LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein.

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.

Immunotherapy with programmed cell death 1 ligand 1 (PD-L1) blockade was effective in patients with NK/T-cell lymphoma. In addition to PD-L1, indoleamine 2,3-dioxygenase-1 (IDO1) is one of the most promising immunotherapeutic targets. High proportions of PD-L1 and IDO1 proteins were observed by immunohistochemistry (IHC) from 230 newly diagnosed patients with NK/T lymphoma with tissue samples from three cancer centers and were associated with poor overall survival (OS) in patients with NK/T lymphoma. Importantly, the coexpression of PD-L1 and IDO1 was related to poor OS and short restricted mean survival time in patients with NK/T lymphoma and was an independent prognostic factor in the training cohorts, and which was also validated in 58 NK/T lymphoma patients (GSE90597). Moreover, a nomogram model constructed with PD-L1 and IDO1 expression together with age could provide concise and precise predictions of OS rates and median survival time. The high-risk group in the nomogram model had a positive correlation with CD4 + T-cell infiltration in the validation cohort, as did the immunosuppressive factor level. Therefore, high PD-L1 and IDO1 expression was associated with poor OS in patients with NK/T lymphoma. PD-L1 and IDO1 might be potential targets for future immune checkpoint blockade (ICB) therapy for NK/T lymphoma.

Association between remnant cholesterol and metabolic dysfunction-associated steatotic liver disease in the elderly.

BACKGROUND & AIMS: Whether maintaining optimal remnant cholesterol (RC) levels later in life may improve metabolic dysfunction-associated steatotic liver disease (MASLD) outcomes remained ambiguous. This study aimed to investigate the relationship between RC and MASLD in the elderly Chinese population. METHODS: A total of 131,868 subjects aged ≥ 65 years were included in this study. The association of RC with MASLD, and severity of MASLD was analyzed by logistic regression. In addition, stratified analysis was conducted to test the potential interaction. RESULTS: MASLD prevalence and RC concentration decreased with age. After adjustment for possible confounders, the odds ratio of MASLD at the highest quartile of RC compared to the lowest quartile was 1.587(95% CI: 1.524-1.652), and this effect remained in MASLD with liver fibrosis. Stratified analysis showed a more prominent effect on the MASLD in males, those aged 65-69 years, those without central obesity, those with diabetes, and normal level of total cholesterol, low-density lipoprotein cholesterol (Pfor interaction<0.05). CONCLUSIONS: In the elderly subset of the Chinese population, higher RC levels achieved a significant risk effect against MASLD. More RC monitoring should be given to older for the prevention and intervention of MASLD.

Diagnosis value of the blood urea nitrogen to creatinine ratio in determining the need for intervention of acute upper gastrointestinal bleeding.

INTRODUCTION: The blood urea nitrogen (BUN) to creatinine (Cr) ratio (BUN/Cr ratio) may be used to evaluate the need for intervention of acute upper gastrointestinal bleeding (AUGIB). This study aimed to explore the predictive value of the BUN/Cr ratio in the need for intervention of AUGIB. METHODS: This retrospective observational study included patients with AUGIB in the hospital's emergency department between August 2019 and May 2023. The patients were grouped according to whether they underwent an intervention for AUGIB. Patients treated between August 2019 and May 2022 were selected as the training set and the others as the validation set. RESULTS: A total of 466 patients (328 males, 138 females) with AUGIB were enrolled in the intervention group (n=167) and the no-intervention group (n=299). In the training set, multivariable logistic regression showed that the BUN/Cr ratio (OR: 1.013, 95%CI: 1.003-1.023, P=0.009), hemoglobin (OR: 0.989, 95%CI: 0.981-0.997, P=0.010), and a previous history of esophageal variceal bleeding (OR: 6.898, 95%CI: 3.989-11.929, P<0.001) were independently associated with intervention for AUGIB. The area under receiver operating characteristic curve of BUN/Cr ratio and the prediction model based on logistic regression to predict the need for intervention of AUGIB were 0.604 (95%CI: 0.544-0.664) and 0.759 (95%CI: 0.706-0.812) in the training set and 0.634 (95%CI: 0.529, 0.740) and 0.708 (95% CI: 0.609, 0.806) in the validation set, respectively. CONCLUSION: The BUN/Cr ratio was associated with the need for AUGIB intervention. Combining it with other parameters might improve its diagnostic value to predict the need for intervention of AUGIB.

