Oncoprotein-induced transcript 3 protein-enriched extracellular vesicles promotes NLRP3 ubiquitination to alleviate acute lung injury after cardiac surgery.

Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.

Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

Development and validation of a prognostic prediction model for cervical cancer patients treated with radical radiotherapy: a study based on TCGA database.

Background: Radiotherapy or concurrent chemoradiotherapy is the standard treatment for patients with locally advanced or inoperable cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, treatment failure for CESC patients treated with radical radiotherapy still occurs due to local recurrence and distant metastasis. The previous prediction models were focused on all CESC patients, neglecting the prognostic differences under different treatment modalities. Therefore, there is a pressing demand to explore novel biomarkers for the prognosis and sensitivity of radiotherapy in CESC patients treated with radical radiotherapy. As a single biomarker has limited effect in stratifying these patients, our objective was to identify radioresponse-related mRNAs to ameliorate forecast of the prognosis for CESC patients treated with radical radiotherapy. Methods: Sample data on CESC patients treated with radical radiotherapy were obtained from The Cancer Genome Atlas (TCGA) database. We randomly separated these patients into a training and test cohorts using a 1:1 ratio. Differential expression analysis was carried out to identify radioresponse-related mRNA sets that were significantly dysregulated between complete response (CR) and radiographic progressive disease (RPD) groups, and univariate Cox regression analyses, least absolute shrinkage and selection operator (LASSO) method and multivariate Cox regression were performed to identify the radioresponse-related signature in the training cohort. we adopted survival analysis to measure the predictive value of the radioresponse-related signature both in the test and entire cohorts. Moreover, we developed a novel nomogram to predict the overall survival (OS) of CESC patients treated with radical radiotherapy. In addition, immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to preliminarily explore possible mechanisms. Results: This study included a total of 92 CESC patients subjected to radical radiotherapy. We developed and verified a risk score model based on radioresponse-related mRNA. The radioresponse-related mRNA signature and International Federation of Gynecology and Obstetrics (FIGO) stage were served as independent prognostic factors for CESC patients treated with radical radiotherapy. Moreover, a nomogram integrating radioresponse-related mRNA signature with FIGO stage was established to perform better for predicting 1-, 3-, and 5-year survival rates. Mechanically, the low-risk group under the risk score of this model had a better survival status, and the distribution of CD4 T cells was potentially involved in the regulation of radiotherapy response in CESC, leading to a better survival outcome in the low-risk group. Conclusions: This study presents a new radioresponse-related mRNA signature that shows promising clinical efficacy in predicting the prognosis of CESC patients treated with radical radiotherapy.

An Atlas of Dietary Intakes and Medication Uses on Risk of Bladder Cancer: A Wide-Angle Mendelian Randomization Analysis.

BACKGROUND: Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways. METHODS: We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed. RESULTS: The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly. CONCLUSION: In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.HighlightsThe current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiotaOur results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.

A systematic literature review of human papillomavirus vaccination strategies in delivery systems within national and regional immunization programs.

The uptake of human papillomavirus (HPV) vaccine remains suboptimal despite being a part of routine vaccination within national immunization program(s). This indicates probable challenges with the implementation of HPV immunization program(s) in various countries. The objective of this systematic literature review (SLR) was to identify implementation strategies for HPV vaccination within national and regional immunization programs worldwide with an aim to provide guidance for countries targeting to increase their HPV vaccine coverage rate (VCR). A comprehensive literature search was conducted across Medline and Embase and included articles published between January 2012 and January 2022. Of the 2,549 articles retrieved, 168 met inclusion criteria and were included in the review. Strategies shown to improve HPV vaccination uptake in the reviewed literature include campaigns to increase community awareness and knowledge of HPV, health care provider trainings, integrating HPV vaccination within school settings, coordinated efforts via multi-sectoral partnerships, and vaccination reminder and recall systems. Findings may help national authorities understand key considerations for HPV vaccination when designing and implementing programs aiming to increase HPV VCR in adolescents.

Combined toxicity of microplastics and copper on Goniopora columns.

