Exploring the characteristics and antecedents of clinically significant long COVID: A longitudinal cohort study.

BACKGROUND: A significant number of coronavirus disease 2019 (COVID-19) survivors are experiencing long COVID, with symptoms lasting beyond three months. While diverse long COVID symptoms are established, there are gaps in understanding its long-term trends, intensity, and risk factors, requiring further investigation. AIMS: This study aimed to investigate the long COVID characteristics and associated factors by following COVID-19 survivors for one year post-infection and comparing them with healthy counterparts. MAIN METHODS: In this longitudinal, correlational study, COVID-19 survivors diagnosed between November 2021 and February 2023 were monitored every three months for a year. Participants aged ≥18 years who had reported a positive COVID-19 test were recruited via social media and healthcare provider referrals. KEY FINDINGS: Out of 182 survivors who initially agreed to participate, 176 completed the study. The mean age was 47.56 years (SD = 16.2), and 51.1 % were female. There was a clinically significant decline in cognitive function and health-related quality of life over time, with symptoms like shortness of breath, reduced physical fitness, and increased health concerns. Those with severe acute COVID-19 symptoms experienced greater cognitive and physical declines and more shortness of breath a year later. Lower financial status was linked to poorer health-related quality of life and increased health concerns. SIGNIFICANCE: A year post-infection, COVID-19's impact on cognitive function and health-related quality of life remains significant, affecting individuals and communities. Survivors with severe initial symptoms and economic disadvantages need more attention. Future research should identify additional predictors of severe long COVID.

Interleukin 11 therapy causes acute left ventricular dysfunction.

AIMS: Interleukin 11 (IL11) was initially thought important for platelet production, which led to recombinant IL11 being developed as a drug to treat thrombocytopenia. IL11 was later found to be redundant for haematopoiesis and its use in patients is associated with unexplained and severe cardiac side effects. Here we aim to identify, for the first time, direct cardiomyocyte toxicities associated with IL11, which was previously believed cardioprotective. METHODS AND RESULTS: We injected recombinant mouse lL11 (rmIL11) into mice and studied its molecular effects in the heart using immunoblotting, qRT-PCR, bulk RNA-seq, single nuclei RNA-seq (snRNA-seq) and ATAC-seq. The physiological impact of IL11 was assessed by echocardiography in vivo and using cardiomyocyte contractility assays in vitro. To determine the activity of IL11 specifically in cardiomyocytes we made two cardiomyocyte-specific Il11ra1 knockout (CMKO) mouse models using either AAV9-mediated and Tnnt2-restricted (vCMKO) or Myh6 (m6CMKO) Cre expression and an Il11ra1 floxed mouse strain. In pharmacologic studies, we studied the effects of JAK/STAT inhibition on rmIL11-induced cardiac toxicities. Injection of rmIL11 caused acute and dose-dependent impairment of left ventricular ejection fraction (saline: 62.4% ± 1.9; rmIL11: 32.6% ± 2.9, p<0.001, n=5). Following rmIL11 injection, myocardial STAT3 and JNK phosphorylation were increased and bulk RNA-seq revealed upregulation of pro-inflammatory pathways (TNFα, NFκB and JAK/STAT) and perturbed calcium handling. snRNA-seq showed rmIL11-induced expression of stress factors (Ankrd1, Ankrd23, Xirp2), activator protein-1 (AP-1) transcription factor genes and Nppb in the cardiomyocyte compartment. Following rmIL11 injection, ATAC-seq identified the Ankrd1 and Nppb genes and loci enriched for stress-responsive, AP-1 transcription factor binding sites. Cardiomyocyte-specific effects were examined in vCMKO and m6CMKO mice, which were both protected from rmIL11-induced left ventricular impairment and molecular pathobiologies. In mechanistic studies, inhibition of JAK/STAT signalling with either ruxolitinib or tofacitinib prevented rmIL11-induced cardiac dysfunction. CONCLUSIONS: Injection of IL11 directly activates IL11RA/JAK/STAT3 in cardiomyocytes to cause acute heart failure. Our data overturn the earlier assumption that IL11 is cardioprotective and explain the serious cardiac side effects associated with IL11 therapy.

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.

Artemisia argyi mitigates doxorubicin-induced cardiotoxicity by inhibiting mitochondrial dysfunction through the IGF-IIR/Drp1/GATA4 signaling pathway.

