Impact of Preoperative Sleep Disturbances on Postoperative Delirium in Patients with Intracranial Tumors: A Prospective, Observational, Cohort Study.

Background: Postoperative delirium (POD) is prevalent in craniotomy patients and is associated with high mortality. Sleep disturbances are receiving increasing attention from clinicians as associated risk factors for postoperative complications. This study aimed to determine the impact of preoperative sleep disturbances on POD in craniotomy patients. Methods: We recruited 130 patients undergoing elective craniotomy for intracranial tumors between May 1st and December 30th, 2022. Preoperative subjective sleep disturbances were assessed using the Pittsburgh Sleep Quality Index on the day of admission. We also measured objective perioperative sleep patterns using a dedicated sleep monitoring device 3 days before and 3 days after the surgery. POD was assessed twice daily using the Confusion Assessment Model for the Intensive Care Unit within the first week after craniotomy. Results: Preoperative sleep disturbances were diagnosed in 49% of the study patients, and POD was diagnosed in 22% of all the study patients. Sleep disturbances were an independent risk factor for POD (OR: 2.709, 95% CI: 1.020-7.192, P = 0.045). Other risk factors for POD were age (OR: 3.038, 95% CI: 1.195-7.719, P = 0.020) and the duration of urinary catheterization (OR: 1.246, 95% CI: 1.025-1.513, P = 0.027). Perioperative sleep patterns (including sleep latency, deep sleep duration, frequency of awakenings, apnea-hypopnea index, and sleep efficiency) were significantly associated with POD. Conclusion: This study demonstrated that preoperative sleep disturbances predispose patients undergoing craniotomy to POD, also inferred a correlation between perioperative sleep patterns and POD. The targeted screening and intervention specifically for sleep disturbances during the perioperative period are immensely required.

Associations between perioperative sleep patterns and clinical outcomes in patients with intracranial tumors: a correlation study.

Objective: Although the quality of perioperative sleep is gaining increasing attention in clinical recovery, its impact role remains unknown and may deserve further exploration. This study aimed to investigate the associations between perioperative sleep patterns and clinical outcomes among patients with intracranial tumors. Methods: A correlation study was conducted in patients with intracranial tumors. Perioperative sleep patterns were assessed using a dedicated sleep monitor for 6 consecutive days. Clinical outcomes were gained through medical records and follow-up. Spearman's correlation coefficient and multiple linear regression analysis were applied to evaluate the associations between perioperative sleep patterns and clinical outcomes. Results: Of 110 patients, 48 (43.6%) were men, with a median age of 57 years. A total of 618 days of data on perioperative sleep patterns were collected and analyzed. Multiple linear regression models revealed that the preoperative blood glucose was positively related to the preoperative frequency of awakenings (ß = 0.125; 95% CI = 0.029-0.221; P = 0.011). The level of post-operative nausea and vomiting was negatively related to perioperative deep sleep time (ß = -0.015; 95% CI = -0.027--0.003; P = 0.015). The level of anxiety and depression was negatively related to perioperative deep sleep time, respectively (ß = -0.048; 95% CI = -0.089-0.008; P = 0.020, ß = -0.041; 95% CI = -0.076-0.006; P = 0.021). The comprehensive complication index was positively related to the perioperative frequency of awakenings (ß = 3.075; 95% CI = 1.080-5.070; P = 0.003). The post-operative length of stay was negatively related to perioperative deep sleep time (ß = -0.067; 95% CI = -0.113-0.021; P = 0.005). The Pittsburgh Sleep Quality Index was positively related to perioperative sleep onset latency (ß = 0.097; 95% CI = 0.044-0.150; P < 0.001) and negatively related to perioperative deep sleep time (ß = -0.079; 95% CI = -0.122-0.035; P < 0.001). Conclusion: Perioperative sleep patterns are associated with different clinical outcomes. Poor perioperative sleep quality, especially reduced deep sleep time, has a negative impact on clinical outcomes. Clinicians should, therefore, pay more attention to sleep quality and improve it during the perioperative period. Clinical trial registration: http://www.chictr.org.cn, identifier: ChiCTR2200059425.

The Effects of Perioperative Probiotics on Postoperative Gastrointestinal Function in Patients with Brain Tumors: A Randomized, Placebo-Controlled Study.