As microplastics (MP) become ubiquitous, their interactions with heavy metals threatens the coral ecosystem. This study aimed to assess the combined toxicity of MP and copper (Cu) in the environment of coral. Goniopora columna was exposed to polyethylene microplastics (PE-MP) combined with Cu2+ at 10, 20, 50, 100, and 300 µg/L for 7 days. Polyp length and adaptability were recorded daily, and coral samples were collected at 1, 3, 5, and 7 days to analyse zooxanthellae density and antioxidant activity. Tissue observations and the analysis of MP and Cu2+ accumulation were conducted on the 7th day. After 1 day of exposure, PE-MP combined with different concentrations of Cu2+ significantly decreased polyp length and adaptability compared with PE-MP alone. Simultaneously, a significant increase in malondialdehyde (MDA) content, lead to coral oxidative stress, which was a combined effect with PE-MP. After 3 days of exposure, PE-MP combined with Cu2+ at >50 µg/L significantly reduced zooxanthellae density, damaging the coral's symbiotic relationship. In antioxidant enzyme activity, superoxide dismutase (SOD) activity decreased significantly after 1 day of exposure. After 3 days of exposure, glutathione peroxidase (GPx) activity significantly increased with Cu2+ at >20 µg/L. After 5 days of exposure, PE-MP combined with different concentrations of Cu2+ significantly reduced catalase (CAT), glutathione (GSH), and glutathione transferase (GST) activity, disrupting the antioxidant enzyme system, and acting antagonistically to PE-MP alone. Tissue observations revealed that the PE-MP combined with Cu2+ at >50 µg/L caused severe mesenteric atrophy, vacuolar, and Cu2+ accumulation in the coral mesenteric compared with PE-MP alone. The results suggest that combined exposure of PE-MP and copper leads to more severe oxidative stress, disruption antioxidant enzyme system, tissue damage, and Cu2+ accumulation, resulting in a significant maladaptation of corals to the environment.

Endothelial extracellular vesicles induce acute lung injury via follistatin-like protein 1.

Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles (eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of eEVs after cardiopulmonary bypass, remains unclear. Plasma plasminogen-activated inhibitor-1 (PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice (C57BL/6, Toll-like receptor 4 knockout (TLR4-/-) and inducible nitric oxide synthase knockout (iNOS-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3 (JAK2/3)-signal transducer and activator of transcription 3 (STAT3)-interferon regulatory factor 1 (IRF-1) pathway, along with iNOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors (AG490 or S3I-201, respectively), and was relieved in TLR4-/- and iNOS-/- mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1 (FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.

Health impact and cost effectiveness of implementing gender-neutral HPV vaccination in Japan.

OBJECTIVE: To assess the public health impact and cost effectiveness of gender-neutral vaccination (GNV) versus female-only vaccination (FOV) with human papillomavirus (HPV) vaccination in Japan. METHODS: We modeled the public health impact and cost effectiveness of GNV versus FOV to prevent HPV-associated diseases in Japan over the next 100 years. We used one-way sensitivity analyses to examine the impact of varying key model input parameters and conducted scenario analyses to explore the effects of varying the vaccination coverage rate (VCR) of each cohort. RESULTS: In the base-case analysis, GNV averted additional cancer cases (17,228 female/6,033 male) and deaths (1,892 female/1,849 male) compared to FOV. When all HPV-associated diseases were considered, GNV had an incremental cost-effectiveness ratio of ¥4,732,320 (US$35,987)/quality-adjusted life year gained compared to FOV. The model was most sensitive to the discount rate and the disutility associated with HPV-related diseases. GNV had greater relative public health benefits when the female VCR was lower and was cost effective at a female VCR of 30%. CONCLUSIONS: Immediate implementation of GNV would reduce the disease burden and mortality associated with HPV in Japan, and would be cost effective compared to FOV if the female VCR remains low (30%).

Human papillomavirus (HPV) is a common sexually transmitted infection and, in Japan, the prevalence of HPV infection and the incidence of its associated diseases are high among both men and women. In the present manuscript we modeled the public health impact and cost effectiveness of gender-neutral vaccination versus female-only vaccination to prevent HPV-associated diseases in Japan over the next 100 years and found that immediate implementation of a gender-neutral vaccination strategy would reduce the burden and mortality associated with HPV in Japan.

Assessing the burden of HPV-related head and neck cancers in mainland China: protocol of a nationwide, multisite, cross-sectional study.