Doxorubicin (DOX) is mostly utilized as a wide range of antitumor anthracycline to treat different cancers. The severe antagonistic impacts of DOX on cardiotoxicity constrain its clinical application. Many mechanisms are involved in cardiac toxicity induced by DOX in the human body. Mitochondria is a central part of fatty acid and glucose metabolism. Thus, impaired mitochondrial metabolism can increase heart failure risk, which can play a vital role in cardiomyocyte mitochondrial dysfunction. This study aimed to assess the possible cardioprotective effect of water-extracted Artemisia argyi (AA) against the side effect of DOX in H9c2 cells and whether these protective effects are mediated through IGF-IIR/Drp1/GATA4 signaling pathways. Although several studies proved that AA extract has benefits for various diseases, its cardiac effects have not yet been identified. The H9c2 cells were exposed to 1 µM to establish a model of cardiac toxicity. The results revealed that water-extracted AA could block the expression of IGF-IIR/calcineurin signaling pathways induced by DOX. Notably, our results also showed that AA treatment markedly attenuated Akt phosphorylation and cleaved caspase 3, and the nuclear translocation markers NFATC3 and p-GATA4. Using actin staining for hypertrophy, we determined that AA can reduce the effect of mitochondrial reactive oxygen species and cell size. These findings suggest that water-extracted AA could be a suitable candidate for preventing DOX-induced cardiac damage.

Rapid and noninvasive estimation of human arsenic exposure based on 4-photo-set of the hand and foot photos through artificial intelligence.

Chronic exposure to arsenic is linked to the development of cancers in the skin, lungs, and bladder. Arsenic exposure manifests as variegated pigmentation and characteristic pitted keratosis on the hands and feet, which often precede the onset of internal cancers. Traditionally, human arsenic exposure is estimated through arsenic levels in biological tissues; however, these methods are invasive and time-consuming. This study aims to develop a noninvasive approach to predict arsenic exposure using artificial intelligence (AI) to analyze photographs of hands and feet. By incorporating well water consumption data and arsenic concentration levels, we developed an AI algorithm trained on 9988 hand and foot photographs from 2497 subjects. This algorithm correlates visual features of palmoplantar hyperkeratosis with arsenic exposure levels. Four pictures per patient, capturing both ventral and dorsal aspects of hands and feet, were analyzed. The AI model utilized existing arsenic exposure data, including arsenic concentration (AC) and cumulative arsenic exposure (CAE), to make binary predictions of high and low arsenic exposure. The AI model achieved an optimal area under the curve (AUC) values of 0.813 for AC and 0.779 for CAE. Recall and precision metrics were 0.729 and 0.705 for CAE, and 0.750 and 0.763 for AC, respectively. While biomarkers have traditionally been used to assess arsenic exposure, efficient noninvasive methods are lacking. To our knowledge, this is the first study to leverage deep learning for noninvasive arsenic exposure assessment. Despite challenges with binary classification due to imbalanced and sparse data, this approach demonstrates the potential for noninvasive estimation of arsenic concentration. Future studies should focus on increasing data volume and categorizing arsenic concentration statistics to enhance model accuracy. This rapid estimation method could significantly contribute to epidemiological studies and aid physicians in diagnosis.

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.

[Retracted] Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose­derived stem cells into fibroblasts.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical images shown in Fig. 2B and C on p. 896 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published before this paper was received at International Journal of Molecular Medicine (several of which have been retracted). Moreover, the flow-cytometric data shown in Fig. 2A appeared to be potentially anomalous. In view of the fact that the abovementioned data had already apparently been published prior to the submission of this paper to International Journal of Molecular Medicine, the Editor has decided that the article should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 890-900, 2019; DOI: 10.3892/ijmm.2018.4006].

The proliferation and differentiation of skeletal muscle stem cells are enhanced in a bioreactor.

