Hypoxic Exosomal circPLEKHM1-Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis.

Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell-derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non-small cell lung cancer (NSCLC) cells, a hypoxia-induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1-targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA-mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

An analysis of the efficacy of botulinum neurotoxin type a in treating cervical dystonia.

BACKGROUND: The first-line treatment for cervical dystonia (CD) consists of repeated intramuscular injections of botulinum toxin (BoNT). However, the efficacy in some patients may be unsatisfactory and they may discontinue treatment. OBJECTIVE: To examine the factors associated with the maximum rate of remission in patients with CD after initial botulinum neurotoxin type A (or botulinum toxin type A abbreviated as BTX-A or BoNT-A) treatment. METHODS: Patients with CD who received BoNT-A injections were evaluated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Tsui scale, with follow-up endpoints lasting until the start of the second injection. Patients who did not receive a second injection of BoNT-A were followed up for at least 5 months. The maximum remission rates were determined using the lowest Tsui and TWSTRS total scores during the follow-up period. We obtained basic information about these patients such as age, gender, duration of disease, presence of additional disease, types of torticollis, presence of anxiety, depression, tremors, single-photon emission computed tomography (SPECT) findings, injected dose, and so on from their medical records. RESULTS: A total of 70 patients with CD participated in this study, with males comprising 35.7% (25 individuals) with an average age of 45 ± 14 years old. The duration of disease was an independent risk factor for determining whether a complete remission has been attained using the Tsui scale (odds ratio [OR] = 0.978, 95% confidence interval [CI]: 0.959-0.997, P= 0.026). The optimal cut-off point for predicting patients who were unable to achieve complete remission based on duration of disease was 7.5 months (AUG = 0.711). Patients with CD with additional disease had greater difficulty achieving complete remission than those with CD alone based on TWSTRS assessments (P= 0.049). During the study, approximately 17% of all participants reported experiencing adverse reactions that lasted between 1 to 3 weeks before disappearing. CONCLUSION: BoNT is an effective and safe method for treating CD. The maximum remission rates of patients after their first injections are influenced by the duration of their disease. Thus, treatment using BoNT injections must be administered as soon as possible.

High-resolution magnetic resonance imaging investigation of the connection between the triglyceride-glucose index and intracranial arterial remodeling: a retrospective cross-sectional study.

Background: Insulin resistance (IR) is associated with atherosclerotic plaque progression and the occurrence of stroke, with the triglyceride-glucose (TyG) index serving as a surrogate indicator. The present study aimed to investigate the association between TyG index levels and intracranial arterial remodeling in patients with acute ischemic stroke (AIS). Methods: Patients with AIS who visited the Neurology Department of the Second Hospital of Hebei Medical University and underwent high-resolution magnetic resonance imaging (HR-MRI) between September 2018 and October 2021 were enrolled. A total of 123 patients were finally included in the study, with 81 excluded. The TyG index levels were measured, and the characteristics of intracranial atherosclerotic stenosis (ICAS) plaques were evaluated using HR-MRI. A logistic regression model was employed to analyze the relationship between TyG index levels and remodeling mode. Patients were divided into two groups, positive remodeling (PR) and non-positive remodeling (non-PR), based on the remodeling index (RI). Results: Patients in the PR group had a higher TyG index than those in the non-PR group {median [interquartile range (IQR)]: 9.11 (8.82-9.51) vs. 8.72 (8.30-9.23), P<0.001}. After adjusting factors such as age and gender, the TyG index was found to be significantly correlated with intracranial arterial PR [odds ratio (OR): 3.169, 95% confidence interval (CI): 1.327-7.569, P=0.009]. In non-diabetes mellitus (DM) patients, the TyG index level in the PR group was significantly higher than that in the non-PR group (8.95±0.42 vs. 8.50±0.45, P<0.001), whereas there was no such difference in patients with DM. Conclusions: TyG index was correlated with intracranial vessel PR, indicating that the TyG index level may be a useful marker for predicting intracranial vessel PR.

Prevalence of paratuberculosis in cattle in China: A systematic review and meta-analysis.

