Transcriptome analysis to explore the mechanism of downregulated TNIK influencing the effect of risperidone.

Background: Risperidone is one of the most reliable and effective antipsychotics for schizophrenia treatment. However, the mechanism of action of risperidone is not yet fully understood. Traf2 and Nck-interacting protein kinase (TNIK), a schizophrenia susceptibility gene, is associated with risperidone treatment response. Our previous in vitro experiments confirmed that downregulated TNIK affected the effect of risperidone on downstream targets. However, the effect of downregulated TNIK on risperidone-induced molecular expression remains to be further explored. Methods: Transcriptome analysis was performed on U251 cells subjected to risperidone, TNIK siRNA, and no treatment, respectively. Compared to the no-treatment group, two groups of DEGs were screened out and then intersected with the schizophrenia-related genes to screen the cross-talk genes. Those DEGs were analyzed using GO and KEGG. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network for the cross-talk gene. Results: The results showed that the parathyroid hormone synthesis, secretion, and action were significantly enriched after risperidone treatment. Downregulated TNIK could have an impact on the collagen-containing extracellular matrix, signaling receptor activator activity, and PI3K-Akt signaling pathway. Interestingly, bone mineralization function and calcium signaling pathway were enriched in the cross-talk genes. Additionally, FGFR2, FGF1, and FGFR might be the potential targets for TNIK affecting the effects of risperidone. Conclusion: The study indicated that risperidone primarily influences functions and/or pathways associated with bone metabolism, potentially contributing to the adverse effect of osteoporosis. Our study may offer a novel perspective on investigating the mechanisms underlying the adverse effects of risperidone.

Numerical study on the mechanism of microplastic separation from water by cyclonic air flotation.

Microplastics have attracted considerable attention as emerging contaminants that threaten water bodies. The removal of microplastics from a mini-hydrocyclone, enhanced by air flotation, was studied numerically. The three-phase flow was modeled using the Eulerian-Eulerian model coupled with interphase interactions. The characteristics of the flow field and distribution of microplastics and microbubbles were discussed, and the mechanism of cyclonic air flotation separation was analyzed. It was found that injecting microbubbles accelerated the axial migration of microplastics and moved the enriched area upward toward the overflow. The coalescence rate of the bubbles near the axis was higher than their breakage rate, which led to the formation of an air core. The length and diameter of the air core increased with the inlet gas holdup. When the air core size closely matched the overflow, the constrained flow channel prevented the discharge of microplastics. The optimal air holdup must be determined to ensure the efficiency of the cyclonic air flotation process. The sizes of the microbubbles used for cyclonic air flotation should be comparable to those of the separated microplastics. The upper cone angle significantly promoted the migration of microplastics to the axis. This study was conducted to purify microplastic-containing wastewater using an environmentally friendly and energy-efficient technique and to provide a theoretical basis and practical reference for applying microplastic separation technology in water.

Current global research on mandibular defect: A bibliometric analysis from 2001 to 2021.

Background: Mandibular defects can result from congenital deformities, trauma, tumor resection, and osteomyelitis. The shape was irregular because the lower jaw was radians. This involves teeth and jaw functions; therefore, the difficulty of bone repair is greater than that in other body parts. Several standard treatments are available, but they result in various problems, such as difficulties in skin flap transplantation and possible zone dysfunction, artificial material boneless combining ability, and a long treatment period. This study aimed to introduce the present status of research on mandibular defects to analyze the current introduction and predict future research trends through a bibliometric study. Methods: From 2001 to 2021, publications on mandibular defects were collected for bibliometric visualization using VOSviewer, CiteSpace, and Scimago Graphica software based on the Web of Science Core Collection. Results: This study analyzed 4,377 articles, including 1,080 published in the United States, 563 in China, and 359 in Germany, with an increase in the number of articles published over the past 20 years. Wikesjoe and Ulf Mai E had the most publications (p = 36) and citations (citations = 1,553). Shanghai Jiaotong University published the highest number of papers among the research institutions (p = 88). The most productive journal was Journal of Oral and Maxillofacial Surgery, and the cited literature was primarily classified as dentistry, dermatology, and surgery. Cluster Analysis of Co-occurrence Keywords revealed that highest number of core words were mandibular defects, mandibular reconstruction, and bone regeneration. The highest cited words were head and neck cancer, accuracy, and osteogenic differentiation. High-frequency terms of Cluster Analysis of References were osteosynthesis plate, tissue engineering, and rapid distraction rate. Conclusion: Over the past 20 years, the number of studies on mandibular defects has gradually increased. New surgical procedures are increasingly being used in clinical practice. Current frontier topics mainly focus on areas such as computer-aided design, 3D printing of osteotomy and reconstruction guide plates, virtual surgical planning, and bone tissue engineering.

