Mapping global prevalence of menopausal symptoms among middle-aged women: a systematic review and meta-analysis.

BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.

Therapeutic potential of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) in cancer treatment.

Pseudomonas aeruginosa is a Gram-negative bacteria and it has been demonstrated that immunization with the outer membrane proteins of the microbe produces most of the relevant human antibodies. The peritrichous P. aeruginosa strain with MSHA fimbriae (PA-MSHA strain) has been found to be effective in the inhibition of growth and proliferation of different types of cancer cells. Furthermore, it has been revealed that PA-MSHA exhibits cytotoxicity because of the presence of MSHA and therefore it possesses anti-carcinogenic ability against different types of human cancer cell lines including, gastric, breast, hepatocarcinoma and nasopharyngeal cells. Studies have revealed that PA-MSHA exhibits therapeutic potential against cancer growth by induction of apoptosis, arrest of cell cycle, activating NF-κB/TLR5 pathway, etc. In China, PA-MSHA injections have been approved for the treatment of malignant tumor patients from very long back. The present review article demonstrates the therapeutic potential of PA-MSHA against various types of human cancers and explains the underlying mechanism.

Gut microbiota and autoimmune thyroid disease: a bidirectional Mendelian randomization study and mediation analysis.

Background: The gut microbiota (GM) plays a pivotal role in influencing various health outcomes, including immune-mediated conditions, but its potential association with autoimmune thyroid disease (AITD) remains underexplored. We aimed to investigate the potentially pathogenic or protective causal impacts of specific GM on two types of AITD, namely Graves' disease and Hashimoto's thyroiditis, and analyzed the mediating effect of 731 immune cell phenotypes. Methods: Leveraging pooled genome-wide association study (GWAS) data of 211 gut microbiota traits, 731 immune cell phenotypes, and two types of AITD (Hashimoto's thyroiditis and Graves' disease), we performed bidirectional Mendelian randomization (MR) analyses to explore the causal relationships between the GM and AITD. Subsequently, we employed a multivariable MR analysis to discover potential mediating immune cell traits. Additionally, sensitivity analyses were utilized to ensure the reliability of the outcomes. Results: Our analysis revealed that a total of 7 GM taxa were positively associated with AITD, and other 14 taxa showed a negative correlation with AITD. Furthermore, we identified several immune cell traits that mediated the effects of GM on AITD. Most notably, Actinobacteria (p) presented protective effects on Hashimoto's thyroiditis via CCR2 on myeloid Dendritic Cell (5.0%), and Bifidobacterium (g) showed facilitating effects on Graves' disease through CD39+ CD4+ T cell %CD4+ T cell (5.0%) and CD14 on CD33+ HLA DR+ CD14dim (12.2%). Conclusion: The current MR study provides evidence supporting the causal relationships between several specific GM taxa and AITD, and further identified potential mediating immunophenotypes.

Estimating the global prevalence of secondary hyperparathyroidism in patients with chronic kidney disease.

Background: Chronic kidney disease (CKD)-related secondary hyperparathyroidism (SHPT) is associated with higher morbidity and death. The goal of this study was to mine the SHPT data already available to do a meta-analysis on the global prevalence of SHPT caused by CKD. Methods: Embase, Medline, Web of Science, Cochrane Central Databases, and Google Scholar were searched to identify studies on the prevalence of SHPT due to CKD from inception to November 2023. Pooled prevalence was calculated using the DerSimonian-Laird random effects model with a logit transformation. Results: Twenty-one eligible studies involving 110977 patients were included. Our results revealed that the estimated global prevalence of SHPT due to CKD was 49.5% (95% CI 30.20-68.18), regardless of the diagnostic criteria. For subgroup analysis, Southern Asia (84.36%, 95% CI 79.35-88.34) had a significantly higher SHPT prevalence than other geographic regions. SHPT due to CKD was most prevalent in China (85.14%, 95% CI 81.74-88.00). Conclusions: SHPT due to CKD is highly prevalent. This necessitates awareness and therapeutic approaches from primary care physicians, medical professionals, and health strategy authorities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024514007.

Global Prevalence of Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analysis.