Bovine paratuberculosis is a chronic infectious disease caused by Mycobacterium avium subspecies paratuberculosis (MAP). Here, a systematic literature review was conducted to investigate the bovine paratuberculosis distribution and associated risk factors in China before 2022. The databases CNKI, VIP, WanFang, PubMed, and ScienceDirect were used to search for articles. The random effect model of the "Meta" package of "R" software was used, and the Arcsine transformation was chosen for the rate conversion analysis. To reveal the factors that led to research heterogeneity, the research data were used for subgroup analysis and univariate meta-regression analysis. Among the 1238 identified articles, 54 met the eligibility criteria. Based on data obtained from the selected articles, the combined positive rate of bovine paratuberculosis was 6.95% in China. In the sampling year subgroup, the positive rate of bovine paratuberculosis before 2013 was 4.94%, which was lower than in other time periods. In the sampling season subgroup, the highest positive rate of bovine paratuberculosis in cattle was 14.60% in the autumn. Furthermore, in the detection method subgroup, the highest positive rate of bovine paratuberculosis was 7.21%, which was detected by using ELISA. In the age subgroup, the positive rate of bovine paratuberculosis was 17.47% in cattle > 12 months old, significantly higher than other age subgroups. The highest positive rate of bovine paratuberculosis was 11.35% for female cattle in the gender subgroup, while in the geographic region subgroup, the highest positive rate was 8.12% for East China, which was significantly higher than in other regions. The highest positive rate of bovine paratuberculosis was for dairy cattle (8.00%), and the highest positive rate by rearing method was 11.03% for non-scale farming. The effects of different geographical and climatic factors on the positive rate of bovine paratuberculosis were evaluated. In summary, we recommend focusing on screening cattle infected with MAP in warm and humid areas.

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma: A propensity score-matched study.

BACKGROUND: Gallbladder mucinous adenocarcinoma (GBMAC) is a rare subtype of gallbladder adenocarcinoma (GBAC), with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis. AIM: To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field. METHODS: This study was conducted using data from the Surveillance, Epidemiology, and End Results database, including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017. The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts. In addition, propensity score matching (PSM) analysis was performed to balance the selection biases. Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). The Kaplan-Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients. RESULTS: The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC. They included a larger proportion of patients with unmarried status, advanced American Joint Committee on Cancer (AJCC) stage, higher T stage, higher N1 stage rate and lower N0 and N2 stage rates (P < 0.05). Multivariate analyses demonstrated that surgery [OS: Hazard ratio (HR) = 2.27, P = 0.0037; CSS: HR = 2.05, P = 0.0151], chemotherapy (OS: HR = 6.41, P < 0.001; CSS: HR = 5.24, P < 0.001) and advanced AJCC stage (OS: Stage IV: HR = 28.99, P = 0.0046; CSS: Stage III: HR = 12.31, P = 0.015; stage IV: HR = 32.69, P = 0.0015) were independent prognostic indicators for OS and CSS of GBMAC patients. Furthermore, after PSM analysis, there was no significant difference between GBMAC and matched typical GBAC patients regarding OS (P = 0.82) and CSS (P = 0.69). CONCLUSION: The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC. However, they show similar survival prognoses. Surgery, chemotherapy, and lower AJCC stage were associated with better survival outcomes. Further research is needed in the future to verify these results.

Pro-inflammatory action of formoterol in human bronchial epithelia.

Despite the wide usage of ß2-adrenoceptor agonists in asthma treatment, they do have side effects such as aggravating inflammation. We previously reported that isoprenaline induced Cl- secretion and IL-6 release via cAMP-dependent pathways in human bronchial epithelia, but the mechanisms underlying the inflammation-aggravation effects of ß2-adrenoceptor agonists remain pooly understood. In this study, we investigated formoterol, a more specific ß2-adrenoceptor agonist, -mediated signaling pathways involved in the production of IL-6 and IL-8 in 16HBE14o- human bronchial epithelia. The effects of formoterol were detected in the presence of PKA, exchange protein directly activated by cAMP (EPAC), cystic fibrosis transmembrane conductance regulator (CFTR), extracellular signal-regulated protein kinase (ERK)1/2 and Src inhibitors. The involvement of ß-arrestin2 was determined using siRNA knockdown. Our results indicate that formoterol can induce IL-6 and IL-8 secretion in concentration-dependent manner. The PKA-specific inhibitor, H89, partially inhibited IL-6 release, but not IL-8. Another intracellular cAMP receptor, EPAC, was not involved in either IL-6 or IL-8 release. PD98059 and U0126, two ERK1/2 inhibitors, blocked IL-8 while attenuated IL-6 secretion induced by formoterol. Furthermore, formoterol-induced IL-6 and IL-8 release was attenuated by Src inhibitors, namely dasatinib and PP1, and CFTRinh172, a CFTR inhibitor. In addition, knockdown of ß-arrestin2 by siRNA only suppressed IL-8 release when a high concentration of formoterol (1 µM) was used. Taken together, our results suggest that formoterol stimulates IL-6 and IL-8 release which involves PKA/Src/ERK1/2 and/or ß-arrestin2 signaling pathways.

