Epidemiological analysis of drinking water-type fluorosis areas and the impact of fluorosis on children's health in the past 40 years in China.

This study analyzed the effect of China's fluorosis prevention and control program, which has been in effect for more than 40 years, and the impact of fluorosis on children's health. Relevant research studies were retrieved from the following online databases from the time of their inception to May 2022: PubMed, ScienceDirect, Embase, Cochrane, China National Knowledge Infrastructure, and Wanfang. The Review Manager 5.3 software was used in statistical analyses. This article included seventy studies: Thirty-eight studies reported the effect of improving water quality and reducing fluoride content, the incidence rate of dental fluorosis in children, and the level of urinary fluoride, and thirty-two studies reported the intelligence quotient (IQ) and health status of children. Following water improvement strategies, the fluoride levels in drinking water decreased significantly; urinary fluoride levels and dental fluorosis decreased significantly in children. With regard to the effect of fluorosis on the IQ of children, the results showed that the IQ of children in areas with a high fluoride of fluorosis was lesser than that in areas with a low fluoride, and this difference was significant. Based on the prevalence of dental fluorosis and its effect on the intelligence of children, it appears that reducing fluoride levels in drinking water and monitoring water quality are important strategies for the prevention and treatment of fluorosis.

Intelligent and Bioactive Osseointegration of the Implanted Piezoelectric Bone Cement with the Host Bone Is Realized by Biomechanical Energy.

Poly methyl methacrylate (PMMA) bone cement is widely used in orthopedic surgeries, including total hip/knee arthroplasty and vertebral compression fracture treatment. However, loosening due to bone resorption is a common mid-to-late complication. Therefore, developing bioactive bone cement that promotes bone growth and integration is key to reducing aseptic loosening. In this study, we developed a piezoelectric bone cement comprising PMMA and BaTiO3 with excellent electrobioactivity and further analyzed its ability to promote bone integration. Experiments demonstrate that the PMMA and 15 wt % BaTiO3 cement generated an open-circuit voltage of 37.109 V under biomimetic mechanical stress, which effectively promoted bone regeneration and interfacial bone integration. In vitro experiments showed that the protein expression levels of ALP and RUNX-2 in the 0.65 Hz and 20 min group increased by 1.74 times and 2.31 times. In vivo experiments confirmed the osteogenic ability of PMMA and 15 wt % BaTiO3, with the increment of bone growth in the non-movement and movement groups being 4.67 and 4.64 times, respectively, at the second month after surgery. Additionally, Fluo-4 AM fluorescence staining and protein blotting experiments verified that PMMA and 15 wt % BaTiO3 electrical stimulation promoted osteogenic differentiation of BMSCs by activating calcium-sensitive receptors and increasing calcium ion inflow by 1.41 times when the stimulation reached 30 min. Therefore, piezoelectric bioactive PMMA and 15 wt % BaTiO3 cement has excellent application value in orthopedic surgery systems where stress transmission is prevalent.

Efficacy and safety of lenalidomide in the treatment of B-cell non-Hodgkin lymphoma.

BACKGROUND: The combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma. METHODS: The PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated. RESULTS: A total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74-0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57-0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04-1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00-1.39; P = 0.05) between the treatment and control groups. CONCLUSIONS: Lenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

Mechanism of action of Asparagus officinalis extract against multiple myeloma using bioinformatics tools, in silico and in vitro study.

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune system-enhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification. Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein-protein interaction (PPI) networks and further screening of core targets. Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that "steroid receptor activity" and the "PI3K/AKT signaling pathway" were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase. Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data.

Exploration of the SIRT1-mediated BDNF-TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis.

Introduction: Fluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF-TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments. Methods: This study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting. Results: All rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities. Discussion: Currently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.

Effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells.

BACKGROUND: 3D cancer stem cell (CSC) cultures are widely used as in vitro tumor models. In this study, we determined the effects of enriching HCT116 tumor spheres initially cultured in serum-free medium with different concentrations of serum, focusing on the effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells (CCSCs). METHODS: CCSCs were enriched in standard serum-free medium and serum-free medium with different concentrations of serum for 1 week. The expression of CSC-associated markers in CCSCs, and the presence and relative proportion of CSCs (CD133/CD44 cell sorting) were then determined to elucidate the effect of the microserum environment on the preservation of CSC-related features. Further, the tumorigenic capacity of CCSCs was evaluated in an immunodeficiency mouse model. RESULTS: Our data indicated that a significantly greater number of spheres with a greater size range and high viability without drastic alteration in biological and structural features, which maintained self-renewal potential after sequential passages were formed after serum supplementation. Real-time analysis showed that both serum spheres and serum-free spheres displayed similar expression patterns for key stemness genes. Serum spheres showed higher expression of the CSC surface markers CD133 and CD44 than did CSCs spheres cultured in serum-free medium. Adherent cultures in complete medium could adapt to the serum-containing microenvironment faster and showed higher proliferation ability. The addition of serum induced EMT and promoted the migration and invasion of serum globular cells. Compared with serum-free cells and adherent cells, serum spheres showed higher tumor initiation ability. CONCLUSIONS: Microserum environment stimulation could be an effective strategy for reliable enrichment of intact CCSCs, and a more efficient CSC enrichment method.

