Combining Network Pharmacology and Experimental Verification to Ascertain the Mechanism of Action of Asparagus officinalis Against the Brain Damage Caused by Fluorosis.

Asparagus officinalis (ASP) has antioxidation, anti-inflammatory, antiaging, and immune system-enhancing effects. We explored the preventive and therapeutic consequences of ASP on the brain damage elicited by fluorosis through network pharmacology and in vivo experimental validation. We ascertained the pharmaceutically active ingredients and drug targets of ASP from the Traditional Chinese Medicine Systems Pharmacology database, predicted the disease targets of fluorosis-induced brain injury using GeneCards and Online Mendelian Inheritance in Man databases, obtained target protein-protein interaction networks in the Search Tool for the Retrieval of Interacting Genes/Proteins database, used Cytoscape to obtain key targets and active ingredients, and conducted enrichment analyses of key targets in the Database for Annotation, Visualization and Integrated Discovery. Enrichment analyses showed that "mitogen-activated protein kinase" (MAPK), "phosphoinositide 3-kinase/protein kinase B" (PI3K-Akt), "nuclear factor-kappa B" (NF-κB), and the "neurotrophin signaling pathway" were the most enriched biological processes and signaling pathways. ASP could alleviate fluorosis-based injury, improve brain-tissue damage, increase urinary fluoride content, and improve oxidation levels and inflammatory-factor levels in the body. ASP could also reduce dental fluorosis, bone damage, fluoride concentrations in blood and bone, and accumulation of lipid peroxide. Upon ASP treatment, expression of silent information regulator (SIRT)1, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), MAPK, NF-κB, PI3K, Akt, and B-cell lymphoma-2 in rat brain tissue increased gradually, whereas that of Bax, caspase-3, and p53 decreased gradually. We demonstrated that ASP could regulate the brain damage caused by fluorosis through the SIRT1/BDNF/TrkB signaling pathway, and reported the possible part played by ASP in preventing and treating fluorosis.

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.

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.

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.

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.

Electroacupuncture Treats Myocardial Infarction by Influencing the Regulation of Substance P in the Neurovascular to Modulate PGI2/TXA2 Metabolic Homeostasis via PI3K/AKT Pathway: A Bioinformatics-Based Multiomics and Experimental Study.

Acute myocardial infarction (AMI) is the most severe form of coronary heart disease caused by ischemia and hypoxia. The study is aimed at investigating the role of neuropeptides and the mechanism of electroacupuncture (EA) in acute myocardial infarction (AMI) treatment. Compared with the normal population, a significant increase in substance P (SP) was observed in the serum of patients with AMI. PGI2 expression was increased in the SP-treated AMI mouse model, and TXA2 expression was decreased. And PI3K pathway-related genes, including Pik3ca, Akt, and Mtor, were upregulated in myocardial tissue of SP-treated AMI patients. Human cardiomyocyte cell lines (HCM) treated with SP increased mRNA and protein expression of PI3K pathway-related genes (Pik3ca, Pik3cb, Akt, and Mtor). Compared to MI control and EA-treated MI rat models, Myd88, MTOR, Akt1, Sp, and Irak1 were differentially expressed, consistent with in vivo and in vitro studies. EA treatment significantly enriched PI3K/AKT signaling pathway genes within MI-associated differentially expressed genes (DEGs) according to Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, it was confirmed by molecular docking analysis that PIK3CA, AKT1, and mTOR form stable dockings with neuropeptide SP. PI3K/AKT pathway activity may be affected directly or indirectly by EA via SP, which corrects the PGI2/TXA2 metabolic imbalance in AMI. MI treatment is now better understood as a result of this finding.

Finite Time Thermodynamic Modeling and Performance Analysis of High-Temperature Proton Exchange Membrane Fuel Cells.

In order to improve the output performance of high-temperature proton exchange membrane fuel cells (HT-PEMFC), a finite time thermodynamic (FTT) model for HT-PEMFC was established. Several finite time thermodynamic indexes including power density, thermodynamic efficiency, exergy efficiency, exergetic performance efficient (EPC), entropy production rate and ecological coefficient of performance (ECOP) were derived. The energetic performance, exergetic performance and ecological performance of the HT-PEMFC were analyzed under different parameters. Results showed that operating temperature, doping level and thickness of membrane had a significant effect on the performance of HT-PEMFC and the power density increased by 58%, 31.1% and 44.9%, respectively. When the doping level reached 8, the output performance of HT-PEMFC wa optimal. The operating pressure and relative humidity had little influence on the HT-PEMFC and the power density increased by 8.7%% and 17.6%, respectively.

