Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1α After Treatment: A Cell Regulation Study

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Interfacial Polarization Locked Flexible ß-Phase Glycine/Nb2 CTx Piezoelectric Nanofibers.

Biomolecular piezoelectric materials show great potential in the field of wearable and implantable biomedical devices. Here, a self-assemble approach is developed to fabricating flexible ß-glycine piezoelectric nanofibers with interfacial polarization locked aligned crystal domains induced by Nb2 CTx nanosheets. Acted as an effective nucleating agent, Nb2 CTx nanosheets can induce glycine to crystallize from edges toward flat surfaces on its 2D crystal plane and form a distinctive eutectic structure within the nanoconfined space. The interfacial polarization locking formed between O atom on glycine and Nb atom on Nb2 CTx is essential to align the ß-glycine crystal domains with (001) crystal plane intensity extremely improved. This ß-phase glycine/Nb2 CTx nanofibers (Gly-Nb2 C-NFs) exhibit fabulous mechanical flexibility with Young's modulus of 10 MPa, and an enhanced piezoelectric coefficient of 5.0 pC N-1 or piezoelectric voltage coefficient of 129 × 10-3 Vm N-1 . The interface polarization locking greatly improves the thermostability of ß-glycine before melting (≈210°C). A piezoelectric sensor based on this Gly-Nb2 C-NFs is used for micro-vibration sensing in vivo in mice and exhibits excellent sensing ability. This strategy provides an effective approach for the regular crystallization modulation for glycine crystals, opening a new avenue toward the design of piezoelectric biomolecular materials induced by 2D materials.

Soft ferroelectret ultrasound receiver for targeted peripheral neuromodulation.

Bioelectronic medicine is a rapidly growing field where targeted electrical signals can act as an adjunct or alternative to drugs to treat neurological disorders and diseases via stimulating the peripheral nervous system on demand. However, current existing strategies are limited by external battery requirements, and the injury and inflammation caused by the mechanical mismatch between rigid electrodes and soft nerves. Here we report a wireless, leadless, and battery-free ferroelectret implant, termed NeuroRing, that wraps around the target peripheral nerve and demonstrates high mechanical conformability to dynamic motion nerve tissue. As-fabricated NeuroRing can act as an ultrasound receiver that converts ultrasound vibrations into electrostimulation pulses, thus stimulating the targeted peripheral nerve on demand. This capability is demonstrated by the precise modulation of the sacral splanchnic nerve to treat colitis, providing a framework for future bioelectronic medicines that offer an alternative to non-specific pharmacological approaches.

Comparison of cell subsets in chronic obstructive pulmonary disease and controls based on single-cell transcriptome sequencing.

BACKGROUND: Currently, chronic obstructive pulmonary disease (COPD) significantly impacts patients' quality of life and survival as it has a high morbidity and mortality rate. COPD progression is associated with infiltration of adaptive inflammatory immune cells that form lymphatic follicles into the lung. OBJECTIVE: The rapid development of single-cell RNA sequencing technology (scRNA-seq) provided us with powerful tools for studying the classification of cell subtypes. Additionally, it is known that COPD is closely related to the abnormal function of long-chain non-coding RNAs (lncRNAs), and scRNA-seq can help to study the expression of lncRNA from a single cell level. METHODS: We reanalyzed the scRNA-seq data of peripheral blood mononuclear cells of COPD patients downloaded from Gene Expression Omnibus (GEO) database, and performed the mRNA-based and lncRNA-based single cell clustering to compare the cell subsets in COPD and controls without COPD. Furthermore, we performed Gene Ontology (GO) enrichment analysis for the top ranked differentially expressed genes and target genes of differentially expressed lncRNAs in different cell subtypes for COPD and controls respectively. RESULTS: Differences in cell subtypes were found between COPD and controls. CONCLUSION: This study may help us to further understand the mechanism of the human adaptive immune cell response of COPD.

Meta-analysis of outcomes related to the quality of life after orthodontic-surgical treatment.

