Combination of Different Sectional Elastography Techniques with Age to Optimize the Downgrading of Breast BI-RAIDS Class 4a Nodules.

OBJECTIVE: This study aims to optimize the downgrading of BI-RADS class 4a nodules by combining various sectional elastography techniques with age. MATERIALS AND METHODS: We performed conventional ultrasonography, strain elastography (SE), and shear wave elastography (SWE) on patients. Quantitative parameters recorded included age, cross-sectional and longitudinal area ratios (C-EI/B, L-EI/B), strain rate ratios (C-SR, L-SR), overall average elastic modulus values (C-Emean1, L-Emean1), five-point average elastic modulus values (C-Emean2, L-Emean2), and maximum elastic modulus values (C-Emax, L-Emax). RESULTS: Histopathological evaluations showed that out of 230 lesions, 45 were malignant, and 185 were benign. The sensitivity and specificity of conventional ultrasonography were 100% and 0%, respectively. In contrast, SE and SWE exhibited higher specificity but lower sensitivity. Crosssectional parameters (C-EI/B, C-SR, C-Emean1, C-Emean2, and C-Emax) outperformed their longitudinal counterparts, with C-SR and C-Emax showing the highest specificity (72.43% and 73.51%) and satisfactory sensitivity (80.00% and 88.89%). Combining age with C-SR and C-Emax significantly improved diagnostic efficiency, achieving a sensitivity of 97.78% and a specificity of 77.30%. CONCLUSION: Integrating age with C-SR and C-Emax effectively reduces unnecessary biopsies for most BI-RADS 4a benign lesions while maintaining a very low misdiagnosis rate.

Zinc Finger Protein 536 is a Potential Prognostic Biomarker that Promotes Neuroblastoma Progression via VEGFR2-PI3K-AKT Pathway.

BACKGROUND: Neuroblastoma (NB) is a well-known pediatric malignancy intertwined with neurodevelopment. Previously implicated in neuronal differentiation, Zinc Finger Protein 536 (ZNF536) has emerged as a promising prognostic and immune-related biomarker in our pan-cancer analysis. METHODS: Single-cell RNA transcriptome sequencing, bulk transcriptome analysis, and immuno-histochemistry were used to assess ZNF536 expression and its association with prognosis. Cell proliferation, migration, invasion, and differentiation in ZNF536-knockdown NB cell lines were detected to evaluate the effect of ZNF536 on tumor cells. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), a potential target of ZNF536, and its downstream PI3K/AKT signaling cascade were investigated using transcriptome sequencing, CUT&Tag, quantitative real-time PCR (qRT-PCR), and Western blotting. The role of ZNF536 in tumorigenesis and the potential regulation axis was evaluated in vivo using a BALB/c nude mouse xenograft tumor model. RESULTS: ZNF536 mRNA and protein expression were significantly higher in NB patients with poor prognosis. In vitro, ZNF536 knockdown curtailed proliferation, migration, and invasion of NB cells while fostering differentiation. ZNF536 regulated VEGFR2 expression, thus activating the PI3K-AKT pathway. In vivo, ZNF536 knockdown reduced tumor growth and proliferation via the VEGFR2-PI3K-AKT pathway. CONCLUSION: ZNF536 resulted as a novel prognostic biomarker in NB, promoting oncogenesis through VEGFR2-PI3K-AKT signaling axis modulation, suggesting its therapeutic potential in managing NB progression.

Cepharanthine sensitizes gastric cancer cells to chemotherapy by targeting TRIB3-FOXO3-FOXM1 axis to inhibit autophagy.