Skeletal muscle (SKM) is the largest organ in mammalian body and it can repair damages by using the residential myogenic stem cells (MuSC), but this repairing capacity reduces with age and in some genetic muscular dystrophy. Under these circumstances, artificial amplification of autologous MuSC in vitro might be necessary to repair the damaged SKM. The amplification of MuSC is highly dependent on myogenic signals, such as sonic hedgehog (Shh), Wnt3a, and fibroblast growth factors, so formulating an optimum myogenic kit composed of specific myogenic signals might increase the proliferation and differentiation of MuSC efficiently. In this study, various myogenic signals have been tested on C2C12 myoblasts and primary MuSC, and a myogenic kit consists of insulin, lithium chloride, T3, and retinoic acid has been formulated, and we found it significantly increased the fusion index and MHC expression level of both C2C12 and MuSC myotubes. A novel bioreactor providing cyclic stretching (CS) and electrical stimulation (ES) has been fabricated to enhance the myogenic differentiation of both C2C12 and MuSC. We further found that coating the bioreactor substratum with collagen gave the best effect on proliferation and differentiation of MuSC. Furthermore, combining the collagen coating and physical stimuli (CS + ES) in the bioreactor can generate more proliferative primary MuSC cells. Our results have demonstrated that the combination of myogenic kit and bioreactor can provide environment for efficient MuSC proliferation and differentiation. These MuSC and mature myotubes amplified in the bioreactor might be useful for clinical grafting into damaged SKM in the future.

Unravelling nitrate transformation mechanisms in karst catchments through the coupling of high-frequency sensor data and machine learning.

Nitrate dynamics within a catchment are critical to the earth's system process, yet the intricate details of its transport and transformation at high resolutions remain elusive. Hydrological effects on nitrate dynamics in particular have not been thoroughly assessed previously and this knowledge gap hampers our understanding and effective management of nitrogen cycling in watersheds. Here, machine learning (ML) models were employed to reconstruct the annual variation trend in nitrate dynamics and isotopes within a typical karst catchment. Random forest model demonstrates promising potential in predicting nitrate concentration and its isotopes, surpassing other ML models (including Long Short-term Memory, Convolutional Neural Network, and Support Vector Machine) in performance. The ML-modeled NO3--N concentrations, δ15N-NO3-, and δ18O-NO3- values were in close agreement with field data (NSE values of 0.95, 0.80, and 0.53, respectively), which are notably challenging to achieve for process models. During the transition from dry to wet period, approximately 23.0 % of the annual precipitation (∼269.1 mm) was identified as the threshold for triggering a rapid response in the wet period. The modeled nitrate isotope values were significantly supported by the field data, suggesting seasonal variations of nitrogen sources, with precipitation as the primary driving force for fertilizer sources. Mixing of multiple sources appeared to be the main control of the transport and transformation of nitrate during the rising limb in the wet period, whereas process control (denitrification) took precedence during the falling limb, and the fate of nitrate was controlled by biogeochemical processes during the dry period.

An fusaric acid-based CRISPR library screen identifies MDH2 as a broad-spectrum regulator of Fusarium toxin-induced cell death.

Fusarium mycotoxins are of great concern because they are the most common food-borne mycotoxins and environmental contaminants worldwide. Fusaric acid (FA), Deoxynivalenol (DON), Zearalenone (ZEA), T-2 toxin (T-2), and Fumonisin B1 (FB1) are important Fusarium toxins contaminating feeds and food and can cause serious health problems. FA can synergize with some other Fusarium toxins to enhance overall toxicity. However, the underlying molecular mechanism remains poorly understood. In this study, our CRISPR screening revealed Malate dehydrogenase 2 (MDH2) and Pyruvate dehydrogenase E1 subunit beta (PDHB) are the key genes for FA-induced cell death. Pathways associated with mitochondrial function, notably the TCA cycle, play a significant role in FA cytotoxicity. We found that MDH2 and PDHB depletion reduced FA-induced cell death, ROS accumulation, and the expression of caspase-3 and HIF-1α. The cell viability assays and flow cytometry demonstrated that MDH2 knockout but not PDHB decreased DON, ZEA, T-2, and FB1-induced cytotoxicity, apoptosis, and ROS accumulation. MDH2 inhibitor LW6 also decreased DON, ZEA, T-2, and FB1-induced toxicity. This suggested that MDH2, but not PDHB, is a common regulator of broad-spectrum Fusarium toxin (FA, DON, ZEA, T-2, and FB1)-induced cell death. Our work provides new avenues for the treatment of Fusarium toxin toxicity.

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.

Evaluating ECM stiffness and liver cancer radiation response via shear-wave elasticity in 3D culture models.