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.

Performance of a deep learning-based lung nodule detection system as an alternative reader in a Chinese lung cancer screening program.

OBJECTIVE: To evaluate the performance of a deep learning-based computer-aided detection (DL-CAD) system in a Chinese low-dose CT (LDCT) lung cancer screening program. MATERIALS AND METHODS: One-hundred-and-eighty individuals with a lung nodule on their baseline LDCT lung cancer screening scan were randomly mixed with screenees without nodules in a 1:1 ratio (total: 360 individuals). All scans were assessed by double reading and subsequently processed by an academic DL-CAD system. The findings of double reading and the DL-CAD system were then evaluated by two senior radiologists to derive the reference standard. The detection performance was evaluated by the Free Response Operating Characteristic curve, sensitivity and false-positive (FP) rate. The senior radiologists categorized nodules according to nodule diameter, type (solid, part-solid, non-solid) and Lung-RADS. RESULTS: The reference standard consisted of 262 nodules ≥ 4 mm in 196 individuals; 359 findings were considered false positives. The DL-CAD system achieved a sensitivity of 90.1% with 1.0 FP/scan for detection of lung nodules regardless of size or type, whereas double reading had a sensitivity of 76.0% with 0.04 FP/scan (P = 0.001). The sensitivity for detection of nodules ≥ 4 - ≤ 6 mm was significantly higher with DL-CAD than with double reading (86.3% vs. 58.9% respectively; P = 0.001). Sixty-three nodules were only identified by the DL-CAD system, and 27 nodules only found by double reading. The DL-CAD system reached similar performance compared to double reading in Lung-RADS 3 (94.3% vs. 90.0%, P = 0.549) and Lung-RADS 4 nodules (100.0% vs. 97.0%, P = 1.000), but showed a higher sensitivity in Lung-RADS 2 (86.2% vs. 65.4%, P < 0.001). CONCLUSIONS: The DL-CAD system can accurately detect pulmonary nodules on LDCT, with an acceptable false-positive rate of 1 nodule per scan and has higher detection performance than double reading. This DL-CAD system may assist radiologists in nodule detection in LDCT lung cancer screening.

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation.

This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine and donor lymphocyte infusion (DLI) in treating patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-six AML patients who relapsed after allo-HSCT were enrolled and treated with venetoclax plus azacitidine and DLI. Complete remission with incomplete recovery (CRi), partial remission (PR), and objective remission rate (ORR) were assessed, and then event-free survival (EFS) and overall survival (OS) were evaluated. Besides, adverse events were documented. Additionally, whole exome sequencing was performed in bone marrow samples. The CRi, PR, and ORR rates were 26.9%, 34.6%, and 61.5%, respectively. The median time of EFS and OS was 120 (95% CI: 71-610) days and 284.5 (95% CI: 81-610) days, respectively. The most common adverse events were hematologic system adverse events including agranulocytosis, anemia, and thrombocytopenia, while the adverse events of other systems were relatively less and milder. In addition, no serious adverse events existed. Of note, there were 6 (23.1%) patients who developed GVHD. As for gene mutation, 49 mutated genes were found, which were categorized as first-, second-, and third-class mutations, and then further analysis revealed that the first-class mutations were not correlated with EFS or OS. Additionally, the most frequent mutated genes were FLT3, CEBPA, DNMT3A, KIT, KRAS, and NRAS. Venetoclax plus azacitidine and DLI is efficient and tolerant in treating patients with relapsed AML after allo-HSCT, implying this combined therapy as a potential treatment option in the studied patients.

Cost-effectiveness of lung cancer screening by low-dose CT in China: a micro-simulation study.

Background: The effectiveness of lung cancer screening with low-dose computed tomography (LDCT) has been established. The current study evaluates the cost-effectiveness of lung cancer screening with LDCT in a general population in China. Methods: A previously validated micro-simulation model was used to simulate a cohort of men and women on a lifetime horizon in the presence and absence of LDCT screening. The modeling data were collected from numerous national and international sources. Simulated screening scenarios included different combinations of screening intervals and start and stop ages. Additional costs (valued in Chinese Yuan, CNY; 1 USD = 6.8976 CNY, 1 EUR = 7.8755 CNY in 2020), life-years gained (LYG) and mortality reduction due to screening were also determined. The costs and life-years were discounted by 3%. All results were scaled to 1,000 individuals. The average cost-effectiveness ratio (ACER) was calculated. A willingness-to-pay threshold of CNY 217.3k / LYG was considered. A healthcare system perspective was adopted. Results: Compared to no screening, lung cancer screening by LDCT in a general Chinese population yielded 21.0 - 36.7 LYG in men and 9.2 - 16.6 LYG in women across the scenarios. For men, biennial LDCT screening yielded an ACER of CNY 171.4k - 306.3k / LYG relative to no screening. Biennial screening performed between 55 and 75 years of age was optimal at the defined threshold; it resulted in CNY 174.6k / LYG and a lung cancer mortality reduction of 9.1%, and this scenario had a 75% probability of being cost-effective. For women, the ACER ranged from CNY 364.2k to 1193.3k / LYG. Conclusions: In China, lung cancer screening with LDCT in the general population including never smokers could be cost-effective for men with 75% probability, but not for women. The optimal strategy for men would be performing biennial screening between 55 and 75 years of age.

Community-based lung cancer screening by low-dose computed tomography in China: First round results and a meta-analysis.

OBJECTIVE: To evaluate the efficiency of low-dose computed tomography (LDCT) screening for lung cancer in China by analyzing the baseline results of a community-based screening study accompanied with a meta-analysis. METHODS: A first round of community-based lung cancer screening with LDCT was conducted in Tianjin, China, and a systematic literature search was performed to identify LDCT screening and registry-based clinical studies for lung cancer in China. Baseline results in the community-based screening study were described by participant risk level and the lung cancer detection rate was compared with the pooled rate among the screening studies. The percentage of patients per stage was compared between the community-based study and screening and clinical studies. RESULTS: In the community-based study, 5523 participants (43.6% men) underwent LDCT. The lung cancer detection rate was 0.5% (high-risk, 1.2%; low-risk, 0.4%), with stage I disease present in 70.0% (high-risk, 50.0%; low-risk, 83.3%), and the adenocarcinoma present in 84.4% (high-risk, 61.5%; low-risk, 100%). Among all screen-detected lung cancer, women accounted for 8.3% and 66.7% in the high- and low-risk group, respectively. In the screening studies from mainland China, the lung cancer detection rate 0.6% (95 %CI: 0.3%-0.9%) for high-risk populations. The proportions with carcinoma in situ and stage I disease in the screening and clinical studies were 76.4% (95 %CI: 66.3%-85.3%) and 15.2% (95 %CI: 11.8%-18.9%), respectively. CONCLUSIONS: The stage shift of lung cancer due to screening suggests a potential effectiveness of LDCT screening in China. Nearly 70% of screen-detected lung cancers in low-risk populations are identified in women.

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study.

BACKGROUND: Acute coronary syndrome (ACS) has become a vital disease with high mortality in the Uygur populations. Clopidogrel plays an important role in reducing the risk of recurrent cardiovascular events after ACS; however, it is a prodrug that requires biotransformation by cytochrome P450 (CYP450). OBJECTIVES: To determine the effect of genetic polymorphisms in CYP2C19*2, *3, and *17, and along with clinical, demographic factors, on variation in response to clinical outcomes in Uygur patients. METHODS: A total of 351 patients with ACS were treated with clopidogrel and aspirin for at least 12 months; we recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Multivariable logistic regression analyses were carried out to identify factors associated with MACE or bleeding. RESULTS: We analyze risk factors include age, BMI (body mass index), smoking, alcohol intake, NSTEMI (non-ST-segment elevation myocardial infarction), hypertension, dyslipidemia, concomitant medication, CYP2C19*2 carriers, CYP2C19*17 carriers and metabolizer phenotype. CYP2C19*2 carriers had an odds of having MACE of 2.51 (95% CI: 1.534-4.09) compared with noncarriers (P < .001). However, no factors were significantly associated with bleeding (P > 0.05). CONCLUSION: The CYP2C19*2 gene polymorphism contributes to the risk of MACE in dual clopidogrel-treated Uygur population with ACS with or without PCI (percutaneous coronary intervention). These data may provide valuable insights into the genetic polymorphisms affecting clopidogrel metabolism among minority groups in China.

Efficacy of mesenchymal stem cell transplantation therapy for type 1 and type 2 diabetes mellitus: a meta-analysis.