The Promoting Effect of a Local Pulsatile Parathyroid Hormone Delivery on Healing of the Mandibular Fracture in Rats.

Parathyroid hormone (PTH) can promote bone formation and mineralization in mandibular fractures, and is systemically administered through daily injections. In this study, the local delivery of PTH using carboxymethyl chitosan/polyvinyl alcohol and alginate was investigated. Bovine serum albumin was used as a drug substitute, and the delivery system was verified to release drugs in a pulsed rhythm. After the delivery system was subcutaneously implanted in Sprague-Dawley (SD) rats, no rejection reaction was detected, indicating that it has good biocompatibility and biodegradability in vivo. Then, an SD rat model of mandibular fracture was established, and 24 rats were randomly divided into two groups. The control group was reduced and fixed with screws and a microplate, and the experimental group received pulsatile PTH release system (14 µg PTH) + screws and microplate fixation. The animals were euthanized on postoperative weeks 1-4. Observation of gross specimens, digital radiography, and hematoxylin and eosin showed that the local PTH pulsatile release system promoted osteogenesis and accelerated fracture healing. In summary, PTH can be loaded by biomaterials to locally target the fracture and stimulate bone formation. Moreover, the pulsatile PTH release system provides a potential therapeutic protocol for mandibular fracture. Impact statement Our study prepares a drug release system that could impulsively release parathyroid hormone. The system could enhance bone regeneration in rats with mandibular fracture. These data provide a foundation for future studies aimed to understand and optimize the use of bioactive molecule pulsatile delivery for bone regeneration and tissue engineering applications.

The influence of TNIK gene polymorphisms on risperidone response in a Chinese Han population.

Aim: To investigate whether the TNIK gene affects risperidone treatment outcomes in the Chinese population. Methods: A total of 148 unrelated inpatients who received risperidone for six weeks were enrolled. The selected single nucleotide polymorphisms (SNPs; rs2088885, rs7627954 and rs13065441) were genotyped using the MassARRAY® SNP IPLEX platform. Results: The analysis showed that one novel SNP of TNIK, rs7627954, had a significant association with the response to risperidone (χ2 = 4.472; p = 0.034). This work also identified rs2088885 as significantly associated with risperidone response (χ2 = 5.257; p = 0.022). The result revealed that the rs2088885-rs7627954 C-T haplotype was more prevalent in good responders than in poor responders (p = 0.0278). Conclusion: This study revealed that the rs2088885 and rs7627954 SNPs of TNIK are associated with risperidone treatment response.

TNIK influence the effects of antipsychotics on Wnt/ß-catenin signaling pathway.

RationaleTraf2- and Nck-interacting kinase (TNIK), a member of germinal center kinase (GCK) family, has been implicated as a risk factor in schizophrenia and bipolar disorder as well as the action of antipsychotics. TNIK is an essential activator of Wnt/ß-catenin signaling pathway which has been identified involved in the mechanism underlying the effects of antipsychotics. Thus, the effects of TNIK on antipsychotics may be achieved by influencing Wnt/ß-catenin signaling pathway proteins.Objectives and methodsIn the current study, the effects of up- or downregulated TNIK on ß-catenin, T-cell factor 4 (TCF-4), glycogen synthase kinase-3ß (GSK3ß), and phosphorylated GSK3ß (p-GSK3ß) were examined in the human glioma U251 cells. Then, we observed the effects of antipsychotics (clozapine and risperidone) on the above proteins and evaluated the role of differentially expressed TNIK on antipsychotic-treated cell groups.ResultsThe result showed that clozapine treatment decreased ß-catenin and TCF-4 levels in U251 cells, and risperidone had the similar effects on ß-catenin and p-GSK3ß. The downregulated TNIK using siRNA impeded the regulation of antipsychotics on Wnt pathway proteins via increasing the expression levels of TCF-4, ß-catenin, or p-GSK3ß, whereas the upregulated TNIK made no significant change.ConclusionsThe influence of TNIK on the effects of antipsychotics may be partly through Wnt/ß-catenin signaling pathway.