The incidence of postoperative gastrointestinal dysfunction among neurosurgical patients is as high as 80%. Probiotics help to maintain gastrointestinal barrier defense, provide competitive adherence to mucus and epithelial cells, and regulate gastrointestinal motility. Therefore, the purpose of this study was to investigate whether probiotics enhance gastrointestinal health after craniotomy in patients with brain tumors. This study was a 15-day, prospective, randomized, double-blind, placebo-controlled trial for patients being treated with elective craniotomy for brain tumors. Participants were randomly divided into the probiotics group (4 g probiotics, twice daily) and placebo group. The primary outcome was the time of first stool after surgery. The secondary outcomes included assessments of the gastrointestinal function, changes in gastrointestinal permeability and clinical outcomes. We enrolled a total of 200 participants (probiotics: 100; placebo: 100) and followed the principles of intention-to-treat analysis. The time of first stool and flatus were significantly shorter in the probiotics group compared to the placebo group (P < 0.001, respectively). No significant trends were observed for any other of the secondary outcome variables. Our findings suggest that probiotics can improve the gastrointestinal mobility of patients received craniotomy, and this improvement cannot be explained by changes in gastrointestinal permeability.

Vascular endothelial growth factor and risk of malignant brain tumor: A genetic correlation and two-sample Mendelian randomization study.

Objective: The relationship between vascular endothelial growth factor (VEGF) and the risk of malignant brain tumors has always been a concern in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders, coinheritability and reverse causality. We aimed to investigate the causal relationship between VEGF and different types of malignant brain tumors. Methods: Using publicly available summary data from genome-wide association studies (GWAS) of VEGF (n=16,112) and different types of malignant brain tumors (n=174,097-174,646), we adopted a standard two-sample bidirectional Mendelian randomization (MR) to estimate potential causal associations of circulating VEGF levels and the risk of malignant brain tumors. Inverse variance weighted (IVW) was used as the primary analysis method to estimate causality. MR-Egger regression, weighted median (WM), penalty weighted median (PWM), MR robust adjusted profile score (MR.RAPS) and causal analysis using summary effect estimates (CAUSE) methods were used in sensitivity analyses to verify the robustness of the findings. Meanwhile, we applied the MR pleiotropy residual sum and outlier (MR-PRESSO) test and PhenoScanner tool to identify and remove potential horizontal pleiotropic single nucleotide polymorphisms (SNPs). Additionally, linkage disequilibrium score regression (LDSC) analysis was conducted to assess the coinheritability of exposure and outcome. Results: A total of 6 (VEGF), 12 (malignant brain tumor), 13 (brain glioblastoma) and 12 (malignant neoplasm of meninges) SNPs were identified as valid instrumental variables. No evidence supported a causal relationship between circulating VEGF levels and the risk of malignant brain tumors (forwards: odds ratio (OR) = 1.277, 95% confidence interval (CI), 0.812~2.009; reversed: ß = 0.005, 95% CI, -0.029~0.038), brain glioblastoma (forwards: OR (95% CI) = 1.278(0.463~3.528); reversed: ß = 0.010, 95% CI, -0.002~0.022) and malignant neoplasm of meninges (forwards: OR (95% CI) = 0.831(0.486~1.421); reversed: ß = 0.010, 95% CI, -0.030~0.050) using the main IVW method. Outliers and pleiotropy bias were not detected by sensitivity analyses and pleiotropy-robust methods in any estimates. LDSC failed to identify genetic correlations between VEGF and different types of malignant brain tumors. Conclusions: Our findings reported no coinheritability and failed to provide evidence for causal associations between VEGF and the risk of different types of malignant brain tumors. However, certain subtypes of VEGF for which genetic predictors have not been identified may play a role and need to be further investigated.

Genetic association and causal inference between lung function and venous thromboembolism.

