Iron metabolism: backfire of cancer cell stemness and therapeutic modalities.

Cancer stem cells (CSCs), with their ability of self-renewal, unlimited proliferation, and multi-directional differentiation, contribute to tumorigenesis, metastasis, recurrence, and resistance to conventional therapy and immunotherapy. Eliminating CSCs has long been thought to prevent tumorigenesis. Although known to negatively impact tumor prognosis, research revealed the unexpected role of iron metabolism as a key regulator of CSCs. This review explores recent advances in iron metabolism in CSCs, conventional cancer therapies targeting iron biochemistry, therapeutic resistance in these cells, and potential treatment options that could overcome them. These findings provide important insights into therapeutic modalities against intractable cancers.

[Research progress on ferroptosis in tumor immunity].

Ferroptosis is a novel form of cell death that is induced by excessive accumulation of ferrous ions and lipid peroxides. It triggers the release of damage-associated molecular patterns through autophagy-dependent mechanisms, serving as an adjunct to immunogenic cell death and activating both adaptive and innate immunity. In the tumor microenvironment, the regulation and influence of tumor cells and immune cells undergoing ferroptosis are regulated by various factors, which plays a crucial role in tumor development, treatment, and prognosis. This article provides an overview of the biological effects of ferroptosis on immune cells such as T cells, macrophages, neutrophils and B cells and tumor cells in the tumor microenvironment.

Prognostic predictive value of urothelial carcinoma of the bladder after TURBT based on multiphase CT radiomics.

OBJECTIVE: To investigate multiphase computed tomography (CT) radiomics-based combined with clinical factors to predict overall survival (OS) in patients with bladder urothelial carcinoma (BLCA) who underwent transurethral resection of bladder tumor (TURBT). METHODS: Data were retrospectively collected from 114 patients with primary BLCA from February 2016 to February 2018. The regions of interest (ROIs) of the plain, arterial, and venous phase images were manually segmented. The Cox regression algorithm was used to establish 3 basic models for the plain phase (PP), arterial phase (AP), and venous phase (VP) and 2 combination models (AP + VP and PP + AP + VP). The highest-performing radiomics model was selected to calculate the radiomics score (Rad-score), and independent risk factors affecting patients' OS were analyzed using Cox regression. The Rad-score and clinical risk factors were combined to construct a joint model and draw a visualized nomogram. RESULTS: The combined model of PP + AP + VP showed the best performance with the Akaike Information Criterion (AIC) and Consistency Index (C-index) in the test group of 130.48 and 0.779, respectively. A combined model constructed with two independent risk factors (age and Ki-67 expression status) in combination with the Rad-score outperformed the radiomics model alone; AIC and C-index in the test group were 115.74 and 0.840, respectively. The calibration curves showed good agreement between the predicted probabilities of the joint model and the actual (p < 0.05). The decision curve showed that the joint model had good clinical application value within a large range of threshold probabilities. CONCLUSION: This new model can be used to predict the OS of patients with BLCA who underwent TURBT.

Meals, Education, and Gardens for In-School Adolescents: A Cluster Randomized Trial of an Adolescent Nutrition Intervention Package in Tanzania.

PURPOSE: This study aimed to implement and evaluate integrated, school-based nutrition intervention packages for adolescents in Dodoma, Tanzania. METHODS: A cluster randomized controlled trial was conducted among six secondary schools in Dodoma, Tanzania. Two schools received the full-intervention package of school meals, nutrition education, school gardens, and community workshops. Two schools received the partial-intervention package without the school meals component. Two schools served as the controls and did not receive any intervention. The intervention was implemented over one academic year. The analytical sample included 534 adolescents aged 14 to 17 at baseline and 286 parents. Outcomes included nutrition knowledge, food preferences, diet quality, food insecurity, physical activity, growth, and anemia. Linear models were used to estimate mean differences, and logistic regression models were used to estimate odds ratios (ORs). RESULTS: Compared to the control, both the partial (OR: 0.59; 95% confidence interval [CI]: 0.35, 1.00) and full (OR: 0.49; 95% CI: 0.40, 0.59) interventions were associated with lower odds of poor diet quality among adolescents. Among the parents, both the partial (OR: 0.28; 95% CI: 0.20, 0.40) and full (OR: 0.28; 95% CI: 0.13, 0.58) interventions were associated with lower odds of poor diet quality. The partial (OR: 0.29; 95% CI: 0.18, 0.47) and full (OR: 0.47; 95% CI: 0.30, 0.72) interventions were associated with lower odds of adolescent overweight or obesity. DISCUSSION: School-based nutritional intervention packages incorporating multiple actions may improve the diet quality of adolescents and their household members and reduce the double burden of adolescent malnutrition.

