Rhodium-Rhenium Alloy Nanozymes for Non-inflammatory Photothermal Therapy.

Analogous to thermal ablation techniques in clinical settings, cell necrosis induced during tumor photothermal therapy (PTT) can provoke an inflammatory response that is detrimental to the treatment of tumors. In this study, we employed a straightforward one-step liquid-phase reduction process to synthesize uniform RhRe nanozymes with an average hydrodynamic size of 41.7 nm for non-inflammatory photothermal therapy. The obtained RhRe nanozymes showed efficient near-infrared (NIR) light absorption for effective PTT, coupled with a remarkable capability to scavenge reactive oxygen species (ROS) for anti-inflammatory treatment. After laser irradiation, the 4T1 tumors were effectively ablated without obvious tumor recurrence within 14 days, along with no obvious increase in pro-inflammatory cytokine levels. Notably, these RhRe nanozymes demonstrated high biocompatibility with normal cells and tissues, both in vitro and in vivo, as evidenced by the lack of significant toxicity in female BALB/c mice treated with 10 mg/kg of RhRe nanozymes over a 14 day period. This research highlights RhRe alloy nanoparticles as bioactive nanozymes for non-inflammatory PTT in tumor therapy.

2D Is Better: Engineering Polydopamine into Cationic Nanosheets to Enhance Anti-Inflammatory Capability.

Polydopamine nanomaterials have emerged as one of the most popular organic materials for the management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfactory because of limited phenolic hydroxyl groups, and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, 2D cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability are reported. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibit three- to fourfold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules are absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms reveal that cationic PDA NSs can concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviate the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid.

The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life.

Radiation-related teeth damage is a common complication in nasopharyngeal carcinoma (NPC) patients undergoing radiotherapy (RT) that seriously affects their oral health-related quality of life (OHRQoL). However, few studies have focused on protecting teeth function. This study aimed to calculate dental dose limits based on OHRQoL. Analysis was performed on 96 NPC patients who received RT (all received routine pre-radiotherapy dental interventions in our department). Based on the General Oral Health Assessment Index (GOHAI), OHRQoL was assigned into poor (<46) and good condition groups (≥46). The binary logistic regression analysis model was used for single-factor and multivariate analyses to identify the independent factors affecting OHRQoL. The cut-off value of dose received by teeth was obtained by drawing a receiver operating characteristic curve. NPC patients experienced a decline in OHRQoL following RT (P < 0.05). Univariate analysis of GOHAI revealed that the average dose of maxillary anterior teeth, the average dose received by the oral cavity, tumor volume (GTVnx), and liking of the sweet food all affected GOHAI (P < 0.05). Multivariate analysis indicated that the average dose of maxillary anterior teeth and liking sweet food were independent factors that influenced the OHRQoL of NPC patients with RT. When the average dose received by maxillary anterior teeth is greater than 28.78 Gy, and there is a tendency in sweet food, the OHRQoL will deteriorate. NPC patients who received RT had a better OHRQoL if the average dose to maxillary anterior teeth was limited to less than 28.78 Gy and the intake of high-sugar foods was reduced.

RIG-I Promotes Tumorigenesis and Confers Radioresistance of Esophageal Squamous Cell Carcinoma by Regulating DUSP6.