BACKGROUND: The stiffness of the tumor microenvironment (TME) directly influences cellular behaviors. Radiotherapy (RT) is a common treatment for solid tumors, but the TME can impact its efficacy. In the case of liver cancer, clinical observations have shown that tumors within a cirrhotic, stiffer background respond less to RT, suggesting that the extracellular matrix (ECM) stiffness plays a critical role in the development of radioresistance. METHODS: This study explored the effects of ECM stiffness and the inhibition of lysyl oxidase (LOX) isoenzymes on the radiation response of liver cancer in a millimeter-sized three-dimensional (3D) culture. We constructed a cube-shaped ECM-based millimeter-sized hydrogel containing Huh7 human liver cancer cells. By modulating the collagen concentration, we produced two groups of samples with different ECM stiffnesses to mimic the clinical scenarios of normal and cirrhotic livers. We used a single-transducer system for shear-wave-based elasticity measurement, to derive Young's modulus of the 3D cell culture to investigate how the ECM stiffness affects radiosensitivity. This is the first demonstration of a workflow for assessing radiation-induced response in a millimeter-sized 3D culture. RESULTS: Increased ECM stiffness was associated with a decreased radiation response. Moreover, sonoporation-assisted LOX inhibition with BAPN (ß-aminopropionitrile monofumarate) significantly decreased the initial ECM stiffness and increased RT-induced cell death. Inhibition of LOX was particularly effective in reducing ECM stiffness in stiffer matrices. Combining LOX inhibition with RT markedly increased radiation-induced DNA damage in cirrhotic liver cancer cells, enhancing their response to radiation. Furthermore, LOX inhibition can be combined with sonoporation to overcome stiffness-related radioresistance, potentially leading to better treatment outcomes for patients with liver cancer. CONCLUSIONS: The findings underscore the significant influence of ECM stiffness on liver cancer's response to radiation. Sonoporation-aided LOX inhibition emerges as a promising strategy to mitigate stiffness-related resistance, offering potential improvements in liver cancer treatment outcomes.

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.

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.

Bidirectional wavelength-division-multiplexing fibre-free-space optical communications using polarisation multiplexing technique and tunable optical vestigial sideband filter.

To address the growing demand from emerging applications, high transmission capacity is essential for both fibre backbones and last-mile communications. This can be achieved by integrating optical fibre with optical wireless technologies, facilitating the development of fibre-free-space optical communications. Here we report a bidirectional wavelength-division-multiplexing fibre-free-space optical communication employing polarisation multiplexing technique and tunable optical vestigial sideband filter. The transmission capacity is considerably increased by integrating the polarisation multiplexing technique with the wavelength-division-multiplexing scheme. The transmission performance is extensively enhanced by using a tunable optical vestigial sideband filter and vestigial sideband-four-level pulse amplitude modulation. Moreover, the optical wireless link is substantially extended through the operation of triplet lenses. Low bit error rates and clear vestigial sideband-four-level pulse amplitude modulation eye diagrams are attained with a high aggregate transmission capacity of 480 Gb/s for downstream/upstream transmission. This capability of bidirectional fibre-free-space optical communications holds substantial potential for enhancing advanced wired-wireless communications.

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.

Post-thaw CD34+ cell recovery likely degraded under extreme graft platelet concentrations.

Impaired post-thaw CD34 cell (postCD34) viability in autologous haematopoietic stem cell transplant (ASCT) could indicate delayed engraftment where multiple factors might complicate the relationship. Despite of a couple of unconfirmed reports of a negative correlation of platelet concentration with postCD34 viability, how platelets might be involved in the relationship is largely unknown. Therefore, this question was addressed in this retrospective study of 82 ASCT patients with a total of 150 collections of peripheral blood stem cells in New Zealand. A significant negative correction between platelet concentration and postCD34 recovery (r = -0.18, p = 0.028) was observed overall, but upon further analysis only confirmed in the subset with graft platelets 1500-2000 ×109/L. Importantly, the postCD34 recovery was clearly reduced in the subgroups with either the lowest or the highest platelet concentration. The lowest subgroup was enriched with collections from patients with Hodgkin or non-Hodgkin lymphoma, whereas the highest subgroup from patients with multiple myeloma, both with clearly male preponderance. We hypothesized that graft platelet concentrations probably indicated CD34 cell state (e.g. cell cycle and cell adhesion highly related to platelet functions) that sustained when platelet concentrations were within a niche range but went out of kilter otherwise.