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia-endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathway and enhancing endothelial angiogenic metabolism to promote angiogenesis. These results suggest that Gal3 may be a novel and effective target in the treatment of retinal angiogenesis.

Recent advances in targeted therapy for pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is a fatal disease with a 5-year survival rate of 8% and a median survival of 6 mo. In PDAC, several mutations in the genes are involved, with Kirsten rat sarcoma oncogene (90%), cyclin-dependent kinase inhibitor 2A (90%), and tumor suppressor 53 (75%-90%) being the most common. Mothers against decapentaplegic homolog 4 represents 50%. In addition, the self-preserving cancer stem cells, dense tumor microenvironment (fibrous accounting for 90% of the tumor volume), and suppressive and relatively depleted immune niche of PDAC are also constitutive and relevant elements of PDAC. Molecular targeted therapy is widely utilized and effective in several solid tumors. In PDAC, targeted therapy has been extensively evaluated; however, survival improvement of this aggressive disease using a targeted strategy has been minimal. There is currently only one United States Food and Drug Administration-approved targeted therapy for PDAC - erlotinib, but the absolute benefit of erlotinib in combination with gemcitabine is also minimal (2 wk). In this review, we summarize current targeted therapies and clinical trials targeting dysregulated signaling pathways and components of the PDAC oncogenic process, analyze possible reasons for the lack of positive results in clinical trials, and suggest ways to improve them. We also discuss emerging trends in targeted therapies for PDAC: combining targeted inhibitors of multiple pathways. The PubMed database and National Center for Biotechnology Information clinical trial website (www.clinicaltrials.gov) were queried to identify completed and published (PubMed) and ongoing (clinicaltrials.gov) clinical trials (from 2003-2022) using the keywords pancreatic cancer and targeted therapy. The PubMed database was also queried to search for information about the pathogenesis and molecular pathways of pancreatic cancer using the keywords pancreatic cancer and molecular pathways.

Manual development and efficacy of Mindful Living Group activities to promote trauma healing during the COVID-19 pandemic in China.

Introduction: Disasters can be traumatic with a profound and lasting impact on individuals. During the COVID-19 pandemic, our team developed the Mindful Living Group (MLG) activities manual based on Eastern body-mind wisdom and Western trauma healing theory to provide psychological assistance for trauma healing. Methods: In this study, we introduce a framework developed for the 10-session MLG activities manual, which consists of three core modules. Thirty-one participants living all over the country who had experienced traumatic stress resulting from the COVID-19 pandemic received the MLG intervention. This single-arm intervention study offered psychological assistance during the pandemic. The MLG intervention included 10 weekly 2-h sessions held online. Participants completed the initial interview, pre-test, post-test, and 1-month follow-up interviews. The effectiveness of the MLG activities manual was evaluated using psychological measures, including Self-Rating Depression Scale, Self-Rating Anxiety Scale, Mindful Attention Awareness Scale, Post-traumatic Growth Inventory, General Self-Efficacy Scale, and the Perceived Social Support Scale. Results: Compared with the pretest level, the post-test levels of depression (F = 42.78, p < 0.001, η 2 = 0.59) and anxiety (F = 23.40, p < 0.001, η 2 = 0.44) were significantly lower; and mindfulness (F = 12.98, p =0.001, η 2 =0.30), posttraumatic growth (F = 27.06, p < 0.001, η 2 = 0.48), general self-efficacy (F = 13.20, p = 0.001, η 2 = 0.31), and perceived social support (F = 16.27, p < 0.001, η 2 = 0.35) were significantly higher (ANOVA). Further correlation analysis revealed a significant negative relationship of mindfulness with both depression (r = -0.43, p = 0.015) and anxiety (r = -0.35, p = 0.053), and significant positive relationships of mindfulness with posttraumatic growth (r = 0.40, p = 0.025), general self-efficacy (r = 0.52, p = 0.003), and perceived social support (r = 0.40, p = 0.024). Discussion: These preliminary findings showed the effectiveness of MLG activities for trauma healing. The mechanisms underlying mindfulness promoting trauma healing are discussed based on both Eastern body-mind wisdom and Western theories of trauma healing. Clinical trial registration: Identifier, ChiCTR2000034164.