Parathyroid hormone promotes cartilage healing after free reduction of mandibular condylar fractures by upregulating Sox9.

After high fractures of the mandibular condyle, the insufficient blood supply to the condyle often leads to poor bone and cartilage repair ability and poor clinical outcome. Parathyroid hormone (PTH) can promote the bone formation and mineralization of mandibular fracture, but its effects on cartilage healing after the free reduction and internal fixation of high fractures of the mandibular condyle are unknown. In this study, a rabbit model of free reduction and internal fixation of high fractures of the mandibular condyle was established, and the effects and mechanisms of PTH on condylar cartilage healing were explored. Forty-eight specific-pathogen-free (SPF) grade rabbits were randomly divided into two groups. In the experimental group, PTH was injected subcutaneously at 20 µg/kg (PTH (1-34)) every other day, and in the control group, PTH was replaced with 1 ml saline. The healing cartilages were assessed at postoperative days 7, 14, 21, and 28. Observation of gross specimens, hematoxylin eosin staining and Safranin O/fast green staining found that every-other-day subcutaneous injection of PTH at 20 µg/kg promoted healing of condylar cartilage and subchondral osteogenesis in the fracture site. Immunohistochemistry and polymerase chain reaction showed that PTH significantly upregulated the chondrogenic genes Sox9 and Col2a1 in the cartilage fracture site within 7-21 postoperative days in the experimental group than those in the control group, while it downregulated the cartilage inflammation gene matrix metalloproteinase-13 and chondrocyte terminal differentiation gene ColX. In summary, exogenous PTH can stimulate the formation of cartilage matrix by triggering Sox9 expression at the early stage of cartilage healing, and it provides a potential therapeutic protocol for high fractures of the mandibular condyle.

Gene expression signatures differentiating major depressive disorder from subsyndromal symptomatic depression.

Subsyndromal symptomatic depression (SSD) and major depressive disorder (MDD) have been classified as distinct diseases, due to their dissimilar gene expression profiles and responses to venlafaxine. To identify specific biomarkers of these two diseases, we conducted a secondary analysis of the gene expression signatures of SSD patients, MDD patients and healthy controls (n=8/group) from the study of Yi et al. Global, individual, specific, enrichment and co-expression analyses were used to compare the transcriptomic profiles of peripheral blood lymphocytes from the three groups. The global and individual analyses revealed that different genes were up- and downregulated in the SSD and MDD groups. Through our specific analysis, we identified 1719 and 3278 differentially expressed genes specifically associated with MDD and SSD, respectively. Enrichment and co-expression analyses demonstrated that the genes specific to MDD were enriched in pathways associated with hormone levels and immune responses, while those specific to SSD were associated with immune function. The specific hub gene for the MDD co-expression network was transmembrane protein 132B (TMEM132B), while the hub genes for SSD were actin-related protein 2/3 complex (ARPC2) and solute carrier family 5 member 5 (SLC5A5). This bioinformatic analysis has provided potential biomarkers that can distinguish SSD from MDD.

Spatio-temporal discrimination of molecular, aerosol and cloud scattering and polarization using a combination of a Raman lidar, Doppler cloud radar and microwave radiometer.

The combined data from the ESA Mobile Raman Polarization and Water Vapor Lidar (EMORAL), the LATMOS Bistatic Doppler Cloud Radar System for Atmospheric Studies (BASTA), and the INOE Microwave Radiometer (HATPRO-G2) have been used to explore the synergy for the spatio-temporal discrimination of polarization and molecular, aerosol and cloud scattering. The threshold-based methodology is proposed to perform an aerosol-cloud typing using the three instruments. It is demonstrated for 24 hours of observations on 10 June 2019 in Rzecin, Poland. A new scheme for target classification, developed collaboratively by the FUW and the OUC, can help determine molecules, aerosol (spherical, non-spherical, fine, coarse), cloud phase (liquid, ice, supercooled droplets) and precipitation (drizzle, rain). For molecular, aerosol, and cloud discrimination, the thresholds are set on the backward scattering ratio, the linear particle depolarization ratio and the backscatter colour ratio, all calculated from lidar signals. For the cloud phase and precipitation categorization, the thresholds are set on the reflectivity and the Doppler velocity derived from cloud radar signals. For boundary layer particles, precipitation, and supercooled droplets separation, the thresholds are set on the profiles of temperature and relative humidity obtained by the microwave radiometer. The algorithm is able to perform separation even under complicated meteorological situation, as in the presented case study.