BACKGROUND: Previous studies have indicated that lower lung function is related to a higher risk of venous thromboembolism (VTE). However, causal inferences may be affected by confounders, coheritability or reverse causality. We aimed to explore the causal association between lung function and VTE. METHODS: Summary data from public genome-wide association studies (GWAS) for lung function and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly related to exposure were filtered as proxy instruments. We adopted linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (MR) analyses to infer the genetic backgrounds and causal associations between different lung functions and VTE events. RESULTS: LDSC showed a genetic correlation between forced expiratory volume in one second (FEV1) and deep vein thrombosis (DVT) (rg = - 0.189, P = 0.005). In univariate MR (UVMR), there was suggestive evidence for causal associations of genetically predicted force vital capacity (FVC) with DVT (odds ratio (OR) 0.774; 95% confidence interval (CI) 0.641-0.934) via forwards analysis and genetically predicted pulmonary embolism (PE) with FVC (OR 0.989; 95% CI 0.979-0.999) via reverse analysis. Multivariate MR (MVMR) analyses of lung function-specific SNPs suggested no significant direct effects of lung function on VTE, and vice versa. Of note is the borderline causal effect of PE on FEV1 (OR 0.921; 95% CI 0.848-1.000). CONCLUSIONS: Our findings identified a coheritability of FEV1 (significant) and FVC (suggestive) with DVT. There was no convincing causal relationship between lung function and the risk of VTE events. The borderline causal effect of PE on FEV1 and the significant genetic correlation of FEV1 with DVT may have clinical implications for improving the quality of existing prevention and intervention strategies.

Vascular endothelial growth factor and the risk of venous thromboembolism: a genetic correlation and two-sample Mendelian randomization study.

BACKGROUND: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. METHODS: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran's Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. RESULTS: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95% confidence interval (CI), 1.009-1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (ß = -0.021, 95% CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. CONCLUSIONS: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.

Awareness of initiative practice for health in the Chinese population: A questionnaire survey based on a network platform.

BACKGROUND: In 2016, the Chinese government issued the Healthy China 2030 plan, which also produced the initiative practice for health (IPFH) concept. However, people's knowledge and awareness of the IPFH are unclear. AIM: To investigate awareness of IPFH in the Chinese population and explore the relevant influential factors. METHODS: An internet-based self-designed questionnaire survey was used to collect respondents' demographic characteristics and awareness of health and the IPFH from March 26 to April 18, 2020. IPFH consciousness was assessed by the scores for different related questions. The Student's t test, the Chi-square test, and multiple logistic regression analysis were performed to analyze the differences and influencing factors. RESULTS: A total of 2678 valid questionnaires were collected. Of the respondents, 973 (36.3%) had heard of the IPFH concept. In addition, 89.5% of participants agreed with the view that the IPFH is beneficial to improving quality of life, and over half thought that a regular schedule, a reasonable diet, tobacco and alcohol control, a cheerful mood, specific life goals and plans, taking the initiative to accept health-related education and implement health knowledge, good interpersonal relationships, and regular physical examinations were closely related to the IPFH. The majority of respondents paid attention to their health and usually obtained health-related knowledge via social media and were also willing to promote the IPFH. Most of the participants underestimated the role of hospitals, family doctors, and health managers in promoting the IPFH. Age, monthly income, and medical-related work experience were the influencing factors for IPFH awareness. CONCLUSION: The Chinese population has limited knowledge of the IPFH. People with strong IPFH awareness are older, earn more, and have medical-related work experience.

Construction and validation of steroid-induced rabbit osteonecrosis model.

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if appropriate treatment is not given in time. The clinical usage of high-dose steroid is one of the common causes of osteonecrosis. In several studies, the intravenous injection of steroid with or without lipopolysaccharide is the most commonly used strategy to construct osteonecrosis animal model. However, the injection dose, frequency, and interval of steroid and validation of successful model construction lack generally accepted protocol, and the survival and model formation rates are unsatisfactory. We have optimized the construction protocol of osteonecrosis animal model based on the previously reported ones and established a mature animal model of osteonecrosis for future studies.•A rabbit model of osteonecrosis was constructed by multiple injections of high-dose methylprednisolone.•The multidisciplinary biomedical examinations demonstrated the successful construction of osteonecrosis model in the rabbit.

Study on the role of pyroptosis in bone resorption induced by occlusal trauma with or without periodontitis.

BACKGROUND AND OBJECTIVE: Occlusal trauma is considered to be a contributing factor to bone loss associated with inflammatory periodontal disease. We hypothesized that pyroptosis, a recently discovered inflammation-induced programmed cell death pathway, plays a role in occlusal trauma. MATERIALS AND METHODS: The occlusal trauma model was established using a cemented 1-mm elevated computer-aided design and manufacturing (CAD/CAM) metal crown. The periodontitis model was established by periodontal wire ligation with lipopolysaccharide (LPS) injection. The rats were sacrificed at 1, 2, 3, and 4 weeks. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of pyroptosis-, inflammation-, and osteoclast-related markers. Micro-computed tomography (micro-CT) was used to determine bone morphology parameters. Tissue morphology was evaluated using hematoxylin and eosin staining (H&E). Osteoclasts were identified using tartrate-resistant acid phosphatase (TRAP) staining. The expression and distribution of factors related to pyroptosis and inflammation were evaluated by immunohistochemistry (IHC). The colocalization of dead cells and cysteinyl aspartate-specific proteinase-1 (caspase-1)-positive cells was analyzed by immunofluorescence. RESULTS: Quantitative real-time polymerase chain reaction and IHC results showed that occlusal trauma induced the expression of pyroptotic factors during the early stages, while occlusal trauma with periodontitis upregulated the expression of pyroptotic factors at the later stages. The results of qRT-PCR, TRAP staining, and micro-CT showed that occlusal trauma with periodontitis increased the production of proinflammatory cytokines, leading to severe bone loss. Glyburide, an NOD-like receptor pyrin domain containing protein 3 (NLRP3)inhibitor, reduced the expression of pyroptosis markers induced by occlusal trauma with periodontitis and reversed bone resorption. CONCLUSIONS: Pyroptosis was involved in bone loss induced by occlusal trauma with or without periodontitis, while glyburide reversed inflammation and bone resorption.

Evaluating the accuracy of three intraoral scanners using models containing different numbers of crown-prepared abutments.

BACKGROUND/PURPOSE: The scanning accuracy of intraoral scanners' data collection plays a key role in the success of the final treatment. However, few studies start from scanning technology itself to directly evaluate it. The aim of this study was to evaluate the scanning accuracy of three intraoral scanners, to provide a reference for relevant research and clinical applications. MATERIALS AND METHODS: Six types of resin models containing different numbers of crown-prepared abutments were three-dimensionally printed, and a model scanner, as well as three intraoral scanners, were used to digitally scan the six models. The obtained data were uploaded to three-dimensional reverse software for registration and comparison, and the accuracy of the models were analyzed. RESULTS: When scanning the six groups of models, the Omnicam outperformed both the TRIOS and iTero in terms of accuracy in all groups except the second molar group. The TRIOS and iTero scanners also exhibited decreased degrees of accuracy when scanning the long dental arch. The accuracy decreased as the scanning scope increased; however, the Omnicam scanner exhibited a relatively high degree of accuracy when scanning the three-unit fixed bridge and anterior areas. All scanners exhibited the lowest degree of accuracy when scanning the full-arch model. Certain deviations were observed, and the scanning areas at the incisal edges of the anterior teeth and end of the dental arch exhibited relatively large deviations. CONCLUSION: With the model scanner data as reference, the scanning accuracy of the three scanners exhibited differences and certain deviations, which were within clinical tolerance.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.

Biofunctionalized composite scaffold to potentiate osteoconduction, angiogenesis, and favorable metabolic microenvironment for osteonecrosis therapy.

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if no appropriate treatment is performed in time. Core decompression is a general treatment modality for early osteonecrosis. However, effective bone regeneration in the necrotic area is still a significant challenge. This study developed a biofunctionalized composite scaffold (PLGA/nHA30 VEGF) for osteonecrosis therapy through potentiation of osteoconduction, angiogenesis, and a favorable metabolic microenvironment. The composite scaffold had a porosity of 87.7% and compressive strength of 8.9 MPa. PLGA/nHA30 VEGF had an average pore size of 227.6 µm and a water contact angle of 56.5° with a sustained release profile of vascular endothelial growth factor (VEGF). After the implantation of PLGA/nHA30 VEGF, various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment. Additionally, the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30 VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis. The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.

Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study.