BACKGROUND: Persistent human papillomavirus (HPV) infection is a known cause of a subset of head and neck cancers (HNCs). In the last two decades, the proportion of HNCs attributable to HPV infection has increased worldwide, notably the oropharyngeal cancers. However, the trend of HPV-related HNC burden is not clearly understood yet in China. Thus, the absolute burden of HPV-related head and neck cancers in China (BROADEN-China) will be conducted to estimate the proportion of HNCs attributable to HPV infection, per anatomic site, by genotype, in three time periods (2008-2009, 2013-2014 and 2018-2019). METHODS AND ANALYSIS: BROADEN-China is a nationwide, multisite, cross-sectional study. A stratified, multistage, non-randomised cluster sampling method will be used to select 2601 patients with HNC from 14 hospitals across seven regions, based on population density in China. Patients with formalin-fixed paraffin-embedded tissue samples collected prior to treatment induction during three time periods will be included, and factors (eg, smoking status, alcohol consumption, betel nut chewing, Epstein-Barr virus, teeth loss, etc) associated with HNC will be assessed. HPV testing (HPV-DNA, HPV-mRNA and p16INK4a immunohistochemistry) and histological diagnosis of the tissue samples will be conducted at a central laboratory.The study protocol and all required documents have been submitted for review and approval to the Independent Ethics Committees of all the participating sites. The informed consent was waived for all participants and all the recorded data will be treated as confidential.We have included 14 hospitals as our participating sites, of which Henan Cancer Hospital is the leading site. The study has been approved by the independent ethics committees of the leading site on 3 December 2020. The other 13 participating site names of ethics committee and IRB that have approved this study.

Exploring Possible Diagnostic Precancerous Biomarkers for Oral Submucous Fibrosis: A Narrative Review.

Oral submucous fibrosis (OSF) stands as a progressive oral ailment, designated as a potentially malignant disorder. OSF has gained widespread recognition as a significant precursor to malignant transformation. In the pursuit of dependable, straightforward, and non-invasive diagnostic measures for the early detection of oral malignant progression, research has delved into potential diagnostic biomarkers of OSF. This comprehensive review delves into current investigations that explore the correlation between various biomarkers and OSF. The molecular biomarkers of OSF are categorized based on cytology and sampling methods. Moreover, this review encompasses pertinent studies detailing how these biomarkers are acquired and processed. Within this scope, we scrutinize four potential biomarkers that hold the promise of facilitating the development of diagnostic tools for detecting early-stage OSF.

Exploring the Anti-Cancer Effects of Fish Bone Fermented Using Monascus purpureus: Induction of Apoptosis and Autophagy in Human Colorectal Cancer Cells.

Fish bone fermented using Monascus purpureus (FBF) has total phenols and functional amino acids that contribute to its anti-oxidant and anti-inflammatory properties. Colorectal cancer, one of the most prevalent cancers and the third largest cause of death worldwide, has become a serious threat to global health. This study investigates the anti-cancer effects of FBF (1, 2.5 or 5 mg/mL) on the cell growth and molecular mechanism of HCT-116 cells. The HCT-116 cell treatment with 2.5 or 5 mg/mL of FBF for 24 h significantly decreased cell viability (p < 0.05). The S and G2/M phases significantly increased by 88-105% and 25-43%, respectively (p < 0.05). Additionally, FBF increased the mRNA expression of caspase 8 (38-77%), protein expression of caspase 3 (34-94%), poly (ADP-ribose) polymerase (PARP) (31-34%) and induced apoptosis (236-773%) of HCT-116 cells (p < 0.05). FBF also increased microtubule-associated protein 1B light chain 3 (LC3) (38-48%) and phosphoinositide 3 kinase class III (PI3K III) (32-53%) protein expression, thereby inducing autophagy (26-52%) of HCT-116 cells (p < 0.05). These results showed that FBF could inhibit HCT-116 cell growth by inducing S and G2/M phase arrest of the cell cycle, apoptosis and autophagy. Thus, FBF has the potential to treat colorectal cancer.

Oral Human Papillomavirus Prevalence and Genotyping Among a Healthy Adult Population in the US.

