Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation, causing structural damage and lung failure. Stem cell therapy and mesenchymal stem cells-extracellular vesicles (MSC-EVs) offer new hope for PF treatment. AIM: To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis, oxidative stress, and immune inflammation in A549 cells and bleomycin (BLM)-induced mouse model. METHODS: The effect of MSC-EVs on A549 cells was assessed by fibrosis markers [collagen I and α-smooth muscle actin (α-SMA), oxidative stress regulators [nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and inflammatory regulators [nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-1ß, and IL-2]. Similarly, they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection. MSC-EVs ion PF mice were detected by pathological staining and western blot. Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice. RESULTS: Transforming growth factor (TGF)-ß1 enhanced fibrosis in A549 cells, significantly increasing collagen I and α-SMA levels. Notably, treatment with MSC-EVs demonstrated a remarkable alleviation of these effects. Similarly, the expression of oxidative stress regulators, such as Nrf2 and HO-1, along with inflammatory regulators, including NF-κB p65 and IL-1ß, were mitigated by MSC-EV treatment. Furthermore, in a parallel manner, MSC-EVs exhibited a downregulatory impact on collagen deposition, oxidative stress injuries, and inflammatory-related cytokines in the lungs of mice with PF. Additionally, the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response. The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes, oxidative stress, and inflammatory responses associated with PF. CONCLUSION: MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition, oxidative stress, and immune-inflammatory responses.

An unsupervised learning model based on CT radiomics features accurately predicts axillary lymph node metastasis in breast cancer patients-diagnostic study.

BACKGROUND: The accuracy of traditional clinical methods for assessing the metastatic status of axillary lymph nodes is unsatisfactory. In this study, we propose the use of radiomic technology and three-dimensional (3D) visualization technology to develop an unsupervised learning model for predicting axillary lymph node metastasis in patients with breast cancer, aiming to provide a new method for clinical axillary lymph node assessment in patients with this disease. METHODS: In this study, we retrospectively analyzed the data of 350 patients with invasive breast cancer who underwent lung-enhanced CT and axillary lymph node dissection (ALND) surgery at the Department of Breast Surgery of the XXX Hospital of XXX University. We used 3D visualization technology to create a 3D atlas of axillary lymph nodes and identified the region of interest (ROI) for the lymph nodes. Radiomic features were subsequently extracted and selected, and a prediction model for axillary lymph nodes was constructed using the K-means unsupervised algorithm. To validate the model, we prospectively collected data from 128 breast cancer patients who were clinically evaluated as negative at our center. RESULTS: Using 3D visualization technology, we extracted and selected a total of 36 CT radiomics features. The unsupervised learning model categorized 1737 unlabeled lymph nodes into two groups, and the analysis of the radiomic features between these groups indicated potential differences in lymph node status. Further validation with 1397 labeled lymph nodes demonstrated that the model had good predictive ability for axillary lymph node status, with an area under the curve (AUC) of 0.847 (0.825-0.869). Additionally, the model's excellent predictive performance was confirmed in the 128 axillary clinical assessment negative cohort (cN0) and the 350 clinical assessment positive (cN+) cohort, for which the correct classification rates (CCR) were 86.72% and 87.43%, respectively, which were significantly greater than those of clinical assessment methods. CONCLUSIONS: We created an unsupervised learning model that accurately predicts the status of axillary lymph nodes. This approach offers a novel solution for the precise assessment of axillary lymph nodes in patients with breast cancer.

Circulating tumor DNA: from discovery to clinical application in breast cancer.

Breast cancer (BC) stands out as the cancer with the highest incidence of morbidity and mortality among women worldwide, and its incidence rate is currently trending upwards. Improving the efficiency of breast cancer diagnosis and treatment is crucial, as it can effectively reduce the disease burden. Circulating tumor DNA (ctDNA) originates from the release of tumor cells and plays a pivotal role in the occurrence, development, and metastasis of breast cancer. In recent years, the widespread application of high-throughput analytical technology has made ctDNA a promising biomarker for early cancer detection, monitoring minimal residual disease, early recurrence monitoring, and predicting treatment outcomes. ctDNA-based approaches can effectively compensate for the shortcomings of traditional screening and monitoring methods, which fail to provide real-time information and prospective guidance for breast cancer diagnosis and treatment. This review summarizes the applications of ctDNA in various aspects of breast cancer, including screening, diagnosis, prognosis, treatment, and follow-up. It highlights the current research status in this field and emphasizes the potential for future large-scale clinical applications of ctDNA-based approaches.