Background: Observational studies have identified impaired lung function accessed by forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or the ratio of FEV1 over FVC (FEV1/FVC) as an independent risk factor for atrial fibrillation (AF). However, the result may be affected by confounders or reverse causality. Methods: We performed univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR to jointly estimate the causality of lung function with AF. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, three complementary sensitive analyses approaches including MR-Egger regression, weighted median (WM) MR and Pleiotropy Residual Sum and Outlier (MR-PRESSO) in uvMR as well as mvMR-Egger and mvMR-PRESSO in mvMR were applied to control for pleiotropy. Linkage disequilibrium score (LDSC) regression was applied to estimate genetic correlation between lung function and AF. Results: All forward and reverse uvMR analyses consistently suggested absent causal relations between lung function and AF risk [forward IVW: odds ratio (OR)FEV1 = 1.031, 95% CI = 0.909-1.169, P = 0.630; ORFVC = 1.002, 95% CI = 0.834-1.204, P = 0.982; ORFEV1/FVC = 1.076, 95% CI = 0.966-1.199, P = 0.182; reverse IVW: ORFEV1 = 0.986, 95% CI = 0.966-1.007, P = 0.187; ORFVC = 0.985, 95% CI = 0.965-1.006, P = 0.158; ORFEV1/FVC = 0.994, 95% CI = 0.973-1.015, P = 0.545]. The forward MR-Egger showed that each standard deviation (SD) increase in FEV1/FVC was related to a higher AF risk (OR = 1.502, 95% CI = 1.178-1.915, P = 0.006) without heterogeneity (Q_pval = 0.064), but pleiotropy effect exist (intercept = -0.017, P = 0.012). However, this significant effect disappeared after adjustment of FEV1 and FVC (OR = 1.523, 95% CI = 0.445-5.217, P = 0.503) in mvMR. No evidence was found for independent causal effects of FEV1 and FVC on AF in mvMR analysis by using mvIVW method (ORFEV1 = 0.501, 95% CI = 0.056-4.457, P = 0.496; ORFVC = 1.969, 95% CI = 0.288-13.474, P = 0.490). Notably, the association between lung function and AF were replicated using the FinnGen cohort data. Conclusions: Our findings reported no coheritability between lung function and AF, and failed to find substantial causal relation between decreased lung function and risk of AF. However, lung function and AF were both associated with inflammation, which may be potential pathway, warranting further study.

The role of autophagy in the process of osseointegration around titanium implants with micro-nano topography promoted by osteoimmunity.

Osteoimmunity plays an important role in the process of implant osseointegration. Autophagy is a conservative metabolic pathway of eukaryotic cells, but whether the interaction between autophagy and osteoimmunity plays a key role in osseointegration remains unclear. In this study, we prepared smooth titanium disks and micro-nano topography titanium disks, to study the immune microenvironment of RAW264.7 cells, and prepared the conditioned medium to study the effect of immune microenvironment on the osteogenesis and autophagy of MC3T3-E1 cells. Autophagy inhibitor 3-MA was used to inhibit autophagy to observe the change of expression of osteogenic markers. The results showed that the micro-nano topography titanium disks could stimulate RAW264.7 cells to differentiate into M2 type, forming an anti-inflammatory immune microenvironment; compared with the control group, the anti-inflammatory immune microenvironment promoted the proliferation and differentiation of osteoblasts better. The anti-inflammatory immune environment activated the autophagy level of osteoblasts, while the expression of osteogenic markers was down-regulated after inhibition of autophagy. These results indicate that anti-inflammatory immune microenvironment can promote cell proliferation and osteogenic differentiation, autophagy plays an important role in this process. This study further explains the mechanism of implant osseointegration in osteoimmune microenvironment, and provides reference for improving implant osseointegration.

Mechanism of Exosomes Involved in Osteoimmunity Promoting Osseointegration Around Titanium Implants With Small-Scale Topography.

Exosomes are nanoscale extracellular vesicles. Several studies have shown that exosomes participate in intercellular communication and play a key role in osseointegration. However, it is unclear whether exosomes and their contents participate in the communication between the immune and skeletal systems in the process of osseointegration. In this study, we obtained smooth titanium disks by polishing and small-scale topography titanium disks by sandblasted large-grit acid-etched (SLA) technology combined with alkali thermal reaction. After stimulating mouse RAW264.7 cells with these two kinds of titanium disks, we co-cultured the MC3T3-E1 cells and the RAW264.7 cells, obtained and identified the exosomes derived from RAW264.7 cells, and studied the effect of the osteoimmune microenvironment and the exosomes on the osseointegration of mouse MC3T3-E1 cells. Cell counting kit-8 (CCK-8), real time quantitative PCR, western blotting, alizarin red staining, and quantitative and confocal fluorescence microscopy were used to study the effects of exosomes on MC3T3-E1 cells; RNA sequencing and correlation analysis were performed. We found that the osteoimmune microenvironment could promote the osseointegration of MC3T3-E1 cells. We successfully isolated exosomes and found that RAW264.7 cell-derived exosomes can promote osteogenic differentiation and mineralization of MC3T3-E1 cells. Through RNA sequencing and gene analysis, we found differentially expressed microRNAs that targeted the signal pathways that may be related, such as mTOR, AMPK, Wnt, etc., and thus provide a reference for the mechanism of osteoimmunue regulation of implant osseointegration. The study further elucidated the mechanism of implant osseointegration and provided new insights into the effect of exosomes on implant osseointegration, and provided reference for clinical improvement of implant osseointegration and implant success rate.

