Public knowledge and willingness in the use of public access defibrillation of Hubei Province in China: A cross-sectional study.

To understand the current status of public knowledge of automated external defibrillator (AED) and their willingness to use public AED in Hubei Province, along with the influencing factors. A self-designed questionnaire was used for convenience sampling of the public in Hubei Province. The questionnaire consists of three parts: basic information, AED knowledge questions, and willingness to use public AED and influencing factors. Data was collected between May 2022 and March 2023. A total of 1561 valid questionnaires were collected from 1602 distributed. In the study conducted in Hubei Province, it was found that 875 respondents (56.05%) had knowledge of automated external defibrillator, and they achieved an average score of 39.27 ± 29.17. The pass rate for the survey was 28.11%. Several factors were identified as significant influencing factors, including gender, age, education level, occupation related to medicine, residential location in the past three years, family members with cardiovascular disease, marital status, residential population density, whether there are family members over 65 years old, and participation in AED-related training (P < .05).Furthermore, 692 respondents (72.99%) expressed their willingness to cardiopulmonary resuscitation for someone experiencing cardiac arrest. On the other hand, 686 respondents (43.95%) had no knowledge of AED. Among those who were not willing to perform defibrillation, the highest percentages cited "fear of incorrect use" (129, 31.2%) and "fear of harming the patient" (121, 29.3%) as their reasons. The study also found statistically significant differences in the willingness to use public AED based on participation in training, education level, residential location, family members with cardiovascular disease, population density, and the presence of elderly family members aged 65 or over (P < .05). In conclusion, the study highlights the general lack of public knowledge regarding AED in Hubei Province. However, there is a strong willingness among respondents to provide help during cardiac arrest situations. To improve the chances of survival for cardiac arrest patients, it is crucial to strengthen public AED training programs.

Cross-talk between Myeloid and B Cells Shapes the Distinct Microenvironments of Primary and Secondary Liver Cancer.

The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments. B cells displayed distinct developmental trajectories in HCC and CRLM. Single-cell analysis revealed that IgG+ plasma cells preferentially accumulated in HCC, whereas IgA+ plasma cells were preferentially enriched in CRLM. Mechanistically, IgG+ plasma cells in HCC were recruited by tumor-associated macrophages via the CXCR3-CXCL10 axis, whereas IgA+ plasma cells in CRLM were recruited by metastatic tumor cells via CCR10-CCL28 signaling. Functionally, IgG+ plasma cells preferentially promoted protumorigenic macrophages formation in HCC, and IgA+ plasma cells preferentially induced granulocytic myeloid-derived suppressor cells activation in CRLM. Clinically, increased infiltration of IgG+ plasma cells and macrophages in HCC was correlated to worse survival, whereas increased intratumoral IgA+ plasma cells and neutrophils in CRLM indicated poor prognosis. Taken together, this study demonstrated plasma and myeloid cell-mediated immunosuppression in HCC and CRLM, suggesting that selectively modulating primary or secondary tumor-related immunosuppressive regulatory networks might reprogram the microenvironment and provide an immunotherapeutic strategy for treating liver cancer. SIGNIFICANCE: The immunomodulatory patterns of tumor-infiltrating B cells are distinct in primary and secondary liver cancer, with plasma cells mediating important physiologic processes that drive cancer progression.

Oxidative stress induced by berberine-based mitochondria-targeted low temperature photothermal therapy.