Importance: Overweight and obesity in childhood and adolescence is a global health issue associated with adverse outcomes throughout the life course. Objective: To estimate worldwide prevalence of overweight and obesity in children and adolescents from 2000 to 2023 and to assess potential risk factors for and comorbidities of obesity. Data Sources: MEDLINE, Web of Science, Embase, and Cochrane. Study Selection: The inclusion criteria were: (1) studies provided adequate information, (2) diagnosis based on body mass index cutoffs proposed by accepted references, (3) studies performed on general population between January 2000 and March 2023, (4) participants were younger than 18 years. Data Extraction and Synthesis: The current study was performed in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. DerSimonian-Laird random-effects model with Free-Tukey double arcsine transformation was used for data analysis. Sensitivity analysis, meta-regression, and subgroup analysis of obesity among children and adolescents were conducted. Main Outcomes and Measures: Prevalence of overweight and obesity among children and adolescents assessed by World Health Organization, International Obesity Task Force, the US Centers for Disease Control and Prevention, or other national references. Results: A total of 2033 studies from 154 different countries or regions involving 45 890 555 individuals were included. The overall prevalence of obesity in children and adolescents was 8.5% (95% CI 8.2-8.8). We found that the prevalence varied across countries, ranging from 0.4% (Vanuatu) to 28.4% (Puerto Rico). Higher prevalence of obesity among children and adolescents was reported in countries with Human Development Index scores of 0.8 or greater and high-income countries or regions. Compared to 2000 to 2011, a 1.5-fold increase in the prevalence of obesity was observed in 2012 to 2023. Substantial differences in rates of obesity were noted when stratified by 11 risk factors. Children and adolescents with obesity had a high risk of depression and hypertension. The pooled estimates of overweight and excess weight in children and adolescents were 14.8% (95% CI 14.5-15.1) and 22.2% (95% CI 21.6-22.8), respectively. Conclusions and Relevance: This study's findings indicated 1 of 5 children or adolescents experienced excess weight and that rates of excess weight varied by regional income and Human Development Index. Excess weight among children and adolescents was associated with a mix of inherent, behavioral, environmental, and sociocultural influences that need the attention and committed intervention of primary care professionals, clinicians, health authorities, and the general public.

Cancer-associated fibroblasts nurture LGR5 marked liver tumor-initiating cells and promote their tumor formation, growth, and metastasis.

BACKGROUND & AIMS: In liver cancer, leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) compartment represents an important tumor-initiating cell (TIC) population and served as a potential therapeutic target. Cancer-associated fibroblasts (CAFs) is a critical part of the tumor microenvironment, heavily influenced TIC function and fate. However, deeply investigations have been hindered by the lack of accurate preclinical models to investigate the interaction between CAFs and TIC. Organoids model have achieved major advancements as a precious research model for recapitulating the morphological aspects of organs, and thus also serving as a candidate model to investigate the mutual interaction between different cell types. Consequently, this study aimed to construct a three-dimensional (3D) co-culture organoid model of primary LGR5-expressing tumor stem cells from primary murine liver tumors with CAFs to investigate the impact of CAFs on LGR5 marked TICs in liver cancer. MATERIALS AND METHODS: First, both of the transgenic LGR5-diphtheria toxin receptor (DTR)-GFP knock-in mice and transgenic Rosa26-mT mice developed primary liver tumors by diethylnitrosamine (DEN) administration. Tumor organoids and CAFs were generated from those primary liver cancer separately. Second, LGR5-expressing TICs organoid with CAFs were established ex vivo based on cell-cell contact or trans-well co-culture system, and the mutual influence between those two types of cells was further investigated. Subsequently, immunodeficient mouse-based xenograft model was further adopted to evaluate the influence of CAFs to LGR5 tumor stem cell, tumor formation, and metastasis. RESULTS: The co-culture organoid model composed of murine liver tumor LGR5+ tumor-initiating cells and CAFs in 3D co-culture was successfully established, with the intention to investigate their mutual interaction. The existence of CAFs upon engrafting tumor organoids resulted in dramatic higher number of LGR5+ cells in the neoplasia when compared with engrafting tumor organoids alone. Furthermore, ex vivo culture of isolated LGR5+ cells from tumors of co-engrafted mice formed significantly larger size of organoids than mono-engrafted. Our results also indicated significantly larger size and number of formed organoids, when LGR5+ cells co-cultured with CAF in both cell-cell contact and paracrine signaling in vitro, comparing to LGR5+ cells alone. Furthermore, we found that specific knockout of LGR5 expressing cells suppressed CAF-mediated promotion of tumor formation, growth, and metastasis in the experimental mice model. CONCLUSIONS: Altogether, in a 3D co-culture type of murine liver LGR5+ cells and cancer-associated fibroblasts, we have demonstrated robust effects of CAFs in the promotion of LGR5 marked liver TICs. We also further revealed the influence of tumor microenvironment on stem cell-related therapy, suggesting the possibility of combing CAF-targeted and tumor stem cell targeted therapy in treating liver cancer.