TERC promotes non-small cell lung cancer progression by facilitating the nuclear localization of TERT.

The core of telomerase consists of the protein subunit telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). So far, the role of TERC in cancer development has remained elusive. Here, we found TERC expression elevated in non-small cell lung cancer (NSCLC) tissues, which was associated with disease progression and poor prognosis in patients. Using NSCLC cell lines and xenograft models, we showed that knockdown of TERC caused cell cycle arrest, and inhibition of cell proliferation and migration. Mechanistically, TERC was exported to the cytoplasm by nuclear RNA export factor 1 (NXF1), where it mediated the interaction of TERT with other telomerase subunits. Depletion of TERC hindered the assembly and subsequent nuclear localization of the telomerase complex, preventing TERT from functioning in telomere maintenance and transcription regulation. Our findings suggest that TERC is a potential biomarker for NSCLC diagnosis and prognosis and can be a target for NSCLC treatment.

Factors affecting long-term myopic regression after corneal refractive surgery for civilian pilots in southwest China.

BACKGROUND: The purpose of this study was to analyze myopic regression after corneal refractive surgery (CRS) in civilian pilots and to explore the factors that may cause long-term myopic regression. METHODS: We included civilian pilots who had undergone CRS to correct their myopia and who had at least 5 years of follow-up. We collected retrospective data and completed eye examinations and a questionnaire to assess their eye habits. RESULTS: A total of 236 eyes were evaluated in this study. 211 eyes had Intrastromal ablations (167 eyes had laser in situ keratomileusis, LASIK, 44 eyes had small incision lenticule extraction, SMILE) and 25 eyes had subepithelial ablations (15 eyes had laser epithelial keratomileusis, LASEK and 10 eyes had photorefractive keratectomy, PRK). The mean preoperative spherical equivalent (SE) was - 2.92 ± 1.11 D (range from - 1.00 to -5.00 D). A total of 56 eyes (23.6%) suffered from myopic regression after CRS. Comparisons of individual and eye characteristics between the regression and non-regression groups revealed statistically significant differences in age, cumulative flight time, postoperative SE (at 6 months and current), uncorrected visual acuity (UCVA), accommodative amplitude (AA), positive relative accommodation (PRA), postoperative period, types of CRS and eye habits. Generalized propensity score weighting (GPSW) was used to balance the distribution of covariates among different age levels, types of CRS, cumulative flying time, postoperative period and continuous near-work time. The results of GPS weighted logistic regression demonstrated that the associations between age and myopic regression, types of CRS and myopic regression, continuous near-work time and myopic regression were significant. Cumulative flying time and myopic regression, postoperative period and myopic regression were no significant. Specifically, the odds ratio (OR) for age was 1.151 (P = 0.022), and the OR for type of CRS was 2.769 (P < 0.001). The OR for continuous near-work time was 0.635 with a P value of 0.038. CONCLUSIONS: This is the first report to analyze myopic regression after CRS in civilian pilots. Our study found that for each year increase in age, the risk of civilian pilots experiencing myopic regression was increased. Intrastromal ablations had a lower risk of long-term myopia regression than subepithelial ablations. There is a higher risk of myopic progression with continuous near-work time > 45 min and poor accommodative function may be related factors in this specific population.

Comparison of neoadjuvant chemotherapy response and prognosis between HR-low/HER2-negative BC and TNBC: an exploratory real-world multicentre cohort study.

Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.

Transcriptomic and targeted metabolomic analyses provide insights into the flavonoids biosynthesis in the flowers of Lonicera macranthoides.