Orthognathic surgery causes functional and aesthetic changes, which could affect patients' quality of life (QOL). The current analysis assessed the impact of orthodontic-surgical treatment on the parameters affecting the QOL using different scoring systems. The criteria for inclusion were studies written in various languages that compared the effects of the intervention on patients' QOL before surgery and at various periods after surgery (3 weeks to several months), which resulted in including 19 studies into this meta-analysis. The outcomes of these studies underwent random-effect modeling to calculate the mean difference (MD) and 95% confidence intervals (95% CIs) of the impact of different surgical techniques on clinical parameters, and publication bias was analyzed with Begg's test. According to the total score of the Orthognathic Quality of Life Questionnaire (OQLQ), surgery significantly affected patients' QOL after 2 months or less (p = 0.049), up to 6 months (p < 0.001), and when comparing 2 months or less with up to 6 months (2-6 months) (p < 0.001). In addition, the total Oral Health Impact Profile-14 (OHIP-14) score showed a significant difference in the QOL after 6 months (p = 0.003) and up to 12 months (p = 0.002) after surgery. Therefore, orthodontic-surgical treatment significantly improves patients' QOL after surgery compared to before surgery.

Advances in applications of piezoelectronic electrons in cell regulation and tissue regeneration.

Bioelectricity plays a significant role in major biological processes and electrical stimulation is an effective and non-invasive way to promote cellular growth, differentiation and tissue regeneration. In tissue engineering, piezoelectric materials not only act as modulators to regulate behaviors and functions of cells and tissues, but are also used as scaffolds to regulate and guide cell growth and matrix synthesis, thus promoting the formation of new tissue. Piezoelectronic electrons are produced from piezoelectric materials upon mechanical stimuli and have similar effects on cells as an external electrical field. Devices based on piezoelectronics have been widely applied in bioelectronics and biomedical fields. In this review, the effects of piezoelectronic electrons on cells and their possible mechanisms are briefly introduced. Then, we overview the applications of piezoelectronic electrons in cell regulation and tissue regeneration according to the type of cells and tissues. Finally, future perspectives and challenges are also provided.

Facial morphological characteristics of mouth breathers vs. nasal breathers: A systematic review and meta-analysis of lateral cephalometric data.

The present systematic review and meta-analysis was performed to assess the association between mouth breathing and facial morphological characteristics in children and adolescents. PubMed, Medline, Scopus and Google Scholar databases were searched for cross-sectional case-control studies published between 1st January 1980 and 1st April 2019. Studies comparing cephalometric data of mouth breathers and nasal breathers were included, while studies on adults were excluded. Meta-analysis was performed regarding 11 angular and 4 linear measurements. A total of 19 studies were included in the systematic review and data from 18 studies were extracted for the meta-analysis. The results indicated statistically significant decreases in Sella-Nasion-Point A (SNA) angle [mean difference (MD)=-1.33; 95% CI -2.03 to -0.63; P=0.0002] and Sella-Nasion-Point B (SNB) angle of mouth breathers as compared to nasal breathers (MD=-1.33; 95% CI -2.18 to -0.49; P=0.002). There was no difference in Point A-Nasion-Point B (ANB) angle between the two groups (MD=0.25; 95% CI -0.26 to 0.75; P=0.34). Mouth breathers demonstrated an increased mandibular plane angle, total and lower anterior facial height and decreased posterior facial height. Within the limitations of the study, the results indicated that mouth breathers tended to have a retrognathic maxilla and mandible, vertical growth pattern with high mandibular plane angle, downward and backward rotation of the mandible and an increase in total and lower anterior facial height and decrease in posterior facial height. Further high-quality studies are required to strengthen the evidence on this subject.

The Association between Immune Infiltration and Clinical Phenotypes and Prognosis of Prostate Cancer.