Effect of the immune responses induced by implants in a integrated three-dimensional micro-nano topography on osseointegration.

In order to explore the abilities of an integrated three-dimensional micro-nano topography in immunomodulation and promoting bone formation, present study focuses on the titanium sheets used in the micro-nano topography by treating them with the sandblasted, large-grit and acid-etched (SLA)and alkaline thermal reaction. Further, we characterized and obtained the surface morphology, roughness, and hydrophilicity of the titanium sheets. Moreover, we detected their in vitro cytocompatibility and cell proliferation as well. In addition, investigation was carried out for the immunomodulatory ability of the titanium sheets in a micro-nano topography by observing the expression of M1 (classical activated macrophage) and M2 (alternatively activated macrophage) type marker factors, inflammatory factors, and morphological changes of RAW264.7 cells cultured on the titanium sheets in different topographies. Through cell migration experiments and coculture, we observed the effects of different titanium sheet immune environments on osteoblast migration, extracellular matrix mineralization, and osteoblast gene expression. These results showed that the micro-nano topography constructed through SLA and alkaline thermal treatment improved the hydrophilicity and promoted the cell proliferation. Moreover, it promoted RAW264.7 cells to polarize as M2 phenotype, thereby leading to the anti-inflammatory effect of local microenvironments. This facilitated osteoblasts to secrete bone morphogenetic protein-2 (BMP2) and vascular endothelial growth factor. Nonetheless, these findings provided a theoretical basis for the molecular biological mechanism related to implants in a micro-nano topography which promoted the osteointegration while offering a meaningful theoretical basis for the clinical treatment of such implants.

Correlation between clinical parameters of crown and gingival morphology of anterior teeth and periodontal biotypes.

BACKGROUND: In this study, we conducted a quantitative analysis of the clinical parameters of crown and gingival morphology (CGM) of the maxillary anterior teeth (MAT). We also analyzed the correlation of these parameters with periodontal biotype (PB), with a view to providing objective standards for PB diagnosis. METHODS: The three-dimensional (3D) maxillary digital models of 56 individuals were obtained using an intra-oral scanner. The following parameters were measured with the SpaceClaim software: gingival angle (GA), papilla width (PW), papilla height (PH), crown length (CL), crown width (CW), crown width/crown length ratio (CW/CL), bucco-lingual width of the crown (BLW), contact surface width (CSW), and contact surface height/crown length ratio (CS/CL). The PB were determined based on the transparency of the periodontal probe through the gingival sulcus. Independent factors influencing PB were analyzed by logistic regression, and the optimal cutoff values for the independent influencing factors were analyzed using receiver operating characteristic curves (ROC curves). RESULTS: There was no significant difference in the parameters of CGM of the MAT at the left and right sides. The thick biotype accounted for 69.6%, and the parameters of GA, PW, PH, CW, CW/CL and CS/CL were significantly correlated with PB (P ≤ 0.2). GA (odds ratio (OR) = 1.206) and PW (OR = 5.048) were identified as independent predictive factors of PB, with areas under the ROC curve (AUC) of 0.807 and 0.881, respectively, and optimal cutoff values of 95.95° and 10.01 mm, respectively. CONCLUSION: The CGMs of the MAT at the left and right side are symmetrical. The thin biotype accounts for a small proportion, and GA and PW are independent influencing factors of PB. GA of 95.95° and PW of 10.01 mm are the optimal cutoff values for categorization of individuals as thick biotype. This indicates that when the GA and PW of the right maxillary central incisor are G ≥ 95.95° and ≥ 10.01 mm, respectively, there is a higher probability that these individuals will be categorized as thick biotype.

Verification of osteoblast differentiation on airborne-particle abrasion, large-grit, acid-etched surface of titanium implants regulated by yes-associated protein and transcriptional coactivator with PDZ-binding motif.