Clinical Application of Tonsillectomy with Preservation of Capsule and Support Tissue.

Objective: The clinical effect of tonsillectomy with the preservation of tonsillar capsule and stent tissue and punctuated suture of tonsillar capsule and stent tissue was analyzed retrospectively. Methods: From January 2013 to January 2022, a total of 960 patients underwent tonsillectomy, consisting of 530 males and 430 females with ages ranging from 4 to 60 years (median age: 11 years). The capsule and scaffold tissues were preserved in all patients during the operation, and the surrounding mucosa, capsule, and scaffold tissues were sutured without tension. Indexes such as operation time, intraoperative blood loss, tonsillar white membrane, incidence of postoperative bleeding, postoperative pain score, and incidence of tonsillar remnant were recorded, and the school attendance of children (≤12 years old) was recorded. Results: The mucosal covering of tonsillar fossa healed well in all patients, and the sutures were completely removed at 4 weeks after reexamination. All patients were followed up for 1-8 years, and there was no residual hyperplasia or residual inflammation. Children under 12 years old could return to school 4 days after surgery without any postoperative complications. Conclusion: Tonsillectomy, preserving the tonsillar capsule and scaffold tissue followed by punctate suturing, offered several advantages: it resulted in less intraoperative blood loss and postoperative pain. Patients could resume a normal diet 6 hours after the surgery without an increased risk of complications. Moreover, it significantly reduced the risk of postoperative bleeding.

Enzyme-Directed and Organelle-Specific Sphere-to-Fiber Nanotransformation Enhances Photodynamic Therapy in Cancer Cells.

Employing responsive nanoplatforms as carriers for photosensitizers represents an effective strategy to overcome the challenges associated with photodynamic therapy (PDT), including poor solubility, low bioavailability, and high systemic toxicity. Drawing inspiration from the morphology transitions in biological systems, a general approach to enhance PDT that utilizes enzyme-responsive nanoplatforms is developed. The transformation of phosphopeptide/photosensitizer co-assembled nanoparticles is first demonstrated into nanofibers when exposed to cytoplasmic enzyme alkaline phosphatase. This transition is primarily driven by alkaline phosphatase-induced changes of the nanoparticles in the hydrophilic and hydrophobic balance, and intermolecular electrostatic interactions within the nanoparticles. The resulting nanofibers exhibit improved ability of generating reactive oxygen species (ROS), intracellular accumulation, and retention in cancer cells. Furthermore, the enzyme-responsive nanoplatform is expanded to selectively target mitochondria by mitochondria-specific enzyme sirtuin 5 (SIRT5). Under the catalysis of SIRT5, the succinylated peptide/photosensitizer co-assembled nanoparticles can be transformed into nanofibers specifically within the mitochondria. The resulting nanofibers exhibit excellent capability of modulating mitochondrial activity, enhanced ROS formation, and significant anticancer efficacy via PDT. Consequently, the enzyme-instructed in situ fibrillar transformation of peptide/photosensitizers co-assembled nanoparticles provides an efficient pathway to address the challenges associated with photosensitizers. It is envisaged that this approach will further expand the toolbox for enzyme-responsive biomaterials for cancer therapy.

Intratumoral and peritumoral CT-based radiomics for predicting the microsatellite instability in gastric cancer.