BACKGROUND: Some evidences show that immune infiltration is closely related to the clinical outcomes in cancers such as colorectal cancer. However, previous studies have not explained the diversity of cell types that make up the immune response. In particular, although some studies and reviews have shown that immunotherapy is important for cancer treatment, few studies have elucidated the relationship between prostate cancer (PCa) phenotype and immune infiltration. OBJECTIVES: In this study, we analyzed whether different types of tumor-infiltrating immune cells would affect the clinical phenotypes and survival of PCa based on a deconvolution algorithm and annotated gene expression profiles. MATERIALS AND METHODS: The 22 subsets of immune cells inferred by CIBERSORT and the infiltration abundance of 6 immune cells calculated by TIMER were used to determine the associations between them and the PCa traits and survival response. In addition, the survival tree models were constructed to classify PCa patients into four subtypes, and the traits and prognosis were compared among these subtypes. RESULTS: As a result, we found that some PCa patients with high death risk lacking immune infiltration were related to the poor prognosis. For the cell subsets studied and subtypes analysis, a low proportion of mast resting cells and T-cells follicular helper exhibited the obvious association with poor outcome. CONCLUSIONS: In summary, our study suggested the differences in the cellular composition of the immune infiltrate in PCa, and these differences might be important determinants for PCa traits and prognosis.

Exploration of genetics commonness between bladder cancer and breast cancer based on a silcio analysis on disease subtypes.

BACKGROUND AND OBJECTIVE: Muscle-invasive bladder cancers (MIBCs) are heterogeneous cancers and can be grouped into basal-like and luminal subtypes that are highly reminiscent of those found in breast cancer. Like basal-like breast cancers, basal-like MIBCs are associated with advanced stage and metastatic disease. However, the biological and clinical significance of molecular subtypes of MIBCs remain unclear. Therefore, we implemented a serious of bioinformatics methods to explore genetic similarities between bladder and breast cancers. METHODS AND RESULTS: In the current study, by the application of multiple levels data analysis including random forest analysis, PPI and transcription factor regulation network construction, Gene Ontology (GO) and KEGG pathway enrichment analysis, we explored the genetics commonness between MIBC and breast cancers from the molecular heterogeneity based on the disease subtypes. CONCLUSIONS: Our study identified some basal-related and luminal-related genes shared by two cancers. These studies can help shed light on the potential relationships between MIBC and breast cancer as a whole.

Prediction of microRNA and gene target from an integrated network in chronic obstructive pulmonary disease based on canonical correlation analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex disorder with a high mortality. The pathophysiology of COPD has not been characterized till date. OBJECTIVE: To identify COPD-related biomarkers by a bioinformatics analysis. METHODS: Here, we conducted the canonical correlation analysis to extract the potential COPD-related miRNAs and mRNAs based on the miRNA-mRNA dual expression profiling data. After identifying miRNAs and mRNAs related to COPD, we constructed an interaction network by integrating three validated miRNA-target sources. Then we expanded the network by adding miRNA-mRNA pairs, which were identified by Spearman rank correlation test. For miRNAs involved in the network, we further performed the Gene Ontology (GO) functional enrichment analysis of their targets. To validate COPD-related mRNAs involved in the network, we performed receiver operating characteristic (ROC) curve analysis and Support Vector Machine (SVM) classification on only those mRNAs that overlapped with COPD-related mRNAs of Online Mendelian Inheritance in Man (OMIM) database. RESULTS: The results indicate that some identified miRNAs and their targets in the constructed network might be potential biomarkers of COPD. CONCLUSIONS: Our study helps us to predict the potential risk biomarkers of COPD, and it can certainly help in further elucidating the genetic etiology of COPD.

Gene Regulation Network Based Analysis Associated with TGF-ßeta Stimulation in Lung Adenocarcinoma Cells.

BACKGROUND: Transforming growth factor (TGF)-ß is over-expressed in a wide variety of cancers such as lung adenocarcinoma. TGF-ß plays a major role in cancer progression through regulating cancer cell proliferation and remodeling of the tumor micro-environment. However, it is still a great challenge to explain the phenotypic effects caused by TGF-ß stimulation and the effect of TGF-ß stimulation on tumor micro-environment. OBJECTIVES: To address this issue, in the present study we used two time-course microarray data in human lung adenocarcinoma cells and applied bioinformatics methods to explore the gene regulation network responding to TGF-ß stimulation in lung adenocarcinoma cells. MATERIALS AND METHODS: The time-dependent reverse-engineering method, protein-protein interaction network analyses, and calculation of the similarity measures between the links were used to construct gene regulatory network and to extract gene clusters. RESULTS: Utilizing the constructed gene regulation network, we predicted NEFL and LUC7A show the opposite and the same change with C21orf90 if HAND2 is knocked-out after treatment with TGF-ß1 for 4 hours and for 12 hours respectively. FGG and HSPC009 are predicted to display the opposite change with NEFL if CSMD1 is knocked out after treatment with TGF-ß1 for 12 hours. Additionally, by integrating two datasets, we specially identified several nested clusters which included those genes regulated by TGF-ß stimulation in lung adenocarcinoma cells. CONCLUSIONS: Our analysis can help a better understanding regarding how TGF-ß stimulation causes the expression change of a number of the genes and provide a novel insight into TGF-ß stimulation effect on lung adenocarcinoma cells.

Integration of multi-microarray datasets to identify chronic obstructive pulmonary disease-related miRNAs.

Currently, the mechanisms underlying chronic obstructive pulmonary disease (COPD) remain unclear. As potential biomarkers, microRNAs (miRNAs), which modulate the levels of specific genes and proteins, are important for enhancing our understanding of the mechanisms behind COPD. Although there have been a number of miRNA expression profiling analyses strategies used to document miRNA expression changes during physiological and pathological processes or used to identify differentially expressed miRNAs in disease or control samples, the study results have been inconsistently replicated using different datasets. For this reason, many findings cannot be well synthesized and interpreted. To address this issue, we used a multiple co-inertia analysis (MCIA) method to extract potential COPD-related miRNAs using three COPD microarray datasets. The results showed that miR-223, miR-132, and miR-199a-5p are obviously associated with COPD, and these results are consistent with the highly significant differentially-expressed miRNAs that were observed across three microarray datasets. Moreover, when miR-223, miR-132, and miR-199a-5p are taken as predictors to classify the samples of three datasets, the pooled sensitivity and specificity is 0.96 and 0.75, respectively, thereby suggesting that these three miRNAs can effectively distinguish COPD patients and controls.

Knowledge-based analysis of genetic associations of rheumatoid arthritis to inform studies searching for pleiotropic genes: a literature review and network analysis.

INTRODUCTION: Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. Gene variants directly affect the normal processes of a series of physiological and biochemical reactions, and therefore cause a variety of diseases traits to be changed accordingly. Moreover, a shared genetic susceptibility mechanism may exist between different diseases. Therefore, shared genes, with pleiotropic effects, are important to understand the sharing pathogenesis and hence the mechanisms underlying comorbidity. METHODS: In this study, we proposed combining genome-wide association studies (GWAS) and public knowledge databases to search for potential pleiotropic genes associated with rheumatoid arthritis (RA) and eight other related diseases. Here, a GWAS-based network analysis is used to recognize risk genes significantly associated with RA. These RA risk genes are re-extracted as potential pleiotropic genes if they have been proved to be susceptible genes for at least one of eight other diseases in the OMIM or PubMed databases. RESULTS: In total, we extracted 116 potential functional pleiotropic genes for RA and eight other diseases, including five hub pleiotropic genes, BTNL2, HLA-DRA, NOTCH4, TNXB, and C6orf10, where BTNL2, NOTCH4, and C6orf10 are novel pleiotropic genes identified by our analysis. CONCLUSIONS: This study demonstrates that pleiotropy is a common property of genes associated with disease traits. Our results ascertained the shared genetic risk profiles that predisposed individuals to RA and other diseases, which could have implications for identification of molecular targets for drug development, and classification of diseases.

Influence of casein phosphopeptide-amorphous calcium phosphate application, smear layer removal, and storage time on resin-dentin bonding.