Two Novel Loci of RELN Associated With Antipsychotics Response in Chinese Han Population.

BACKGROUND: There are great individual differences in the drug responses; however, there are few prognostic drug response biomarkers available. RELN is one of the more extensively examined schizophrenia candidate genes. The purpose of this study was to determine whether RELN can affect antipsychotics response in the Chinese population. This may lead to the discovery of relevant novel drug response markers. METHODS: The unrelated 260 Chinese Han inpatients with schizophrenia were enrolled in the present study. The enrolled subjects have been prescribed antipsychotic medication during the study. A total of 15 SNPs of RELN were genotyped by MassARRAY® platform. The association of the RELN gene with therapeutic response to antipsychotics was analyzed based on sex and age at onset. RESULTS: Two novel SNPs of RELN were found to be associated with antipsychotic treatment response (rs155333, p = 0.010 and rs6465938, p = 0.049) at nominal significance threshold, but not after multiple correction. Our study also revealed highly significant association of a haplotype consisting of three SNPs (rs362814-rs362626-rs2237628) with antipsychotic treatment response. Even after permutation, the p-value indicated significant association (rs362814-rs362626-rs2237628: ACT, χ2 = 6.353, p = 0.0117, permuted p = 0.04). Furthermore, a novel SNP, rs2535764, was found to be associated with antipsychotic response under overdominant genetic model at a marginal significant level of 0.046 (C/T vs. C/C + T/T: p = 0.046, AIC = 314.7, BIC = 321.6). CONCLUSION: Our data indicated that RELN can affect antipsychotic treatment outcomes in the Chinese population. SNPs of RELN could be used as predictive biomarkers for future personalized medicine of antipsychotic drug treatment. However, none of the three novel SNPs (rs155333, rs6465938, and rs2535764) remained significant after Bonferroni correction. Therefore, validation is needed in larger pharmacogenetic studies.

Association of Corticotropin-Releasing Hormone Receptor-1 Gene Polymorphisms and Personality Traits with Violent Aggression in Male Adolescents.

There is evidence that corticotropin-releasing hormone receptor 1 (CRHR1) gene polymorphisms and indifferent impulsive personality traits play an important role in violent aggression in male adolescents. Genotyping for two tag single-nucleotide polymorphisms (SNP) (rs242924, rs17689966) was conducted using TaqMan SNP for 138 violent young male criminals, 98 nonviolent young male criminals, and 153 noncriminal adults. The general situation and personality traits (SSP) questionnaire was given to the young violent and nonviolent male criminal groups. The results showed that the frequency of the G allele in rs242924 of the CRHR1 gene in the violent aggression group was higher than that in the normal adult controls (P < 0.025, OR = 2.29, 95% CI = 1.13-4.62). The difference in genotype distribution was significant among the three groups (P < 0.05), and when the violent group was compared with the two control groups, no significant difference was found (P > 0.025). The impulsiveness, trait irritability, verbal trait aggression, and physical trait aggression scores in the violent group were significantly higher than those in the nonviolent group of adolescents. These findings suggest that the variance in CRHR1 gene polymorphisms and personality traits may play a role in violent aggression in male adolescents, and that the interaction of the CRHR1 gene and the impulsive personality trait may cause an increased susceptibility to violence towards others.

Co-Expression Network Analysis Revealed That the ATP5G1 Gene Is Associated With Major Depressive Disorder.

Major depressive disorder (MDD) is a leading cause of disability worldwide, although its etiology and mechanism remain unknown. The aim of our study was to identify hub genes associated with MDD and to illustrate the underlying mechanisms. A weighted gene co-expression network analysis (WGCNA) was performed to identify significant gene modules and hub genes associated with MDD in peripheral blood mononuclear cells (PBMCs) (n = 45). In the blue module (R 2 = 0.95), five common hub genes in both co-expression network and protein-protein interaction (PPI) network were regarded as "real" hub genes. In another independent dataset, GSE52790, four genes were still significantly down-regulated in PBMCs from MDD patients compared with the controls. Furthermore, these four genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in PBMCs from 33 MDD patients and 41 healthy controls. The qRT-PCR analysis showed that ATP synthase membrane subunit c locus 1 (ATP5G1) was significantly down-regulated in samples from MDD patients than in control samples (t = -2.89, p-value = 0.005). Moreover, this gene was significantly differentially expressed between patients and controls in the prefrontal cortex (z = -2.83, p-value = 0.005). Highly significant differentially methylated positions were identified in the Brodmann area 25 (BA25), with probes in the ATP5G1 gene being significantly associated with MDD: cg25495775 (t = 2.82, p-value = 0.008), cg25856120 (t = -2.23, p-value = 0.033), and cg23708347 (t = -2.24, p-value = 0.032). These findings indicate that the ATP5G1 gene is associated with the pathogenesis of MDD and that it could serve as a peripheral biomarker for MDD.