BACKGROUND: Flavonoids are one of the bioactive ingredients of Lonicera macranthoides (L. macranthoides), however, their biosynthesis in the flower is still unclear. In this study, combined transcriptomic and targeted metabolomic analyses were performed to clarify the flavonoids biosynthesis during flowering of L. macranthoides. RESULTS: In the three sample groups, GB_vs_WB, GB_vs_WF and GB_vs_GF, there were 25, 22 and 18 differentially expressed genes (DEGs) in flavonoids biosynthetic pathway respectively. A total of 339 flavonoids were detected and quantified at four developmental stages of flower in L. macranthoides. In the three sample groups, 113, 155 and 163 differentially accumulated flavonoids (DAFs) were detected respectively. Among the DAFs, most apigenin derivatives in flavones and most kaempferol derivatives in flavonols were up-regulated. Correlation analysis between DEGs and DAFs showed that the down-regulated expressions of the CHS, DFR, C4H, F3'H, CCoAOMT_32 and the up-regulated expressions of the two HCTs resulted in down-regulated levels of dihydroquercetin, epigallocatechin and up-regulated level of kaempferol-3-O-(6''-O-acetyl)-glucoside, cosmosiin and apigenin-4'-O-glucoside. The down-regulated expressions of F3H and FLS decreased the contents of 7 metabolites, including naringenin chalcone, proanthocyanidin B2, B3, B4, C1, limocitrin-3,7-di-O-glucoside and limocitrin-3-O-sophoroside. CONCLUSION: The findings are helpful for genetic improvement of varieties in L.macranthoides.

Adolescents' relationships with parents and romantic partners in eight countries.

INTRODUCTION: Creating romantic relationships characterized by high-quality, satisfaction, few conflicts, and reasoning strategies to handle conflicts is an important developmental task for adolescents connected to the relational models they receive from their parents. This study examines how parent-adolescent conflicts, attachment, positive parenting, and communication are related to adolescents' romantic relationship quality, satisfaction, conflicts, and management. METHOD: We interviewed 311 adolescents at two time points (females = 52%, ages 15 and 17) in eight countries (China, Colombia, Italy, Kenya, the Philippines, Sweden, Thailand, and the United States). Generalized and linear mixed models were run considering the participants' nesting within countries. RESULTS: Adolescents with negative conflicts with their parents reported low romantic relationship quality and satisfaction and high conflicts with their romantic partners. Adolescents experiencing an anxious attachment to their parents reported low romantic relationship quality, while adolescents with positive parenting showed high romantic relationship satisfaction. However, no association between parent-adolescent relationships and conflict management skills involving reasoning with the partner was found. No associations of parent-adolescent communication with romantic relationship dimensions emerged, nor was there any effect of the country on romantic relationship quality or satisfaction. CONCLUSION: These results stress the relevance of parent-adolescent conflicts and attachment as factors connected to how adolescents experience romantic relationships.

How adolescents' lives were disrupted over the course of the COVID-19 pandemic: A longitudinal investigation in 12 cultural groups in 9 nations from March 2020 to July 2022.

It is unclear how much adolescents' lives were disrupted throughout the COVID-19 pandemic or what risk factors predicted such disruption. To answer these questions, 1,080 adolescents in 9 nations were surveyed 5 times from March 2020 to July 2022. Rates of adolescent COVID-19 life disruption were stable and high. Adolescents who, compared to their peers, lived in nations with higher national COVID-19 death rates, lived in nations with less stringent COVID-19 mitigation strategies, had less confidence in their government's response to COVID-19, complied at higher rates with COVID-19 control measures, experienced the death of someone they knew due to COVID-19, or experienced more internalizing, externalizing, and smoking problems reported more life disruption due to COVID-19 during part or all of the pandemic. Additionally, when, compared to their typical levels of functioning, adolescents experienced spikes in national death rates, experienced less stringent COVID-19 mitigation measures, experienced less confidence in government response to the COVID-19 pandemic, complied at higher rates with COVID-19 control measures, experienced more internalizing problems, or smoked more at various periods during the pandemic, they also experienced more COVID-19 life disruption. Collectively, these findings provide new insights that policymakers can use to prevent the disruption of adolescents' lives in future pandemics.