[Effect of lncRNA AWPPH on human periodontal ligament cell proliferation and osteogenic differentiation by regulating Notch signaling pathway].

PURPOSE: To explore the effect and molecular mechanism of long non-coding RNA(lncRNA) AWPPH on proliferation and osteogenic differentiation of human periodontal ligament cells by regulating the Notch signaling pathway. METHODS: Human periodontal ligament cells were cultured in vitro, and osteogenic differentiation was induced. Quantitative real-time polymerase chain reaction (qRT-PCR) experiment were used to detect the AWPPH expression level of cells at 0, 3, 7, and 14 days. Human periodontal ligament cells were divided into blank control group (NC), empty vector group (vector), AWPPH overexpression group (AWPPH), and overexpression AWPPH+ pathway inhibitor group (AWPPH+DAPT). qRT-PCR experiment was used to detect the expression level of AWPPH; thiazole blue (MTT), cloning experiment was used to detect cell proliferation. Western blot was performed to detect the protein expression of alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), Notch1 and Hes1. SPSS 21.0 software package was used for statistical analysis. RESULTS: The AWPPH expression level in periodontal ligament cells decreased after 0, 3, 7, and 14 days of osteogenic differentiation. Overexpression of AWPPH increased the A value of periodontal ligament cells, the number of cloned cells, and up-regulated the protein expression of ALP, OPN, OCN, Notch1, and Hes1. After adding the pathway inhibitor DAPT, the A value and the number of cloned cells decreased, and the protein expression of Notch1, Hes1, ALP, OPN, and OCN decreased. CONCLUSIONS: Overexpression of AWPPH may inhibit the proliferation and osteogenic differentiation of periodontal ligament cells by reducing the expression of related proteins in the Notch signaling pathway.

Prevalence and molecular characterization of Clostridioides difficile infection in China over the past 5 years: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to provide an overview of the prevalence and molecular characteristics of Clostridioides difficile infection (CDI) in China in the past 5 years. METHODS: A systematic literature review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Nine databases were searched for relevant studies published between January 2017 and February 2022. The Joanna Briggs Institute critical appraisal tool was used to assess the quality of included studies, and R software version 4.1.3 was used for data analysis. Funnel plots and Egger regression tests were also performed to assess publication bias. RESULTS: A total of 50 studies were included in the analysis. The pooled prevalence of CDI in China was 11.4% (2696/26,852). The main circulating C. difficile strains in southern China were ST54, ST3, and ST37, consistent with the overall situation in China. However, the most prevalent genotype in northern China was ST2, which was previously underappreciated. CONCLUSION: Based on our findings, increased awareness and management of CDI is necessary to reduce the prevalence of CDI in China.

Effects of sericin and egg white on the inflammation of damaged skin in mice.

Sericin and egg white (EW) have shown the ability to promote wound healing. However, there have been insufficient studies regarding the effects of sericin and EW mixtures on wound healing. This study aimed to investigate the effects of a hybrid sericin and EW solution on wound repair and inflammation-related indicators in mouse skin. In this work, sericin with a low molecular weight was first mixed with homogeneous EW to prepare a hybrid wound dressing. Histology evaluation, the expression of C-reactive protein (CRP) and inflammatory cytokines in mice were tested to determine the effects of this dressing on skin injuries in mice. The results showed that sericin and the hybrid solution of sericin and EW effectively promoted wound healing in mouse skin. The wound recovery rates of mice 12 days after treatment with a medium dose of sericin (0.2 g ml-1) and the same dosage of sericin with added EW were 1.32 and 1.65 times that of mice treated with phosphate buffer saline as a control, respectively. In addition, the mixture solution was more effective in wound healing than sericin alone. Sericin with EW significantly reduced the expression of CRP and inflammatory cytokines in mice during wound healing. A sericin and EW hybrid solution can effectively shorten the time needed for wound healing and reduce inflammation-related indicators in mice, making it a promising candidate for wound dressing.