Accuracy of 11 intraocular lens calculation formulas in shallow anterior chamber eyes.

PURPOSE: To evaluate the performance of intraocular lens (IOL) calculation formulas and the effect of anterior chamber depth (ACD), axial length (AL) and lens thickness (LT) on the prediction accuracy in shallow ACD eyes. METHODS: This retrospective, consecutive case-series study included 648 eyes of 648 patients with an ACD < 3.0 mm who underwent phacoemulsification and IOL implantation. Eleven formulas were evaluated: Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, Hill-Radial Basis Function (RBF) 3.0, Hoffer QST, Kane, Olsen, Pearl-DGS and traditional formulas (Haigis, Hoffer Q, Holladay 1 and SRK/T). Subgroup analysis was performed based on ACD, AL and LT. RESULTS: Overall, the Hoffer QST and Kane showed no systematic bias. The Kane, EVO 2.0, Hill-RBF 3.0 and Hoffer QST had relatively lower mean absolute error and higher percentages of prediction error within ±0.5 D. For the ACD of 2.5-3.0 mm and AL < 22.0 mm subgroup, the Pearl-DGS exhibited the lowest MAE (0.45 D) and MedAE (0.41 D). Most formulas had a significant myopic bias (-0.43 to -0.18 D, p < 0.05) in the LT < 4.3 mm subgroup and a significant hyperopic bias (0.09-0.29 D, p < 0.05) in the LT ≥ 5.1 mm subgroup. CONCLUSION: The Kane and Hoffer QST were recommended for shallow ACD eyes. In eyes with an ACD between 2.5 and 3.0 mm and a short AL, the Pearl-DGS showed excellent performance. Clinicians need to fine-tune the target refraction according to LT in shallow ACD eyes.

The role of EDIL3 in maintaining cartilage extracellular matrix and inhibiting osteoarthritis development.

Aims: Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods: We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results: EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of ß1 and ß3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate ß1 and ß3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1ß-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/ß) and phospholipase C gamma 1 (PLC-γ1). Conclusion: EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA.

Characterization and Advancement of an Evaluation Method for the Treatment of Spontaneous Osteoarthritis in STR/ort Mice: GRGDS Peptides as a Potential Treatment for Osteoarthritis.

STR/ort mice spontaneously exhibit the typical osteoarthritis (OA) phenotype. However, studies describing the relationship between cartilage histology, epiphyseal trabecular bone, and age are lacking. We aimed to evaluate the typical OA markers and quantify the subchondral bone trabecular parameters in STR/ort male mice at different weeks of age. We then developed an evaluation model for OA treatment. We graded the knee cartilage damage using the Osteoarthritis Research Society International (OARSI) score in STR/ort male mice with or without GRGDS treatment. We measured the levels of typical OA markers, including aggrecan fragments, matrix metallopeptidase-13 (MMP-13), collagen type X alpha 1 chain (COL10A1), and SRY-box transcription factor 9 (Sox9), and quantified epiphyseal trabecular parameters. Compared to the young age group, elderly mice showed an increased OARSI score, decreased chondrocyte columns of the growth plate, elevated expression of OA markers (aggrecan fragments, MMP13, and COL10A1), and decreased expression of Sox9 at the articular cartilage region in elderly STR/ort mice. Aging also significantly enhanced the subchondral bone remodeling and microstructure change in the tibial plateau. Moreover, GRGDS treatment mitigated these subchondral abnormalities. Our study presents suitable evaluation methods to characterize and measure the efficacy of cartilage damage treatments in STR/ort mice with spontaneous OA.