Differences in accelerated tooth movement promoted by recombinant human parathyroid hormone after mandibular ramus osteotomy.

INTRODUCTION: This study investigated the effects of different doses of parathyroid hormone (PTH) on orthodontic tooth movement after mandibular ramus osteotomy and the associated dose-response relationship. METHODS: One-hundred twenty rabbits were divided into 2 experimental groups (A and B) and 2 control groups (control group and negative control group). An experimental model of mandibular ramus osteotomy with installation of an orthodontic tooth movement device was established in groups A and B and the control group. After surgery, groups A and B received intermittent subcutaneous injections of PTH, 20 and 40 µg/kg, respectively, and the control group received injections of normal saline solution. The negative control group underwent installation of the orthodontic tooth movement device without mandibular ramus osteotomy and received normal saline solution after surgery. Changes in expression of RANKL and RUNX2 in the periodontal tissues of the first molars were evaluated by means of immunohistochemical analysis and quantitative fluorescence polymerase chain reaction. RESULTS: Movement of the first molars was more rapid in group B than in group A in the 21 days after surgery. Significantly higher RANKL mRNA levels and lower RUNX2 mRNA levels were detected on the compression side of the periodontal tissues in groups A and B than in the control groups. There was a significant difference in RANKL and RUNX2 expression levels between group B and the control groups at all time points. CONCLUSIONS: Mandibular ramus osteotomy combined with high-dose PTH can increase catabolism on the compressed periodontal tissues, thereby accelerating remodeling of periodontal bone and promoting orthodontic tooth movement after surgery.

Comparative Study of Molecular Basket Sorbents Consisting of Polyallylamine and Polyethylenimine Functionalized SBA-15 for CO2 Capture from Flue Gas.

Polyallylamine (PAA)-based molecular basket sorbents (MBS) have been studied for CO2 capture in comparison with polyethylenimine (PEI)-based MBS. The characterizations including N2 physisorption, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and thermogravimetric analysis (TGA) showed that PAA (Mn =15 000) is more rigid and has more steric hindrance inside SBA-15 pores than PEI owing mainly to its different polymer structure. The effects of temperature and PAA loading on the CO2 sorption capacity of PAA-based MBS have been examined by TGA by using 100 % CO2 gas stream and compared with PEI/SBA-15. It was found that the capacity of the PAA/SBA-15 sorbent increased with increasing temperature. The optimum capacity of 88 mgCO2 gsorb-1 was obtained at 140 °C for PAA(50)/SBA-15 whereas the optimum sorption temperature was 75 and 90 °C for PEI-I(50)/SBA-15 (PEI-I, Mn =423) and PEI-II(50)/SBA-15 (PEI-II, Mn =25 000), respectively. The capacity initially increased with the increase of PAA loading and then dropped at high amine contents, owing to the increased diffusion barrier. The highest CO2 capacity of 109 mgCO2 gsorb-1 was obtained at a PAA loading of 65 wt %, whereas the PAA(50)/SBA-15 sorbent gave the best amine efficiency of 0.23 molCO2 molN-1 . The effect of moisture was examined in a fixed-bed flow system with simulated flue gas containing 15 % CO2 and 4.5 % O2 in N2 . It was found that the presence of moisture significantly enhanced CO2 sorption over PAA(50)/SBA-15 and greatly improved its cyclic stability and regenerability. Compared with PEI/SBA-15, PAA/SBA-15 possesses a better thermal stability and higher resistance to oxidative degradation. However, the CO2 sorption rate over the PAA(50)/SBA-15 sorbent was much slower.

Association analysis between mitogen-activated protein/extracellular signal-regulated kinase (MEK) gene polymorphisms and depressive disorder in the Han Chinese population.

