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Abstract A large-scale, high-speed, long-runout landslide occurred in Xinmo Village, Maoxian, Sichuan Province, China, on June 24, 2017. It was characterized by fast sliding speed, rapid volume growth, and large impact area. The dynamic process of such landslides and the influence of erosion on the dynamic process are studied by field investigation, numerical inversion and simulation. The results showed that entrainment erosion was a major factor of landslide volumetric change and a salient feature of the landslide process. An exponential equation relating the erosion rate and the deposition volume was established. Moreover, the study found that a slight change of the erosion rate (1e-4) also had a significant impact on the lateral spreading, longitudinal runout, and vertical erosion. As the erosion rate increased, the lateral spreading, longitudinal runout, and vertical erosion of this type of landslide became more obvious. By using the coefficient of variation method, it was obtained that the erosion rate had a greater influence on the vertical erosion than on the lateral spreading and longitudinal runout. In the study of the velocity of the rock avalanche under different erosion conditions, it was found that the erosion amount and the landslide velocity were not strictly linearly related. This study has important significance for understanding the dynamic process and erosion effect of rock avalanche, and provides useful references and insights for future research in related fields.

Abstract Currently, due to limited long-term evidence, there remains some controversy surrounding the recommended postoperative monitoring strategy for primary low-risk gastrointestinal stromal tumors (GISTs). This study recruited a total of 532 patients diagnosed with very low-risk and low-risk GISTs who underwent endoscopic resection from 2015 to 2021, including 460 very low-risk patients and 72 low-risk patients. Descriptive statistical analysis was used to evaluate the clinical and pathological characteristics of GIST patients, and Kaplan–Meier methods were employed for survival analysis. The results showed that the 5-year recurrence-free survival rates for very low-risk and low-risk patients were 98.5% and 95.9%, respectively. The 5-year disease-specific survival rates for both groups were 100%. Additionally, the 5-year overall survival rates were 99.7% for very low-risk patients and 100% for low-risk patients (P = 0.69). Therefore, it is suggested that routine follow-up monitoring, including endoscopic surveillance and imaging, may not be necessary for very low-risk and low-risk GISTs after endoscopic resection.

Src-homology region 2 domain-containing phosphatase 1 (SHP-1) is considered an anti-inflammatory factor, but its role in chronic obstructive pulmonary disease (COPD) remains unknown. Herein, overexpression of SHP-1 was utilized to explore the functions of SHP-1 in COPD models established by stimulating 16HBE cells with cigarette smoke extracts (CSE) in vitro. SHP-1 was downregulated in both COPD patients and CES-treated 16HBE cells. SHP-1 overexpression reinforced cell viability and significantly prevented CSE-induced cell apoptosis in 16HBE cells. Furthermore, SHP-1 overexpression greatly reversed the CSE-induced migration, epithelial–mesenchymal transition (EMT), and pro-inflammatory factor production in 16HBE cells. In addition, CSE activated the P65 and PI3K/AKT pathways in 16HBE cells, which was also reversed by SHP-1 overexpression. Our findings indicated that SHP-1 alleviated CSE-induced EMT and inflammation in 16HBE cells, suggesting that SHP-1 regulated the development of COPD, and these functions may be linked to the inhibition of the PI3K/AKT pathway.

The standardized workflow of computer-aided static guided implant surgery includes preoperative examination, data acquisition, guide design, guide fabrication and surgery. Errors may occur at each step, leading to irreversible cumulative effects and thus impacting the accuracy of implant placement. However, clinicians tend to focus on factors causing errors in surgical operations, ignoring the possibility of irreversible errors in nonstandard guided surgery. Based on the clinical practice of domestic experts and research progress at home and abroad, this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection, data collection, guide designing and manufacturing and describes strategies to resolve errors so as to gain expert consensus. Consensus recommendation: 1. Preoperative considerations: the appropriate implant guide type should be selected according to the patient's oral condition before surgery, and a retaining screw-assisted support guide should be selected if necessary. 2. Data acquisition should be standardized as much as possible, including beam CT and extraoral scanning. CBCT performed with the patient’s head fixed and with a small field of view is recommended. For patients with metal prostheses inside the mouth, a registration marker guide should be used, and the ambient temperature and light of the external oral scanner should be reasonably controlled. 3. Optimization of computer-aided design: it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers. Properly designing the retaining screws, extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors. 4. Improving computer-aided production: it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postprocessing procedures.

Autophagy, a process that isolates intracellular components and fuses them with lysosomes for degradation, plays an important cytoprotective role by eliminating harmful intracellular substances and maintaining cellular homeostasis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity for self-renewal that can give rise to a subset of tissues and therefore have potential in regenerative medicine. However, a variety of variables influence the biological activity of MSCs following their proliferation and transplantation in vitro. The regulation of autophagy in MSCs represents a possible mechanism that influences MSC differentiation properties under the right microenvironment, affecting their regenerative and therapeutic potential. However, a deeper understanding of exactly how autophagy is mobilized to function as well as clarifying the mechanisms by which autophagy promotes MSCs differentiation is still needed. Here, we review the current literature on the complex link between MSCs differentiation and autophagy induced by various extracellular or intracellular stimuli and the molecular targets that influence MSCs lineage determination, which may highlight the potential regulation of autophagy on MSCs’ therapeutic capacity, and provide a broader perspective on the clinical application of MSCs in the treatment of a wide range of diseases.