NONO regulates multiple cytokine production in sepsis via the ERK1/2 signaling pathway.

The massive release of pro-inflammatory cytokines is a crucial step in triggering the inflammatory cascade in sepsis. Exploring the key molecules regulating the expression and release of multiple cytokines has important value for revealing the mechanism of the cytokine storm in sepsis. This study aimed to investigate the role of multifunctional nuclear protein non-POU domain containing octamer-binding protein (NONO) in the sepsis cytokine storm and to elucidate the underlying mechanism. We found that NONO expression in tissues and cells of sepsis mice was significantly upregulated. Downregulation of NONO expression inhibited the mRNA expression of multiple cytokines, including IL-6, IL-1ß, MCP-1, MIP-1α, and MIP-1ß in inflammatory cells from mice and human leukemic monocyte-THP1 cells challenged with lipopolysaccharide (LPS), and significantly decreased the level of these cytokines and TNF-α in the supernatant of THP1 cells challenged by LPS. Nono knockout also reduced the levels of TNF-α, IL-6, MIP-1α, and MIP-1ß in serum, alleviated hepatocyte edema, and improved the survival rate of sepsis mice. Reduced NONO expression decreased the phospho-ERK1/2 level in inflammatory cells from sepsis mice or THP1 cells challenged by LPS. Phospho-ERK1/2 inhibitor decreased the mRNA expression and concentration of cytokines in the culture supernatant of LPS-induced THP1 cells, similar to the effect of NONO knockdown. After LPS challenge, the levels of phospho-ERK1/2 and NONO were increased, with obvious colocalization in the nucleus and vesicular-like organelles in macrophages. NONO knockdown decreased nuclear translocation of phospho-ERK1/2 in LPS-challenged THP1 cells. These results suggest that NONO is a potentially critical molecule involved in multiple cytokine production in sepsis. Upregulated NONO in sepsis may promote the expression and release of multiple cytokines to participate in a sepsis cytokine storm by promoting ERK1/2 phosphorylation.

Progress in research on pyroptosis and its role in hepatocellular carcinoma / 中国生物制品学杂志

@#Abstract：Pyroptosis is a new programmed cell death mode，which plays a dual role in the pathogenesis of hepatocellular carcinoma（HCC）. On the one hand，inflammasomes causing pyroptosis and inflammatory mediators released during cell pyroptosis promote the occurrence and development of HCC；On the other hand，pyroptosis can inhibit the proliferation， metastasis and invasion of HCC cells. With the deepening of research，the role of pyroptosis in HCC has become increasingly prominent. This paper reviews the potential effects of pyroptosis on the progression of HCC and its role in anticancer therapy. Keywords：Pyroptosis；Inflammasome；Hepatocellular carcinoma（HCC）；Gasdermin D（GSDMD）

Associations between psycho-behavioral risk factors and diabetic retinopathy: NHANES (2005-2018).