Intraindividual variability in parental acceptance-rejection predicts externalizing and internalizing symptoms across childhood/adolescence in nine countries.

Parenting that is high in rejection and low in acceptance is associated with higher levels of internalizing (INT) and externalizing (EXT) problems in children and adolescents. These symptoms develop and can increase in severity to negatively impact adolescents' social, academic, and emotional functioning. However, there are two major gaps in the extant literature: (a) nearly all prior research has focused on between-person differences in acceptance/rejection at the expense of examining intraindividual variability (IIV) across time in acceptance/rejection; and (b) no prior studies examine IIV in acceptance/rejection in diverse international samples. The present study utilized six waves of data with 1,199 adolescents' families living in nine countries from the Parenting Across Cultures study to test the hypotheses that (1) higher amounts of youth IIV in mother acceptance/rejection predict higher internalizing and (2) externalizing symptoms, and (3) that higher youth IIV in father acceptance/rejection predict higher internalizing, and (4) externalizing symptoms. Meta-analytic techniques indicated a significant, positive effect of IIV in child-reported mother and father acceptance/rejection on adolescent externalizing symptoms, and a significant positive effect of IIV in father acceptance/rejection on internalizing symptoms. The weighted effect for mother acceptance/rejection on internalizing symptoms was not statistically significant. Additionally, there was significant heterogeneity in all meta-analytic estimates. More variability over time in experiences of parental acceptance/rejection predicts internalizing and externalizing symptoms as children transition into adolescence, and this effect is present across multiple diverse samples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Drug-drug interactions between propofol and ART drugs: Inhibiting neuronal activity by affecting glucose metabolism.

BACKGROUND: The use of two or more drugs carries the potential risk of drug-drug interactions (DDIs), which may result in adverse reactions. Some human immunodeficiency virus (HIV)-infected patients who receive antiretroviral therapy (ART) may require general anesthesia with propofol (PRL) before undergoing surgical treatment. Both PRL and ART drugs may lead to neuronal dysfunction, which can be accompanied by energy metabolism disorders. Neurons take in glucose mainly through glucose transporter 3 (Glut3) which is specifically expressed on the cell membranes of neurons. However, to date, no study has examined whether the DDIs of PRL and ART drugs interfere with glucose metabolism and Glut3 expression in neurons. METHODS: An in vitro model was constructed using the primary cultures of neurons. PRL and ART drugs (EFV, AZT, and 3TC), were added at different concentrations (low, medium, and high). The neurons were exposed to the drugs for 1, 4, 8, and 12 h. The optimal drug concentration and exposure time were selected. The cellular survival rate, glucose concentration, electrophysiology, and the expression of Glut3 were detected. RESULTS: There were no significant changes in the cellular survival rates of the neurons that were exposed to both PRL and ART drugs at low concentrations for 1 h. However, the survival rates of the neurons decreased significantly as the drug concentrations and durations increased. The glucose concentration of the neurons that were exposed to both PRL and the ART drugs was significantly decreased. The glucose concentration of the neurons was not affected by any individual drug. The amplitude of the action potential and the expression of Glut3 were decreased in the neurons that were exposed to both PRL and ART drugs. CONCLUSIONS: The main adverse reactions induced by the DDIs between PRL and the ART drugs were decreased glucose metabolism and neuronal damage, which were caused by inhibiting the expression of Glut3. More importantly, we found that decreases in glucose metabolism predated neuronal damage.

Developmental Trajectories of Parental Self-Efficacy as Children Transition to Adolescence in Nine Countries: Latent Growth Curve Analyses.

