Search

Maximillian S Wu, Hanan Goldberg Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USACorrespondence: Hanan Goldberg, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13520, USA, Tel +1-315-271-4173, Email gohanan@gmail.comAbstract: Prostate cancer is one of the most common types of cancer worldwide and has strong genetic associations. This is important for the development of therapeutics for the condition, as metastatic castrate-resistant prostate cancer (mCRPC) is resistant to standard androgen deprivation therapy (ADT) and has a relatively poor prognosis. We conducted a literature review on rucaparib, a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor that is currently indicated for the treatment of patients with mCRPC who harbor mutations in BRCA1/2 (homologous recombination repair [HRR] genes) and who have already tried androgen receptor-axis-targeted therapies (ARAT) and a taxane chemotherapy. We describe rucaparib’s FDA approval, which was based on the results of the single-arm, open-label, Phase II TRITON2 clinical trial, which found an objective response rate (ORR) of 43.5%, a duration of response (DOR) of over six months in length and an acceptable safety profile. Rucaparib’s dosage and clinical considerations for use were also discussed. We also compared rucaparib’s use and safety profile with Olaparib, niraparib and talazoparib, three other PARP inhibitors tested for the treatment of mCRPC. Overall, initial results show that the safety profile of all four drugs in mCRPC was relatively similar, and further testing is currently indicated for all four. Differences in their metabolism, however, also warrant further research. The clinical validity of rucaparib will be tested by the follow-up TRITON3 clinical trial, which is comparing the effect of rucaparib compared to standard therapies for mCRPC harboring BRCA1/2 or ATM mutations. Other than TRITON3, other clinical trials are testing rucaparib’s ability against other cancers (prostate or otherwise) with HRR mutations, and also the efficacy of combination therapies involving rucaparib. Finally, more research is needed to elucidate rucaparib’s effect on HRR mutations other than BRCA1/2. Advancements in understanding the genetic landscape of mCRPC will also assist in understanding rucaparib’s full therapeutic potential.Keywords: metastatic castrate-resistant prostate cancer, homologous recombination repair, PARP inhibitors, literature review

Ying-Chun Shen,1,2,* Pei-Chang Lee,3,4,* Yu-Lun Kuo,5 Wei-Kai Wu,6 Chieh-Chang Chen,7 Chengh-Hau Lei,7 Ching-Ping Yeh,8 Chiun Hsu,1,2 Chih-Hung Hsu,2,8 Zhong-Zhe Lin,1,8 Yu-Yun Shao,2,8 Li-Chun Lu,2,8 Tsung-Hao Liu,2,8 Chien-Hung Chen,7,9 Ming-Shiang Wu,7,10 Yi-Hsiang Huang,4,11,* Ann-Lii Cheng1,10,* 1Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; 2Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan; 4Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 5Biotools Co., Ltd, New Taipei City, Taiwan; 6Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; 7Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 8Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 9Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Taipei, Taiwan; 10Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 11Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Ann-Lii ChengNational Taiwan University Cancer Center, No. 57, Ln. 155, Sec. 3, Keelung Road, Da-an Dist., Taipei City, 106, TaiwanEmail alcheng@ntu.edu.twYi-Hsiang HuangDepartment of Internal Medicine, Taipei Veterans General Hospital, Taipei, TaiwanEmail yhhuang@vghtpe.gov.twBackground: Gut microbiome has been associated with the efficacy of immune checkpoint inhibitors (ICI) in patients with various types of cancers but not yet in hepatocellular carcinoma (HCC).Aims: To investigate the association between gut microbiome and efficacy of ICI in patients with HCC.Methods: Patients with HCC who were scheduled to receive ICI were prospectively enrolled. Fecal samples were collected within 7 days before initiation of ICI (baseline) and 8 weeks later. Gut microbiome was assessed using 16S rRNA sequencing and shotgun whole-genome sequencing and correlated with objective response (complete or partial response), disease control (objective response or stable disease for ≥ 16 weeks), and overall survival.Results: Thirty-six patients with HCC were enrolled, and 20 of them provided both baseline and 8-week feces. Alpha diversity, richness, and compositions of baseline gut microbiome indicated no difference between responders and nonresponders or between disease control and nondisease control groups. For the 20 paired feces, immunotherapy did not change any of the major microbiome features. No specific taxa were enriched in patients with objective response. Three taxa—Bifidobacterium, Coprococcus, and Acidaminococcus—were enriched in patients with disease control. However, the baseline abundance of these three taxa did not predict overall survival benefit.Conclusions: In this exploratory study, we failed to disclose any overt association of gut microbiome with the efficacy of ICI in patients with HCC. A larger prospective study is warranted for definite conclusion.Keywords: gut microbiome, biomarkers, immune checkpoint inhibitor, hepatocellular carcinoma

