes. In addition, overexpression of RAC1 attenuated the efficacy of irradiation, while inhibition of RAC1 enhanced sensitivity of irradiation in xenograft tumors in vivo. Collectively, we further found that RAC1 enhanced radioresistance by promoting EMT via targeting the PAK1-LIMK1-Cofilins signaling in lung cancer. Our finding provides the evidences to explore RAC1 as a therapeutic target for radioresistant lung cancer cells.

A fundamental ability for humans is to monitor and process multiple temporal events that occur at different spatial locations simultaneously. A great number of studies have demonstrated simultaneous temporal processing (STP) in human and animal participants, i.e., multiple 'clocks' rather than a single 'clock'. However, to date, we still have no knowledge about the exact limitation of the STP in vision. Here we provide the first experimental measurement to this critical parameter in human vision by using two novel and complementary paradigms. The first paradigm combines merits of a temporal oddball-detection task and a capacity measurement widely used in the studies of visual working memory to quantify the capacity of STP (CSTP). The second paradigm uses a two-interval temporal comparison task with various encoded spatial locations involved in the standard temporal intervals to rule out an alternative, 'object individuation'-based, account of CSTP, which is measured by the first paradigm. Our results of both paradigms indicate consistently that the capacity limit of simultaneous temporal processing in vision is around 3 to 4 spatial locations. Moreover, the binding of the 'local clock' and its specific location is undermined by bottom-up competition of spatial attention, indicating that the time-space binding is resource-consuming. Our finding that the capacity of STP is not constrained by the capacity of visual working memory (VWM) supports the idea that the representations of STP are likely stored and operated in units different from those of VWM. A second paradigm confirms further that the limited number of location-bound 'local clocks' are activated and maintained during a time window of several hundreds milliseconds.