BACKGROUND: This meta-analysis was first conducted to evaluate the efficacy and safety of transplantation of mesenchymal stem cells in the treatment of type 1 and type 2 diabetes mellitus (T1DM and T2DM). METHODS: We systematically searched PubMed, ScienceDirect, Google Scholar, CNKI, EMBASE, Web of Science, MEDLINE, and the Cochrane Library for studies published from the establishment of the databases to November 2020. Two researchers independently screened the identified studies, based on inclusion and exclusion criteria. The combined standard mean difference (SMD) and 95% confidence interval (CI) of data from the included studies were calculated using fixed- or random-effects models. RESULTS: We included 10 studies in our meta-analysis (4 studies on T1DM and 6 on T2DM, with 239 participants) to examine the efficacy of mesenchymal stem cells (MSCs) therapy in the treatment of diabetes mellitus. According to the pooled estimates, the glycated hemoglobin (HbA1c) level of the MSC-treated group was significantly lower than it was at baseline (mean difference (MD) = -1.51, 95% CI -2.42 to -0.60, P = 0.001). The fasting C-peptide level of the MSC-treated group with T1DM was higher than that of the control group (SMD = 0.89, 95% CI 0.36 to 1.42, P = 0.001), and their insulin requirement was significantly lower than it was at baseline (SMD = -1.14, 95% CI -1.52 to -0.77, P < 0.00001). CONCLUSION: Transplantation of mesenchymal stem cells has beneficial effects on diabetes mellitus, especially T1DM, and no obvious adverse reactions.

Bioinformatics analysis of Myelin Transcription Factor 1.

BACKGROUND AND OBJECTIVE: We aimed to further study the role of Myelin Transcription Factor 1(MyT1) in tumor and other diseases and epigenetic regulation, and better understand the regulatory mechanism of MyT1. METHODS: Using bioinformatics analysis, the structure and function of MyT1sequence were predicted and analyzed using bioinformatics analysis, and providing a theoretical basis for further experimental verification and understanding the regulatory mechanism of MyT1. The first, second and third-level structures of MyT1 were predicted and analyzed by bioinformatics analysis tools. RESULTS: MyT1 is found to be an unstable hydrophilic protein, rather than a secretory protein, with no signal peptide or trans-membrane domain; total amino acids located on the surface of the cell membrane. It contains seven zinc finger domains structurally. At sub-cellular level, MyT1 is localized in the nucleus. The phosphorylation site mainly exists in serine, and its secondary structure is mainly composed of random coils and alpha helices; the three-dimensional structure is analyzed by modeling. CONCLUSIONS: In this study, the structure and function of MyT1 protein were predicted, thereby providing a basis for subsequent expression analysis and functional research; it laid the foundation for further investigation of the molecular mechanism involved in the development of diseases.

Comparison of National Comprehensive Cancer Network and European Position Statement protocols for nodule management in low-dose computed tomography lung cancer screening in a general Chinese population.

BACKGROUND: Low-dose computed tomography (LDCT) lung cancer screening often refers individuals to unnecessary examinations. This study aims to compare the European Position Statement (EUPS) and National Comprehensive Cancer Network (NCCN) protocols in management of participants at baseline screening round. METHODS: LDCT lung cancer screening was prospectively performed in a Chinese asymptomatic population aged 40-74 years. A total of 1,000 consecutive baseline LDCT scans were read twice independently. All screen-detected lung nodules by the first reader were included. The first reader manually measured the diameter of lung nodules (NCCN protocol), and the second reader semi-automatically measured the volume and diameter (EUPS volume and diameter protocols). The protocols were used to classify the participants into three management groups: next screening round, short-term repeat LDCT scan and referral to a pulmonologist. Groups were compared using Wilcoxon test for paired samples. Number of lung cancers by protocols was provided. RESULTS: Of the 1,000 participants (61.4±6.7 years old), 168 lung nodules in 124 participants were visually detected and manually measured in the first reading, and re-measured semi-automatically. Applying the NCCN protocol, EUPS volume and diameter protocol, the proportion of referrals among all participants was 0.6%, 1.9%, and 1.4%, respectively. The proportion of short-term repeat scans was 4.5%, 9.7% and 4.5%, respectively. Among the 10 lung cancer patients, one would have been diagnosed earlier if the EUPS volume protocol would have been followed. CONCLUSIONS: In a first round screening in a Chinese general population, the lower threshold for referral in the EUPS protocol as compared to the NCCN protocol, leads to more referrals to a pulmonologist, with the potential of earlier cancer diagnosis. The EUPS volume protocol recommends fewer participants to short-term repeat LDCT scan than the EUPS diameter protocol. Follow-up studies should show the impact of both protocols on (interval) cancer diagnosis.

Glucocorticoid resistance induced by ANXA5 overexpression in B-cell acute lymphoblastic leukemia.

Development of chemo­resistance is ultimately responsible for treatment failure and relapse in B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism underlying glucocorticoid (GC) resistance remains unclear. This study was performed to identify GC resistance-related genes using the transcriptome chip from the GEO database, and preliminarily analyze drug resistance mechanism in B-ALL. Here, we found that ANXA5 expression was upregulated in B-ALL cells and high-level ANXA5 was associated with dexamethasone (DEX) resistance. Then, small interfering RNA (siRNA) was designed to silence ANXA5 expression in the B-ALL cell lines, and the apoptotic rate of cells treated with DEX was detected by flow cytometry. As a result, cell apoptosis was dramatically promoted in B-ALL cells following silencing of ANXA5 and DEX administration versus that in ANXA5-silenced alone or DEX-treated alone cells. It was further found that down-regulation of ANXA5 in B-ALL cells significantly increased the relative amount of cleaved Caspase 3 and Caspase 9 induced by DEX. Collectively, inhibition of ANXA5 gene expression may represent a novel method to restore the sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death, which is of important clinical significance to overcome drug resistance associated with B-ALL.

SNHG17 promotes the proliferation and migration of colorectal adenocarcinoma cells by modulating CXCL12-mediated angiogenesis.

BACKGROUND: Colorectal adenocarcinoma (CRA) is one of the leading causes of cancer-related deaths in the world. Long non-coding RNAs (lncRNAs) have been implicated to be effective regulators in the disease course of human cancers, including CRA. Small nucleolar RNA host gene 17 (SNHG17) belongs to lncRNAs, and it has been reported in breast cancer and gastric cancer. However, the function of SNHG17 and its mechanism in CRA progression remain largely unknown. In this study, we attended to shedding some light on the role of SNHG17 in CRA. METHODS: RT-qPCR was used to assess SNHG17 expression in CRA cells. CCK-8 assay, colony formation and transwell assay were carried out to detect the regulatory effect of SNHG17 silencing on CRA cell proliferation and migration. The angiogenesis of SNHG7-downregulated CRA cells was analyzed by tube formation assay. Mechanism experiments were conducted to identify the interaction between miR-23a-3p and SNHG17 or C-X-C motif chemokine ligand 12 (CXCL12). RESULTS: SNHG17 possessed with high expression in CRA cells. Knockdown of SNHG17 caused the inhibition on CRA cell proliferation and migration. SNHG17 promoted CRA cell proliferation and migration by sponging miR-23a-3p to upregulate CXCL12. CONCLUSION: SNHG17 promotes the proliferation and migration of CRA cells by inhibiting miR-23a-3p to modulate CXCL12-mediated angiogenesis.

Aberrant methylation­mediated decrease of lncRNA HNF1A­AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT.

Aberrant methylation is one of the most frequent epigenetic alterations that regulate the expression levels of genes, including long non­coding RNAs (lncRNAs), in tumors. However, to the best of our knowledge, the expression and function of hepatic nuclear factor 1α antisense RNA 1 (HNF1A­AS1) and its methylation condition have not yet been reported in the development and progression of laryngeal squamous cell carcinoma (LSCC). In the present study, the expression and methylation of HNF1A­AS1 were first examined by reverse transcription­quantitative PCR, bisulfite genomic sequencing and methylation­specific polymerase chain reaction in samples from patients with LSCC, which were based on the in silico analysis using The Cancer Genome Atlas data, and were then further verified in LSCC cell lines with and without 5­Aza­2'­deoxycytidine (5­Aza­dC) treatment. Subsequently, proliferation, cell cycle distribution, migration and invasion of LSCC cells following either knockdown or overexpression of HNF1A­AS1 were determined in vitro. Furthermore, the characteristic of HNF1A­AS1 on epithelial­mesenchymal transition (EMT) changes was investigated in vitro and in vivo. The associations between the expression levels of HNF1A­AS1 and tumorigenicity and cervical lymph node metastasis were assessed in a xenograft model in nude mice. In the present study, downregulation and hypermethylation in CpG sites of HNF1A­AS1 were detected in LSCC tissues as well as metastatic cervical lymph nodes samples when compared with those in the adjacent non­tumor tissues. Additionally, HNF1A­AS1 inhibited proliferation, migration and invasion of LSCC cells in vitro by regulating the process of EMT. Furthermore, HNF1A­AS1 inhibited tumor growth and metastasis by regulating EMT in vivo. Additionally, the migration and invasion abilities, and the expression levels of HNF1A­AS1 and EMT markers in LSCC cells were significantly reversed by treatment with 5­Aza­dC. In summary, HNF1A­AS1 was downregulated by hypermethylation in LSCC and laryngeal cancer cells. These findings suggested that HNF1A­AS1 could serve as a tumor suppressor lncRNA in LSCC by regulating the EMT process, leading to the discovery of novel therapeutic targets and strategies for the treatment of patients with LSCC.