Introduction: Mitochondria-targeted low-temperature photothermal therapy (LPTT) is a promising strategy that could maximize anticancer effects and overcome tumor thermal resistance. However, the successful synthesis of mitochondria-targeted nanodrug delivery system for LPTT still faces diverse challenges, such as laborious preparations processes, low drug-loading, and significant systemic toxicity from the carriers. Methods: In this study, we used the tumor-targeting folic acid (FA) and mitochondria-targeting berberine (BBR) derivatives (BD) co-modified polyethylene glycol (PEG)-decorated graphene oxide (GO) to synthesize a novel mitochondria-targeting nanocomposite (GO-PEG-FA/BD), which can effectively accumulate in mitochondria of the osteosarcoma (OS) cells and achieve enhanced mitochondria-targeted LPTT effects with minimal cell toxicity. The mitochondria-targeted LPTT effects were validated both in vitro and vivo. Results: In vitro experiments, the nanocomposites (GO-PEG-FA/BD) could eliminate membrane potential (ΔΨm), deprive the ATP of cancer cells, and increase the levels of reactive oxygen species (ROS), which ultimately induce oxidative stress damage. Furthermore, in vivo results showed that the enhanced mitochondria-targeted LPTT could exert an excellent anti-cancer effect with minimal toxicity. Discussion: Taken together, this study provides a practicable strategy to develop an ingenious nanoplatform for cancer synergetic therapy via mitochondria-targeted LPTT, which hold enormous potential for future clinical translation.

Investigating potential ferroptosis-related differentially expressed genes of UVB-induced skin photodamage.

OBJECTIVES: Ultraviolet B (UVB) is one of the most dangerous insults for skin, which can cause skin sunburn, pigment disease, photoaging, and photocarcinogenesis. This study aimed to identify pathogenic genes related to ferroptosis in the skin of humans after UVB radiation. METHODS: The gene expression profiles (GSE41078, GSE54413) were downloaded from the Gene Expression Omnibus (GEO) database, and the ferroptosis-related genes (FRGs) were downloaded from the Genecards database. To identify the differentially expressed genes (DEGs) and obtain differentially expressed FRGs by intersecting DEGs with FRGs. To identify the functional annotation and potential pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Differentially expressed FRGs-associated protein-protein interaction network (PPI) was performed by STRING database and Cytoscape software. RESULTS: A total of 628 co-expressed DEGs of the two profiles (GSE41078 and GSE54413) were identified, including 371 upregulated and 257 downregulated DEGs. A total of 32 differentially expressed FRGs were identified. The results of GO analyses showed that, in the biological processes, UVB had a great influence on the response to oxidative stress; in the molecular functions, UVB had a great influence on antioxidant activity; in the cellular components, UVB had a great influence on endocytic vesicle lumen. The key pathways of differentially expressed FRGs were identified by KEGG analyses. The most significant 12 central node genes were identified by PPI network. CONCLUSION: We identified differentially expressed FRGs candidate genes and pathways in UVB-induced skin photodamage, which could contribute to the development of new therapeutic targets for skin photodamage.

Application and prospect of ROS-related nanomaterials for orthopaedic related diseases treatment.

The importance of reactive oxygen species (ROS) in the occurrence and development of orthopaedic related diseases is becoming increasingly prominent. ROS regulation has become a new method to treat orthopaedic related diseases. In recent years, the application of nanomaterials has become a new hope for precision and efficient treatment. However, there is a lack of reviews on ROS-regulated nanomaterials for orthopaedic related diseases. Based on the key significance of nanomaterials for the treatment of orthopaedic related diseases, we searched the latest related studies and reviewed the nanomaterials that regulate ROS in the treatment of orthopaedic related diseases. According to the function of nanomaterials, we describe the scavenging of ROS related nanomaterials and the generation of ROS related nanomaterials. In this review, we closely integrated nanomaterials with the treatment of orthopaedic related diseases such as arthritis, osteoporosis, wound infection and osteosarcoma, etc., and highlighted the advantages and disadvantages of existing nanomaterials. We also looked forward to the design of ROS-regulated nanomaterials for the treatment of orthopaedic related diseases in the future.

ALA-PDT combined with oral acitretin in the treatment of refractory condyloma acuminatum in anal canal.