We investigated the expression and biological function of retinoic acid inducible gene I (RIG-I) in esophageal squamous cell carcinoma (ESCC). Materials and methods: An immunohistochemical analysis was performed on 86 pairs of tumor tissue and adjacent normal tissue samples of patients with ESCC. We generated RIG-I-overexpressing ESCC cell lines KYSE70 and KYSE450, and RIG-I- knockdown cell lines KYSE150 and KYSE510. Cell viability, migration and invasion, radioresistance, DNA damage, and cell cycle were evaluated using CCK-8, wound-healing and transwell assay, colony formation, immunofluorescence, and flow cytometry and Western blotting, respectively. RNA sequencing was performed to determine the differential gene expression between controls and RIG-I knockdown. Tumor growth and radioresistance were assessed in nude mice using xenograft models. RIG-I expression was higher in ESCC tissues compared with that in matched non-tumor tissues. RIG-I overexpressing cells had a higher proliferation rate than RIG-I knockdown cells. Moreover, the knockdown of RIG-I slowed migration and invasion rates, whereas the overexpression of RIG-I accelerated migration and invasion rates. RIG-I overexpression induced radioresistance and G2/M phase arrest and reduced DNA damage after exposure to ionizing radiations compared with controls; however, it silenced the RIG-I enhanced radiosensitivity and DNA damage, and reduced the G2/M phase arrest. RNA sequencing revealed that the downstream genes DUSP6 and RIG-I had the same biological function; silencing DUSP6 can reduce the radioresistance caused by the overexpression of RIG-I. RIG-I knockdown depleted tumor growth in vivo, and radiation exposure effectively delayed the growth of xenograft tumors compared with the control group. RIG-I enhances the progression and radioresistance of ESCC; therefore, it may be a new potential target for ESCC-targeted therapy.

Renal Clearable Mo-Based Polyoxometalate Nanoclusters: A Promising Radioprotectant against Ionizing Irradiation.

In response to diffused ionizing radiation damage throughout the body caused by nuclear leaks and inaccurate radiotherapy, radioprotectants with considerable free radical scavenging capacities, along with negligible adverse effects, are highly regarded. Herein, unlike being performed as toxic chemotherapeutic drug candidates, molybdenum-based polyoxometalate nanoclusters (Mo-POM NCs) were developed as a non-toxic potent radioprotectant with impressive free radical scavenging capacities for ionizing radiation protection. In comparison to the clinically used radioprotectant drug amifostine (AM), the as-prepared Mo-POM NCs exhibited effective shielding capacity by virtue of their antioxidant properties resulting from a valence shift of molybdenum ions, alleviating not only ionizing radiation-induced DNA damage but also disruption of the radiation-sensitive hematopoietic system. More encouragingly, without trouble with long-term retention in the body, ultra-small sized Mo-POM NCs prepared by the mimetic Folin-Ciocalteu assay can be removed from the body through the renal-urinary pathway and the hepato-enteral excretory system after completing the mission of radiation protection. This work broadened the biological applications of metal-based POM chemotherapeutic drugs to act as a neozoic radioprotectant.

Effect of Oral Nutritional Supplements on Patients with Esophageal Cancer During Radiotherapy.

Background: This study investigated the effect of oral nutritional supplements (ONS) on patients with esophageal cancer during radiotherapy. Materials and Methods: Patients with esophageal cancer undergoing radiotherapy were randomly divided into nutritional intervention (NI) and routine treatment (RT) groups. All patients received one-on-one nutritional counseling and dietary advice, and patients in the NI group received ONS. Body mass index (BMI), a patient-generated subjective global assessment (PG-SGA), serum albumin (ALB), hemoglobin (Hb), white blood cell (WBC) count, prealbumin (PA), and platelets (PLTs) were recorded before and after radiotherapy in both the NI group and the RT group. Further, the adverse reactions during the treatment were evaluated. Results: In the NI group, the BMI after radiotherapy was significantly higher than that before radiotherapy, and the PG-SGA score after radiotherapy was significantly lower than that before radiotherapy (p < 0.05). In the RT group, the levels of BMI, Hb, ALB, PA, PLTs, and WBC after radiotherapy were significantly lower than those before radiotherapy, and the PG-SGA score was worse after radiotherapy (p < 0.05). After radiotherapy, the levels of BMI, Hb, ALB, and PA in the NI group were similar to those in the RT group (p > 0.05); whereas the levels of WBC and PLTs in the NI group were lower than those in the RT group (p < 0.05). During the treatment, the toxic reactions of radiation esophagitis, myelosuppression, nausea, and vomiting were decreased in the NI group compared with the RT group. Conclusions: ONS can reduce weight loss and improve the nutritional status of patients with esophageal cancer during radiotherapy.