Combining Network Pharmacology and Experimental Validation to Study the Action and Mechanism of Water extract of Asparagus Against Colorectal Cancer.

Asparagus (ASP) is a well-known traditional Chinese medicine with nourishing, moistening, fire-clearing, cough-suppressing, and intestinal effects. In addition, it exerts anti-inflammatory, antioxidant, anti-aging, immunity-enhancing, and anti-tumor pharmacological effect. The anti-tumor effect of ASP has been studied in hepatocellular carcinoma. However, its action and pharmacological mechanism in colorectal cancer (CRC) are unclear. The present study aimed to identify the potential targets of ASP for CRC treatment using network pharmacology and explore its possible therapeutic mechanisms using in vitro and in vivo experiments. The active compounds and potential targets of ASP were obtained from the TCMSP database, followed by CRC-related target genes identification using GeneCards and OMIM databases, which were matched with the potential targets of ASP. Based on the matching results, potential targets and signaling pathways were identified by protein-protein interaction (PPI), gene ontology (GO) functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, in vitro and in vivo experiments were performed to further validate the anti-cancer effects of ASP on CRC. Network pharmacology analysis identified nine active components from ASP from the database based on oral bioavailability and drug similarity index, and 157 potential targets related to ASP were predicted. The PPI network identified tumor protein 53 (TP53), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and AKT serine/threonine kinase 1 (AKT1) as key targets. GO analysis showed that ASP might act through response to wounding, membrane raft, and transcription factor binding. KEGG enrichment analysis revealed that ASP may affect CRC through the phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/AKT/mechanistic target of rapamycin kinase (mTOR) signaling pathway. In vitro, ASP inhibited cell proliferation, migration, and invasion of HCT116 and LOVO cells, and caused G0/G1 phase arrest and apoptosis in CRC cells. In vivo, ASP significantly inhibited the growth of CRC transplanted tumors in nude mice. Furthermore, pathway analysis confirmed that ASP could exert its therapeutic effects on CRC by regulating cell proliferation and survival through the PI3K/AKT/mTOR signaling pathway. This study is the first to report the potential role of ASP in the treatment of colorectal cancer.

Acupuncture and acupressure with improved cancer-related depression of retrospective studies.

Introduction: Acupuncture and acupressure are widely used for treating cancer pain and depression and recognized as safe and effective by the international medical community. In this study, we systematically evaluated the efficacy, safety, and clinical significance of acupuncture and acupressure in treating cancer-related depression. Methods: We searched MEDLINE, PubMed, Science Direct, Google Scholar, Web of Science and Embase and Chinese-language databases for randomized clinical trials (RCTs). To assess efficacy, rating scales administered by clinicians or experts were preferred, including the Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Quality of Life Questionnaire-Core 30 (QLQ-C30) and the total effective rate after treatment. In all, Sixteen RCTs involving 1019 cancer patients were included in the Meta-analysis. Results: Eleven (69%) of these studies reported the post-treatment total effective rate. Three hundred fifty-three patients received antidepressants; the total effective rate was 72.5%. Three hundred sixty-one patients underwent acupuncture and acupressure; the total effective rate was 90%. Meta-analysis results showed I2 = 0%, no heterogeneity, (Z = 5.84, p < 0.00001); and combined OR = 3.55, (95% CI = 2.32 to 5.43). Discussion: This study found that acupuncture and acupressure are as effective as medication in the treatment of cancer-related depression, provide a reliable basis for the clinical use of acupuncture to treat cancer-related depression, help promote nonpharmacological treatment for cancer-related complications. These approaches thus help reduce drug resistance and adverse reactions and improve patients' quality of life.

TKIs combined with chemotherapy followed by allo-HSCT in Philadelphia chromosome-positive myelodysplastic syndrome: A case report and literature review.

INTRODUCTION: Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients seem to have a poor prognosis, so the disease deserves attention. Here, we describe the history of a woman with Ph-positive MDS and perform a systematic review of related literature. PATIENT CONCERNS AND DIAGNOSIS: We report a 38-year-old woman with Ph-positive MDS. INTERVENTIONS AND OUTCOMES: She received chemotherapy with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (DCAG) combined with imatinib mesylate and achieved a bone marrow remission. She then underwent an allogeneic hematopoietic stem cell transplant. The condition is good and no recurrence of the disease has been observed. CONCLUSION: Ph-positive MDS is a very rare disease. Ph may aid in the malignant progression of MDS leaving such patients with a very poor prognosis. Tyrosine kinase inhibitors (TKIs) plus chemotherapy followed by allogeneic hematopoietic stem cell transplantation has provided these patients with satisfactory outcomes.