BACKGROUND: Recent research findings suggest that BDNF and BDNF signaling pathways participate in the development of major depressive disorder. Mitogen-activated extracellular signal-regulated kinase (MEK) is the most important kinase in the extracellular signal-regulated kinase pathway, and the extracellular signal-regulated kinase pathway is the key signaling pathway of BDNF, so it may play a role in development of depressive disorder. The aim of this study is to investigate the association between polymorphisms of the MAP2K1 (also known as MEK) gene and depressive disorder. RESULTS: Three single nucleotide polymorphisms (SNPs), were significantly associated with depressive disorder: rs1549854 (p = 0.006), rs1432441 (p = 0.025), and rs7182853 (p = 0.039). When subdividing the sample by gender, two of the SNPs remained statistically associated with depressive disorder in females: rs1549854 (p = 0.013) and rs1432441 (p = 0.04). CONCLUSION: The rs1549854 and rs1432441 polymorphisms of the MAP2K1 gene may be associated with major depressive disorder, especially in females. This study is the first to report that the MAP2K1 gene may be a genetic marker for depressive disorder.

Electric-Field-Controlled Dopant Distribution in Organic Semiconductors.

Stable electrical doping of organic semiconductors is fundamental for the functionality of high performance devices. It is known that dopants can be subjected to strong diffusion in certain organic semiconductors. This work studies the impact of operating conditions on thin films of the polymer poly(3-hexylthiophene) (P3HT) and the small molecule Spiro-MeOTAD, doped with two differently sized p-type dopants. The negatively charged dopants can drift upon application of an electric field in thin films of doped P3HT over surprisingly large distances. This drift is not observed in the small molecule Spiro-MeOTAD. Upon the dopants' directional movement in P3HT, a dedoped region forms at the negatively biased electrode, increasing the overall resistance of the thin film. In addition to electrical measurements, optical microscopy, spatially resolved infrared spectroscopy, and scanning Kelvin probe microscopy are used to investigate the drift of dopants. Dopant mobilities of 10-9 to 10-8 cm2 V-1 s-1 are estimated. This drift over several micrometers is reversible and can be controlled. Furthermore, this study presents a novel memory device to illustrate the applicability of this effect. The results emphasize the importance of dynamic processes under operating conditions that must be considered even for single doped layers.

An Examination of Differences in the New Bone Formation Promoted by Different Doses of Recombinant Human Parathyroid Hormone during Mandibular Distraction Osteogenesis.

BACKGROUND: The administration of different doses of parathyroid hormone to promote mandibular distraction osteogenesis remains unclear. The objective of the present study was to examine the effects of recombinant human parathyroid hormone on new bone formation during mandibular distraction osteogenesis and to investigate the dose-effect relationship associated with this phenomenon. METHODS: A total of 45 rabbits were used to establish the mandibular distraction osteogenesis model. The rabbits were divided into a control group (that received a subcutaneous injection of 1 ml of saline every other day) and experimental groups A, B, C, and D (that received subcutaneous injections of 10, 20, 30, and 40 µg/kg of recombinant human parathyroid hormone, respectively, every other day). On days 1, 7, and 14 of the consolidation period after the distraction had been completed, new bone in the distraction region was examined through histomorphometric investigation and bone mineral density testing. RESULTS: On days 1, 7, and 14 of the fixation period, the number of osteoblasts, trabecular bone area, and bone mineral density were greater in each experimental group than in the control group. On day 1 of the consolidation period, group C featured the highest average number of osteoblasts. On day 14 of the consolidation period, group C exhibited the highest bone mineral densities and largest trabecular bone areas. CONCLUSIONS: Intermittent subcutaneous injections of recombinant human parathyroid hormone can promote new bone formation during mandibular distraction osteogenesis. Different doses of recombinant human parathyroid hormone promoted mandibular distraction osteogenesis to differing extents.

APOE Genotype Affects Cognitive Training Response in Healthy Shanghai Community-Dwelling Elderly Individuals.