Constructing novel molecular subtypes and an 11-gene signature based on pyroptosis signaling for lung adenocarcinoma.

Pyroptosis plays important roles in various cancers. In this study, we focused on lung adenocarcinoma (LUAD) and aimed to develop new molecular subtypes based on pyroptosis signaling. Pyroptosis-related genes were used as a basis to classify molecular subtypes through unsupervised consensus clustering. Gene set enrichment analysis was performed to characterize tumor microenvironment (TME) and functional pathways. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify prognostic genes for establishing a prognostic model. Three molecular subtypes were established with distinct overall survival, TME and enriched pathways. C3 subtype had the longest survival and the highest immune infiltration. 11 prognostic genes were screened to build a prognostic signature for predicting LUAD prognosis. This study emphasized the important role of pyroptosis in LUAD development. Pyroptosis was considered to play critical roles in regulating TME. Moreover, the 11-gene signature could serve as an indicator for predicting LUAD prognosis, and was potential targets for developing targeted drugs.

Upconversion nanoparticles@AgBiS2 core-shell nanoparticles with cancer-cell-specific cytotoxicity for combined photothermal and photodynamic therapy of cancers.

UCNPs@AgBiS2 core-shell nanoparticles that AgBiS2 coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS2 can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS2. The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upconversion emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS2 shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/Nd@NaYF4:Nd@AgBiS2 core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nanostructures for applications such as fighting against cancers.

Diagnostic accuracy of dynamic contrast-enhanced magnetic resonance imaging for distinguishing pseudoprogression from glioma recurrence: a meta-analysis.

BACKGROUND: It is crucial to differentiate accurately glioma recurrence and pseudoprogression which have entirely different prognosis and require different treatment strategies. This study aimed to assess the diagnostic accuracy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a tool for distinguishing glioma recurrence and pseudoprogression. METHODS: According to particular criteria of inclusion and exclusion, related studies up to May 1, 2019, were thoroughly searched from several databases including PubMed, Embase, Cochrane Library, and Chinese biomedical databases. The quality assessment of diagnostic accuracy studies was applied to evaluate the quality of the included studies. By using the "mada" package in R, the heterogeneity, overall sensitivity, specificity, and diagnostic odds ratio were calculated. Moreover, funnel plots were used to visualize and estimate the publication bias in this study. The area under the summary receiver operating characteristic (SROC) curve was computed to display the diagnostic efficiency of DCE-MRI. RESULTS: In the present meta-analysis, a total of 11 studies covering 616 patients were included. The results showed that the pooled sensitivity, specificity, and diagnostic odds ratio were 0.792 (95% confidence interval [CI] 0.707-0.857), 0.779 (95% CI 0.715-0.832), and 16.219 (97.5% CI 9.123-28.833), respectively. The value of the area under the SROC curve was 0.846. In addition, the SROC curve showed high sensitivities (>0.6) and low false positive rates (<0.5) from most of the included studies, which suggest that the results of our study were reliable. Furthermore, the funnel plot suggested the existence of publication bias. CONCLUSIONS: While the DCE-MRI is not the perfect diagnostic tool for distinguishing glioma recurrence and pseudoprogression, it was capable of improving diagnostic accuracy. Hence, further investigations combining DCE-MRI with other imaging modalities are required to establish an efficient diagnostic method for glioma patients.

PEGylated Indium Nanoparticles: A Metallic Contrast Agent for Multiwavelength Photoacoustic Imaging and Second Near-Infrared Photothermal Therapy.

Indium, a low melting point metal, is well-known for constructing eutectic gallium-indium liquid metal. However, unlike liquid metal nanoparticles, the biomedical applications of metallic indium nanoparticles (In NPs) remain in their infancy. Herein, an ultrasound-assisted liquid-reduction synthesis strategy was developed to prepare PEGylated In NPs, which were then used as a high-performance contrast agent for enhancing multiwavelength photoacoustic imaging and second near-infrared (NIR-II) photothermal therapy of the 4T1 breast tumor. The obtained In NPs depicted remarkable optical absorption from the first near-infrared (NIR-I) to NIR-II region and a high photothermal conversion efficiency of 41.3% at 1064 nm, higher than the majority of conventional NIR-II photothermal agents. Upon injection into the tumor, the photoacoustic intensities of the tumor section post-injection were obviously increased by 2.59-, 2.62-, and 4.27-fold of those of pre-injection by using excitation wavelengths of 750, 808, and 970 nm, respectively, depicting an excellent multiwavelength contrast capability of photoacoustic imaging. In addition, efficient ablation of the 4T1 tumor was achieved through the photothermal performance of PEGylated In NPs under NIR-II laser irradiation. Importantly, as the widely used element in the clinic, In NPs were highly biocompatible in vitro and in vivo. Therefore, this work pioneered the biomedical applications of PEGylated In NPs for cancer diagnosis and treatment.

Thermochromic Polyvinyl Alcohol-Iodine Hydrogels with Safe Threshold Temperature for Infectious Wound Healing.

Iodophor (povidone-iodine) has been widely used for antibacterial applications in the clinic. Yet, limited progress in the field of iodine-based bactericides has been achieved since the invention of iodophor. Herein, a blue polyvinyl alcohol-iodine (PAI) complex-based antibacterial hydrogel is explored as a new generation of biocompatible iodine-based bactericides. The obtained PAI hydrogel maintains laser triggered liquefaction, thermochromic, and photothermal features for highly efficient elimination of bacteria. In vitro antibacterial test reveals that the relative bacteria viabilities of Escherichia coli (E.coli) and methicillin-resistant Staphylococcus aureus (MRSA) incubated with PAI hydrogel are only 8% and 3.8%, respectively. Upon single injection of the PAI hydrogel, MRSA-infected open wounds can be efficiently healed in only 5 days, and the healing speed is further accelerated by laser irradiation due to the dynamic interaction between iodine and polyvinyl alcohol, causing up to ∼29% of wound area being closed on day 1. In addition, a safe threshold temperature of skin scald (∼45 °C) emerges for PAI hydrogels because of thermochromic properties, avoiding thermal injuries during irradiation. In addition, no observed toxicity or skin irritation is observed for the PAI hydrogel. This work expands the category of iodine-based bactericides for safe and controllable management of infected wounds.

Screening and bioinformatical analysis of differentially expressed genes in nasopharyngeal carcinoma.

Objective: To identify differentially expressed genes via bioinformatical analysis for nasopharyngeal carcinoma (NPC) and explore potential biomarkers for NPC. Methods: We downloaded the NPC gene expression datasets (GSE40290, GSE53819) and obtained differentially expressed genes (DEGs) via GEO2R. Functional analysis of DEGs was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In order to explore the interaction of DEGs and screen the core genes, we established protein-protein interaction (PPI) network. Then the expression level, prognostic and diagnostic analysis of the core genes in NPC were performed to reveal their potential effects on NPC. Furthermore, we obtained the transcription factors (TF) and microRNAs of core genes to construct the coregulatory network. Results: We obtained 124 up-regulated genes and 190 down-regulated genes in total. These genes were found to be related to signal transduction, extracellular matrix organization and cell adhesion based on GO analysis. KEGG analysis revealed that the NF-kappa B (NF-κB) signaling pathway, pathways in cancer were mainly enriched signaling pathways. 25 core genes were obtained by constructing PPI network. Then the high expression of 10 core genes in NPC were verified via GEPIA, Oncomine databases and laboratory experiments. The TF-microRNA coregulatory network of the 10 core genes was built. Survival and diagnostic analysis indicated that SPP1 had negative influence on the prognosis of NPC patients based on two datasets and nine up-regulated core genes (FN1, MMP1, MMP3, PLAU, PLAUR, SERPINE1, SPP1, COL8A1, COL10A1) might be diagnostic markers for NPC. Conclusions: Core genes of NPC were screened out by bioinformatical analysis in the present study and these genes may serve as prognostic and diagnostic biomarkers for NPC.