Importance: In the US, oropharyngeal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection, is the most frequent HPV-associated cancer, surpassing cervical cancer. However, little is known about oral HPV prevalence and genotype distribution in the general population. Objective: To assess oral HPV prevalence and factors associated with HR and low-risk infection in a general US population. Design, Setting, and Participants: PROGRESS (Prevalence of Oral HPV Infection, a Global Assessment) was a cross-sectional observational study conducted between November 2021 and March 2022 in 43 dental offices in the US (24 urban, 13 urban cluster, and 6 rural sites), spanning 21 states. Eligible participants were aged 18 to 60 years, visiting dental clinics for routine dental examination. Dental clinics used targeted sampling to recruit equal distributions of men and women and across age groups. Exposure: Participants provided an oral gargle specimen for HPV DNA and genotyping and completed behavioral questionnaires, and dentists reported oral health status. Detection of HPV DNA and genotyping was performed using the SPF10/DEIA/LiPA25 system at a central laboratory. Main Outcome: Oral HPV prevalence. Results: Of the 3196 participants enrolled, mean (SD) age was 39.6 (12.1) years, and 55.5% were women. Oral HPV prevalence was 6.6% (95% CI, 5.7%-7.4%) for any HPV genotype, and 2.0% (95% CI, 1.5%-2.5%), 0.7% (95% CI, 0.4%-1.0%), and 1.5% (95% CI, 1.1%-1.9%) for HR, HPV-16, and 9-valent-HPV vaccine types, respectively. Among HPV-positive participants, HPV-16 was the most prevalent genotype (12.4% among men and 8.6% among women). Prevalence of HPV was higher in men than women and highest among men aged 51 to 60 years (16.8%, 6.8%, and 2.1% for any HPV, HR HPV, and HPV-16, respectively). Factors associated with HR oral infection included being male (adjusted odds ratio [AOR], 3.1; 95% CI, 1.2-8.5), being aged 51 to 60 years (AOR, 3.3; 95% CI, 1.5-7.3), having 26 or more lifetime male sex partners (AOR, 6.5; 95% CI, 2.3-18.7), and having 6 to 25 lifetime female oral sex partners (AOR, 3.4; 95% CI, 1.3-8.7). Conclusions and Relevance: In this cross-sectional study, oral HPV burden was highest among older men who may be at higher risk of developing oropharyngeal cancer. In addition to male sex and older age, HR oral HPV infection was also associated with sexual behaviors, including increasing number of male sex partners and female oral sex partners.

Changes in vaccine administration trends across the life-course during the COVID-19 pandemic in the United States: a claims database study.

BACKGROUND: This study provides an updated and expanded analysis of the impact of the COVID-19 pandemic on routine vaccinations across the life-course in the United States. RESEARCH DESIGN AND METHODS: Routine wellness visits and vaccination rates were calculated using structured claims data for each month during the impact period (January 2020 to August 2022) and compared to the respective baseline period (January 2018 to December 2019). Monthly rates were aggregated as annual accumulated and cumulative percent changes. RESULTS: The complete monthly rate interactive dataset can be viewed at https://vaccinationtrends.com. The greatest decrease in annual accumulated administration rates in the 0-2 and 4-6 years age groups was for the measles, mumps, and rubella vaccine; for adolescents and older adults, it was for human papillomavirus and pneumococcal vaccines, respectively. Routine in-person wellness visit rates recovered faster and more completely than vaccination rates in all age groups, indicating potential missed opportunities to administer vaccines during visits. CONCLUSIONS: This updated analysis reveals that the negative impact of the COVID-19 pandemic on routine vaccination continued through 2021 and into 2022. Proactive efforts to reverse this decline are needed to increase individual- and population-level vaccination coverage and avoid the associated preventable morbidity, mortality, and health care costs.

Evaluation of antioxidant and anti-obesity potential of Sargassum extracts.

Sargassum are brown algae belonging to the class Phaeophyceae. Brown algae are rich in nutrients and widely used in food. Most previous experiments have focused on the functional evaluation of organic solvent extracts of Sargassum. Considering food safety, this study investigated the antioxidant and antiobesity activities of Sargassum hemiphyllum water extract (SE). The antioxidant activity of SE (500-4000 mg/mL) was determined in vitro. The results indicated that SE has good DPPH radical scavenging activity (14-74%), reducing power (20-78%), ABTS+ radical scavenging activity (8-91%), and Fe2+ chelating ability (5-25%). Furthermore, the antiobesity activity of SE (50-300 mg/mL) was analysed in a 3T3-L1 adipocyte model. SE effectively inhibited lipid accumulation (determined by methods including measuring the absorbance of Oil red O after staining and the triglyceride content, which were decreased by 10% and 20%, respectively) by reducing peroxisome proliferator-activated receptor gamma (PPARγ) protein expression in 3T3-L1 adipocytes. This study suggested that SE has good antioxidant and antiobesity properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05707-1.