Little is known about the developmental trajectories of parental self-efficacy as children transition into adolescence. This study examined parental self-efficacy among mothers and fathers over 3 1/2 years representing this transition, and whether the level and developmental trajectory of parental self-efficacy varied by cultural group. Data were drawn from three waves of the Parenting Across Cultures (PAC) project, a large-scale longitudinal, cross-cultural study, and included 1178 mothers and 1041 fathers of children who averaged 9.72 years of age at T1 (51.2% girls). Parents were from nine countries (12 ethnic/cultural groups), which were categorized into those with a predominant collectivistic (i.e., China, Kenya, Philippines, Thailand, Colombia, and Jordan) or individualistic (i.e., Italy, Sweden, and USA) cultural orientation based on Hofstede's Individualism Index (Hofstede Insights, 2021). Latent growth curve analyses supported the hypothesis that parental self-efficacy would decline as children transition into adolescence only for parents from more individualistic countries; parental self-efficacy increased over the same years among parents from more collectivistic countries. Secondary exploratory analyses showed that some demographic characteristics predicted the level and trajectory of parental self-efficacy differently for parents in more individualistic and more collectivistic countries. Results suggest that declines in parental self-efficacy documented in previous research are culturally influenced.

Feature-Tracking-Derived Strain Analysis for Identification of Subendocardium-Involved Late Gadolinium Enhancement in Load-Induced Left Ventricular Hypertrophy: A Multicenter Study of Cardiac Magnetic Resonance Data.

BACKGROUND: Subendocardium-involved late gadolinium enhancement (SILGE) is a significant predictor of poor prognosis in patients with load-induced left ventricular hypertrophy (LVH). OBJECTIVES: This multicenter study aimed to investigate whether the diagnostic performance of cardiac magnetic resonance feature-tracking (CMR-FT)-derived strain analysis for detecting subtle subendocardial injury would be influenced by its load dependence in patients with load-induced LVH. METHODS: A total of 149 patients with load-induced LVH were recruited from three centers and underwent enhanced CMR imaging. The patients were divided into two groups based on the presence or absence of SILGE on CMR (SILGE+ group: n = 56; SILGE- group: n = 93). Clinical and CMR parameters were evaluated in both groups. RESULTS: The LV systolic pressure (LVSP) and LV end-diastolic pressure (LVEDP) in the SILGE+ group were higher than those in the SILGE- group (each with p < 0.05), and LVSP and LVEDP were correlated with the LV global longitudinal strain (GLS) (each with p < 0.05) in research center 1. The LV strain parameters were significantly lower in the SILGE+ group than those in the SILGE- group (each with p < 0.05). Logistic regression analysis identified GLS (OR 1.325; 95% CI 1.180 to 1.487, p < 0.001) as a predictive factor of SILGE in the patients with load-induced LVH. The receiver operating characteristic (ROC) curve analysis results indicated that the areas under the curve (AUC) of global radial strain (GRS), global circumferential strain (GCS), and GLS were 0.68, 0.69, and 0.76, respectively. De Long's test results implied that GLS had the best diagnostic performance for SILGE (p = 0.04). CONCLUSION: Despite the load dependency of CMR-FT-derived strain analysis, the GLS exhibits reasonable accuracy in the identification of SILGE and can potentially serve as a feasible alternative for detecting subendocardial involvement in patients with load-induced LVH who are contraindicated for LGE.

The impact of growth monitoring and promotion on health indicators in children under five years of age in low- and middle-income countries.