The aim of this study is to evaluate the influence of Tooth Mousse (TM) application, smear layer removal, and storage time on resin-dentin microtensile bond strength (µTBS). Dentin specimens were divided into two groups: (1) smear layer covered; (2) smear layer removed using 15% EDTA for 90 s. In each group, half the specimens were treated once with TM for 60 min. After bonding procedures using a two-step self-etching adhesive (Clearfil SE Bond (CSE); Kuraray Medical, Tokyo, Japan), an all-in-one adhesive (G-Bond (GB); GC Corp, Tokyo, Japan), and a total-etch adhesive (Adper Single Bond 2 (SB); 3M ESPE, St. Paul, MN, USA), the specimens were stored for 3 d or 6 months in deionized water at 37 °C, and µTBS was tested and analyzed. With the exception of SB (no TM application) and GB, the µTBS was significantly increased for CSE and SB using EDTA pre-conditioning and 3 d of storage (P≤0.001). Bond strength of GB decreased significantly when using EDTA (3 d storage, P<0.05). TM application only increased the µTBS of GB (no EDTA) and SB (with EDTA) after 3 d (P≤0.02). Comparing the adhesives after 3 d of storage, CSE exhibited the greatest µTBS values followed by GB and SB (P≤0.02). The factors of adhesive, EDTA, and TM did not show any significant impact on µTBS when specimens were stored for 6 months (P>0.05). The additional application of TM and EDTA for cavity preparation seems only to have a short-term effect, and no influence on µTBS of dentin bonds after a period of 6 months.

[Spinal muscular atrophy with open bite: A case report].

Spinal muscular atrophy is one rare type of autosomal recessive disorder. The disease is characterized by the progressive degeneration of spinal cord anterior horn motor neurons and brainstem motor nuclei, which leads to muscle atrophy and paralysis. One case of spinal muscular atrophy with open bite was reported here.

Analysis to a critical state of thermal field in microwave ablation of liver cancer influenced by large vessels.

To study the effect of large blood vessels on the temperature field in invasive microwave ablation, a finite element method was applied based on the convective-type boundary condition on the interface between tissues and blood flow. Whether a large blood vessel is outside of or involved in the lesion area will affect the 54 degrees C effective therapeutic area in different critical conditions. This paper drew the function diagraph on the distance between blood vessel and antenna with the diameter of the blood vessel and put forward the concept of effective therapy radius. It can be used to study the influence of large vessels on the external boundary of the coagulation area and can be used as a theoretical basis to help to decide whether to occlude the large vessels before microwave ablation therapy.

Effect of Ginkgo leaf extract on vascular endothelial function in patients with early stage diabetic nephropathy.

OBJECTIVE: To explore the effect of ginkgo leaf extract (GLE) on vascular endothelial function (VEF) in patients with early stage diabetic nephropathy (DN). METHODS: Sixty-four patients were randomized equally by a randomzing digital table into two groups, the treated group and the control group. They were all treated for 8 weeks with conventional therapy for diabetes, but GLE tablets were given to the treated group additionally. Changes in VEF were estimated before and after treatment by ultrasonic examination of the brachial artery. In the meantime, changes in plasma levels of the von Willebrand factor (vWF), nitric oxide (NO) and endothelin-1 (ET-1) were observed as well. RESULTS: The brachial arterial endothelium dependent dilating function in the treated group increased from 4.91+/-2.31% before treatment to 6.78+/-3.89% after treatment (P<0.05), while the level of vWF decreased from 182.05+/-64.13% to 128.56+/-48.98%, and that of NO increased from 50.16+/-24.64 micromol/L to 70.65+/-28.71 micromol/L (P<0.01). However, these indexes were not significantly changed in the control group after treatment (P>0.05). CONCLUSION: GLE could decrease the plasma level of vWF, raise the plasma NO level and improve the endothelium dependent vascular dilating function in DN patients.

[Relativity of gene expression and co-regulated gene patterns in feature KEGG pathways].

We revealed the feature pathways by computing the classification error rates of out-of-bag (OOB) by random forests combined with pathway analysis. At each feature pathway, the relativity of gene expression was studied and the co-regulated gene patterns under different experiment conditions were analyzed by MAP (Mining attribute profile) algorithm. The discovered patterns were also clustered by the average-linkage hierarchical clustering technique. The results showed that the expression of genes at the same pathway was similar. The co-regulated patterns were found in two feature pathways of which one contained 108 patterns and the other contained 1 pattern. The results of clusters showed that the smallest Pearson coefficient of the clusters was more than 0.623, indicating that the co-regulated patterns in different experiment conditions were more similar at the same KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway. The methods can provide biological insight into the study of microarray data.