Bih-Ru Wang,1,2,* Yuh-Lih Chang,1,2,* Tzeng-Ji Chen,3,4 Jen-Hwey Chiu,5,6 Jing Chong Wu,7 Min-Shan Wu,1 Chia-Lin Chou,1 Yueh-Ching Chou1,2,81Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; 3Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; 5Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; 6Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Traditional Medicine Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8College of Pharmacy, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workBackground: Many female breast cancer (FBC) patients take Chinese herbal medicine (CHM) and Western medication (WM) concurrently in Taiwan. Despite the possibility of interactions between the CHM and WM mentioned in previous studies, the pattern of these coprescriptions in FBC patients remains unclear. Hence, the aim of the present study is to investigate the utilization of coprescriptions of CHM and WM among the FBC patients in Taiwan.Methods: The study was a cross-sectional survey using the sampled cohort in 2009 obtained from the National Health Insurance Research Database in Taiwan. There were 3,507 FBC patients identified from the registry for catastrophic illness patients. Ambulatory visit records, corresponding prescriptions, and the data of beneficiaries belonging to the FBC patients were further extracted. A total of 1,086 FBC patients used CHM at least once. CHM and WM prescribed within any overlapping duration were defined as coprescriptions.Results: There were 868 (80.0%) patients simultaneously receiving CHM and WM. A total of 4,927 CHM prescriptions and 6,358 WM prescriptions were prescribed concurrently. Among these coprescriptions, the most frequently used CHM was jia-wei-xiao-yao-san (21.2%), and the most frequently coprescribed WM was acetaminophen (38.9%), followed by tamoxifen (25.5%). There were 346 patients using systemic adjuvant therapy and CHM concurrently. The most commonly coprescribed CHM with chemotherapy, endocrine therapy, and trastuzumab was xiang-sha-liu-jun-zi-tang, jia-wei-xiao-yao-san, and zhi-gan-cao-tang, respectively.Conclusion: The combined use of CHM with WM is prevalent. The main purpose of combining CHM with systemic cancer treatment is to alleviate the treatment-related adverse effects. However, the combination may result in the potential risk of drug–herb interactions. Further clinical studies are needed to evaluate the efficacy and safety of the CHM and WM coprescriptions for FBC patients.Keywords: drug utilization patterns, complementary and alternative medicine, pharmacoep-idemiology

Background: An increasing proportion of visits are now delivered via a virtual platform. Virtual visits are limited by the lack of important components of cardiovascular assessment such as physician examination and electrocardiogram. Objectives: The purpose of this study was to evaluate the quality of care delivered by virtual visits compared to office-based visits among adults who sought care for three common cardiac-related symptoms: dyspnea, dizziness, or palpitations. Methods: Retrospective cohort study of 992,526 outpatient visits between January 1, 2017, and December 31, 2021, within an integrated health system, including 356,159 visits for dyspnea, 412,913 for dizziness, and 223,454 for palpitations. We compared the differences in patient characteristics associated with telemedicine visits versus in-office visits, evaluated the referral rates for noninvasive cardiac testing, and examined the association between virtual visits and 30-day clinical outcomes. Results: Among 992,526 visits, 71.5% were office visits, 25.8% telephone visits, and 2.7% video visits. Median age was 59 (IQR: 43-72) years, and 63.1% were women. Patient characteristics associated with increased likelihood of virtual visits included younger age, female sex, being non-Hispanic Black, and being from lower-income households. No association was observed between visit types and 30-day cardiovascular hospitalization for patients with dizziness or palpitations. However, for patients with dyspnea, evaluation via virtual visits was associated with a higher risk of 30-day hospitalization for heart failure (aOR: 1.25; 95% CI: 1.16-1.36 for telephone visits; aOR: 1.45; 95% CI: 1.17-1.80 for video visits). Compared to office-based visits, patients with dyspnea were less likely to be referred for echocardiogram with telephone (aOR: 0.73; 95% CI: 0.72-0.75) or video visits (aOR: 0.92; 95% CI: 0.87-0.98). Conclusions: Virtual visits may be appropriate for some clinical concerns but not all. Optimal alignment of clinical conditions with appropriate care modalities is an important component of a successful telemedicine strategy.

Objectives Pancreatic cancer presents a formidable challenge with its aggressive nature and dismal prognosis, often hampered by elusive early symptoms. The tumor microenvironment (TME) emerges as a pivotal player in pancreatic cancer progression and treatment responses, characterized notably by hypoxia and immunosuppression. In this study, we aimed to identify hypoxia-related genes and develop a prognostic model for pancreatic cancer leveraging these genes. Methods Through analysis of gene expression data from The Cancer Genome Atlas (TCGA) and subsequent GO/KEGG enrichment analysis, hypoxia-related pathways were identified. We constructed a prognostic model using lasso regression and validated it using an independent dataset. Results Our results showed that expression levels of PLAU, SLC2A1, and CA9 exhibited significant associations with prognosis in pancreatic cancer. The prognostic model, built upon these genes, displayed robust predictive accuracy and was validated in an independent dataset. Furthermore, we found a correlation between the risk score of the prognostic model and clinical parameters of pancreatic cancer patients. At the same time, we also explored the relationship between the established hypoxia-related prognostic model and the immune microenvironment at the single-cell level. RT-qPCR results showed notable differences in the expression of hypoxia pathway-related genes between normal PANC-1 and hypoxic-treated PANC-1 cells. Conclusion Our study provides insights into the role of the hypoxic microenvironment in pancreatic cancer and offers a promising prognostic tool for clinical application.

Purpose This study enhances the efficiency of predicting complications in lung cancer patients receiving proton therapy by utilizing large language models (LLMs) and meta-analytical techniques for literature quality assessment. Materials and Methods We integrated systematic reviews with LLM evaluations, sourcing studies from Web of Science, PubMed, and Scopus, managed via EndNote X20. Inclusion and exclusion criteria ensured literature relevance. Techniques included meta-analysis, heterogeneity assessment using Cochran’s Q test and I 2 statistics, and subgroup analyses for different complications. Quality and bias risk were assessed using the PROBAST tool and further analyzed with models such as ChatGPT-4, Llama2-13b, and Llama3-8b. Evaluation metrics included AUC, accuracy, precision, recall, F1 score, and time efficiency (WPM). Results The meta-analysis revealed an overall effect size of 0.78 for model predictions, with high heterogeneity observed (I 2 = 72.88%, P < 0.001). Subgroup analysis for radiation-induced esophagitis and pneumonitis revealed predictive effect sizes of 0.79 and 0.77, respectively, with a heterogeneity index (I 2 ) of 0%, indicating that there were no significant differences among the models in predicting these specific complications. A literature assessment using LLMs demonstrated that ChatGPT-4 achieved the highest accuracy at 90%, significantly outperforming the Llama3 and Llama2 models, which had accuracies ranging from 44% to 62%. Additionally, LLM evaluations were conducted 3229 times faster than manual assessments were, markedly enhancing both efficiency and accuracy. The risk assessment results identified nine studies as high risk, three as low risk, and one as unknown, confirming the robustness of the ChatGPT-4 across various evaluation metrics. Conclusion This study demonstrated that the integration of large language models with meta-analysis techniques can significantly increase the efficiency of literature evaluations and reduce the time required for assessments, confirming that there are no significant differences among models in predicting post proton therapy complications in lung cancer patients.

This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.

Non-ST-segment elevation acute myocardial infarction (NSTEMI) is a life-threatening clinical emergency with a poor prognosis. However, there are no individualized nomogram models to identify patients at high risk of NSTEMI who may undergo death. The aim of this study was to develop a nomogram for in-hospital mortality in patients with NSTEMI to facilitate rapid risk stratification of patients. A total of 774 non-diabetic patients with NSTEMI were included in this study. Least Absolute Shrinkage and Selection Operator regression was used to initially screen potential predictors. Univariate and multivariate logistic regression (backward stepwise selection) analyses were performed to identify the optimal predictors for the prediction model. The corresponding nomogram was constructed based on those predictors. The receiver operating characteristic curve, GiViTI calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. The nomogram model consisting of six predictors: age (OR = 1.10; 95% CI: 1.05-1.15), blood urea nitrogen (OR = 1.06; 95% CI: 1.00-1.12), albumin (OR = 0.93; 95% CI: 0.87-1.00), triglyceride (OR = 1.41; 95% CI: 1.09-2.00), D-dimer (OR = 1.39; 95% CI: 1.06-1.80), and aspirin (OR = 0.16; 95% CI: 0.06-0.42). The nomogram had good discrimination (area under the curve (AUC) = 0.89, 95% CI: 0.84-0.94), calibration, and clinical usefulness. In this study, we developed a nomogram model to predict in-hospital mortality in patients with NSTEMI based on common clinical indicators. The proposed nomogram has good performance, allowing rapid risk stratification of patients with NSTEMI.

Background Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM. Method The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes. Results A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM. Conclusion We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.

Purpose: This study aimed to analyze the efficacy and safety of neoadjuvant and adjuvant immunotherapies for non-small cell lung cancer (NSCLC). Methods: Electronic literature searches were conducted in PubMed, OVID, Web of SCI, Embase, Cochrane Library, and the Chinese National Knowledge Infrastructure databases. The deadline for literature update and retrieval is February 16, 2024. Studies presented at meetings were also screened. Randomized controlled trials (RCTs) and single-arm trials were included, and the data were extracted according to the inclusion and exclusion criteria. Data analysis was performed using Stata (16.0) software. Results: A total of 5850 patients in 11 RCTs and 6 single-arm trial studies involving neoadjuvant and/or adjuvant immune checkpoint inhibitor (ICI)-based therapies were included. Regarding neoadjuvant therapy, the overall complication rate after surgery reached 35% (95% CI, 0.21-0.49). Higher rates of pathological complete response (OR = 7.83; 95% CI, 5.95-10.31; P

Objective: DNA methylation is an essential epigenetic marker governed by DNA methyltransferases (DNMTs), which can influence cancer onset and progression. However, few studies have provided an integrated analysis of the relevance of DNMT family genes to cell stemness, the tumor microenvironment (TME), and immunotherapy biomarkers across diverse cancers. Methods: This study investigated the impact of five DNMTs on transcriptional profiles, prognosis, and their association with Ki67 expression, epithelial–mesenchymal transition signatures, stemness scores, the TME, and immunological markers across 31 cancer types from recognized public databases. Results: The results indicated that DNMT1/DNMT3B/DNMT3A expression increased, whereas TRDMT1/DNMT3L expression decreased in most cancer types. DNMT family genes were identified as prognostic risk factors for numerous cancers, as well as being prominently associated with immune, stromal, and ESTIMATE scores, as well as with immune-infiltrating cell levels. Expression of the well-known immune checkpoints, PDCD1 and CILA4, was noticeably related to DNMT1/DNMT3A/DNMT3B expression. Finally, we validated the role of DNMT1 in MCF-7 and HepG2-C3A cell lines through its knockdown, whereafter a decrease in cell proliferation and migration ability in vitro was observed. Conclusion: Our study comprehensively expounded that DNMT family genes not only behave as promising prognostic factors but also have the potential to serve as therapeutic targets in cancer immunotherapy for various types of cancer.

Objectives: To scrutinize the therapeutic efficiency and safety profile of lenvatinib, accompanied by the programmed cell death protein-1 (PD-1) monoclonal antibody, and interventional treatment in managing intermediate-stage hepatocellular carcinoma. Methods: Retrospective analysis was performed on clinical data from 93 patients suffering from intermediate to advanced hepatocellular carcinoma, treated at our institution from May 2018 to April 2020. Patients were divided based on the therapeutic regimen: 43 cases constituted the control group receiving lenvatinib plus transhepatic artery chemoembolization (TACE), while the remaining 50 cases in the study group were managed with lenvatinib, PD-1 monoclonal antibody, and TACE. Outcome measures included therapeutic efficacy, tumor markers (carcinoembryonic antigen [CEA], alpha-fetoprotein [AFP], α-L-fucosidase [AFU], carbohydrate antigen 199 [CA199]), immune response indices (CD3+, CD4+, CD8+, CD4+/CD8+ ratio), pertinent cytokine levels (vascular endothelial growth factor [VEGF], matrix metalloproteinase-9 [MMP-9], basic fibroblast growth factor [aFGF], acidic fibroblast growth factor [bFGF]), quality of life (as per Quality of Life Assessment Scale for Cancer Patients [QOL-LC] scores), adverse effects, and survival rates. Results: The study group exhibited a significantly enhanced total effective rate compared to the control group (74.00% vs 53.49%, P .05). Moreover, the study group reported significantly higher 1-, 2-, and 3-year survival rates than the control group ( P

Objectives Prostate cancer (PRAD) is a highly malignant disease with poor prognosis, and its development is regulated by a complex network of genes and signaling pathways. LncRNAs and miRNAs have significant regulatory roles in PRAD through the ceRNA network. Cuproptosis is a unique form of programmed cell death that is involved in various signaling pathways and biological processes related to tumor development. Nuclear factor of activated T cells 5 (NFAT5), a transcription factor that activates T cells, has been implicated in cuproptosis. However, the regulatory mechanism by which NFAT5 is involved in the ceRNA network in PRAD remains unclear. Methods Through bioinformatics analysis, we found the ceRNA axis that regulates cuproptosis. By performing ROS assay and copper ion concentration assay, we demonstrated that inhibiting NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. By using luciferase assay, we discovered that AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. Results In this study, we found that lncRNA AP000842.3, as a ceRNA of miR-206, was involved in the regulation of levels of the transcription factor NFAT5 associated with cuproptosis in PRAD. First, knocking down NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. Meanwhile, changes in the expression of AP000842.3 and miR-206 could affect the proliferation of PRAD by regulating NFAT5. Mechanistically, AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. In addition, the effects of lncRNA AP000842.3 on malignant progression of PRAD and NFAT5 were partially dependent on miR-206. Conclusion Taken together, our study reveals a key ceRNA regulatory network in PRAD and can be regarded as a new potential target for PRAD diagnosis and treatment.

Background: Solute carrier family 3 member 2 (SLC3A2) is highly expressed in various types of cancers, including bladder cancer (BLCA). However, the role and mechanism of SLC3A2 in the onset and progression of BLCA are still unclear. Methods: The interfering plasmid for SLC3A2 was constructed and transfected into BLCA cells. Cell proliferation, invasion, and migration abilities were assessed to evaluate the impact of SLC3A2 silencing on BLCA cell growth. M1 and M2 macrophage polarization markers were detected to evaluate macrophage polarization. The levels of reactive oxygen species (ROS), lipid peroxidation, and Fe 2+ , as well as the expression of ferroptosis-related proteins, were measured to assess the occurrence of ferroptosis. Ferroptosis inhibitors were used to verify the mechanism. Results: The experimental results showed that SLC3A2 was highly expressed in BLCA cell lines. The proliferation, invasion, and migration of BLCA cells were reduced after interfering with SLC3A2. Interference with SLC3A2 led to increase the expression of M1 macrophage markers and decreased the expression of M2 macrophage markers in M0 macrophages co-cultured with tumor cells. Additionally, interference with SLC3A2 led to increased levels of ROS, lipid peroxidation, and Fe 2+ , downregulated the expression of solute carrier family 7 member11 (SLC7A11) and glutathione peroxidase 4 (GPX4), while upregulated the expression of acyl-coA synthetase long chain family member 4 (ACSL4) and transferrin receptor 1 (TFR1) in BLCA cells. However, the impact of SLC3A2 interference on cell proliferation and macrophage polarization was impeded by ferroptosis inhibitors. Conclusion: Interference with SLC3A2 inhibited the growth of BLCA cells and the polarization of tumor-associated macrophages by promoting ferroptosis in BLCA cells.

Objective: The purpose of this overview is to assess systematic reviews (SRs)/ meta-analyses (MAs) of Huachansu (HCS) combination chemotherapy for treating non-small cell lung cancer (NSCLC) and provide summarized evidence for clinical decision making. Methods: From the creation of the database to JUNE 2023, 8 databases in English and Chinese were searched. SRs/MAs that met the inclusion and exclusion criteria were included. Two reviewers independently screened research, extracted data and assessed methodological quality, risk of bias, report quality and evidence quality by using relevant criteria from AMSTAR-2, ROBIS scale, PRISMA, and GRADE system. Results: The short-term effect, long-term effect, quality of life improvement, safety and pain relief effect in 8 included SRs/MAs were assessed in this overview according to quantitative synthesis. Results assessed by AMSTAR-2, PRISMA, and ROBIS were generally unsatisfactory, with the results of the AMSTAR-2 assessment showing that all of them were of low or critically low quality; the number of items in the included research that were fully reported (compliance was 100%) by the PRISMA checklist was only 50%, while there were 38.10% of the research reporting less than 60% completeness; the ROBIS assessment showed a small number of systems to be low risk of bias. In addition, 26 items were rated as moderate quality, while 50.94% of items were rated as low or critically low quality by GRADE. Conclusion: HCS may be a promising adjuvant therapy for NSCLC. However, high-quality SRs/MAs and randomized control trials (RCTs) should be conducted to provide sufficient evidence so as to draw a definitive conclusion.

Objectives: This study aimed to explore the role of inhibin subunit beta A (INHBA) in the progression of cervical cancer (CCa) and investigate its potential as a therapeutic target. Specifically, the objectives were to assess the expression levels of INHBA in CCa, examine its correlation with patient survival, and elucidate its impact on CCa cell proliferation, cell cycle regulation, migration, invasion, and in vivo tumor growth and metastasis. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. INHBA expression in CCa was analyzed, and its association with patient survival was assessed using clinical data. In vitro experiments involved the investigation of INHBA's effects on CCa cell proliferation, cell cycle dynamics, migration, and invasion through the epithelial–mesenchymal transition (EMT) process. Additionally, in vivo experiments were performed to evaluate the influence of INHBA on CCa growth and lung metastasis. Results: The results of this study revealed upregulated expression of INHBA in CCa, with a significant association between high INHBA expression and poor patient survival. Functionally, INHBA was found to promote the proliferation of CCa cells, regulate the cell cycle, and enhance migration and invasion through the EMT process in vitro. Moreover, in vivo experiments demonstrated that INHBA facilitated the growth and lung metastasis of CCa. Conclusion: In conclusion, our findings suggest that INHBA plays a crucial role in the progression of cervical cancer. The upregulation of INHBA is associated with poor patient survival, and its involvement in promoting key aspects of cancer progression makes it a potential therapeutic target for CCa treatment. These results provide valuable insights into the molecular mechanisms underlying CCa and offer a foundation for further exploration of targeted therapeutic interventions.

Purpose: To evaluate the diagnostic yield of ultrasonography (US)-guided core needle biopsy (CNB) in the diagnosis of soft tissue tumors (STTs) and to analyze the failure factors. Methods: 139 patients with STTs that underwent both US-guided CNB and surgical resection were collected retrospectively. Compared with the histopathological results of surgical resection, the biopsy failure was defined as the following conditions: indefinitive diagnosis, including insufficient samples and unknown subtypes with correct biological potential classification; wrong diagnosis, including wrong biological potential classification and wrong subtypes with correct biological potential classification. Univariate and multivariate analyses from the perspectives of histopathological, demographic and US features together with biopsy procedures were performed to determine risk factors for diagnostic failure. Results: The diagnostic yield of US-guided CNB for STTs in our study was 78.4%, but when only considering the correct biological potential classification of STTs, the diagnostic yield was 80.6%. The multivariate analysis showed that adipocytic tumors (odds ratio (OR) = 10.195, 95% confidence interval (CI): 1.062 - 97.861, p = 0.044), vascular tumors (OR = 41.710, 95% CI: 3.126 - 556.581, p = 0.005) and indeterminate US diagnosis (OR = 8.641, 95% CI: 1.852 - 40.303, p = 0.006) were correlated with the diagnostic failure. The grade III vascular density (OR = 0.019, 95% CI: 0.001 - 0.273, p = 0.007) enabled a higher diagnostic accuracy. Conclusion: US-guided CNB can be an effective modality for the diagnosis of STTs. The diagnostic yield can be increased when the tumor vascular density was grade III in Color Doppler US, but can be decreased in adipocytic tumors, vascular tumors and masses with indeterminate US diagnosis.

Purpose: To understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the centrosomal protein 290 (CEP290) gene. Design: Phase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial. Participants: A homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15–41 years) selected for detailed analyses. Medical histories of 4 participants were consistent with congenital binocular blindness, whereas 1 participant showed evidence of spatial vision in early life that was later lost. Intervention: Participants received a single intravitreal injection of sepofarsen (160 or 320 μg) into the study eye. Main Outcome Measures: Full-field stimulus testing (FST), visual acuity (VA), and transient pupillary light reflex (TPLR) were measured at baseline and for 3 months after the injection. Results: All 5 participants with LP vision demonstrated severely abnormal FST and TPLR findings. At baseline, FST threshold estimates were 0.81 and 1.0 log cd/m2 for control and study eyes, respectively. At 3 months, study eyes showed a large mean improvement of –1.75 log versus baseline (P < 0.001), whereas untreated control eyes were comparable with baseline. Blue minus red FST values were not different than 0 (P = 0.59), compatible with cone mediation of remnant vision. At baseline, TPLR response amplitude and latency estimates were 0.39 mm and 0.72 seconds, respectively, for control eyes, and 0.28 mm and 0.78 seconds, respectively, for study eyes. At 3 months, study eyes showed a mean improvement of 0.44 mm in amplitude and a mean acceleration of 0.29 seconds in latency versus baseline (P < 0.001), whereas control eyes showed no significant change versus baseline. Specialized tests performed in 1 participant confirmed and extended the standardized results from all 5 participants. Conclusions: By subjective and objective evidence, intravitreal sepofarsen provides improvement of light sensitivity for individuals with LP vision. However, translation of increased light sensitivity to improved spatial vision may occur preferentially in those with a history of visual experience during early neurodevelopment. Interventions for congenital lack of spatial vision in CEP290-associated Leber congenital amaurosis may lead to better results if performed before visual cortex maturity.

Introduction: BRAF mutations are rare in patients with NSCLC, and treatment options are limited. Dabrafenib plus trametinib (dab-tram) was approved for BRAFV600-mutated advanced NSCLC (aNSCLC), based on results from a phase 2 study (NCT01336634). This retrospective analysis compared the effectiveness of dab-tram, based on previously reported clinical trial data, versus real-world standard of care in patients with BRAF-mutated aNSCLC. Methods: Real-world cohorts were derived from a deidentified real-world database (2011–2020) and included patients with BRAF-mutated aNSCLC receiving first-line platinum-based chemotherapy (PBC), first-line immune checkpoint inhibitors (ICIs) plus PBC, or second-line ICIs. Weighting by odds was used to estimate the average treatment effect of the treated. Results: For first-line dab-tram versus PBC, the hazard ratio (HR; 95% confidence interval) for death in unweighted and weighted analyses was 0.65 (0.39–1.1) and 0.51 (0.29–0.92; p = 0.03), respectively; unweighted and weighted median overall survival was 17.3 (12.3–40.2) versus 14.5 (9.2–19.6) months and 17.3 (14.6-not reached) versus 9.7 (6.4–19.6) months, respectively. Hazard ratio of death in unweighted and weighted analyses was 0.56 (0.29–1.1) and 0.57 (0.28–1.17), respectively, with first-line dab-tram versus PBC plus ICI, and 0.65 (0.39–1.07) and not reported (Cox proportional-hazards assumption violated), respectively, with second-line dab-tram versus ICI. Conclusions: In this indirect comparison in patients with BRAF-mutated aNSCLC, the risk of death was lower and median overall survival was longer with first-line dab-tram versus PBC. In analyses of dab-tram versus first-line PBC plus ICI or second-line ICI, sample sizes were small and findings were inconclusive with overlapping confidence intervals. Despite some limitations, the study provides useful data for this rare patient population.

This study investigated associations between different types of medical insurance and the incidence of catastrophic health expenditure among middle-aged and the aged in China. The data came from the China Health and Retirement Longitudinal Survey implemented in 2013, with 9782 individuals analyzed. Probit regression models and multiple linear regressions were employed to explore the relationship mentioned above and potential mechanisms behind it. It was found that compared with participants in Urban Resident Basic Medical Insurance, individuals participating in New Cooperative Medical Scheme and Coordinating Urban and Rural Basic Medical Insurance was less likely to undergo catastrophic health expenditure ( P < .001, P = .008), especially for low-income and middle-income group. Participants in New Cooperative Medical Scheme and Coordinating Urban and Rural Basic Medical Insurance were more likely to utilize inpatient medical service ( P < .001, P = .020) and choose low-level medical institutions for treatment ( P = .003, P = .006). And individuals participating in New Cooperative Medical Scheme had lower out-of-pocket expenditure ( P = .034). The study showed the significant difference in the incidence of catastrophic health expenditure among participants in different medical insurances. Efforts should be made to improve the service quality of grassroots medical institutions except for the increase of reimbursement ratio, so that rural residents can enjoy high-quality medical services.

Introduction: There is limited research regarding the benefits of mind-body practices such as meditation in hospitalized patients with an active diagnosis of any cancer type. Methods: We conducted a prospective, randomized, clinical trial (NCT03445572) comparing 2 meditative practices—Isha Kriya (IK) and meditative slow breathing (MSB)—versus wait-list controls in hospitalized cancer patients. Our aim was to determine the feasibility of meditation practice in cancer inpatients. Feasibility was defined as recruitment of more than 50% of the eligible patients approached and at least 60% of the patients having meditated at least 4 days by day 7. Acceptability was assessed on day 7 as a positive response on at least 2 questions on the modified Global Symptom Evaluation (GSE) scale. Results: Forty patients (39% of the eligible patients approached) consented to participate in the study and were randomly assigned to the MSB (n = 13), IK (n = 14), or wait-list (n = 13) groups. Of the 27 patients assigned to receive MSB and IK meditations, day 7 data were available for 18 patients. Fifteen of the 18 patients meditated at least once in the first 7 days, and most (12/15) responded positively on the GSE. Conclusion: Both IK and MSB meditations were acceptable among the hospitalized cancer patients. Feasibility for enrollment and practice was likely not achieved due to limited uninterrupted time for daily meditation, high levels of morbidity in some participants, and limited research staff support. Shorter term outcomes should be explored in future meditation studies involving hospitalized cancer patients.

Objectives: The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment.Methods: Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655).Results: The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively.Conclusions: A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection. [ABSTRACT FROM AUTHOR]

Context: Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection.Objective: To investigate the association between nucleoside analogue use and risk of tumor recurrence in patients with hepatitis B virus (HBV)--related HCC after curative surgery.Design, Setting, and Participants: A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010.Main Outcome Measures: The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality.Results: The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 [20.5%] vs n = 1765 [43.6%]; P < .001), and lower overall death (n = 55 [10.6%] vs n = 1145 [28.3%]; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89).Conclusion: Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of gastrointestinal (GI) manifestations associated with diabetes mellitus (DM) in a Taiwanese population undergoing bidirectional endoscopies.Research Design and Methods: Subjects voluntarily undergoing upper endoscopy/colonoscopy as part of a medical examination at the National Taiwan University Hospital were recruited during 2009. Diagnosis of DM included past history of DM, fasting plasma glucose ≥ 126 mg/dL, or glycated hemoglobin (HbA(1c)) ≥ 6.5%. Comparisons were made between diabetic and nondiabetic subjects, subjects with lower and higher HbA(1c) levels, and diabetic subjects with and without complications, respectively, for their GI symptoms, noninvasive GI testing results, and endoscopic findings.Results: Among 7,770 study subjects, 722 (9.3%) were diagnosed with DM. The overall prevalence of GI symptoms was lower in DM subjects (30.3 vs. 35.4%, P = 0.006). In contrast, the prevalence of erosive esophagitis (34.3 vs. 28.6%, P = 0.002), Barrett's esophagus (0.6 vs. 0.1%, P = 0.001), peptic ulcer disease (14.8 vs. 8.5%, P < 0.001), gastric neoplasms (1.8 vs. 0.7%, P = 0.003), and colonic neoplasms (26.6 vs. 16.5%, P < 0.001) was higher in diabetic subjects. Diagnostic accuracy of immunochemical fecal occult blood test for colonic neoplasms was significantly decreased in DM (70.7 vs. 81.7%, P < 0.001). Higher HbA(1c) levels were associated with a decrease of GI symptoms and an increase of endoscopic abnormalities. Diabetic subjects with complications had a higher prevalence of colonic neoplasms (39.2 vs. 24.5%, P = 0.002) than those without.Conclusions: DM and higher levels of HbA(1c) were associated with lower prevalence of GI symptoms but higher prevalence of endoscopic abnormalities. [ABSTRACT FROM AUTHOR]

BACKGROUND: People who have come close to death may report an unusual experience known as a near-death experience (NDE). This study aims to investigate NDEs and their aftereffects in dialysis patients. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 710 dialysis patients at 7 centers in Taipei, Taiwan. PREDICTOR: Demographic characteristics, life-threatening experience, depression, and religiosity. OUTCOMES: NDE and self-perceived changes in attitudes or behaviors. MEASUREMENTS: Greyson's NDE scale, Royal Free Questionnaire, 10-Question Survey, Ring's Weighted Core Experience Index, and Beck Depression Inventory. RESULTS: 45 patients had 51 NDEs. Mean NDE score was 11.9 (95% confidence interval, 11.0 to 12.9). Out-of-body experience was found in 51.0% of NDEs. Purported precognitive visions, awareness of being dead, and 'tunnel experience' were uncommon (<10%). Compared with the no-NDE group, subjects in the NDE group were more likely to be women and younger at life-threatening events. Both frequency of participation in religious ceremonies and pious religious activity correlated significantly with NDE score in patients with NDEs (P < 0.01 and P = 0.01, respectively). The NDE group reported being kinder to others (P = 0.04) and more motivated (P = 0.02) after their life-threatening events than the no-NDE group. LIMITATIONS: Determining the incidence of NDEs is dependent on self-reporting. Many NDEs occurred before the patient began long-term dialysis therapy. Causality between NDE and aftereffects cannot be inferred. CONCLUSIONS: NDE is not uncommon in the dialysis population and is associated with positive aftereffects. Nephrology care providers should be aware of the occurrence and aftereffects of NDEs. The high occurrence of life-threatening events, availability of medical records, and accessibility and cooperativeness of patients make the dialysis population very suitable for NDE research.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

AIMS: Single nucleotide polymorphisms in matrix metalloproteinase-2 (MMP-2) -1306 C/T and tissue inhibitor of metalloproteinase-2 (TIMP-2) -418 G/C abolish the Sp-1 binding site and down-regulate expression of these genes. We aim to elucidate the role of MMP-2 and TIMP-2 in clinicopathological manifestations of gastric cancer. METHODS: We enrolled 240 gastric cancer patients and 283 controls. DNA was extracted from peripheral blood leucocytes. MMP-2 and TIMP-2 genotypes were analysed by PCR-direct sequencing and PCR-RFLP method, respectively. RESULTS: MMP-2 and TIMP-2 genotypes were not associated with gastric cancer development. However, patients with MMP-2 -1306 C/C genotype showed higher risk of lymphatic invasion (odds ratio (OR)=2.77, p=0.01) and venous invasion (OR=2.93, p=0.012). TIMP-2 G/G genotype was associated with serosal invasion (OR=1.89, p=0.009), lymph node metastasis (OR=2.19, p=0.021), lymphatic invasion (OR=2.87, p=0.016) and venous invasion (OR=2.65, p=0.033). CONCLUSION: Our results suggest MMP-2 and TIMP-2 genotypes play a crucial role in gastric cancer invasion, but not with development of gastric cancer. [ABSTRACT FROM AUTHOR]

This open-label, randomized, placebo-controlled, incomplete-block, 3-period crossover pilot study investigated the effects of peroxisome proliferator-activated receptor alpha- and gamma-agonists on biomarkers of lipid and glucose metabolism in 12 nondiabetic subjects. Plasma samples were collected before and after each 14-day treatment with placebo, fenofibrate (201 mg/d), rosiglitazone (4 mg twice daily), and combined fenofibrate (201 mg/d) plus rosiglitazone (4 mg twice daily). Except for triglycerides (P < .042) and free fatty acids (P < .074), no significant interaction was demonstrated between fenofibrate and rosiglitazone; thus, the effect due to each drug alone was evaluated (presence/absence of drug). Fenofibrate significantly (P < .050) increased lipoprotein lipase activity (35%) and decreased apolipoproteins B (13%) and C-III (20%). Rosiglitazone significantly (P < .050) decreased fasting glucose (7.3%) and increased apolipoprotein C-III (19%) and adiponectin (137%). Fenofibrate and rosiglitazone also produced effects on triglycerides and free fatty acids, but it was not possible to determine if these effects were synergistic in nature. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the attitudes of pharmacists towards the issue of dispensing errors. METHOD: A postal survey was undertaken among all Tasmanian-registered pharmacists residing in Australia. The anonymous questionnaire sought opinions on whether the risk of dispensing errors and the actual numbers of errors are increasing, the major factors contributing to the occurrence of dispensing errors, factors that can best minimize the risk of dispensing errors, the number of prescription items that one pharmacist can safely dispense in a day and whether Australia should have a regulatory maximum dispensing load, and an estimation of the number of recent errors at the pharmacist's workplace. RESULTS: Completed questionnaires were received from 209 pharmacists (50% response rate). Most pharmacists (82%) believed that the risk of dispensing errors is increasing. The principal contributing factors nominated were: high prescription volumes, pharmacist fatigue, pharmacist overwork, interruptions to dispensing, and similar or confusing drug names. The main factors identified as being important in reducing the risk of dispensing errors were: having mechanisms for checking dispensing procedures, having a systematic dispensing workflow, checking the original prescription (duplicate) when dispensing repeats, improving the packaging and labelling of drug products, having drug names that are distinctive, counselling patients at the time of supply, keeping one's knowledge of drugs up-to-date, avoiding interruptions, reducing workloads on pharmacists, improving doctors' handwriting, and privacy when counselling patients. Most pharmacists (72%) stated that they were aware of dispensing errors that had left the pharmacy undetected, in their place of practice during the past 6 months. The median number of such dispensing errors that they were aware of was three. A median of 150 was nominated as the maximum number of prescription items that can be safely dispensed per 9-h day (i.e. 17 items per hour) by or in the presence of one pharmacist. Most pharmacists (58%) stated that there should be a regulatory guideline for the safe dispensing load in Australia. CONCLUSION: Dispensing errors are occurring in numbers well above reports to regulatory authorities or professional indemnity insurance companies, and seem to be accepted as part of practice. High prescription volumes, pharmacist fatigue and overwork appear to be important factors. The profession needs to be proactive and standards must be set appropriately high (i.e. zero error tolerance). [ABSTRACT FROM AUTHOR]

Background: Left bundle branch pacing (LBBP) is a physiological pacing that captures the main left bundle or its proximal branch. Electromechanical activation time (EMAT) is an acoustic cardiographic metric that provides a simple method for evaluating left ventricular (LV) synchrony. Prolonged EMAT reflects impaired LV electromechanical coupling. Objective: The purpose of this study was to explore whether EMAT can confirm that LBBP produces more satisfactory LV electromechanical synchronization than conventional right ventricular pacing modalities. Methods: Patients with standard pacing indications and narrow QRS duration were recruited for this study. Unipolar pacing under 3 different modalities—right ventricular apical pacing (RVAP), right ventricular high septal pacing (RVHSP), and LBBP—were successively performed in each patient. Pacing parameters, echocardiographic characteristics, and acoustic cardiographic parameters at different pacing modalities and during normal rhythm were collected. Results: A total of 55 patients were enrolled, and all had successful LBBP. Left ventricular activation time (LVAT) was significantly associated with EMAT, with LVAT vs EMAT correlation coefficient of 0.665 (P