BACKGROUND: Undernutrition in the critical first 1000 days of life is the most common form of childhood malnutrition, and a significant problem in low- and middle-income countries (LMICs). The effects of undernutrition in children aged under five years are wide-ranging and include increased susceptibility to and severity of infections; impaired physical and cognitive development, which diminishes school and work performance later in life; and death. Growth monitoring and promotion (GMP) is a complex intervention that comprises regular measurement and charting of growth combined with promotion activities. Policymakers, particularly in international aid agencies, have differing and changeable interpretations and perceptions of the purpose of GMP. The effectiveness of GMP as an approach to preventing malnutrition remains a subject of debate, particularly regarding the added value of growth monitoring compared with promotion alone. OBJECTIVES: To evaluate the effectiveness of child growth monitoring and promotion for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children under five years of age in low- and middle-income countries. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 3 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cohort studies, and controlled before-after studies that compared GMP with standard care or nutrition education alone in non-hospitalised children aged under five years. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods to conduct a narrative synthesis. Our primary outcomes were anthropometric indicators, infant and child feeding practices, and health service usage. Secondary outcomes were frequency and severity of childhood illnesses, and mortality. We used GRADE to assess the certainty of evidence for each primary outcome. MAIN RESULTS: We included six studies reported in eight publications. We grouped the findings according to intervention. Community-based growth monitoring and promotion (without supplementary feeding) versus standard care We are unsure if GMP compared to standard care improves infant and child feeding practices, as measured at 24 months by the proportion of infants who have fluids other than breast milk introduced early (49.7% versus 70.5%; 1 study; 4296 observations; very low-certainty evidence). We are unsure if GMP improves health service usage, as measured at 24 months by the proportion of children who receive vitamin A (72.5% versus 62.9%; 1 study; 4296 observations; very low-certainty evidence) and the proportion of children who receive deworming (29.2% versus 14.6%; 1 study; 4296 observations; very low-certainty evidence). No studies reported selected anthropometric indicators (weight-for-age z-score or height-for-age z-score) at 12 or 24 months, infant and child feeding practices at 12 months, or health service usage at 12 months. Community-based growth monitoring and promotion (with supplementary feeding) versus standard care Two studies (with 569 participants) reported the mean weight-for-age z-score at 12 months, providing very low-certainty evidence: in one study, there was little or no difference between GMP and standard care (mean difference (MD) -0.07, 95% confidence interval (CI) -0.19 to 0.06); in the other study, mean weight-for-age z-score worsened in both groups, but we were unable to calculate a relative effect. GMP versus standard care may make little to no difference to the mean height-for-age z-score at 12 months (MD -0.15, 95% CI -0.34 to 0.04; 1 study, 337 participants; low-certainty evidence). Two studies (with 564 participants) reported a range of outcome measures related to infant and child feeding practices at 12 months, showing little or no difference between the groups (very low-certainty evidence). No studies reported health service usage at 12 or 24 months, feeding practices at 24 months, or selected anthropometric indicators at 24 months. AUTHORS' CONCLUSIONS: There is limited uncertain evidence on the effectiveness of GMP for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children aged under five years in LMICs. Future studies should explore the reasons for the apparent limited impact of GMP on key child health indicators. Reporting of GMP interventions and important outcomes must be transparent and consistent.

The Biological Significance Of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression.

As a member of the AF4/FMR2 (AFF) family, AFF4 is a scaffold protein in the superelongation complex (SEC). In this mini-view, we discuss the role of AFF4 as a transcription elongation factor that mediates HIV activation and replication and stem cell osteogenic differentiation. AFF4 also promotes the progression of head and neck squamous cell carcinoma, leukemia, breast cancer, bladder cancer and other malignant tumors. The biological function of AFF4 is largely achieved through SEC assembly, regulates SRY-box transcription factor 2 (SOX2), MYC, estrogen receptor alpha (ESR1), inhibitor of differentiation 1 (ID1), c-Jun and noncanonical nuclear factor-κB (NF-κB) transcription and combines with fusion in sarcoma (FUS), unique regulatory cyclins (CycT1), or mixed lineage leukemia (MLL). We explore the prospects of using AFF4 as a therapeutic in Acquired immunodeficiency syndrome (AIDS) and malignant tumors and its potential as a stemness regulator.

Exploring the global immune landscape of peripheral blood mononuclear cells in H5N6-infected patient with single-cell transcriptomics.