Risk of Adverse Events and Delirium after COVID-19 Vaccination in Patients Living with Dementia.

OBJECTIVES: The aim of this study was to compare incidences of adverse events of special interest (AESI) and delirium in 3 cohorts: after COVID-19 vaccination, prepandemic, and SARS-CoV-2 polymerase chain reaction (PCR) test positive. DESIGN: This is a population-based cohort study using electronic medical records linked with vaccination records in Hong Kong. SETTING AND PARTICIPANTS: A total of 17,449 older people with dementia received at least 1 dose of CoronaVac (n = 14,719) or BNT162b2 (n = 2730) between February 23, 2021, and March 31, 2022. Moreover, 43,396 prepandemic and 3592 SARS-CoV-2 test positive patients were also included in this study. METHODS: The incidences of AESI and delirium up to 28 days after vaccination in the vaccinated dementia cohort were compared with the prepandemic and SARS-CoV-2 test positive dementia cohorts by calculating incidence rate ratios (IRRs). Patients who received multiple doses were followed up separately for each dose, up to the third dose. RESULTS: We did not detect an increased risk of delirium and most AESI following vaccination compared to the prepandemic period and those tested positive for SARS-CoV-2. No AESI group nor delirium incidence exceeded 10 per 1000 person-days in vaccinated individuals. CONCLUSIONS AND IMPLICATIONS: The findings provide evidence for the safe use of COVID-19 vaccines in older patients with dementia. In the short run, benefit appears to outweigh the harm due to vaccine; however, longer follow-up should be continued to identify remote adverse events.

Distribution and associated factors of crystalline lens volume in noncataract adolescents and adults and patients with cataract in a Chinese population.

PURPOSE: To explore the distribution of lens volume (VOL) and its associated factors in noncataract adolescents and adults and patients with cataract in a Chinese population. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Cross-sectional study. METHODS: 1674 eyes from 1674 Chinese participants (690 adolescents and 363 adults without cataract, and 621 patients with cataract) aged from 7 to 90 years were included. Lens thickness (LT) and lens diameter (LD) were measured using swept-source anterior segment optical coherence tomography (SS-AS OCT) to calculate VOL. Axial length (AL) was measured by IOL-Master 700. Pearson correlation analysis and multivariate linear regression models were used to evaluate the potential associated factors of lens dimensions. RESULTS: The mean VOL was 167.74 ± 12.18 mm 3 in noncataract adolescents, 185.20 ± 14.95 mm 3 in noncataract adults, and 226.10 ± 49.25 mm 3 in patients with cataract. VOL had no significant correlation with AL in patients with cataract ( P > .05), neither in noncataract adolescents nor noncataract adults, when adjusted with LT, LD, age, and sex ( P > .05). On the other hand, eyes with longer ALs tended to have smaller LTs and larger LDs in all groups (all P -trend < .05). Larger VOL was associated with older age in all groups (all P < .001). CONCLUSIONS: A data set of VOLs in Chinese eyes over a wide age range was presented. It is inaccurate to predict VOL, LT, and LD solely according to AL. The direct measurement and calculation of VOL in vivo and the establishment of the normal range of VOL could help predict the size of lens capsular bag and plan cataract surgery.

RopB represses the transcription of speB in the absence of SIP in group A Streptococcus.

RopB is a quorum-sensing regulator that binds to the SpeB-inducing peptide (SIP) under acidic conditions. SIP is known to be degraded by the endopeptidase PepO, whose transcription is repressed by the CovR/CovS two-component regulatory system. Both SIP-bound RopB (RopB-SIP) and SIP-free RopB (apo-RopB) can bind to the speB promoter; however, only RopB-SIP activates speB transcription. In this study, we found that the SpeB expression was higher in the ropB mutant than in the SIP-inactivated (SIP*) mutant. Furthermore, the deletion of ropB in the SIP* mutant derepressed speB expression, suggesting that apo-RopB is a transcriptional repressor of speB Up-regulation of PepO in the covS mutant degraded SIP, resulting in the down-regulation of speB We demonstrate that deleting ropB in the covS mutant derepressed the speB expression, suggesting that the speB repression in this mutant was mediated not only by PepO-dependent SIP degradation but also by apo-RopB. These findings reveal a crosstalk between the CovR/CovS and RopB-SIP systems and redefine the role of RopB in regulating speB expression in group A Streptococcus.

TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models.

Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8+ T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.

Chemotherapy-Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR Activation.

Senescence is associated with tumor metastasis and chemotherapy resistance, yet the mechanisms remain elusive. Here, it is identified that nasopharyngeal carcinoma (NPC) patients who developed distant metastasis are characterized by senescence phenotypes, in which circWDR37 is a key regulator. CircWDR37 deficiency limits cisplatin or gemcitabine-induced senescent NPC cells from proliferation, migration, and invasion. Mechanistically, circWDR37 binds to and dimerizes double-stranded RNA-activated protein kinase R (PKR) to initiate PKR autophosphorylation and activation. Independent of its kinase activity, phosphorylated PKR induces I-kappaB kinase beta (IKKß) phosphorylation, binds to and releases RELA from NF-κB inhibitor alpha (IκBα) to trigger nuclear factor kappa B (NF-κB) activation, thereby stimulating cyclin D1 (CCND1) and senescence-associated secretory phenotype component gene transcription in a circWDR37-dependent manner. Low circWDR37 levels correlate with chemotherapy response and favorable survival in NPC patients treated with gemcitabine or cisplatin induction chemotherapy. This study uncovers a new mechanism of circWDR37 activated PKR in senescence-driven metastasis and provides appealing therapeutic targets in NPC.

Electrospun membranes filtering 100 nm particles from air flow by means of the van der Waals and Coulomb forces.

Nonwoven fibrous filter membranes are widely used in filtration because of their low cost. They are less effective in intercepting airborne particles of the order of 100 nm, which is of the SARS-CoV-2 (COVID-19) virus's size. Many diseases, including COVID-19, predominantly spread by droplets released by breathing, coughing, sneezing, or medical procedures. It was shown that the smallest droplets can evaporate in air before settling, thus, making viruses airborne and easily penetrating even the best masks and filters. As a result, air-filtering membranes, which are capable of effective interception of ∼100 nm nanoparticles are highly desirable. A traditional way to improve filtration efficiency by overlapping several layers of nonwoven fabrics increases the required pressure drop, and thus, should be avoided as much as possible. Here, we propose and demonstrate an innovative approach to enhance performance of filtration membranes based on (i) a dramatic reduction in the fiber size, and (ii) metal coating of the fibers. The first component of this approach allows one to incorporate a novel physical mechanism of filtration, the short-range van der Waals forces, whereas the second one adds the long-range electric Coulomb forces if the oncoming nanoparticles are pre-charged and the metal-plated membrane grounded. In the present work, the ∼100 nm aluminum nanoparticles are filtered as a model of commensurate airborne single COVID-19 viruses, and Platinum is used as the sputter-coated material for the fiber coating. The resulting filtration efficiency enhanced by the electric Coulomb forces alone is increased by the factor of 1.77, while the filtration efficiency additionally facilitated by the van der Waals forces increased by the factor of 2.44. In comparison to the filter membranes with ∼500 nm fibers without the electric forces involved, the van-der-Waals-electric filter membrane with fibers ∼90 nm is 2.24 × 1.77 = 3.96 times more effective. The quality factor of a membrane which combines the van der Waals and Coulomb forces is 10.6 psi-1, which is almost three times that of a comparable membrane without the electric Coulomb force (with only van der Waals forces being used).

Highly Sensitive, Robust, and Recyclable TiO2/AgNP Substrate for SERS Detection.

Label-free biosensors provide an important platform for detecting chemical and biological substances without needing extra labeling agents. Unlike surface-based techniques such as surface plasmon resonance (SPR), interference, and ellipsometry, surface-enhanced Raman spectroscopy (SERS) possesses the advantage of monitoring analytes both on surfaces and in solutions. Increasing the SERS enhancement is crucial to preparing high-quality substrates without quickly losing their stability, sensitivity, and repeatability. However, fabrication methods based on wet chemistry, nanoimprint lithography, spark discharge, and laser ablation have drawbacks of waste of time, complicated processes, or nonreproducibility in surface topography. This study reports the preparation of recyclable TiO2/Ag nanoparticle (AgNP) substrates by using simple arc ion plating and direct-current (dc) magnetron sputtering technologies. The deposited anatase-phased TiO2 ensured the photocatalytic degradation of analytes. By measuring the Raman spectra of rhodamine 6G (R6G) in titrated concentrations, a limit of detection (LOD) of 10-8 M and a SERS enhancement factor (EF) of 1.01 × 109 were attained. Self-cleaning was performed via UV irradiation, and recyclability was achieved after at least five cycles of detection and degradation. The proposed TiO2/AgNP substrates have the potential to serve as eco-friendly SERS enhancers for label-free detection of various chemical and biological substances.

Non-coding RNA-mediated high expression of SFXN3 as a prognostic biomarker associated with paclitaxel resistance and immunosuppressive microenvironment in head and neck cancer.

Chemoresistance is the leading cause of poor prognosis in head and neck squamous cell carcinoma (HNSC); however, promising biomarkers to identify patients for stratified chemotherapy are lacking. Sideroflexin 3 (SFXN3) is an important mitochondrial serine transporter during one-carbon metabolism, which is involved in the proliferation of cancer cells. However, the specific role of SFXN3 in HNSC remains unknown. In this study, we performed expression and survival analysis for SFXN3 in pan-cancer using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) and found that SFXN3 served as a potential oncogene in HNSC. Notably, SFXN3 expression was found to be positively associated with enriched tumor-infiltrating macrophages, other immune suppressive cells, and immune checkpoint expression and resistance to paclitaxel. Gene, clinical, and immune variables included in the univariate and multivariate analyses showed that SFXN3 expression was an independent risk factor. Moreover, the LINC01270/hsa-miR-29c-3p/SFXN3 axis was identified as the most likely upstream non-coding RNA-related pathway of SFXN3 in HNSC using bioinformatic analysis, expression analysis, correlation analysis, and survival analysis. Taken together, our findings demonstrated that a non-coding RNA-mediated high expression of SFXN3 is a prognostic biomarker and is associated with the immunosuppressive microenvironment in HNSC.

Current Status and Prospects of Research on Ischemia-Reperfusion Injury and Ferroptosis.

The pathogenesis of ischemia-reperfusion injury is not fully understood, most of the current clinical treatment methods mainly relieve symptoms, and cannot prevent fundamentally. The mechanism of Ferroptosis has been extensively studied in recent years, but primarily focused on its therapeutic effects on tumors. After careful comparison, it is easy to find that the symptoms of ischemia-reperfusion injury often accompany by increased lipid peroxidation and increased intracellular iron level are the same as the manifestations of iron-dependent non-apoptotic Ferroptosis. Based on this "coincidence", we launched this survey. After reading a lot of literature, we found that Ferroptosis is the first step of ischemia-reperfusion injury, and cell necrosis and inflammation are the subsequent steps secondary to Ferroptosis. In this review, we have collected and sorted out the current knowledge about the role and targets of Ferroptosis in the process of ischemia-reperfusion injury. And future studies may be biased towards exploring the use of ferroptosis inhibitors in combination with other treatment options.

CircIPO7 Promotes Nasopharyngeal Carcinoma Metastasis and Cisplatin Chemoresistance by Facilitating YBX1 Nuclear Localization.