BACKGROUND: Gastric cancer is among the common solid tumors. Chemotherapy resistance is the most common issue in gastric cancer treatment. Inhibiting intracellular autophagy may be a feasible method for overcoming chemotherapy resistance. Cepharanthine (CEP), a natural small molecule extracted from the stephania cephalantha Hayata plant, has been demonstrated to significantly inhibit cancer growth and can regulate autophagy. Although CEP can significantly inhibit cancer growth, it remains unclear whether CEP can regulate autophagy in gastric cancer. This study aimed to investigate whether CEP can enhance the sensitivity of gastric cancer to chemotherapy and elucidate its molecular mechanism. METHODS: Three gastric cancer cell lines (AGS, SGC7901, and MFC) and one normal gastric mucosal epithelial cell line (GES-1) were used for in vitro experiments. The characterization of autophagy in gastric cancer cells included the detection of autophagy markers and autophagy flux through immunofluorescence staining and Western blotting, as well as the assessment of lysosomal function using fluorescence staining (LysoTracker Red DND-99, Acridine Orange staining) and Western blotting. The cytotoxicity of CEP, autophagy inhibitors (chloroquine [CQ] and 3-methyladenine [3MA]), and chemotherapy drugs (doxorubicin [DOX] and cisplatin [CIS]) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell colony formation, and fluorescence staining techniques (H2DCFDA, Dihydroethidium, and JC-1 staining). The interaction between CEP and autophagy inhibitors was tested in a 615 mice model, and changes in the gut microbiota were determined through accurate 16S absolute quantification sequencing. The signaling pathway and autophagy regulatory target TRIB3-FOXO3-FOXM1 were confirmed through molecular docking, RNA sequencing, bioinformatic analysis, transfection techniques, and Western blotting. RESULTS: CEP blocked autophagic flux in gastric cancer cells without affecting lysosomal function. As a novel autophagy inhibitor, CEP could combine with conventional autophagy inhibitors (CQ and 3MA) to block intracellular autophagy, thereby inhibiting gastric cancer growth. During this process, changes in the gut microbiota were observed, including low-level changes in Odoribacterium, Erysipelatoclostridium, and ParaPrevotella and high-level changes in Ileibacterium, Enterorhabdus, and Bifidobacterium. Additionally, CEP synergistically inhibited the growth of gastric cancer when combined with chemotherapy drugs. Mechanistically, the TRIB3-FOXO3-FOXM1 signaling axis was found to be involved in the inhibition of gastric cancer by CEP combined with autophagy inhibitors and chemotherapy drugs, thereby mediating cell apoptosis. CONCLUSION: This study links the TRIB3-FOXO3-FOXM1 axis with chemotherapy efficacy. Our findings demonstrated that CEP inhibits autophagy by modulating the FOXO3-FOXM1 axis. When combined with chemotherapy drugs (DOX and CIS), CEP, as an autophagy inhibitor, can limit TRIB3 protein expression, thereby regulating the FOXO3-FOXM1 axis and enhancing its ability to prevent gastric cancer growth. These findings may contribute to improving the prognosis of patients with gastric cancer. Furthermore, these results enrich the fundamental understanding of how autophagy inhibition can enhance clinical cancer treatment efficacy and provide insights into the potential mechanisms by which CEP functions as an anti-tumor drug, thereby exploring its value for clinical application.

Integrated analysis of microbiome and metabolome reveals signatures in PDAC tumorigenesis and prognosis.

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system. Emerging evidence suggests the involvement of the microbiome and metabolic substances in the development of PDAC, yet the results remain contradictory. This study aims to identify the alterations and relationships in intratumoral microbiome and metabolites in PDAC. We collected matched tumor and normal adjacent tissue (NAT) samples from 105 PDAC patients and performed a 6-year follow-up. 2bRAD-M sequencing, untargeted liquid chromatography-tandem mass spectrometry, and untargeted gas chromatography-mass spectrometry were performed. Compared with NATs, microbial α-diversity decreased in PDAC tumors. The relative abundance of Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum was higher in PDAC tumor after adjusting for confounding factors body mass index and M stage, and the presence of Ralstonia pickettii_B was found associated with a worse overall survival. Metabolomic analysis revealed distinctive differences in composition between PDAC and NAT, with 553 discriminative metabolites identified. Differential metabolites were revealed to originate from the microbiota and showed significant interactions with shifted bacterial species through KO (KEGG Orthology) genes. These findings suggest that the PDAC microenvironment harbors unique microbial-derived enzymatic reactions, potentially influencing the occurrence and development of PDAC by modulating the levels of glycerol-3-phosphate, succinate, carbonate, and beta-alanine. IMPORTANCE: We conducted a large sample-size pancreatic adenocarcinoma microbiome study using a novel microbiome sequencing method and two metabolomic assays. Two significant outcomes of our analysis are: (i) commensal opportunistic pathogens Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum were enriched in pancreatic ductal adenocarcinoma (PDAC) tumors compared with normal adjacent tissues, and (ii) worse overall survival was found related to the presence of Ralstonia pickettii_B. Microbial species affect the tumorigenesis, metastasis, and prognosis of PDAC via unique microbe-enzyme-metabolite interaction. Thus, our study highlights the need for further investigation of the potential associations between pancreatic microbiota-derived omics signatures, which may drive the clinical transformation of microbiome-derived strategies toward therapy-targeted bacteria.