Introduction: Diabetes mellitus (DM) and diabetic retinopathy (DR) increase the global burden. Since their pathogenesis is complex, it is necessary to use the biopsychosocial model to discover the most effective strategies. The study is aimed to investigate the psycho-behavioral factors of DR and confirm the discrepancies from previous studies. Research design and methods: The study comprised seven cycles of cross-sectional data of the National Health and Nutrition Examination Survey (NHANES) from 2005-2006 to 2017-2018. Samples of DM were selected from this complex multi-stage probability sample and divided into the non-DR and DR groups, where 4,426 samples represented 18,990,825 individuals after weighting. This study comprehensively explored the biological, social, and psychological risk factors of DR, among which the biological factors included blood pressure, blood routine, HbA1c%, blood glucose, the duration of DM, family history, comorbidities, and treatment methods. Social aspects include gender, education, income, insurance, smoking, drinking, sleep habits, and recreational activities. The Patient Health Questionnaire-9 (PHQ-9) was used to assess the psychological state. Taylor series regression was used to examine the connection between factors and DR. Results: Men accounted for 55.5% of the DR group (P = 0.0174). Lymphocyte count, insulin treatment, heart failure, stroke, liver condition, and renal failure showed significant differences in DR (P < 0.05). The incidence of depression in DR was 40.5%. Mild to moderate depression [odds ratio was associated with DR [(OR) = 1.37, 95% confidence interval (CI): 1.06-1.79], but there was no statistical difference in severe depression (OR = 1.34, 95% CI: 0.83-2.17). Although ≤ 6 h of sleep was associated with DR (OR = 1.38, 95% CI: 1.01-1.88), we found no statistical differences in alcohol consumption, recreational activities, or sedentary time between the two groups in our current study (P > 0.05). Conclusions: The biological risk factors of DR are significant. It showed that stroke is associated with DR, and retinal exams have the potential value as a screening tool for the brain. Besides, psycho-behavioral risk factors of DR should also be paid attention. Our study highlights that mild and moderate depression and ≤6 h of sleep are distinguishably associated with DM complicated with DR. It indicates that psycho-behavioral risk factors confer a vital influence on diabetic health care and DR.

Circadian clock-mediated nuclear receptors in cancer.

Circadian system coordinates the daily periodicity of physiological and biochemical functions to adapt to environmental changes. Circadian disruption has been identified to increase the risk of cancer and promote cancer progression, but the underlying mechanism remains unclear. And further mechanistic understanding of the crosstalk between clock components and cancer is urgent to achieve clinical anticancer benefits from chronochemotherapy. Recent studies discover that several nuclear receptors regulating circadian clock, also play crucial roles in mediating multiple cancer processes. In this review, we aim to summarize the latest developments of clock-related nuclear receptors in cancer biology and dissect mechanistic insights into how nuclear receptors coordinate with circadian clock to regulate tumorigenesis and cancer treatment. A better understanding of circadian clock-related nuclear receptors in cancer could help prevent tumorigenesis and improve anticancer efficacy.

Quantitative and Qualitative Research on Management Strategies for Dyspnoea in Elderly Patients with Coronary Heart Disease Complicated with Chronic Heart Failure.

Objective: To investigate the most effective strategies for the management of dyspnoea in elderly patients with coronary atherosclerotic heart disease (CHD) complicated with chronic heart failure (CHF). Methods: The best management plans for dyspnoea were evaluated using quantitative and qualitative research techniques for a total of 120 senior patients with CHD complicated with CHF. A self-made questionnaire on dyspnoea management strategies served as the survey instrument for the cross-sectional quantitative investigation. A phenomenological approach served as the framework for the qualitative study, which involved semi-structured interviews with 12 elderly patients who had CHD complicated by CHF. Data were gathered through audio recordings, and the Colaizzi method was used to analyse the data. Results: A data analysis of the qualitative research results revealed the four strategies for dyspnoea management that were most effective: using drugs, inhaling oxygen, staying in a comfortable position and maintaining air circulation. These were consistent with the most effective strategies identified by the quantitative findings. There was no significant difference in the choice of dyspnoea management strategies for men and women (t = 0.968, P = 0.806); patients tended to use multiple integrated strategies to manage dyspnoea. Conclusion: Health care providers should consider employing individualised combinations of dyspnoea management strategies to assist elders with CHD complicated with CHF during acute exacerbations of dyspnoea.

Genome-wide CRISPR Screening Reveals Pyrimidine Metabolic Reprogramming in 5-FU Chronochemotherapy of Colorectal Cancer.