Although airborne-particle abrasion, large-grit, acid-etched (SLA) surface technology can promote implant osseointegration; its mechanism remains unclear. By preparing the SLA titanium (Ti) plate (SLA Ti) and Polished Ti plate (Polished Ti), this experiment investigates the expression and distribution of the Yes-associated protein (YAP) and transcriptional coactivator with the PDZ-binding motif (TAZ) in MC3T3-E1 cells. In addition, gene YAP and TAZ silencing on the SLA Ti was conducted to observe changes in the osteoblast differentiation markers, runt-related transcription factor-2 (Runx2) and bone sialoprotein (BSP). The results demonstrated that SLA Ti surface microtopography could induce YAP/TAZ's transfer from the cytoplasm to the nuclei of MC3T3-E1 cells. The expression of YAP/TAZ increased in terms of mRNA and protein. After silencing the YAP/TAZ genes, Runx2 and BSP decreased, suggesting that YAP/TAZ plays an important regulatory role in this process. Meanwhile, the results also showed that SLA microtopography enhanced the expression of integrins α1, α2, and ß1. After silencing the integrin α1, α2, and ß1 genes, YAP and TAZ decreased in terms of mRNA and protein. Therefore, this experiment was the first to confirm that SLA surface microtopography facilitates osteoblast differentiation by regulating YAP/TAZ and confirms that the process can be related to integrins α1, α2, and ß1.

Peroxisome proliferator-activated receptor gamma participates in the acquisition of brain ischemic tolerance induced by ischemic preconditioning via glial glutamate transporter 1 in vivo and in vitro.

Glial glutamate transporter 1 (GLT-1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further explained. The aim of this study was to investigate whether peroxisome proliferator-activated receptor gamma (PPARγ) participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPARγ and GLT-1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPARγ was also increased. At the same time, the up-regulation of PPARγ expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPARγ and glial fibrillary acidic protein. Then, the mechanism by which PPARγ regulates GLT-1 was studied in rat cortical astrocyte-neuron cocultures. We found that IPC [45 min of oxygen glucose deprivation (OGD)] protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPARγ occurred earlier than the up-regulation of GLT-1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPARγ antagonist T0070907 or PPARγ siRNA significantly attenuated GLT-1 up-regulation and the neuroprotective effects induced by IPC in vitro. Finally, the effect of the PPARγ antagonist on GLT-1 expression and BIT was verified in vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose-dependently attenuated the up-regulation of GLT-1 and BIT induced by cerebral IPC in rats. In conclusion, PPARγ participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Cover Image for this issue: doi: 10.1111/jnc.14532. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.

One-year effect of wearing orthokeratology lenses on the visual quality of juvenile myopia: a retrospective study.

OBJECTIVE: To study the one-year effect of wearing orthokeratology (OK) lenses on the visual quality of juvenile myopia. METHODS: The right eyes of 36 juvenile myopias were retrospectively studied in this work. Q-value, e-value, corneal curvature, strehl ratio (SR), modulation transfer function (MTF) and wavefront aberration (WA) were compared before and at 1, 3 and 12 months after wearing OK lenses. The SR, MTF and WA of cornea, internal optic and ocular were analyzed separately. The spherical and cylinder diopter, vision acuity, compensating factor (CF) and compensative rate (CF%) were compared before and at 12 months after wearing OK lenses. RESULTS: (1) The vision of LogMAR increased and the corneal curvature decreased significantly after wearing OK lenses. There was no significant difference for the e-value before and after wearing OK lenses. The Q-value increased at 1 month but decreased at 3 and 12 months remarkably. (2) The ocular and internal optic SR and MTF increased significantly at 1 month and then remained stable. The MTF in different spacial frequencies increased after wearing OK lenses. There was no significant difference for the corneal SR before and after wearing OK lenses, and the corneal MTF decreased significantly after wearing OK lenses. (3) For the ocular, the total higher order aberration (HOA), spherical, coma and trefoil aberrations increased, and the total aberration, total lower order aberration (LOA) and defocus aberration decreased obviously except astigmatism. The corneal aberrations increased significantly after wearing OK lenses except astigmatism. For the internal optic, the total aberration, total LOA and defocus aberration decreased, and the total HOA, coma and trefoil aberration increased significantly except the astigmatism and spherical aberrations. (4) The CF and CF% of total aberration, total LOA, total HOA and coma aberrations increased, and those of astigmatism and spherical decreased at 12 months. CONCLUSIONS: Orthokeratology is effective in correcting the refractive error and improving the vision quality of juvenile myopia over the one-year follow-up period.