BACKGROUND: Cognitive training may contribute to the ability to maintain cognitive function in healthy elderly adults. Whether genotype modifies training effects remains unknown. OBJECTIVE: Assess influence of APOE on cognitive function over time in community-dwelling elderly adults participating in multi-domain cognitive training. METHODS: Healthy individuals ≥70 years of age were screened from one urban community in Shanghai. 145 healthy Chinese older adults met inclusion criteria and were assigned to intervention (n = 88) or control (n = 57) groups. Multi-domain cognitive training involved 24 sessions of different content taking place over 12 weeks. Neuropsychological testing was administered at baseline, immediately after training, six months and twelve months post-intervention; composite measures of cognitive function were identified via factor analysis. RESULTS: Three factors explained the majority of variance in function (verbal memory, processing speed, executive function). The intervention attenuated 12-month declines in processing speed, regardless of APOE genotype (p = 0.047). Executive function declined in APOEɛ4 carriers over 12 months, regardless of intervention (p = 0.056). There was a significant interaction after 12 months where intervention ɛ4 carriers had better processing speed than ɛ4 controls (p = 0.003). Intervention ɛ2 carriers had better executive function immediately after training (p = 0.02) and had better verbal memory 6-months post-intervention (p = 0.04). These effects remained significant after false-discovery rate correction. CONCLUSION: Multi-domain cognitive training reduces declines in processing speed over time. APOEɛ4 is associated with reductions in executive function over time, and training may attenuate ɛ4-associated declines in processing speed. APOEɛ2 carriers may also benefit from training, particularly on measures of executive function and verbal memory.

Association study of VEGFA polymorphisms with schizophrenia in Han Chinese population.

Vascular endothelial growth factor A (VEGFA) has been implicated in neurotrophy and neurogenesis, which play a pivotal role in brain development and may be involved in the pathophysiology of schizophrenia (SCZ). We hypothesized that common genetic variants in the VEGFA gene may be associated with SCZ. In our study, seven tag single nucleotide polymorphisms (SNPs) within VEGFA were genotyped in 1034 SCZ patients and 952 healthy controls in the Han Chinese population. No significant differences of allele and genotype distributions of the 7 tag SNPs were identified between SCZ patients and healthy controls. The AA genotype of rs699947 nominally decreased the risk of SCZ in recessive inheritance model (p=0.03, OR=0.65, 95%CI=0.44-0.95, adjusted p=0.18). No significant associations were found between different haplotypes and the risk of SCZ (p>0.05). Our findings suggested that the selected tag SNPs of VEGFA may not confer a susceptibility of SCZ in the Han Chinese population.

An experimental study addressing the promotion of mandibular defect repair through the intermittent subcutaneous injection of parathyroid hormone.

PURPOSE: Parathyroid hormone (PTH) is a major regulator of bone metabolism. Various animal studies and clinical trials have addressed the treatment of osteoporosis and fracture healing with the intermittent administration of PTH, whereas few studies have investigated the effects of PTH on mandibular defect repair. This study sought to examine the feasibility of using recombinant human PTH (rhPTH) to promote the repair of mandibular defects and to provide a preliminary investigation of the underlying mechanisms of this phenomenon. MATERIALS AND METHODS: A mandibular defect model was established using Japanese white rabbits. The experimental animals were randomly divided into a control group that received postoperative subcutaneous injections of normal saline on alternate days and an experimental group that received postoperative subcutaneous injections of rhPTH 25 µg on alternate days. The experimental animals were sacrificed at 1, 2, 3, and 4 weeks after the operation to perform x-ray imaging and bone histomorphometric examinations of the defect areas. Changes in serum levels of bone-specific alkaline phosphatase (bALP) and osteoprotegerin (OPG) over time were examined. RESULTS: Compared with the control group, the experimental group exhibited newly generated bone matrix in the mandibular defect area at earlier stages. In the experimental group, the bone trabeculae were arranged in an orderly manner, and uniform calcification was observed. Marked hyperplasia of osteoblasts was observed in the new bone tissue of the experimental group, but significantly less hyperplasia of osteoblasts was observed in the control group. In the 2 groups, the average serum bALP and OPG levels increased after the operation and then gradually decreased. In the experimental group, levels of bALP and OPG at 1 week and 2 weeks after the operation were significantly different from preoperative levels. In the control group, the OPG level at 2 weeks after the operation was significantly different from the preoperative OPG level. A comparison of serum bALP and OPG levels at each examined time point showed no significant difference between the 2 groups. CONCLUSION: The intermittent subcutaneous injection of rhPTH 25 µg/day promotes the healing of mandibular defects in rabbits. The application of rhPTH may facilitate mandible regeneration by increasing quantities of osteoblasts, accelerating bone turnover metabolism, and upregulating OPG levels.