Objective: Disruption of the circadian rhythm is associated with cancer occurrence, response to chemotherapy, and poor prognosis. Thus, using internal clock-based chronotherapy to optimize the administration time may improve the therapeutic effects of anticancer drugs while reducing the side effects. Chronotherapy with 5-fluorouracil (5-FU) has been observed in colorectal cancer (CRC) for a long time, but its effect is under controversial and the mechanism remains unclear. Methods: Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening and RNA-sequencing were combined to identify the potential genes or pathways involved in 5-FU chronochemotherapy. Genetic deletion or overexpression of pyrimidine metabolic pathway genes were conducted to examine cellular viability with or without 5-FU via flow cytometry. Western blotting, qPCR, chromatin immunoprecipitation, gain-of-function and loss-of-function assays of several CRC cell lines in vitro and in vivo were used to elaborate and validate the mechanism of 5-FU chronotherapeutic effects. Results: Chronochemotherapeutic effects of 5-FU on CRC in vivo were verified. Furthermore, 5-FU chronochemotherapy related genes such as UPP2, UCK2 and UMPS in the pyrimidine metabolic pathway were identified. Disturbance in these genes, especially UMPS, perturbs 5-FU treatment outcomes in CRC cells. Mechanistically, the core circadian gene, brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), extensively regulate gene expression in pyrimidine metabolic pathway by binding to E-box element in the promoter region of key genes such as UMPS and perturb their enzymatic activities, thereby maintain diurnal efficacy of 5-FU in CRC cells. Conclusion: This study uncovered a new mechanism by which a core circadian gene BMAL1 increases the effectiveness of 5-FU by enhancing the expression and enzymatic activities of key genes in the pyrimidine metabolic pathway in CRC cells. The findings suggest a novel strategy for CRC chemotherapy by targeting chrono-modulated genes of the 5-FU metabolic pathway.

[Theoretical basis of ecology for the influence of global change on resources, environment, and ecosystems.] / å ¨çƒå˜åŒ–å¯¹èµ„æºçŽ¯å¢ƒåŠç”Ÿæ€ç³»ç»Ÿå½±å“çš„ç”Ÿæ€å­¦ç†è®ºåŸºç¡€.

With the deepening of global change research, the applied problems such as global change risk and response for social sustainable development, temporal and spatial allocation of resources and environmental elements and impact assessment of ecosystem are becoming a new trend in the research field of global change. Based on the ecological framework, we focused on clarifying the connotations of resources and the environment and their components. Resources refer to all substances consumed by organisms in the process of producing organic matter from inorganic matter and transferring energy and matter among organisms. These include inorganic resources (e.g., solar radiation, CO2, O2, water, and mineral elements) and organic resources (as a source of food for other organisms). In contrast, the environment can not be consumed or depleted by organisms. In addition, we described the components of global change and the associated variations of resources and environmental factors, as well as current research progress on the responses of ecosystem to global change. We scientifically described the processes and mechanisms of global change in terms of their influence on resources, the environment, and ecosystems within a theoretical framework based on ecological principles. Our goal was to provide a strong theoretical foundation for future research on coping with the risks of global change.

Successful Urgent TAVI for Critical Aortic Valve Stenosis after ECMO Implantation.

Transcatheter aortic valve implantation (TAVI) has evolved to be the treatment of choice for patients with severe aortic stenosis and high perioperative risk. Cardiogenic shock is one of the most severe complications during the TAVI procedure, especially as the prognosis of cardiogenic shock secondary to aortic stenosis is very poor. This situation can be challenging, while extracorporeal membranous oxygenation (ECMO) can be a treatment option. Here, we reported on an 88-year-old female patient who had been diagnosed as non-ST-elevation myocardial infarction (NSTEMI) and critical aortic valve stenosis (AS) with a logistic Euroscore of 25%. Percutaneous coronary angioplasty (PCI) was performed smoothly and developed tachy-brady arrhythmia of atrial fibrillation then cardiac arrest at the beginning of the TAVI procedure. A v-a ECMO was installed at her left femoral side. Afterward, the TAVI procedure was completed accordingly; her consciousness recovered and Levosimendan therapy enhanced her left-ventricular ejection fraction (LVEF) from 22% to 40%. Five days after TAVI, ECMO was replaced by intra-aortic balloon pumping (IABP) and it was removed 3 days later. A minor complication of this therapy, e.g., muscular weakness in her left leg, was noted. The patient underwent rehabilitation for about 2 months, and was discharged from hospital with a wheel chair and clear consciousness. At the 24 month follow-up she was in good recovery and was able to walk upstairs to the second floor again. Our experience suggests that one indication of prophylactic use of ECMO is for patients with an unstable hemodynamic condition.