Epithelial cell adhesion molecule promotes breast cancer resistance protein-mediated multidrug resistance in breast cancer by inducing partial epithelial-mesenchymal transition.

Overexpression of breast cancer resistance protein (BCRP) plays a crucial role in the acquired multidrug resistance (MDR) in breast cancer. The elucidation of molecular events that confer BCRP-mediated MDR is of major therapeutic importance in breast cancer. Epithelial cell adhesion molecule (EpCAM) has been implicated in tumor progression and drug resistance in various types of cancers, including breast cancer. However, the role of EpCAM in BCRP-mediated MDR in breast cancer remains unknown. In the present study, we revealed that EpCAM expression was upregulated in BCRP-overexpressing breast cancer MCF-7/MX cells, and EpCAM knockdown using siRNA reduced BCRP expression and increased the sensitivity of MCF-7/MX cells to mitoxantrone (MX). The epithelial-mesenchymal transition (EMT) promoted BCRP-mediated MDR in breast cancer cells, and EpCAM knockdown partially suppressed EMT progression in MCF-7/MX cells. In addition, Wnt/ß-catenin signaling was activated in MCF-7/MX cells, and the inhibition of this signaling attenuated EpCAM and BCRP expression and partially reversed EMT. Together, this study illustrates that EpCAM upregulation by Wnt/ß-catenin signaling induces partial EMT to promote BCRP-mediated MDR resistance in breast cancer cells. EpCAM may be a potential therapeutic target for overcoming BCRP-mediated resistance in human breast cancer.

Carriage of Clostridioides difficile in healthy infants in the community of Handan, China: A 1-year follow-up study.

OBJECTIVE: Clostridioides difficile may colonize healthy infants and young children asymptomatically and for the long-term. C. difficile genotypes and the rate and determinants of colonization differ substantially and vary among countries and regions. A 1-year follow-up study was performed to determine the incidence, kinetics and influencing factors of C. difficile intestinal colonization. METHODS: Twenty-nine healthy infants (14 girls and 15 boys) living at home with their parents in Handan City were followed by survey from birth to 1 year of age, specifically from October 2014 through December 2015. C. difficile isolates were typed by PCR ribotyping and analyzed for the presence of toxin genes. RESULTS: During the follow-up study period in the first year of life, 20 of the 29 total enrolled infants acquired C. difficile. A total of 437 fecal samples were obtained, and 111 (25.4%) samples contained C. difficile, including 79 (71.2%) toxigenic strains. The toxigenic isolates comprised six PCR ribotypes, and two PCR ribotypes were identified as nontoxigenic strains. CONCLUSION: Our study showed that C. difficile colonization increase with age during the 12-month period, and the dominant toxigenic types of C. difficile isolates in infants were those involved in long-term colonization. Feeding patterns may affect the dynamic progress of C. difficile colonization.

Nickel-Catalyzed Asymmetric Reductive Carbo-Carboxylation of Alkenes with CO2.

Reductive carboxylation of organo (pseudo)halides with CO2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo-carboxylation of unsaturated hydrocarbons via CO2 fixation is a highly challenging but desirable approach for structurally diverse carboxylic acids. There are only a few reports and no examples of alkenes via transition metal catalysis. We report the first asymmetric reductive carbo-carboxylation of alkenes with CO2 via nickel catalysis. A variety of aryl (pseudo)halides, such as aryl bromides, aryl triflates and inert aryl chlorides of particular note, undergo the reaction smoothly to give important oxindole-3-acetic acid derivatives bearing a C3-quaternary stereocenter. This transformation features mild reaction conditions, wide substrate scope, facile scalability, good to excellent chemo-, regio- and enantioselectivities. The method highlights the formal synthesis of (-)-Esermethole, (-)-Physostigmine and (-)-Physovenine, and the total synthesis of (-)-Debromoflustramide B, (-)-Debromoflustramine B and (+)-Coixspirolactam A; thereby, opening an avenue for the total synthesis of chiral natural products with CO2 .

Epidemiological investigation of Clostridioides difficile colonization in Chinese community infants.