Genetic and clinical profiles of 160 papillary thyroid cancers with lateral neck lymph node metastasis.

Background: Lymph node metastasis is widespread in papillary thyroid cancer (PTC). Patients are more vulnerable than those with central lymph node metastasis if they have lateral neck lymph node metastasis (LLNM). There are few researches focus on the correlation between clinical characteristics and genetic profile of PTC with LLNM. In this study, we aimed to analyze the clinical and genetic features of PTC with LLNM. Methods: A total of 160 primary tumor samples derived from PTC patients with LLNM were involved. Targeted next-generation sequencing was carried out on all samples with 57 known thyroid-cancer-related genes. The associations between genomic alternations and clinical characteristics of PTC with LLNM were statistically evaluated. Results: The median age of patients was 37 years, ranging from 5 to 77 years and the female/male ratio was 1.86. The most frequently altered genes in our series were BRAF mutation (68%), followed by RET fusion (17%), TERT promoter mutation (5%) and PIK3CA mutation (2%). To be noted, all PTC patients with LLNM of TERT promoter mutations appeared along with BRAF mutations (8/8) and half of them experienced a relapse. Intriguingly, we found more metastatic lymph nodes in patients with RET fusion, but there was no statistically significant difference in metastatic lymph node ratio than those with BRAF mutation or without mutation. A high rate of gene fusion (70%) was found in the pediatric population, with aggressive late-onset disease. Conclusions: PTC patients with LLNM is characterized by a high rate of BRAF mutation. Due to the observed clinicopathological differences in those patients among different alterations, further prospective studies are needed to verify our results and to evaluate the most suitable treatment strategies.

Bioactive Decellularized Extracellular Matrix Derived from 3D Stem Cell Spheroids under Macromolecular Crowding Serves as a Scaffold for Tissue Engineering.

Scaffolds for tissue engineering aim to mimic the native extracellular matrix (ECM) that provides physical support and biochemical signals to modulate multiple cell behaviors. However, the majority of currently used biomaterials are oversimplified and therefore fail to provide a niche required for the stimulation of tissue regeneration. In the present study, 3D decellularized ECM (dECM) scaffolds derived from mesenchymal stem cell (MSC) spheroids and with intricate matrix composition are developed. Specifically, application of macromolecular crowding (MMC) to MSC spheroid cultures facilitate ECM assembly in a 3D configuration, resulting in the accumulation of ECM and associated bioactive components. Decellularized 3D dECM constructs produced under MMC are able to adequately preserve the microarchitecture of structural ECM components and are characterized by higher retention of growth factors. This results in a stronger proangiogenic bioactivity as compared to constructs produced under uncrowded conditions. These dECM scaffolds can be homogenously populated by endothelial cells, which direct the macroassembly of the structures into larger cell-carrying constructs. Application of empty scaffolds enhances intrinsic revascularization in vivo, indicating that the 3D dECM scaffolds represent optimal proangiogenic bioactive blocks for the construction of larger engineered tissue constructs.

Transplantation of 3D MSC/HUVEC spheroids with neuroprotective and proangiogenic potentials ameliorates ischemic stroke brain injury.

Ischemic stroke, and the consequent brain cell death, is a common cause of death and disability worldwide. Current treatments that primarily aim to relieve symptoms are relatively inefficient in achieving brain tissue regeneration and functional recovery, and thus novel therapeutic options are urgently needed. Although cell-based therapies have shown promise for treating the infarcted brain, a recurring challenge is the inadequate retention and engraftment of transplanted cells at the target tissue, thereby limiting the ultimate therapeutic efficacy. Here, we show that transplantation of preassembled three-dimensional (3D) spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs) results in significantly improved cell retention and survival compared with conventional mixed-cell suspensions. The transplanted 3D spheroids exhibit notable neuroprotective, proneurogenic, proangiogenic and anti-scarring potential as evidenced by clear extracellular matrix structure formation and paracrine factor expression and secretion; this ultimately results in increased structural and motor function recovery in the brain of an ischemic stroke mouse model. Therefore, transplantation of MSCs and ECs using the 3D cell spheroid configuration not only reduces cell loss during cell harvesting/administration but also enhances the resultant therapeutic benefit, thus providing important proof-of-concept for future clinical translation.