PURPOSE: Cisplatin-based chemotherapy effectively improves the distant-metastasis control in nasopharyngeal carcinoma (NPC), but approximately 30% of patients develop treatment failure due to chemoresistance. However, the underlying mechanisms remain poorly understood. EXPERIMENTAL DESIGN: Circular RNA (circRNA) sequencing data were used to identify metastasis-specific circRNAs and the expression of circIPO7 was validated in NPC tissues as well as NPC cell lines by qRT-PCR. The whole transcriptional profile upon circIPO7 knockdown was applied to explore the biological function and regulatory mechanism, which were further confirmed by in vitro and in vivo metastasis/chemosensitivity assays. We also evaluated the value of circIPO7 expression in predicting NPC metastasis and cisplatin chemoresistance by analyzing a cohort of 183 NPC patients. RESULTS: In this study, circIPO7, a novel circRNA, is found to be specifically overexpressed in NPC patients with distant metastasis. Knockdown of circIPO7 in NPC cells suppresses their metastasis and increases sensitivity to cisplatin treatment in vitro and in vivo. Mechanistically, circIPO7 binds to Y-box binding protein-1 (YBX1) protein in the cytoplasm and facilitates its phosphorylation at serine 102 (p-YBX1S102) by the kinase AKT, which further promotes YBX1 nuclear translocation and activates FGFR1, TNC, and NTRK1 transcription. Clinically, higher circIPO7 expression indicates unfavorable distant metastasis-free survival in NPC patients given cisplatin-based chemotherapy. CONCLUSIONS: Altogether, this study identifies oncogenic circIPO7 as a prognostic marker after cisplatin-based chemotherapy and as a potential therapeutic target for overcoming metastasis and chemoresistance in NPC.

Association of Intratumoral Microbiota With Prognosis in Patients With Nasopharyngeal Carcinoma From 2 Hospitals in China.

Importance: Microbiota-tumor interactions have qualified microbiota as a promising prognostic biomarker in various types of cancers. Although the nasopharynx acts as a crucial niche of the upper respiratory tract microbiome, whether the intratumoral microbiota exists and its clinical significance in nasopharyngeal carcinoma (NPC) remain uncertain. Objective: To evaluate the clinical significance of intratumoral microbiota for individual prognostication in patients with NPC. Design, Setting, and Participants: This retrospective cohort study included NPC biopsy samples from 2 hospitals: Sun Yat-sen University Cancer Center (Guangzhou, China) and Zhejiang Cancer Hospital (Hangzhou, China) between January 2004 and November 2016, with follow-up through November 2020. A total of 802 patients were included according to the following criteria: with histologically proven NPC, without distant metastasis at initial diagnosis, had not received antitumor treatment before biopsy sampling, aged between 18 and 70 years, with complete medical records and regular follow-up, without a history of cancer, and successfully extracted enough DNA for experiments. Main Outcomes and Measures: The primary end point was disease-free survival, and the secondary end points included distant metastasis-free survival and overall survival. To assess the existence and load of intratumoral microbiota in 96 patients with NPC with or without tumor relapse, 16S rRNA sequencing and quantitative polymerase chain reaction were used. The associations between intratumoral bacterial load and clinical outcome were evaluated in 241 fresh-frozen NPC samples (training cohort) and validated in paraffin-embedded NPC samples of internal (n = 233) and external (n = 232) validation cohorts. Metagenomic and transcriptome analyses were performed to ascertain the origin and underlying mechanism of intratumoral bacteria. Results: A total of 802 patients with NPC (mean [SD] age, 46.2 [10.6] years; 594 [74.1%] male) were enrolled. Microbiota presented within NPC tumor tissues, among which Corynebacterium and Staphylococcus predominated. Patients with a high bacterial load in the training cohort had inferior rates of disease-free survival (hazard ratio [HR], 2.90; 95% CI, 1.72-4.90; P < .001), distant metastasis-free survival (HR, 3.18; 95% CI, 1.58-6.39; P < .001), and overall survival (HR, 3.41; 95% CI, 1.90-6.11, P < .001) than those with a low bacterial load, a finding that was validated by the internal and external validation cohorts. Single-nucleotide variant analysis revealed that the nasopharyngeal microbiota was the main origin of NPC intratumoral bacteria. Transcriptome and digital pathology analyses demonstrated that a higher intratumoral bacterial load was negatively associated with T-lymphocyte infiltration. Conclusions and Relevance: Intratumoral bacterial load was a robust prognostic tool for patients with NPC in this cohort study, indicating potential guidance for treatment decisions in patients at different levels of risk of malignant progression.