Clostridioides difficile is a colonizer of the human gut; asymptomatic colonization has been reported to be more common in infants and is highly variable across regions even with no symptoms of diarrhea or death. Antibiotic treatment strategies might increase the antibiotic resistance of C. difficile. We performed a one-point study involving 1098 healthy infants (0-36 months) to address the deficiency of reports on C. difficile colonization in Chinese community infants. The C. difficile colonization rate was 22.8% (250/1098), and more than half of the strains (55.2%) were toxigenic isolates. Among the 138 toxigenic isolates, 111 were of the A+B+CDT- genotype, 26 strains were A-B+CDT-, and one strain was A+B+CDT+. Fifteen different PCR ribotypes were found among the 250 isolates, and PCR-ribotype HB03 appeared to be dominant type, accounting for 19.6% (49/250). High levels of resistance to antimicrobial agents were observed. Our study showed that age and hospitalization before stool collection were positively correlated with the C. difficile colonization rate, whereas the delivery term was negatively related to the colonization rate. Particular attention should be paid to the increasing resistance of C. difficile to rifamycin.

[Recent advances in natural product induced DNA damage response in cancer cells].

The DNA structures could be altered or even damaged by exogeous or endogenous factors during cell proliferation. Failure of effective and timely repair will lead to cell cycle arrest or apoptosis. By taking the advantage of the quick proliferation of cancer cells, DNA damage induction, cell cycle arrest and apoptosis promotion have become important strategies for ant-cancer chemotherapy. Previous reports showed that an array of natural compounds inhibit cancer cell proliferation by inducing DNA damage, which have therapeutic potentials for anti-cancer drug research and development.

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.

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 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.

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.

The Age Effects on the Cognitive Processes of Intention-Based and Stimulus-Based Actions: An ERP Study.

The functional decline in action among older adults is caused not only by physical weakness but also by cognitive decline. In this study, we aimed to compare the cognitive effects of age between intention-based and stimulus-based action modes electrophysiologically. Because age-related declines in cognitive function might proceed distinctly according to specific action modes and processes, four specific cognitive processes, action-effect binding, stimulus-response linkage, action-effect feedback control, and effect-action retrieval, were investigated. We recorded event-related potentials (ERPs) during a modified acquisition-test paradigm in young (mean age = 21, SD = 2) and old (mean age = 69, SD = 5) groups. A temporal bisection task and a movement pre-cuing task were used during the acquisition and test phases, respectively. Using ERP indices including readiness potential (RP), P3, N2 and contingent negative variation (CNV) to identify these four specific processes for the two action modes, we revealed the effects of age on each ERP index. The results showed similar patterns of waveforms but consistently decreasing amplitudes of all four ERP indices in the old age group compared with the young age group, which indicates not only generally declining functions of action preparation in older adults but also age effects specific to the action modes and processes that might otherwise be mixed together under confounding experimental conditions. Particularly, an interference effect indexed by the differences in the amplitudes of CNV between congruent and incongruent tasks was observed in the young age group, which is consistent with previous behavioral reports. However, this effect was absent in the old age group, indicating a specific age-related deficit in the effect-action retrieval process of intention-based action, which might be caused by an age-related deficit in associative memory. In sum, this study investigated the cognitive processes of two action modes from a developmental perspective and suggests the importance of adding associative memory training to interventions for older adults with the aim of improving intention-based action.

Linking Inter-Individual Variability in Functional Brain Connectivity to Cognitive Ability in Elderly Individuals.

Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity-cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases.

The ERP Effects of Combined Cognitive Training on Intention-Based and Stimulus-Based Actions in Older Chinese Adults.

Age-related decreases in action are caused by neuromuscular weakness and cognitive decline. Although physical interventions have been reported to have beneficial effects on cognitive function in older adults, whether cognitive training improves action-related function remains unclear. In this study, we investigated the effects of combined cognitive training on intention-based and stimulus-based actions in older adults using event-related potentials (ERPs). A total of 26 healthy older adults (16 in the training group and 10 in the control group) participated in the study. The training group received 16 sessions of cognitive training, including eight sessions of executive function training and eight sessions of memory strategy training. Before and after training, both groups of participants underwent cognitive assessments and ERP recordings during both the acquisition and test phases with a motor cognitive paradigm. During the acquisition phase, subjects were asked to press one of two keys, either using a self-selected (intention-based) method or based on the preceding stimulus (stimulus-based). During the test phase, subjects were asked to respond to the pre-cues with either congruent or incongruent tasks. Using ERP indices-including readiness potential, P3 and contingent negative variation to identify motor preparation, stimulus processing and interference effect, respectively-we revealed the effects of training on both intention-based and stimulus-based actions. The correlations were also computed between the improved cognitive performance and the ERP amplitudes. It was shown that the improved executive function might extend substantial benefits to both actions, whereas associative memory may be specifically related to the bidirectional action-effect association of intention-based action, although the training effect of memory was absent during the insufficient training hours. In sum, the present study provided empirical evidence demonstrating that action could benefit from cognitive training. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR-OON-16007793.