PURPOSE: To investigate the value of intratumoral and peritumoral radiomics based on contrast-enhanced computer tomography (CECT) to preoperatively predict microsatellite instability (MSI) status in gastric cancer (GC) patients. METHODS: A total of 189 GC patients, including 63 patients with MSI-high (MSI-H) and 126 patients with MSI-low/stable (MSI-L/S), were randomly divided into the training cohort and validation cohort. Intratumoral and 5-mm peritumoral regions' radiomics features were extracted from CECT images. The features were standardized by Z-score, and the Inter- and intraclass correlation coefficient, univariate logistic regression analysis, and least absolute shrinkage and selection operator (LASSO) were applied to select the optimal radiomics features. Radiomics scores (Rad-score) based on intratumoral regions, peritumoral regions, and intratumoral + 5-mm peritumoral regions were calculated by weighting the linear combination of the selected features with their respective coefficients to construct the intratumoral model, peritumoral model, and intratumoral + peritumoral model. Logistic regression was used to establish a combined model by combining clinical characteristics, CT semantic features, and Rad-score of intratumoral and peritumoral regions. RESULTS: Eleven radiomics features were selected to establish a radiomics intratumoral + peritumoral model. CT-measured tumor length and tumor location were independent risk factors for MSI status. The established combined model obtained the highest area under the receiver operating characteristic (ROC) curve (AUC) of 0.830 (95% CI, 0.727-0.906) in the validation cohort. The calibration curve and decision curve demonstrated its good model fitness and clinical application value. CONCLUSION: The combined model based on intratumoral and peritumoral CECT radiomics features and clinical factors can predict the MSI status of GS with moderate accuracy before surgery, which helps formulate personalized treatment strategies.

HDAC6-Activatable Multifunctional Near-Infrared Probe for Glioma Cell Detection and Elimination.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with limited treatment options and high drug resistance, presenting significant challenges in the pursuit of effective treatment strategies. Epigenetic modifications have emerged as promising diagnostic biomarkers and therapeutic targets for GBM. For instance, histone deacetylase 6 (HDAC6) has been identified as a potential pharmacological target for GBM. Furthermore, the overexpression of monoamine oxidase A (MAO A) in glioma has been linked to tumor progression, making it an attractive target for therapy. In this study, we successfully engineered HDAC-MB, an activatable multifunctional small-molecule probe with the goal of efficiently detecting and killing glioma cells. HDAC-MB can be selectively activated by HDAC6, leading to the "turn on" of near-infrared fluorescence and effective inhibition of MAO A, along with potent photodynamic therapy (PDT) effects. Consequently, HDAC-MB not only enables the imaging of HDAC6 in live glioma cells but also exhibits the synergistic effect of MAO A inhibition and PDT, effectively inhibiting glioma invasion and inducing cellular apoptosis. The distinctive combination of features displayed by HDAC-MB positions it as a versatile and highly effective tool for the accurate diagnosis and treatment of glioma cells. This opens up opportunities to enhance therapy outcomes and explore future applications in glioma theranostics.

Boosting chemotherapy of bladder cancer cells by ferroptosis using intelligent magnetic targeting nanoparticles.

A versatile nano-delivery platform was reported to enhance the tumor suppression effect of chemotherapy by augmenting tumor cells' ferroptosis. The platform consists of pomegranate-like magnetic nanoparticles (rPAE@SPIONs) fabricated by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within a reduced poly(ß-amino ester)s-PEG amphiphilic copolymer (rPAE). The resulting platform exhibits several functionalities. Firstly, it promotes the doxorubicin (DOX) release by leveraging the mild hyperthermia generated by NIR irradiation. Secondly, it triggers ferroptosis in tumor cells, inducing their demise. Thirdly, it induces polarization of macrophages towards an anti-tumor M1 phenotype, contributing to ferroptosis of tumor cells and enhanced tumor cell suppression. This study effectively capitalizes on the versatility of SPIONs and offers a simple yet powerful strategy for developing a new nanosized ferroptosis-inducing agent, ultimately improving the inhibition of bladder cancer cells.

Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.

This research aimed to find important genes and pathways related to cellular senescence (CS) in diabetic foot ulcers (DFU) and to estimate the possible pathways through which CS affects diabetic foot healing. The GSE80178 dataset was acquired from the Gene Expression Omnibus (GEO) database, containing six DFU and three diabetic foot skin (DFS) samples. The limma package was used to identify differentially expressed genes (DEGs). At the same time, DEGs associated with CS (CS-DEGs) were found using the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the CS-DEGs. A protein-protein interaction (PPI) network was built using the String database, and the cytoHubba plug-in within Cytoscape helped identify hub genes. Lastly, the miRNA-TF-mRNA regulatory network for these hub genes was established. In total, 66 CS-DEGs were obtained. These genes mainly focus on CS, Kaposi sarcoma-associated herpesvirus infection and Toll-like receptor signalling pathway. Eight hub genes were identified to regulate cell senescence in DFU, including TP53, SRC, SIRT1, CCND1, EZH2, CXCL8, AR and CDK4. According to miRNA-TF-mRNA regulatory network, hsa-mir-132-3p/SIRT1/EZH2 axis is involved in senescence cell accumulation in DFU.