Evaluation of egg white hydrolysates on the hepatoprotective effect in vitro and in vivo.

The small molecule characteristics and nutritional value of egg white hydrolysates have been widely used. In the present study, in vitro and in vivo models were used to investigate the hepatoprotective effect of egg protein hydrolysate (EWH) by regulating the expression of antioxidant enzymes. The in vitro experiment results showed that 0.1, 0.5, and 1 mg/mL of EWH enhanced antioxidant activity in HepG2 cells by increased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels. The in vivo experiment results showed that EWH (L) (38.5 mg/kg BW) and EWH (H) (385 mg/kg BW) alleviated carbon tetrachloride (CCl4)-induced hepatotoxicity in SD rats through reduced levels of serum aspartate aminotransferase (AST) alanine aminotransferase (ALT), and lipid peroxidation products malondialdehyde (MDA). In addition, EWH also ameliorates CCl4-induced hepatotoxicity in SD rats by increasing the antioxidant activity of GSH levels with a decrease in oxidized glutathione (GSSG) levels. Besides, EWH ameliorates liver tissue injuries by CCl4-induction. EWH has the highest glutamic acid in free amino acid composition, the second highest was aspartic acid, and the third was cystine, 204, 141, and 125 mg/100 g, respectively. These results suggest EWH has hepatoprotective potential through reduced lipid peroxidation products and enhanced antioxidant activity.

Anti-inflammatory effects of fish bone fermented using Monascus purpureus in LPS-induced RAW264.7 cells by regulating NF-κB pathway.

Fish bones are the by-products of aquatic and fishery processing, which are often discarded. However, it has been considered having health-promoting by containing many essential nutrients. This study investigates the anti-inflammatory effect of fish bone fermented by Monascus purpureus (FBF) and the NF-κB pathway regulation mechanism in lipopolysaccharides (LPS)-induced RAW 264.7 cells. FBF has inhibited the production of PGE2 (prostaglandin E2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in LPS-induced RAW264.7 cells. The FBF has significantly inhibited mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, FBF has suppressed activation of NF-κB (nuclear factor kappa-B) by increasing IκB mRNA expression and reduced of p65, p50 mRNA expression, as well as nuclear NF-κB DNA binding activity in LPS-induced RAW 246.7 cells. These findings demonstrate that FBF has inhibited LPS-induced inflammation by subsiding the activation of NF-κB in RAW 246.7 cells, implying that FBF could be employed as a promising natural product.

Estimating the prevalence of non-cervical human papillomavirus infection in mainland China (PROGRESS-Plus): protocol of a national cross-sectional study.

INTRODUCTION: Human papillomavirus (HPV) infection is the most common sexually transmissible infection worldwide. Although the prevalence of cervical HPV infection has been extensively reported in women worldwide, few epidemiological studies have examined the prevalence of non-cervical HPV infection among both women and men, especially in China. METHODS AND ANALYSIS: PROGRESS-Plus is a national, multisite, cross-sectional study that aims to estimate the prevalence of non-cervical HPV infection in women and men aged 18-60 years residing in mainland China. More specifically, PROGRESS-Plus will estimate the prevalence rate of HPV DNA in oral samples from both women and men, and that of anogenital samples from men. The secondary study objectives are to (1) report the aforementioned prevalence rates by HPV genotype, age and geographical region, (2) examine the concordance (ie, prevalence of the same HPV genotype) between the oral and anogenital samples among men, (3) explore risk factors associated with oral (in both women and men) and anogenital (in men only) HPV infection and (4) describe study participants' health-related quality of life, health behaviour, sexual behaviour and health status. ETHICS AND DISSEMINATION: The study protocol and all required documents have been submitted for review and approval to the Independent Ethics Committees of all the participating sites. All participants will provide their written informed consent on study entry, and all the recorded data will be treated as confidential.

Early Initiation of HPV Vaccination and Series Completion in Early and Mid-Adolescence.