MAT2B regulates the protein level of MAT2A to preserve RNA N6-methyladenosine.

MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP+-dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP+ remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP+ with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP+. Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.

Nanomedicine in HNSCC therapy-a challenge to conventional therapy.

Squamous cell carcinoma of the head and neck (HNSCC) is a difficult-to-treat cancer and treatment is challenging due to recurrence or metastasis. Therefore, there is an urgent need to explore more effective targeted therapies to improve the clinical outcomes and survival of HNSCC patients. The nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer therapy. In this review, we summarize some important signaling pathways and present the current and potential roles of various nanomaterial drug-delivery formulations in HNSCC treatment, aiming to understand the pathogenesis of HNSCC and further improve the therapeutic efficacy of nanomaterial HNSCC. This article seeks to highlight the exciting potential of novel nanomaterials for targeted cancer therapy in HNSCC and thus provide motivation for further research in this field.

Purified CD34+ Cells Transplantation in Patients with Angiitis-induced Chronic Limb-threatening Ischemia: A Single-center Retrospective Study over A 10-year Period.

BACKGROUND: Angiitis-induced chronic limb-threatening ischemia (AICLTI) is defined as chronic limb-threatening ischemia (CLTI) caused by thromboangiitis obliterans (TAO) or other arteritis-related autoimmunological diseases. In the current study, we aimed to report the 10-year outcomes of AICLTI patients who underwent purified CD34+ cells (PCCs) transplantation. METHODS: AICLTI patients who underwent PCCs transplantation at our center from May 2009 to September 2011 were retrospectively enrolled. The main outcome was major amputation-free survival (MAFS); other outcomes included Rutherford classification, intolerable pain-free walking time (IPFWT), Wong-Baker Faces Pain Rating Scale (WBFPS), recurrence, new lesions, quality of life (QoL) and patients' posttransplantation work conditions. RESULTS: Twenty-four patients were enrolled with a mean age of 41.5±7.8 years. Three underwent major amputation during the follow-up, and the 10-year MAFS was 87.5%. Eight were observed to have recurrence, and 2 had new lesions; the 10-year recurrence-free rate was 66.1%. All patients were unable to work at admission, 17 (70.8%) patients were reemployed after transplantation. CONCLUSION: The current study further demonstrated satisfactory long-term efficacy of PCCs transplantation, with a 10-year MAFS of 87.5%. However, the 10-year recurrence-free rate of 66.1% suggested that strict and regular long-term follow-up is necessary.

HDAC inhibitor SAHA enhances antitumor immunity via the HDAC1/JAK1/FGL1 axis in lung adenocarcinoma.

BACKGROUND: Histone deacetylase (HDAC), a kind of protease that regulates gene expression by modifying protein acetylation levels, is usually aberrantly activated in tumors. The approved pan-HDAC inhibitors (HDACi) have exhibited clinical benefits for hematopoietic malignancies. Recently, HDACis have emerged as enhancers of antitumor immunity. However, the effect of HDACs on the tumor immune microenvironment of lung adenocarcinoma (LUAD) and the underlying mechanism is largely unknown. METHODS: C57BL/6J and BALB/c nude mice with subcutaneous tumors were used for in vivo therapeutic effects and mechanistic investigations. Flow cytometry was used to measure the toxicity and exhaustion of human CD8+T cells after co-culturing with tumor cells and to determine the immunophenotype of tumor-infiltrating CD8+T cells. A series of experimental techniques, including RNA sequencing, quantitative PCR, western blot, ELISA, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation and immunohistochemistry, were used to explore the underlying molecular mechanism. RESULTS: The pan-HDACi vorinostat (SAHA) promoted CD8+T cell infiltration and effector function in LUAD through suppressing FGL1, a newly identified major ligand of LAG-3. Mechanistically, SAHA inhibited the activity of HDAC1, an essential deacetylase of JAK1. This increased the acetylation level of JAK1 at lysine 1109, thus promoting its proteasomal degradation and subsequently reducing STAT3-driven FGL1 transcription. The combination regimen of SAHA and anti-LAG-3 therapy was further explored in an immunocompetent LUAD mouse model. Compared with those receiving control or single agent treatments, mice receiving combination therapy exhibited a lower tumor burden and superior CD8+T-cell-killing activity. CONCLUSIONS: Our results revealed a novel mechanism by which the HDACi SAHA potentiates CD8+T-cell-mediated antitumor activity through the HDAC1/JAK1/FGL1 axis, providing a rationale for the combined use of HDACis and immunotherapy.