Acteoside ameliorates learning and memory impairment in APP/PS1 transgenic mice by increasing Aß degradation and inhibiting tau hyperphosphorylation.

Alzheimer's disease (AD) is a neurodegenerative disease. Senile plaques and intracellular neurofibrillary tangles are pathological hallmarks of AD. Recent studies have described the improved cognitive and neuroprotective functions of acteoside (AS). This study aimed to investigate whether the improved cognition of AS was mediated by Aß degradation and tau phosphorylation in APP/PS1 mice. The open field, Y maze, and novel object recognition tests were used to assess cognitive behavioral changes. We evaluated the levels of Aß40 and Aß42 in serum, cortex, and hippocampus, and Aß-related scavenging enzymes, phosphorylated GSK3ß and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 mice by western blotting. Our results revealed that AS treatment ameliorated anxious behaviors, spatial learning, and memory impairment in APP/PS1 mice and significantly reduced Aß deposition in their serum, cortex, and hippocampus. AS significantly increased Aß degradation, inhibited the hyperphosphorylation of tau, and significantly decreased the activity of GSK3ß, which is involved in tau phosphorylation. Altogether, these findings indicated that the beneficial effects of AS on AD-associated anxious behaviors and cognitive impairments could be attributed to promoting Aß degradation and inhibiting tau hyperphosphorylation, which might be partly mediated by GSK3ß.

Preoperative Noninvasive Evaluation of Tumor Budding in Rectal Cancer Using Multiparameter MRI Radiomics.

RATIONALE AND OBJECTIVES: To assess the value of a multiparametric magnetic resonance imaging (MRI)-based model integrating radiomics features with clinical and MRI semantic features for preoperative evaluation of tumor budding (TB) in rectal cancer. MATERIALS AND METHODS: A total of 120 patients with pathologically confirmed rectal cancer were retrospectively analyzed. The patients were randomized into training and validation cohorts in a 6:4 ratio. Radiomics features were extracted and selected from preoperative T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1-weighted imaging (T1CE) sequences, after which the corresponding radiomics score (RS) was calculated, and the radiomics models (T2WI model, DWI model, and T1CE model) were constructed. Logistic regression analysis was selected to develop a combined model integrated RST2WI, RSDWI, RST1CE, and clinical and MRI semantic features. The efficacy of each model in diagnosing TB grade was observed by the receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to assess the clinical benefits of the models. RESULTS: Seven features were extracted and selected from each T2WI, DWI, and T1CE sequence to calculate the corresponding RS and construct the corresponding radiomics model. MRI reported N stage was an independent risk factor for TB. The area under the ROC curve of the combined model was 0.961 and 0.891 in the training and validation cohorts, respectively. The combined model showed better performance than the other models. DCA showed that the net benefit of the combined model was better than that of the other models in the vast majority of threshold probabilities. CONCLUSION: A combined model integrating radiomics features and MRI semantic features allows for noninvasive preoperative evaluation of TB grading in patients with rectal cancer.

School-based supplementation with iron-folic acid or multiple micronutrient tablets to address anemia among adolescents in Burkina Faso: a cluster-randomized trial.

BACKGROUND: Iron-deficiency anemia is a leading cause of morbidity among adolescents (aged 10-19 y), especially in low- and middle-income settings. Few policies and programs have targeted adolescent health. OBJECTIVES: This study aimed to evaluate the effectiveness of school-based supplementation with iron-folic acid (IFA) or multiple micronutrient supplements (MMSs) in addressing anemia among adolescents in Burkina Faso. METHODS: In this cluster-randomized trial, 3123 secondary school students aged 10 to 18 y in Burkina Faso were either supplemented with weekly IFA, daily MMSs, or received standard nutrition education as controls. Supplementation occurred between April 2021 and April 2022 over 2 supplementation periods (10 wk, then 16 wk) separated by a gap of 20 wk without supplementation. Hemoglobin was evaluated 4 times: at baseline prior to each supplementation period and at the end of each period. Anemia was categorized by the World Health Organization hemoglobin level cutoffs as none, mild, moderate, or severe. Associations between treatment arm and anemia or continuous hemoglobin (g/dL) were assessed using multilevel mixed effects generalized linear models with schools as a random effect, controlling for baseline hemoglobin or anemia status. RESULTS: Baseline anemia prevalence was similar across study arms, with 32.7% in IFA, 31.2% in MMS, and 29.5% in the control arm. Over the full study period, adolescents provided IFA had hemoglobin levels higher than those in the control arm (adjusted ß: 0.32; 95% CI: 0.02, 0.62). No significant associations were observed for MMS or for anemia outcomes; however, the direction and magnitude of nonsignificant associations indicate potential protective effects of IFA and MMSs on anemia. CONCLUSIONS: The results do not provide strong evidence that weekly IFA or daily MMS alone is effective, but supplementation may play a role in addressing adolescent anemia if combined with cointerventions. Additional research is required to determine the best strategy to address anemia. This trial was registered at clinicaltrials.gov as NCT04657640.

Risk factors for inadequate and excessive gestational weight gain in 25 low- and middle-income countries: An individual-level participant meta-analysis.

BACKGROUND: Many women experience suboptimal gestational weight gain (GWG) in low- and middle-income countries (LMICs), but our understanding of risk factors associated with GWG in these settings is limited. We investigated the relationships between demographic, anthropometric, lifestyle, and clinical factors and GWG in prospectively collected data from LMICs. METHODS AND FINDINGS: We conducted an individual participant-level meta-analysis of risk factors for GWG outcomes among 138,286 pregnant women with singleton pregnancies in 55 studies (27 randomized controlled trials and 28 prospective cohorts from 25 LMICs). Data sources were identified through PubMed, Embase, and Web of Science searches for articles published from January 2000 to March 2019. Titles and abstracts of articles identified in all databases were independently screened by 2 team members according to the following eligibility criteria: following inclusion criteria: (1) GWG data collection took place in an LMIC; (2) the study was a prospective cohort or randomized trial; (3) study participants were pregnant; and (4) the study was not conducted exclusively among human immunodeficiency virus (HIV)-infected women or women with other health conditions that could limit the generalizability of the results. The Institute of Medicine (IOM) body mass index (BMI)-specific guidelines were used to determine the adequacy of GWG, which we calculated as the ratio of the total observed weight gain over the mean recommended weight gain. Study outcomes included severely inadequate GWG (percent adequacy of GWG <70), inadequate GWG (percent adequacy of GWG <90, inclusive of severely inadequate), and excessive GWG (percent adequacy of GWG >125). Multivariable estimates from each study were pooled using fixed-effects meta-analysis. Study-specific regression models for each risk factor included all other demographic risk factors measured in a particular study as potential confounders, as well as BMI, maternal height, pre-pregnancy smoking, and chronic hypertension. Risk factors occurring during pregnancy were further adjusted for receipt of study intervention (if any) and 3-month calendar period. The INTERGROWTH-21st standard was used to define high and low GWG among normal weight women in a sensitivity analysis. The prevalence of inadequate GWG was 54%, while the prevalence of excessive weight gain was 22%. In multivariable models, factors that were associated with a higher risk of inadequate GWG included short maternal stature (<145 cm), tobacco smoking, and HIV infection. A mid-upper arm circumference (MUAC) of ≥28.1 cm was associated with the largest increase in risk for excessive GWG (risk ratio (RR) 3.02, 95% confidence interval (CI) [2.86, 3.19]). The estimated pooled difference in absolute risk between those with MUAC of ≥28.1 cm compared to those with a MUAC of 24 to 28.09 cm was 5.8% (95% CI 3.1% to 8.4%). Higher levels of education and age <20 years were also associated with an increased risk of excessive GWG. Results using the INTERGROWTH-21st standard among normal weight women were similar but attenuated compared to the results using the IOM guidelines among normal weight women. Limitations of the study's methodology include differences in the availability of risk factors and potential confounders measured in each individual dataset; not all risk factors or potential confounders of interest were available across datasets and data on potential confounders collected across studies. CONCLUSIONS: Inadequate GWG is a significant public health concern in LMICs. We identified diverse nutritional, behavioral, and clinical risk factors for inadequate GWG, highlighting the need for integrated approaches to optimizing GWG in LMICs. The prevalence of excessive GWG suggests that attention to the emerging burden of excessive GWG in LMICs is also warranted.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma.