Prognostic Value of the Albumin-to-Alkaline Phosphatase Ratio before Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma.

INTRODUCTION: The aim of this study was to evaluate the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) in patients with nonmetastatic nasopharyngeal carcinoma (NPC). METHODS: Patients with nonmetastatic NPC who underwent chemoradiotherapy (CRT) were retrospectively analyzed. The AAPR was calculated using the last value of albumin to alkaline phosphatase that was measured within 1 week before CRT. The optimal cutoff value for the AAPR value was determined by an X-tile plot. Propensity score matching (PSM) was performed to balance the differences of the baseline characteristics. The Kaplan-Meier method and log-rank test were used to calculate the survival. A Cox proportional hazards regression model was conducted for the multivariate analysis. RESULTS: Totally, 87 patients with nonmetastatic NPC who underwent CRT were included in the analysis. The optimal cutoff level for the AAPR was 0.46. The group with an AAPR ≤0.46 was more likely to have poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (p = 0.023, p = 0.031 and p = 0.027, for OS, PFS, and DMFS, respectively). In Cox proportional hazards analysis, high AAPR was a better prognostic predictor. CONCLUSION: AAPR may be a reliable prognostic index for nonmetastatic NPC patients.

Impact of the 2019 Novel Coronavirus Disease (COVID-19) Epidemic on Radiotherapy-Treated Patients with Cancer: A Single-Center Descriptive Study.

INTRODUCTION: The present study investigated hospitalization data of patients receiving radiotherapy at Anhui Cancer Hospital during the COVID-19 epidemic and analyzed the impact of the epidemic on the clinical data of radiotherapy patients to provide references for the feasibility and safety of radiotherapy at other medical institutions. METHODS: The present study performed a retrospective analysis of hospitalization data of patients undergoing radiotherapy at the Radiation Department (from January 5 to March 19, 2020 according to the Chinese lunar calendar), who were defined as the epidemic group. Hospitalization data for patients undergoing radiotherapy during the same period in 2019 were used as the control group for comparison with the epidemic group in terms of sex, age, distribution of various cancer types, hospitalization costs, average length of stay, completion rate of radiotherapy, treatment mode, and purpose of radiotherapy. RESULTS: A total of 79 and 115 patients received radiotherapy in the epidemic group and control group, respectively. The number of patients who received radiotherapy declined 31.3% during the epidemic period. The number of head and neck cancer patients who received radiotherapy was 36 (45.57%) in the epidemic group and 32 (27.83%) in the control group, which was a significant difference (χ2 =6.476, P=0.011). The proportions of patients with other types of cancer decreased, with no significant difference between the two groups (P>0.05). No significant differences between the two groups were found in terms of other hospitalization data (P>0.05). CONCLUSION: The total number of patients who received radiotherapy decreased during the epidemic period, but the proportion of head and neck cancer increased. The epidemic had no significant effect on other hospitalization data. While strengthening prevention and control measures, we should actively perform radiotherapy to ensure that cancer patients receive timely and safe treatment.

MiR-20a-5p promotes radio-resistance by targeting NPAS2 in nasopharyngeal cancer cells.

MicroRNAs (miRNAs) are key players of gene expression involved in diverse biological processes including the cancer radio-resistance, which hinders the effective cancer therapy. Here we found that the miR-20a-5p level is significantly up-regulated in radio-resistant nasopharyngeal cancer (NPC) cells via an RNA-seq and miR-omic analysis. Moreover, we identified that the neuronal PAS domain protein 2 (NPAS2) gene is one of the targets of miR-20a-5p. The involvement of miR-20a-5p and NPAS2 with NPC radio-resistance was further validated by either down- or up-regulation of their levels in NPC cell lines. Taken together, these results not only reveal novel insights into the NPC radio-resistance, but also provide hints for an effective therapeutic strategy to fight against NPC radio-resistance.

Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2-4) and minimum reaction (grades 0-1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients.