Metastatic prostate cancer presenting as generalized lymphadenopathy and progressing with inferior vena cava syndrome: A case report and literature review.

The present study describes the case of a 71-year-old male patient that presented with generalized lymphadenopathy and a pelvic mass, but no signs of bone and visceral metastasis. Their total prostate-specific antigen level was >100 ng/ml. A biopsy of the pelvic mass, situated near the left iliac vessels, confirmed the existence of an adenocarcinoma originating from the prostate and a subsequent prostate biopsy indicated a Gleason score of 4+5. Endocrine treatment with bicalutamide and goserelin (androgen deprivation therapy) resulted in only a partial response of the left iliac metastatic lesions to the treatment. The subsequent treatment plan of androgen deprivation therapy and abiraterone plus docetaxel did not change the progression of the disease. The patient finally developed inferior vena cava syndrome. Subsequently, the patient declined both a re-biopsy of the prostate and enlarged cervical lymph nodes, and interventions by a vascular surgeon. To the best of our knowledge, the present study is the first documented case of a natural progression of metastatic prostate cancer with inferior vena cava syndrome.

Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration.

In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease.

2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC2D2EFG-I'M2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

Pregnancy and survival-related outcomes of uveal melanoma treated with brachytherapy in women of reproductive age.

BACKGROUND: To examine if pregnancy affects the prognosis of uveal melanoma (UM) patients undergoing plaque brachytherapy (PBT) and to assess if PBT has any subsequent impact on pregnancy outcomes. METHODS: A retrospective, single-center study was carried out at Beijing Tongren Hospital, focusing on women of childbearing age diagnosed with UM and treated with iodine-125 plaque brachytherapy. Both the outcomes of pregnancies and the health status of the fetuses were monitored. Survival analyses were conducted using the Kaplan-Meier method, with endpoints being metastasis and death. RESULTS: A total of 13 patients who had full-term pregnancies and 96 non-pregnant women matched by age and tumor size were included. The mean follow-up time was 67.0 ± 27.7 months (median:66.0 months, range:21.0 to 116.0 months). In the pregnant group, two patients developed metastases, one of whom died shortly after delivery; local recurrence of UM occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. None of the other pregnant patients reported any signs of disease progression. In the control group, 18 metastasis cases including 12 deaths were documented. Pregnant patients and matched control subjects showed no statistical difference in both Metastasis-free survival (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15-2.86; P = 0.576) and overall survival (HR: 0.48, 95% CI: 0.06-3.66; P = 0.464). All pregnant patients carried the pregnancy to term and delivered healthy children with no report of placental or infant metastases to date. CONCLUSION: Pregnancy does not appear to negatively impact the prognosis of UM patients undergoing PBT. PBT showed no observable detriment to maternal fertility and exhibited no teratogenic effects on the fetus. However, the long-term implications of PBT on pregnancy remain uncertain, necessitating additional, prolonged follow-up studies.

MicroRNA-376a-3p sensitizes CPT-11-resistant colorectal cancer by enhancing apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) through the IGF1R/PI3K/AKT pathway.

Colorectal cancer (CRC) remains the third most prevalent type of cancer worldwide contributing to an estimated 10 % of all cancer cases. CPT-11 is one of the first-line drugs for CRC treatment. Unfortunately, the development of drug resistance significantly exacerbates the adverse impact of CRC. Consequent tumor recurrences and metastasis, years after treatment are the frequently reported incidences. MicroRNAs (miRNA) are short non-coding RNA with the functionality of gene suppression. The insulin-like growth factor type 1 receptor (IGF1R) is a tyrosine kinase receptor frequently upregulated in cancers and is associated with cell survival and drug resistance. MiRNAs are frequently reported to be dysregulated in cancers including CRC. Evidence suggests that dysregulated miRNAs have direct consequences on the biological processes of their target genes. We previously demonstrated that miRNA-376a-3p is upregulated in CPT-11responsive, CRC cells upon treatment with CPT-11. We therefore aimed to investigate the involvement of miRNA-376a-3p in CPT-11 resistance and its probable association with IGF1R-mediated cancer cell survival. Our experimental approach used knockdown and overexpression experiments supplemented with western blot, RT-qPCR, flow cytometry, MTT, and migration assays to achieve our aim. Our data reveals the mechanism through which IGF1R and miRNA-376a-3p perpetrate and attenuate CPT-11 resistance respectively. MiRNA-376a-3p overexpression negatively regulated the IGF1R-induced cell survival, PI3K/AKT pathway, and reversed the epithelial-mesenchymal transition, hence sensitizing resistant cells to CPT-11. Our findings suggests that the miRNA-376a-3p/IGF1R axis holds promise as a potential target to sensitize CRC to CPT-11 in cases of drug resistance.

Prevalence and associations of dome-shaped maculas. The Beijing Eye Study.

PURPOSE: To explore the prevalence and associated factors of a dome-shaped macula (DSM) in a general population. METHODS: Out of the population-based Beijing Eye Study cohort (n = 3468 participants), the investigation included all eyes with an axial length of ≥25 mm, and a randomized sample of eyes with an axial length of <25 mm. Using optical coherence tomographic (OCT) images, we examined presence and height of DSMs, defined as an inward convexity of the foveal retinal pigment epithelium (RPE)/Bruch's membrane (BM) line, detectable in at least two OCT scans perpendicularly orientated to each other. RESULTS: The study cohort consisted of 366 eyes (314 individuals) with a mean age of 63.7 ± 9.7 years and a mean axial length of 24.8 ± 2.1 mm (median: 25.1 mm; range: 18.96-30.88 mm). Prevalence of DSMs (found in 6/366 eyes; 1.9%; 95%CI: 1.0, 3.0) increased from 0/125 (0%) in non-myopic eyes to 1/152 (0.7%; 95%CI: 0.0, 2.0) in moderately myopic eyes, and to 6/83 (7.2%; 95%CI: 1.7, 12.7) in the highly myopic group. In multivariable analysis, higher DSM prevalence corelated with longer axial length (OR: 2.05; 95%CI: 1.36, 3.08; p < 0.001) and higher stage of myopic macular degeneration (OR: 1.08; 95%CI: 1.01, 1.16; p = 0.03). The mean maximal DSM height was 139 ± 107 µm (median: 100 µm; range: 25-350 µm). It was associated with higher stage of myopic macular degeneration (beta: 0.24; p < 0.001) and higher prevalence of macular BM defects (beta: 0.17; p < 0.001). None of the DSMs showed a serous retinal detachment or relative choroidal thickening. CONCLUSIONS: Higher DSM prevalence correlated non-linearly with longer axial length, with DSM height increasing with the presence of a BM defect. DSMs may be associated with an axial elongation-related BM overproduction in the fundus midperiphery in all meridians.

Radiomic features based on pyradiomics predict CD276 expression associated with breast cancer prognosis.

Background: CD276 is a promising immune checkpoint molecule with significant therapeutic potential. Several clinical trials are currently investigating CD276-targeted therapies. Purpose: This study aims to assess the prognostic significance of CD276 expression levels and to predict its expression using a radiomic approach in breast cancer (BC). Methods: A cohort of 840 patients diagnosed with BC from The Cancer Genome Atlas was included in this study. The Cancer Imaging Archive provided 98 magnetic resonance imaging (MRI) scans, which were randomly allocated to training and validation datasets in a 7:3 ratio. The association between CD276 expression and patient survival was assessed using Cox regression analysis. Feature selection was performed using the maximum relevance minimum redundancy algorithm and recursive feature elimination. Subsequently, support vector machine (SVM) and logistic regression (LR) models were constructed to predict CD276 expression. Results: The expression of CD276 was found to be elevated in BC. It was an independent risk factor for overall survival (hazard ratio = 1.579, 95 % CI: 1.054-2.366). There were eight radiomic features selected in total. In both the training and validation subsets, the SVM and LR models demonstrated favorable predictive abilities with AUC values of 0.744 and 0.740 for the SVM model and 0.742 and 0.735 for the LR model. These results indicate that the radiomic models efficiently differentiate the CD276 expression status. Conclusions: CD276 expression levels can have an impact on cancer prognosis. The MRI-based radiomic signature described in this study can discriminate the CD276 expression status.

Retinal nerve fiber layer defects and chronic kidney disease: the Kailuan Eye Study.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

Screening for Helicobacter pylori to Prevent Gastric Cancer: A Pragmatic Randomized Clinical Trial.

Importance: Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown. Objective: To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality. Design, Setting, and Participants: A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020. Intervention: Invitation for testing for H pylori stool antigen. Main Outcomes and Measures: The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized. Results: Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%). Conclusions and Relevance: Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone. Trial Registration: ClinicalTrials.gov Identifier: NCT01741363.

Jing-Si Herbal Tea Suppresses H2O2-Instigated Inflammation and Apoptosis by Inhibiting Bax and Mitochondrial Cytochrome C Release in HIG-82 Synoviocytes.

Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans; however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing-Si herbal tea (JS), against H2O2-induced inflammation and cellular damage in HIG-82 synoviocytes. We found that JS did not show any significant alterations in cell viability at <188 µg/mL; however, a cytotoxic effect was observed at 188-1883 µg/mL concentrations tested. We found that expressions of inflammation associated extracellular matrix (ECM)-degrading proteases MMP-13, ADAMTS-2, -8, and -17 were abnormally enhanced under H2O2-induced pathological oxidative stress (ROS) in HIG-82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose-dependent manner. Treatment with JS showed enhanced cell viability against H2O2-induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl-2 were increased, whereas MMP-13, ADAMTS-2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF-α treatment, respectively, in HIG-82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2-treated HIG-82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases.