Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.

Objective: To analyze the characteristics and influencing factors of care-seeking delay of adolescent tuberculosis patients in Dongguan City from 2009 to 2018, so as to provide theoretical basis for the tuberculosis control. Methods: The study participants were 8 899 adolescent tuberculosis patients in Dongguan from 2009 to 2018. The Rank-sum test and multiple linear regression were used to analyze the influencing factors of care-seeking days, and the χ 2 test and Logistic regression were used to analyze the influencing factors of care-seeking delay. Results: The median care-seeking days among adolescent tuberculosis patients were 18(6-46) days in Dongguan City from 2009 to 2018, and the prevalence of the care-seeking delay was 56.6%. Multiple linear regression indicated that care-seeking delays were positively associated with being women (B=0.20), living in rural areas (B=0.10), pathogen-positive patients (B=0.69), patients from 2014 to 2018 (B=0.21), and junior school students (B=0.98). Multivariate Logistic regression indicated that care-seeking delay were positively associated with being women (OR=1.35, 95%CI=1.23-1.47), living in rural areas (OR=1.21, 95%CI=1.08-1.37), pathogen-positive patients (OR=2.51, 95%CI=2.26-2.79), patients from 2014 to 2018 (OR=1.24, 95%CI=1.14-1.35), junior-school students (OR=7.58, 95%CI=1.45-39.65), high-school students (OR=5.26, 95%CI=1.04-26.52), university students (OR=7.06, 95%CI=1.39-35.99), and non-students (OR=5.23, 95%CI=1.05-26.08)(P<0.05). Conclusion The prevention and control of tuberculosis among adolescent patients in Dongguan urgently needs to be strengthened. In the future, attention should be paid to the prevalence of care-seeking delay among female, rural, and student tuberculosis patients, and a reasonable prevention and control policy for adolescent patients should be formulated.

Objective:To evaluate the protective effects of hydrogel implantation in prostate cancer patients for radiotherapy.Methods:A search was performed in PubMed, Web of Science, Cochrane Library, Embase, CNKI and VIP to collect controlled clinical research literature concerning hydrogel implantation in prostate cancer for radiotherapy. The Revman 5.3 software was used to perform meta-analyses of rectal V70, rectal D2 cm 3, rectal toxicity effects and bowel symptoms. Results:The review included ten controlled clinical trials involving 1 360 patients (690 in the hydrogel group and 670 in the control group). The result of Meta-analysis showed that the rectal V70 and rectal D2 cm 3 of prostate cancer patients in the hydrogel group were significantly lower than those in the control group( MD=-4.5, 95% CI -7.11 to -1.90, P<0.001; MD=-19.78, 95% CI -25.92 to -13.63, P<0.001), early and late G1 rectal toxic effects in the hydrogel group were significantly lower than those in the control group ( OR=0.64, 95% CI 0.45-0.90, P=0.01; OR=0.28, 95% CI 0.13-0.60, P=0.001)and the late bowel quality of life in the hydrogel group was significantly improved compared with the control group( MD=5.13, 95% CI 3.29-6.98, P<0.001). However, there were no statistically significant differences in early and late ≥G2 rectal toxic effects( OR=0.46, 95% CI 0.17-1.25, P=0.13; OR=0.44, 95% CI 0.09-2.17, P=0.31)and the early bowel symptoms( MD=2.30, 95% CI -1.31-5.91, P=0.21)between the two groups. Conclusions:Hydrogel implantation inprostate cancer for radiotherapy can reduce rectal V70 and rectal D2 cm 3, lower the early and late G1 rectal toxic effects, and reduce improve the late bowel symptoms.

Radiotherapy is an important treatment method for head and neck cancers.However, owing to the complex anatomic structure, the thyroid will be inevitably radiated during radiotherapy.Radiation-induced hypothyroidism (RIHT)and its impacts on somatic function have gradually attracted people′s attention.This review summarizes the clinical characteristics, pathogenesis, risk factors, predictive models, assessment, and treatment of RIHT of patients with head and neck cancers.

Objective:To observe the expression levels of glial fibrillary acidic protein (GFAP), β-tubulin Ⅲ and synaptophsin, and explore the role of tripartite synapse in the mechanism of central nervous system (CNS) injury and the neuroprotective effect of chondroitin sulfate (CS).Methods:One month old clean grade, 48 female Sparague-Dawley rats and 48 male Sparague-Dawley rats, were randomly divided into 8 groups according to body weight (90 - 120 g) by random number table method, with 12 rats in each group, half male and half female. These rats were fed with water containing different concentrations of sodium fluoride (NaF) [ < 0.5 mg/L (control, CN), 10.0 mg/L (low dose fluoride, LF) and 50.0 mg/L (high dose fluoride, HF)]. Some rats were fed directly for 185 days (CN, LF and HF groups). In addition, rats of CN + normal saline (NS), LF + NS, HF + NS groups and LF + CS, HF + CS groups, were intraperitoneally injected with NS or 0.66 mg/kg CS for 5 consecutive days after 180 days of feeding. After the experiment, the pathological changes of hippocampal CA4 of brain tissue in each group were observed by hematoxylin eosin staining under light microscope, and the expression and distribution of GFAP, β-tubulin Ⅲ and synaptophsin in hippocampal CA4 of rats were detected by immunohistochemistry, the expression of GFAP, β-tubulin Ⅲ and synaptophsin at protein level in hippocampus of rats were detected by Western blotting.Results:Under light microscope, eosinophilic change, loss and irregular arrangement of neuron in the hippocampal CA4 were observed in LF, HF, LF + NS and HF + NS groups. The morphology of LF + CS and HF + CS groups was not significantly changed compared with CN group, but was significant changed compared with LF, HF, LF + NS and HF + NS groups. Immunohistochemical results showed that the rates of positive area of GFAP, β-tubulin Ⅲ and synaptophsin in female and male rats in LF and HF groups were significantly decreased than those in CN group ( P < 0.05); the positive area rates of female and male rats in LF + CS and HF + CS groups were higher than those in LF and HF groups, respectively ( P < 0.05). Western blotting results showed that the proten expression levels of GFAP, β-tubulin Ⅲ and synaptophsin of female and male rats in LF and HF groups (LF group: 0.90 ± 0.09, 0.82 ± 0.08, 1.43 ± 0.14, 0.92 ± 0.02, 1.21 ± 0.15, 0.87 ± 0.02, HF group: 0.58 ± 0.14, 0.73 ± 0.03, 0.63 ± 0.06, 0.67 ± 0.03, 0.87 ± 0.04, 0.70 ± 0.05) were lower than those in CN group (1.24 ± 0.08, 1.09 ± 0.10, 2.64 ± 0.30, 1.54 ± 0.09, 1.72 ± 0.10, 1.13 ± 0.06, P < 0.05). Conclusions:The tripartite synapse and extracellular matrix may take part in pathogenesis of the damages of CNS results from chronic fluorosis; CS may reduce the injury to a certain extent.

Radiotherapy is an important treatment for prostate cancer and cervical cancer. However, it can cause damage to the surrounding organs while effectively treating the tumor. Rectal injury is the most common site. It has been reported that in the radiotherapy of prostate cancer or cervical cancer, hydrogels are injected between prostate and rectum or vagina and rectum to increase the gap distance, which can reduce rectal radiation dose and the risk of radiation damage. This article reviews the applications of hydrogels in the treatment of prostate cancer and cervical cancer, to protect the rectum for better quality of life.