OBJECTIVES: Routine human papillomavirus (HPV) vaccination has been recommended in the United States since 2006 but rates remain suboptimal. State-based studies suggest that initiation in late childhood at ages 9 to 10 years compared with the recommended early adolescent ages of 11 to 12 years improves series completion. No study with national scope has explored the early initiation-HPV series completion relationship. This study addresses this knowledge gap and explores whether early initiation might improve series completion by increasing time to target completion age (time pathway) or by moving initiation to an earlier developmental stage (development pathway). METHODS: Using data from the National Immunization Survey-Teen 2017-2020, a retrospective cohort of 19 575 15 to 17 year olds who initiated HPV vaccination between ages 9 and 12 years was assembled. Time pathway endpoints were series completion by ages 13 and 15 years. The development pathway endpoint was completion within 3 years of initiation. RESULTS: Early initiators were more likely to complete by ages 13 (74.0% vs 31.1%, P < .001) and 15 (91.7% vs 82.7%, P < .001) years but less likely to complete within 3 years (82.3% vs 84.9%, P = .007). The association of early initiation to completion was maintained in multivariable analyses for time pathway endpoints (age 13 years adjusted odds ratios [AOR] = 6.16; 95% confidence interval [CI], 5.45-6.96, age 15 years = AOR 2.56; 95% CI, 2.14-3.14) but not the development pathway endpoint (AOR = 0.93; 95% CI, 0.80-1.07). CONCLUSIONS: Moving routine HPV vaccination to ages 9 to 10 may improve vaccination coverage rates in early and mid-adolescence. Providers should be vigilant to patient interactions after HPV series initiation to optimize public health benefits of vaccination.

Challenges of the eighth edition of the American Joint Committee on Cancer staging system for pathologists focusing on early stage lung adenocarcinoma.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer adopts new criteria for tumor size, and for determining pTis, pT1a(mi), and pT1a. The latter is based on the size of stromal invasion. It is quite challenging for lung pathologists. METHODS: All patients who had undergone surgical resection for pulmonary adenocarcinoma (ADC) at Chung Shan Medical University Hospital between January 2014 and April 2018 were reviewed, and restaged according to the eighth AJCC staging system. The clinical characteristics and survival of patients with tumor stage 0 (pTis), I or II were analyzed. RESULTS: In total, 376 patients were analyzed. None of the pTis, pT1a(mi), or pT1a tumors recurred during the follow-up period up to 5 years, but pT1b, pT1c, pT2a, and pT2b tumors all had a few tumor recurrences (p < 0.0001). In addition, 95.2%, 100%, and 77.5% of pTis, pT1a(mi), and pT1a tumors, respectively, had tumor sizes ≤1.0 cm by gross examination. All pTis, pT1a(mi), and pT1a tumors exhibited only lepidic, acinar, or papillary patterns histologically. CONCLUSIONS: This study demonstrated excellent survival for lung ADC patients with pTis, pT1a(mi), and pT1a tumors when completely excised. To reduce the inconsistencies between pathologists, staging lung ADC with tumors of ≤1 cm in size grossly as pTis, pT1a(mi), or pT1a may not be necessary when the tumors exhibit only lepidic, acinar, or papillary histological patterns. A larger cohort study with sufficient follow-up data is necessary to support this proposal.

HPV vaccine initiation at 9 or 10 years of age and better series completion by age 13 among privately and publicly insured children in the US.

The US Advisory Committee on Immunization Practice recommends routine human papillomavirus (HPV) vaccination at 11-12 years of age, but states that vaccination may be initiated as early as 9 years. Our primary goal was to assess whether initiating HPV vaccination at 9-10 years of age, compared to 11-12, was associated with a higher rate of series completion by 13 years of age, and to identify factors associated with series completion by age 13. The study used vaccine claims and other data from the IBM MarketScan Commercial Claims and Encounters (privately insured) and IBM MarketScan Multi-State Medicaid (publicly insured) databases. Participants were 9-12 years of age and initiated HPV vaccination between January 2006 and December 2018 (publicly insured) or February 2019 (privately insured). Among 100,117 privately insured individuals, those initiating the HPV vaccination series at 9-10 years of age had a significantly higher series completion rate by 13 years of age than did those initiating at 11-12 years of age (76.2% versus 48.1%; p < .001). The same pattern was observed for 115,863 publicly insured individuals (70.4% versus 40.0%; p < .001). Provider and health care plan type, female sex, race/ethnicity, and wellness checks or non-HPV vaccinations during the baseline period were significantly associated with series completion by 13 years of age. Proactive initiation of HPV vaccination at 9-10 years of age was associated with higher rates of series completion by 13 years of age. These findings can inform provider education and other interventions to encourage timely HPV vaccination series completion.