BACKGROUND: According to clinical practice guidelines, transarterial chemoembolization (TACE) is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma (HCC). Early prediction of treatment response can help patients choose a reasonable treatment plan. This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival. METHODS: A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed. The tumor response was assessed by modified response evaluation criteria in solid tumors (mRECIST), and the response of the first TACE to each session and its correlation with overall survival were evaluated. The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator (LASSO), and four machine learning models were built with different types of regions of interest (ROIs) (tumor and corresponding tissues) and the model with the best performance was selected. The predictive performance was assessed with receiver operating characteristic (ROC) curves and calibration curves. RESULTS: Of all the models, the random forest (RF) model with peritumor (+10 mm) radiomic signatures had the best performance [area under ROC curve (AUC) = 0.964 in the training cohort, AUC = 0.949 in the validation cohort]. The RF model was used to calculate the radiomic score (Rad-score), and the optimal cutoff value (0.34) was calculated according to the Youden's index. Patients were then divided into a high-risk group (Rad-score > 0.34) and a low-risk group (Rad-score ≤ 0.34), and a nomogram model was successfully established to predict treatment response. The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves. Multivariate Cox regression identified six independent prognostic factors for overall survival, including male [hazard ratio (HR) = 0.500, 95% confidence interval (CI): 0.260-0.962, P = 0.038], alpha-fetoprotein (HR = 1.003, 95% CI: 1.002-1.004, P < 0.001), alanine aminotransferase (HR = 1.003, 95% CI: 1.001-1.005, P = 0.025), performance status (HR = 2.400, 95% CI: 1.200-4.800, P = 0.013), the number of TACE sessions (HR = 0.870, 95% CI: 0.780-0.970, P = 0.012) and Rad-score (HR = 3.480, 95% CI: 1.416-8.552, P = 0.007). CONCLUSIONS: The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

School-based health and nutrition interventions addressing double burden of malnutrition and educational outcomes of adolescents in low- and middle-income countries: A systematic review.

School system is a promising platform for addressing all forms of malnutrition in adolescents. However, little is known about the impact of integrated school health and nutrition programmes on adolescent nutrition and educational outcomes in low- and middle-income countries (LMICs). This systematic review sought to characterize school-based health and nutrition interventions among adolescents in LMICs and analyze their effects on nutritional status and educational outcomes. Four databases were searched for studies evaluating school-based health and nutrition interventions for adolescents in LMICs, reporting changes in either nutritional status or educational outcomes. A narrative synthesis was used to analyze and describe the evidence. Our review included 68 articles evaluating 58 interventions, of which a third had moderate to strong methodological quality. Forty-two studies evaluated single-domain interventions, while 26 evaluated multi-component interventions. A third of all interventions were based on a theoretical framework. Three-fourths of the interventions were shorter than 11 months, which may make identifying their effect difficult. The results of the effectiveness of these interventions were mixed and inconsistent across intervention types. Sixteen out of 21 studies evaluating multi-component interventions and 12 out of 23 studies evaluating nutrition education reported improving nutritional or diet-related outcomes. One out of six studies reported positive effects on educational outcomes. Our review has identified that research needs include: a greater inclusion of theory-based approaches to guide the implementation of interventions; more studies of integrated interventions that involve parents and the wider community in LMICs; and extension of outcomes beyond nutritional status to include educational outcomes.

Comparison of CalliSpheres® microspheres drug-eluting beads and conventional transarterial chemoembolization in hepatocellular carcinoma patients: a randomized controlled trial.

BACKGROUND: This trial aimed to compare the outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres® microspheres (CSM) and conventional transarterial chemoembolization cTACE in the treatment of patients with unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 90 patients were divided into DEB-TACE group (n = 45) and cTACE group (n = 45). The treatment response, overall survival (OS), progression-free survival (PFS), and the safety were compared between the two groups. RESULTS: The objective response rate (ORR) in the DEB-TACE group was significantly higher than that in cTACE group at 1, 3, and 6 months of follow-up (P = 0.031, P = 0.003, P = 0.002). The complete response (CR) in DEB-TACE group was significantly higher than that in cTACE group at 3 months (P = 0.036). Survival analysis revealed that, DEB-TACE group had better survival benefits than cTACE group (median OS: 534 days vs. 367 days, P = 0.027; median PFS: 352 days vs. 278 days P = 0.004). The degree of liver function injury was more serious in DEB-TACE group at 1 week, but was similar between the two groups at 1 month. DEB-TACE with CSM caused a high incidence of fever and a severe abdominal pain (P = 0.031, P = 0.037). CONCLUSIONS: DEB-TACE with CSM showed better treatment response and survival benefits than cTACE group. Although a transient more severe liver damage, high incidence of fever and a severe abdominal pain occurred in the DEB-TACE group, it could be resolved through symptomatic treatment.