Pediatric Angiosarcoma with Novel Phenotypic and Genotypic Profile in Chinese Children.

Introduction: Angiosarcoma is an exceedingly rare entity in pediatric population. Herein, we report two pediatric angiosarcoma with novel phenotypic and genotypic profile. Methods: The two patients' information was summarized by clinical data, histopathology, immunohistochemistry, genetic, treatment, and prognosis. Results: Two Chinese children presented with abdominal mass or consumptive hypothyroidism at 2 and 6 years. A patient presented with a unique histopathology of epithelioid AS with smooth muscle hyperplasia, and carried a novel somatic mutation in FAT1 (c.3929C > T/p. Ser1310Leu) along with germ-line variants in CDK8 (c.895A > C/p. Lys299Gln), FANCI (c.3906-07inv/p. Glu1303Lys), and MST1R (c.3581-83delinsACG/p. Arg1194-Ser1195delinsHisGly). The other patient presented with a novel -clinical phenotype of consumptive hypothyroidism. They received postoperative treatment and were monitored for 20 and 26 months, showing good recovery. Conclusion: The phenotypic and genotypic spectrum of AS in pediatric population was expanded by these two patients, which requires the accumulating more cases to gain a deeper understanding.

Cystoderma yongpingense sp. nov. (Squamanitaceae, Agaricales) a new species from southwestern China.

The present study introduces a novel fungus, Cystoderma yongpingense, which was identified in the southwestern region of China. The new species is characterized by a pileus that ranges in color from light orange-red to orange-red; the pileus has a wrinkled surface and is accompanied by a persistent annulus that is membranous and floccose-scaly. Above the annulus, the color transitions from white to yellowish brown. This proposal is substantiated through analyses encompassing both morphological characteristics and phylogenetic relationships. The phylogenetic position of the newly discovered species has been further corroborated through comprehensive maximum likelihood and Bayesian sequence analyses of the ITS + nrLSU DNA regions. Additionally, the technical description of C. yongpingense is enhanced by detailed illustrations and comparative studies with species that are closely related.

NLRC5 exerts anti-endometriosis effects through inhibiting ERß-mediated inflammatory response.

BACKGROUND: Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor ß (ERß), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERß-mediated endometriosis is still uncertain. This study aimed to assess that relation. METHODS: Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERß were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERß, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERß-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERß and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays. RESULTS: Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERß overexpression. And ERß promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERß-mediated development and inflammatory response of endometriosis. CONCLUSIONS: Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERß-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis.

hFcγRIIa: a double-edged sword in osteoclastogenesis and bone balance in transgenic mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcγRs, especially FcγRIIa (hFcγRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcγRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcγRIIa on osteoclast differentiation through investigations involving hFcγRIIa-transgenic (hFcγRIIa-Tg) mice. Our findings reveal that hFcγRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcγRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-κB ligand (RANKL). Additionally, hFcγRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo, highlighting the osteoclast-promoting role of hFcγRIIa. Mechanistically, bone marrow cells from hFcγRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcγRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcγRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders.

Correlation Between the Expression of DNA Damage Repair Protein OGG1 and Ubiquitination Pathway Protein STUB1 in Pediatric Neuroblastoma.