BACKGROUND: Condyloma acuminatum (CA) of the anal canal is difficult to treat and subject to relapse.. We investigated the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with oral acitretin during therapy of refractory CA in the anal canal. We also conducted a clinical retrospective study for the treatment of intra-anal CA. METHODS: A total of 101 patients diagnosed with intra-anal CA were enrolled. All patients underwent liquid nitrogen cryotherapy as a basic treatment until visible wart clearance. Patients were divided into two groups depending on the treatment modality after cryotherapy. ALA-PDT group with 51 patients was given ALA-PDT treatment, and ALA-PDT plus acitretin group with 50 patients was given ALA-PDT treatment combined with oral acitretin. The cure rate, recurrence rate, and adverse reactions of the two groups were analyzed and recorded. RESULTS: The cure rate in the ALA-PDT plus acitretin group was 94% (47/50), which was significantly higher than 80.4% (41/51) in ALA-PDT group. The recurrence rate in the ALA-PDT plus acitretin group was 6% (3/50), which was lower than 19.6% (10/51) in ALA-PDT group (P<0.05). CONCLUSION: ALA-PDT combined with oral acitretin is effective and safe in the treatment of refractory CA in anal canal, and with further study may become an option for these patients.

Using Systemic Inflammatory Markers to Predict Microvascular Invasion Before Surgery in Patients With Hepatocellular Carcinoma.

Background: Mounting studies reveal the relationship between inflammatory markers and post-therapy prognosis. Yet, the role of the systemic inflammatory indices in preoperative microvascular invasion (MVI) prediction for hepatocellular carcinoma (HCC) remains unclear. Patients and Methods: In this study, data of 1,058 cases of patients with HCC treated in the First Affiliated Hospital of Sun Yat-sen University from February 2002 to May 2018 were collected. Inflammatory factors related to MVI diagnosis in patients with HCC were selected by least absolute shrinkage and selection operator (LASSO) regression analysis and were integrated into an "Inflammatory Score." A prognostic nomogram model was established by combining the inflammatory score and other independent factors determined by multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive efficacy of the model. Results: Sixteen inflammatory factors, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, etc., were selected by LASSO regression analysis to establish an inflammatory score. Multivariate logistic regression analysis showed that inflammatory score (OR = 2.14, 95% CI: 1.63-2.88, p < 0.001), alpha fetoprotein (OR = 2.02, 95% CI: 1.46-2.82, p < 0.001), and tumor size (OR = 2.37, 95% CI: 1.70-3.30, p < 0.001) were independent factors for MVI. These three factors were then used to establish a nomogram for MVI prediction. The AUC for the training and validation group was 0.72 (95% CI: 0.68-0.76) and 0.72 (95% CI: 0.66-0.78), respectively. Conclusion: These findings indicated that the model drawn in this study has a high predictive value which is capable to assist the diagnosis of MVI in patients with HCC.

Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma.

PURPOSE: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma (ICC). However, little is known about the intertumor heterogeneity (ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making. EXPERIMENTAL DESIGN: We obtained 66 tumor samples from 16 patients with multifocal ICC and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA sequencing, methylation microarray, and multiplex immunostaining. Patients were divided into high- or low-ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed. RESULTS: Multifocal ICC presented considerable intertumor genomic, transcriptional, and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor-immune cell interactions, and upregulated IFN-signature expression in high-immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression. CONCLUSIONS: There is comprehensive heterogeneity in the genome, transcriptome, and epigenome of multifocal ICC. On the basis of the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.

Early cannulation arteriovenous graft (Acuseal) versus standard arteriovenous graft in patients with end-stage renal disease.

INTRODUCTION: The use of Acuseal arteriovenous graft (AAVG) is spreading in end-stage renal disease (ESRD) patients for its advantages in early cannulation. However, comparison of clinical outcomes between AAVGs and standard arteriovenous grafts (SAVGs) is limited. In this study, we compared the performance of AAVGs and SAVGs. METHODS: Consecutive ESRD patients underwent prosthetic vascular access between October 2017 and May 2019 at a single center were identified. Patients were divided into AAVG group and SAVG group. Patients' demographics, perioperative characteristics, and clinical outcomes were collected. Primary, primary assisted, and secondary patency rates were compared using Kaplan-Meier analyses. Postsurgery complications were compared using chi-square test or the Fisher's exact test. FINDINGS: A total of 304 arteriovenous grafts (AVGs) were implanted in 145 males and 159 females (mean age, 60.1 years; range, 20-91 years), comprising 143 AAVGs and 161 SAVGs. Median time to first cannulation was 3 days (interquartile range [IQR], 1-15 days) in the AAVG group and 30 days (IQR, 20-52 days) in the SAVG group (P < 0.001). Adjusted primary, primary assisted, and secondary patency at 12 months were not significant different between AAVGs and SAVGs (P = 0.911, P = 0.945, and P = 0.640, respectively). There was no statistical significance in regards to thrombosis (AAVG, 34.3%; SAVG, 26.1%; P = 0.120) and infection (AAVG, 4.9%; SAVG, 2.5%; P = 0.261) between the groups. DISCUSSION: Acuseal grafts provide comparable patency, and complication rates to SAVGs, with less time to first cannulation from the graft implanted.

Promising application of Pulsed Electromagnetic Fields (PEMFs) in musculoskeletal disorders.

Increasing evidence suggests that an exogenous electromagnetic field might be involved in many biologic processes which are of great importance for therapeutic interventions. Pulsed electromagnetic fields (PEMFs) are known to be a noninvasive, safe and effective therapy agent without apparent side effects. Numerous studies have shown that PEMFs possess the potential to become a stand-alone or adjunctive treatment modality for treating musculoskeletal disorders. However, several issues remain unresolved. Prior to their widely clinical application, further researches from well-designed, high-quality studies are still required to standardize the treatment parameters and derive the optimal protocol for health-care decision making. In this review, we aim to provide current evidence on the mechanism of action, clinical applications, and controversies of PEMFs in musculoskeletal disorders.

Successful treatment with ALA-PDT of Refractory condyloma acuminatum of the whole anterior urethra.

Condyloma acuminatum is a sexually transmitted disease caused by human papillomavirus infection, which mostly occurs in the external genitalia, vulva, perianal, and the Intraurethral condyloma acuminatum is relatively rare. Treatment of urethral warts present a challenge especially if the proximal urethra is involved. Here, we report a case of intractable urethral condyloma acuminatum involving the urethral meatus and mid penile urethra with scar. This case suggested that local Photodynamic therapy in condyloma of the whole anterior urethra appears to be not only safe and effective, but also might be able to improve existing scars.

The Personalized Shoulder Reconstruction Assisted by 3D Printing Technology After Resection of the Proximal Humerus Tumours.

BACKGROUND: The reverse shoulder arthroplasty (RSA) may be a promising alternative for proximal humerus tumours because of good postoperative shoulder function. However, the conventional reverse shoulder prosthesis can not meet individual needs and RSA has been associated with a relatively high complication rate. Therefore, implant design and surgical reconstruction technique warrant further study. METHODS: Between September 2015 and May 2018, 7 patients were treated via RSA after en-bloc resection of the proximal humerus tumours. A 3D-printed guiding baseplate was used to assist the implant of the 3D-printed glenoid prosthesis; a personalized humerus prosthesis was used to reconstruct the proximal humerus. The functional outcomes were assessed by range of motion (ROM) of the shoulder joint, Musculoskeletal Tumour Society (MSTS) functional score, and Toronto Extremity Salvage Score (TESS). We also analyzed tumour recurrence, metastases, and complications associated with the reconstruction procedure. RESULTS: All patients were observed for 14 to 36 months, with an average of 23.6 months. At the final follow-up, the mean MSTS score was 85.7% (range, 73.3-93.3%), and the mean TESS score was 90.0% (range, 84.1-95.9%). No instability, infection, scapular notching, loosening or fracture were observed in this series. One patient with GCT suffered from pulmonary metastasis, while one with osteosarcoma died because of pulmonary metastasis. CONCLUSION: The 3D-printed guiding baseplate facilitated the accurate implantation of the glenoid prosthesis. The RSA based on a 3D-printed glenoid prosthesis and a personalized custom-made humerus prosthesis significantly improved the shoulder function and decreased the complication rate. Further studies of a larger scale with longer follow-up are required to validate this technology.