BACKGROUND: Avian influenza viruses (AIV), particularly H5N6, have risen in infection frequency, prompting major concerns. Single-cell RNA sequencing (scRNA-seq) can illustrate the immune cell landscape present in the peripheral circulation of influenza H5N6-infected individuals at the single-cell level. This study attempted to employ scRNA-seq technology to map the potentially hidden single cell landscape of influenza H5N6. METHODS: High-quality transcriptomes were generated from scRNA-seq data of peripheral blood mononuclear cells (PBMCs), which were taken from a critically-ill child diagnosed with H5N6 avian influenza infection and one healthy control donor. Cluster analysis was then performed on the scRNA-seq data to identify the different cell types. The pathways, pseudotime developmental trajectories and gene regulatory networks involved in different cell subpopulations were also explored. RESULTS: In total, 3,248 single cell transcriptomes were captured by scRNA-seq from PBMC of the child infected with H5N6 avian influenza and the healthy control donor and further identified seven immune microenvironment cell types. In addition, a subsequent subpopulation analysis of innate lymphoid cells (ILC) and CD4+ T cells revealed that subpopulations of ILC and CD4+ T cells were involved in cytokine and inflammation-related pathways and had significant involvement in the biological processes of oxidative stress and cell death. CONCLUSION: In conclusion, characterizing the overall immune cell composition of H5N6-infected individuals by assessing the immune cell landscape in the peripheral circulation of H5N6 avian influenza-infected and healthy control donors at single-cell resolution provides key information for understanding H5N6 pathogenesis.

Immunization coverage, knowledge, satisfaction, and associated factors of non-National Immunization Program vaccines among migrant and left-behind families in China: evidence from Zhejiang and Henan provinces.

BACKGROUND: Migrant and left-behind families are vulnerable in health services utilization, but little is known about their disparities in immunization of non-National Immunization Program (NIP) vaccines. This study aims to evaluate the immunization coverage, knowledge, satisfaction, and associated factors of non-NIP vaccines among local and migrant families in the urban areas and non-left-behind and left-behind families in the rural areas of China. METHODS: A cross-sectional survey was conducted in urban areas of Zhejiang and rural areas of Henan in China. A total of 1648 caregivers of children aged 1-6 years were interviewed face-to-face by a pre-designed online questionnaire, and their families were grouped into four types: local urban, migrant, non-left-behind, and left-behind. Non-NIP vaccines included Hemophilus influenza b (Hib) vaccine, varicella vaccine, rotavirus vaccine, enterovirus 71 vaccine (EV71) and 13-valent pneumonia vaccine (PCV13). Log-binomial regression models were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the difference on immunization coverage of children, and knowledge and satisfaction of caregivers among families. The network models were conducted to explore the interplay of immunization coverage, knowledge, and satisfaction. Logistic regression models with odds ratios (ORs) and 95% CIs were used to estimate the associated factors of non-NIP vaccination. RESULTS: The immunization coverage of all non-NIP vaccines and knowledge of all items of local urban families was the highest, followed by migrant, non-left-behind and left-behind families. Compared with local urban children, the PRs (95% CIs) for getting all vaccinated were 0.65 (0.52-0.81), 0.29 (0.22-0.37) and 0.14 (0.09-0.21) among migrant children, non-left-behind children and left-behind children, respectively. The coverage-knowledge-satisfaction network model showed the core node was the satisfaction of vaccination schedule. Non-NIP vaccination was associated with characteristics of both children and caregivers, including age of children (> 2 years-OR: 1.69, 95% CI: 1.07-2.68 for local urban children; 2.67, 1.39-5.13 for migrant children; 3.09, 1.23-7.76 for non-left-behind children); and below caregivers' characteristics: family role (parents: 0.37, 0.14-0.99 for non-left-behind children), age (≤ 35 years: 7.27, 1.39-37.94 for non-left-behind children), sex (female: 0.49, 0.30-0.81 for local urban children; 0.31, 0.15-0.62 for non-left-behind children), physical health (more than average: 1.58, 1.07-2.35 for local urban children) and non-NIP vaccines knowledge (good: 0.45, 0.30-0.68 for local urban children; 7.54, 2.64-21.50 for left-behind children). CONCLUSIONS: There were immunization disparities in non-NIP vaccines among migrant and left-behind families compared with their local counterparts. Non-NIP vaccination promotion strategies, including education on caregivers, and optimization of the immunization information system, should be delivered particularly among left-behind and migrant families.