Objective:To obtain differential expression profiles of circRNAs and miRNAs in peripheral blood of female patients with major depressive disorder based on high-throughput sequencing technology, and then construct an interaction network.Based on the outcome, it made a further exploration of the possible occurrence and development mechanisms of female major depressive disorder through functional annotation and pathway enrichment analysis.Methods:According to the ceRNA theory, circRNA-miRNA network was constructed by TargetScan software via predicting the binding sites.Subsequently, the GO functional enrichment analysis was performed, and KEGG pathway enrichment analysis were utlized to illustrate the target genes of co-expressed miRNAs.Thereby, the key genes related to major depressive disorder could be screened out.Results:A total of 724 differential circRNAs and 26 differential miRNAs were detected in female patients with major depressive disorder.And hsa_circ_0086092 and hsa-miR-146a-3p were the most co-expressed.Go functional annotations pointed out that it involved the regulation of nucleobase-containing compound metabolic process, regulation of RNA splicing, regulation of cell communication, amino acid transfer, regulation of RNA metabolic process, regulation of signaling and other biological processes.KEGG pathway analysis showed that target genes were mainly enriched in neurotrophin signaling pathway, Rap1 signaling pathway, FoxO signaling pathway, AMPK signaling pathway, cocaine addiction, mTOR signaling pathway, Jak-STAT signaling pathway, cAMP signaling pathway, etcetera.Among the predicted target genes, BDNF, FGF2, MAPK14, GRIN2A, GRIN2B, GRM2 and PDE4 have the highest correlation with major depressive disorder.Conclusion:Hsa_circ_0086092 may be involved in the occurrence and development of female major depressive disorder through interaction with hsa-miR-146a-3p.

Objective To design and implement a control algorithm in a 6 degree of freedom (DOF) robotic manipulator, so as to simulate the spinal motion and provide stable and efficient testing plan for biomechanical tests on spinal implants. Methods The recognition method of stiffness matrix for L2-5 spinal system was firstly studied for decoupling purpose. Secondly, the direct force control system under each axial motion was established by combining the 6-axis manipulator control system with the incremental proportion integration differentiation (PID) control algorithm. By using the 6-axis direct force control system, pure moment of 7.5 N·m was applied in the direction of main motion axis to simulate flexion-extension (FE), lateral bending (LB) and axial rotation (AR) motion of L2-5 spinal segment. Results The range of motion (ROM) of L2-5 segment in FE, LB and AR direction was 23.01°,27.92°,9.81°, respectively. A 7.5 N·m pure moment could be achieved in the main motion axis, while maintaining zero force/moment in the unconstrained axis with root mean square (RMS) errors being less than 3 N and 0.1 N·m, respectively. Conclusions The proposed algorithm of direct force control using PID controller with predetermined stiffness decoupling matrix was capable of applying pure moment to the spine under FE, LB, AR motion. The research findings have a relatively high value of engineering application for various biomechanical testing of lumbar vertebrae.

OBJECTIVETo determine the genetic etiology and clinical characteristics of 2 boys featuring development delay (DD).

METHODSRoutine chromosomal banding was performed to analyze the karyotypes of the patients and their parents. Single nucleotide polymorphism array (SNP array) analysis was employed to identify pathogenic deletion/duplication of chromosomes, and quantitative real-time PCR (qPCR) was performed to confirm the results.

RESULTSPatient 1 showed a global developmental delay, especially impaired language development, seizures, behavioral problems belonging to the autism spectrum and mild facial dysmorphism. Patient 2 mainly presented with severely delayed speech and moderate intellectual disability, but did not have obvious facial dysmorphism and autistic-like behavior. The diagnosis of 22q13 syndrome was established based on identification of a heterozygous microdeletion at chromosome 22q13.33 in both patients (69 kb and 587 kb, respectively) by the SNP array analysis. Both patients had deletions of SHANK3 and ACR, which are located at the end of 22q. Quantitative real-time PCR verified that the deletion of SHANK3 gene in both patients were de novo in origin.

CONCLUSIONTwo cases of 22q13 deletion syndrome have been diagnosed by SNP array analysis. Deletion of SHANK3 gene may be the major contributor to the clinical manifestations of the patients. SNP array analysis can facilitate discovery of microdeletions, which has played an important role in the diagnosis and genetic counseling for the family.