Increased expression of HMMR in renal cell carcinoma is an independent prognostic factor.

The present study investigated how abnormal expression of hyaluronan-mediated mobility receptor (HMMR) in renal cell carcinoma (RCC) tissue affects the growth of RCC cells and the association between expression of HMMR and pathological staging and prognosis of patients with RCC. Reverse transcription-quantitative PCR was used to measure the expression of HMMR mRNA in RCC tissue and cell lines. For the prediction of HMMR gene expression, The Cancer Genome Atlas online database was utilized to compare differential gene expression of HMMR in normal renal and RCC tissue. Cell Counting Kit-8 assay was used to examine cell proliferation. The expression of HMMR increased in RCC tissue and renal cancer cell lines. The expression of HMMR was an independent prognostic factor for 5-year and disease-free survival in patients with RCC. The silencing of HMMR expression decreased the expression of Cyclin B1 and inhibited the proliferation of RCC cells. Overexpression of HMMR promoted the expression of Cyclin B1 and cell proliferation. The present study demonstrated that the expression of HMMR was significantly upregulated in RCC and was an independent prognostic factor for RCC. HMMR may be involved in the occurrence of RCC by regulating Cyclin B1.

Porphyrin Centered Paclitaxel Tetrameric Prodrug Nanoassemblies as Tumor-Selective Theranostics for Synergized Breast Cancer Therapy.

Although having undergone decades of development, nanoparticulate drug delivery vehicles for efficient cancer therapy remain a challenge, confined by low drug loading, instability, and poor cancer tissue selectivity. A self-assembled prodrug, the combination of prodrug strategy and the self-assembly merits, represents a special chemical entity which spontaneously organizes into supramolecular composites with defined architecture, therefore also providing a strategy to develop new medications. Paclitaxel (PTX) is still among the most generally prescribed chemotherapeutics in oncology but is restricted by poor solubility. Although photodynamic therapy, with its noninvasive features and barely developed drug resistance, signifies an alternative tool to suppress life-threatening cancer, sole use hardly fulfills its potential. To this end, a reduction-activatable heterotetrameric prodrug with the photosensitizer is synthesized, then formulated into self-assembled nanoparticles (NPs) for tumor imaging and combined chemo- and photodynamic therapy. Coating the NPs with amphiphilic polymer distearylphosphatidylethanolamine-polyethylene glycol-arginine-glycine-aspartate (DSPE-PEG-RGD) offers high stability and enables cancer tissue targeting. The as-prepared NPs enlighten disease cells and reveal more potent cytotoxicity comparing to PTX and the photosensitizer alone. Furthermore, the NPs selectively accumulates into tumors and synergistically inhibits tumor proliferation with reduced side effects in mice.

Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

BACKGROUND: There is abundant evidence showing that iron deficiency is closely linked with delayed brain development, worse school performance, and behavioral abnormalities. However, evidence on the impact of iron supplementation among children and adolescents in low- and middle-income countries (LMICs) has been inconsistent. This study aims to examine the effect of oral iron supplementation on cognitive function among children and adolescents in LMICs. METHODS: A systematic review and meta-analysis was conducted to examine the impact of iron supplementation on cognitive function (including intelligence, attention, short-term memory, long-term memory, and school performance) among children and adolescents aged 5 to 19. We searched PubMed, Embase, Web of Science, CINAHL, and references of related articles published from the inception of the databases to 1 May 2022. Random-effects pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated to estimate the effect of iron supplementation on cognitive function. We also investigated the heterogeneity of the effects using subgroup and meta-regression analyses. This review was registered with PROSPERO (CRD42020179064). RESULTS: Nine studies with 1196 individual participants from five countries were identified and included. Iron had a positive impact on intelligence test scores among children and adolescents (SMD = 0.47, 95% confidence interval [CI]: 0.10, 0.83). Meta-regression showed that the intelligence test scores improved with increasing the iron supplement dose (odds ratio [CI] = 1.02, 95% CI: 1.00, 1.04). There were no significant effects on attention, short-term memory, long-term memory, or school performance. CONCLUSIONS: Oral iron intake can improve the intelligence test scores of children and adolescents in LMICs and should be considered for future nutritional interventions.