BACKGROUND: Neuroblastoma, a pediatric malignancy, is significantly influenced by genetic factors. Prior research indicates that the OGG1 rs1052133 G > C polymorphism correlates with a decreased risk of neuroblastoma. METHODS: We analyzed 57 neuroblastoma and 21 adrenal samples, using immunohistochemistry to measure OGG1 and STUB1 expression levels. We conducted a survival analysis to explore relationship between the expressions and neuroblastoma prognosis. RESULTS: Notably higher OGG1 expression and significantly lower STUB1 expression in neuroblastoma. OGG1 levels were significantly correlated with patient age, tumor location, histological grade, Shimada classification, INSS stage, and risk category. A negative association was observed between OGG1 and STUB1 expressions. Higher OGG1 expression was linked to reduced PFS and OS. Lower STUB1 expression was associated with unfavorable PFS. Additionally, OGG1 expression and risk category emerged as independent predictors of prognosis. CONCLUSION: OGG1 potentially functions as an oncogene in NB, with its activity possibly modulated by STUB1 through the ubiquitination pathway.

Associations of socioeconomic status and healthy lifestyle with incident dementia and cognitive decline: two prospective cohort studies.

Background: Little is known about the complex associations of socioeconomic status (SES) and healthy lifestyle with cognitive dysfunction. Methods: Using data from the Health and Retirement Study (HRS) [2008-2020] and the English Longitudinal Study of Ageing (ELSA) [2004-2018], SES was constructed by latent class analysis using education level, total household income and wealth. Overall healthy lifestyle was derived using information on never smoking, low to moderate alcohol consumption (drinks/day: (0, 1] for women and (0, 2] for men), top tertile of physical activity, and active social contact. Findings: A total of 12,437 and 6565 participants from the HRS and ELSA were included (40.8% and 46.0% men and mean age 69.3 years and 65.1 years, respectively). Compared with participants of high SES, those of low SES had higher risk of incident dementia (hazard ratio 3.17, 95% confidence interval 2.72-3.69 in the HRS; 1.43, 1.09-1.86 in the ELSA), and the proportions mediated by overall lifestyle were 10.4% (7.3%-14.6%) and 2.7% (0.5%-14.0%), respectively. Compared with participants of high SES and favorable lifestyle, those with low SES and unfavorable lifestyle had a higher risk of incident dementia (4.27, 3.40-5.38 in the HRS; 2.02, 1.25-3.27 in the ELSA) and accelerated rate of global cognitive decline (ß = -0.058 SD/year; 95% CI: -0.073, -0.043 in the HRS; ß = -0.049 SD/year; 95% CI: -0.063, -0.035 in the ELSA). Interpretation: Unhealthy lifestyle only mediated a small proportion of the socioeconomic inequality in dementia risk in both US and UK older adults. Funding: This work was supported by grants from the National Natural Science Foundation of China (82088102 and 82370819), the National Key R&D Program of China (2023YFC2506700), the Shanghai Municipal Government (22Y31900300), the Shanghai Clinical Research Center for Metabolic Diseases (19MC1910100), the Innovative Research Team of High-Level Local Universities in Shanghai, the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission (202340084), and Ruijin Hospital Youth Incubation Project (KY20240805). Y.X. is supported by the National Top Young Talents program.

Influences of HPV disease perceptions, vaccine accessibility, and information exposure on social media on HPV vaccination uptake among 11,678 mothers with daughters aged 9-17 years in China: a cross-sectional study.

BACKGROUND: Mothers play a crucial role in influencing their daughters' HPV vaccination decisions. Addressing barriers to receiving HPV vaccination among mothers of girls may achieve two goals in one strike: increasing vaccination coverage among both mothers and their daughters. This study aims to examine the HPV vaccination uptake and its determinants among mothers of girls in China at both the individual and interpersonal levels. METHODS: From July to October 2023, a cross-sectional online study was conducted to investigate HPV vaccine refusal for daughters aged 9-17 years among 11,678 mothers in Shenzhen, China. A randomized selection method was employed, targeting 11 primary schools and 13 secondary schools in Shenzhen. The research team invited mothers of girls to participate in an anonymous online survey. Multilevel logistic regression models (level 1: schools; level 2: individual participants) were employed to analyze the data. RESULTS: Among 11,678 mothers, 41.1% self-reported receiving at least one dose of HPV vaccination. Through multilevel logistic regression analysis, eight items measuring illness representations of HPV, which refers to how people think about HPV, were associated with higher HPV vaccination uptake (AOR: 1.02-1.14). These items included identity (identifying symptoms of HPV), timeline (whether HPV is acute/chronic), negative consequences, personal and treatment control (whether HPV is under volitional control), concern, negative emotions, and coherence (overall understanding of HPV). In addition, participants refusing HPV vaccines for the index daughters (AOR: 0.82, 95%CI: 0.76, 0.89) had lower vaccine uptake. Perceived more difficulties in accessing the 9-valent vaccines (AOR: 1.06, 95%CI: 1.04, 1.08) and more satisfaction with vaccine-related promotional materials (AOR: 1.50, 95%CI: 1.46, 1.54) at the individual level were associated with higher vaccine uptake. At the interpersonal factors, higher frequency of exposure to testimonials given by others about HPV vaccination on social media (AOR: 1.19, 95%CI: 1.14, 1.25) and thoughtful consideration of the veracity of the information (AOR: 1.11, 95%CI: 1.07, 1.16) were correlated with higher HPV vaccination uptake. CONCLUSIONS: These findings offer essential implications for modifying HPV disease perceptions, addressing difficulties in accessing the 9-valent HPV vaccines, and enhancing health communication needs to improve HPV vaccine uptake among mothers of girls.

CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation.

AIMS: As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance and malignant progression of gastric cancer (GC). METHODS: In vitro and in vivo models were conducted to investigate the manifestation and impact of CBX4 on cellular senescence and chemoresistance. High-throughput sequencing, chromatin immunoprecipitation, and co-immunoprecipitation techniques were utilized to identify the upstream regulators and downstream effectors associated with CBX4, revealing its intricate regulatory network. RESULTS: CBX4 diminishes the sensitivity of GC cells to cellular senescence, facilitating chemoresistance and GC development by deactivating the senescence-related Hippo pathway. Mechanistically, low-dose cisplatin transcriptionally downregulates CBX4 through CEBPB. In addition, CBX4 preserves the stability and cytoplasm-nuclear transport of YAP1, the key player of Hippo pathway, by inducing SUMO1 modification at K97 and K280, which competitively inhibits YAP1-S127 phosphorylation. CONCLUSIONS: Our study highlights the anti-senescence role of CBX4 and suggests that CBX4 inhibition in combination with low-dose cisplatin has the potential to overcome chemoresistance and effectively restrict GC progression.

Associations of mothers' decisional conflicts and satisfaction with governmental health promotion materials with their daughters' HPV vaccination uptake in China: A cross-sectional survey.

Background: China started to implement the HPV vaccination program for females in 2016. This study investigated associations between mothers' decisional conflicts, satisfaction with governmental health promotion materials, and their daughters' HPV vaccination uptake. Methods: A cross-sectional online survey was conducted between July and October 2023 among mothers of girls aged 9-17 years in Shenzhen, China. Participants were mothers having a daughter aged 9-17 years at the survey date and a smartphone with internet access. About 3 % of all primary and secondary schools in Shenzhen were randomly selected by the research team (11 primary schools and 13 secondary schools). Teachers at the selected schools invited mothers of female students aged 9-17 years to complete an anonymous online questionnaire. Multivariate logistic regression was fitted. Results: Among 11,728 mothers who completed the survey, 18.9% of their index daughters received at least one dose of HPV vaccination. In multivariate analysis, less decisional conflict about the choice of HPV vaccines for their daughters (AOR: 1.07, 95%CI: 1.05, 1.10), more satisfaction with the government's health promotional materials related to HPV vaccines (AOR: 1.15, 95%CI: 1.12, 1.19), receiving more cue to action from significant others (AOR: 1.23, 95%CI: 1.19, 1.27), and perceived higher self-efficacy related to HPV vaccines (AOR: 1.79, 95%CI: 1.67, 1.92) were associated with a higher uptake of HPV vaccines. Perceived susceptibility to HPV (AOR: 0.79, 95%CI: 0.74, 0.85), perceived barriers to having the index daughter receive HPV vaccines (AOR: 0.82, 95%CI: 0.80, 0.84), and mothers who were hesitant to receive HPV vaccination (AOR: 0.75, 95%CI: 0.68, 0.84) were associated with a lower uptake. Conclusion: HPV vaccination uptake was low among girls in China. Future health promotion should address mothers' decisional conflicts about the choice of HPV vaccines for their daughters and improve the health promotional materials. School-based HPV vaccination programs might be useful.