Risk factors for carriage of antimicrobial-resistant bacteria in community dwelling-children in the Asia-Pacific region: a systematic review and meta-analysis.

Background: Antimicrobial resistance is an increasingly important issue in public health as antibiotics are overused. Resistance to antimicrobial agents can pose significant challenges to infection treatment. Objectives: To evaluate risk factors associated with carriage of antimicrobial-resistant (AMR) bacteria in children in the Asia-Pacific region to consolidate evidence for future implementation of antibiotic prescribing practice. Methods: Three electronic databases-PubMed, EMBASE and Cochrane Library-were searched. Observational studies that investigated the risk factors for carriage of MRSA, penicillin-resistant Streptococcus pneumoniae, ESBL-producing Escherichia coli and Klebsiella pneumoniae among the paediatric population in community settings in the Asia-Pacific region were considered eligible. Summary statistics from the identified studies were pooled using meta-analyses. Results: From the 4145 search results, 25 papers were included in this review. Sixteen papers were included in the meta-analysis based on reported risk factors. Young age of 2-6 months compared with children aged 7-60 months (OR 2.74, 95% CI: 1.75-4.29), antibiotic use within the past 3 months (OR 2.65, 95% CI: 1.70-4.12), daycare attendance (OR 1.49, 95% CI: 1.17-1.91) and hospital admission within the past 3 months (OR 3.43, 95% CI: 2.13-5.51) were found to be significant risk factors for AMR bacterial carriage, whilst breastfeeding (OR 0.69, 95% CI: 0.60-0.81) and concurrent colonization of S. pneumoniae (OR 0.59, 95% CI: 0.38-0.91) are protective factors. Conclusions: The findings support that there are a number of significant risk factors associated with carriage of AMR bacteria in the Asia-Pacific paediatric population. To combat antimicrobial resistance in the future, these risk factors should be considered, and measures taken to mitigate associated carriage.

Self-reported reactogenicity of CoronaVac (Sinovac) compared with Comirnaty (Pfizer-BioNTech): A prospective cohort study with intensive monitoring.

OBJECTIVE: CoronaVac (Sinovac) Covid-19 vaccine has recently been approved for emergency use by the World Health Organization. However, data on its reactogenicity in real-world settings is scant. This study aimed to compare self-reported post-vaccination adverse reactions between CoronaVac and Comirnaty (Pfizer-BioNTech). METHODS: We adopted a prospective cohort study design using online surveys from the day of first-dose vaccination with intensive follow-up through two weeks after the second dose (11 time points). The primary outcome was adverse reactions (any versus none) and secondary outcomes were the sub-categories of adverse reactions (local, systemic, and severe allergic reactions). Potential effect modification across multimorbidity status, older age, and sex was examined. RESULTS: In total, 2,098 participants who were scheduled to complete the 14th-day survey were included, with 46.2% receiving Comirnaty. Retention rate two weeks after the second dose was 81.0% for the CoronaVac group and 83.6% for the Comirnaty group. Throughout the follow-up period, 801 (82.7%) of those receiving Comirnaty and 543 (48.1%) of those receiving CoronaVac reported adverse reactions. Adjusted analysis suggested that compared with Comirnaty, CoronaVac was associated with 83%-reduced odds of any adverse reactions [adjusted odds ratio (AOR) = 0.17, 95% confidence interval (CI) 0.15-0.20], 92%-reduced odds of local adverse reactions (AOR = 0.08, 95% CI 0.06-0.09), and 76%-reduced odds of systemic adverse reactions (AOR = 0.24, 95% CI 0.16-0.28). No significant effect modification was identified. CONCLUSION: This post-marketing study comparing the reactogenicity of Covid-19 vaccines suggests a lower risk of self-reported adverse reactions following vaccination with CoronaVac compared with Comirnaty.