The standardized workflow of computer-aided static guided implant surgery includes preoperative examination, data acquisition, guide design, guide fabrication and surgery. Errors may occur at each step, leading to irreversible cumulative effects and thus impacting the accuracy of implant placement. However, clinicians tend to focus on factors causing errors in surgical operations, ignoring the possibility of irreversible errors in nonstandard guided surgery. Based on the clinical practice of domestic experts and research progress at home and abroad, this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection, data collection, guide designing and manufacturing and describes strategies to resolve errors so as to gain expert consensus. Consensus recommendation: 1. Preoperative considerations: the appropriate implant guide type should be selected according to the patient's oral condition before surgery, and a retaining screw-assisted support guide should be selected if necessary. 2. Data acquisition should be standardized as much as possible, including beam CT and extraoral scanning. CBCT performed with the patient’s head fixed and with a small field of view is recommended. For patients with metal prostheses inside the mouth, a registration marker guide should be used, and the ambient temperature and light of the external oral scanner should be reasonably controlled. 3. Optimization of computer-aided design: it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers. Properly designing the retaining screws, extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors. 4. Improving computer-aided production: it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postprocessing procedures.

ObjectiveTo investigate the current status and influencing factors of hand hygiene practices among primary healthcare workers， and to provide a reference for improving hand hygiene behavior in primary healthcare institutions.MethodsA self-designed questionnaire was used to conduct a survey among medical staff of seven community health service centers in Jiading District， Shanghai， using a cluster random sampling method. The data collected were subjected to descriptive statistics， reliability and validity tests， correlation analysis， and structural equation model fitting.ResultsA statistical difference in hand hygiene compliance was found among medical staff with varying occupational types and educational levels （P

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

Abstract Helicobacter pylori (H. pylori) is a major risk factor of gastric cancer (GC). The SUMO-activating enzyme SAE1(SUMO-activating enzyme subunit 1), which is indispensable for protein SUMOylation, involves in human tumorigenesis. In this study, we used the TIMER and TCGA database to explore the SAE1 expression in GC and normal tissues and Kaplan–Meier Plotter platform for survival analysis of GC patients. GC tissue microarray and gastric samples from patients who underwent endoscopic treatment were employed to detect the SAE1expression. Our results showed that SAE1 was overexpressed in GC tissues and higher SAE1 expression was associated with worse clinical characteristics of GC patients. Cell and animal models showed that H. pylori infection upregulated SAE1, SUMO1, and SUMO2/3 protein expression. Functional assays suggested that suppression of SAE1 attenuated epithelial-mesenchymal transition (EMT) biomarkers and cell proliferation abilities induced by H. pylori. Cell and animal models of ROS inhibition in H. pylori showed that ROS could mediate the H. pylori-induced upregulation of SAE1, SUMO1, and SUMO2/3 protein. RNA sequencing was performed and suggested that knockdown of SAE1 could exert an impact on IGF-1 expression. General, increased SUMOylation modification is involved in H. pylori-induced GC.

With the transformation of medical philosophy, palliative care has become a fundamental component of end-of-life care for patients with life-threatening illnesses, meanwhile ethical issues involved in palliative care are becoming more prominent. This article, through a comprehensive review of both domestic and international ethical research, articulates five crucial ethical issues inherent to palliative care: truth-telling, advance care planning, the use of life-sustaining interventions, palliative sedation, and the relationship between euthanasia, assisted dying, and palliative care. The objective is to offer an ethical perspective for palliative care, help professionals in palliative care to address the critical ethical issues in practice, improve the quality of care for patients and their families, and to inform the development of related legal, regulatory, and policy frameworks.

Background Alcohol drinking among adolescents is associated with their health development. However, the prevalence of alcohol drinking among adolescents in Southwestern China remains largely unexplored. This study aimed to investigate the prevalence of alcohol drinking, with a particular focus on gender differences, among primary and middle school students in Zigong, a city in Southwestern China. Additionally, we examined the association between alcohol consumption and demographic and family factors.Methods A school-based cross-sectional survey was conducted in a city in Southwestern China, encompassing a total of 89 360 students from 132 different ordinary schools, including both primary and middle schools. Participants were recruited through cluster sampling. The Alcohol Use Disorders Identification Test Consumption was employed to assess alcohol consumption. Gender differences in the prevalence of alcohol drinkers across various schools and grades were analysed. Multivariable logistic regression analysis was used to investigate factors associated with hazardous drinking.Results Out of the 89 360 participants, 19.0% reported alcohol drinking, with 2.1% classified as hazardous drinkers. There was a higher prevalence of alcohol drinking among boys compared with girls, as well as hazardous drinking. There were significant gender disparities in alcohol drinking observed across various schools and grade levels. A notable divergence between boys and girls was observed starting from grade 10, with a rising prevalence of hazardous drinking among boys and a decline among girls. Additionally, older age, male gender and being left-behind children were identified as risk factors for hazardous drinking, while belonging to a nuclear family and having parents who do not drink were protective factors against hazardous drinking.Conclusions Alcohol consumption is prevalent among Chinese adolescents, with some even classified as hazardous drinkers. These findings may offer valuable insights for policymakers and caregivers, guiding them in formulating appropriate interventions and support strategies.

Abstract Background Apolipoprotein F (APOF) has been less studied in cancers. Thus, we aimed to perform a pan-cancer analysis of the oncogenic and immunological effects of APOF on human cancer. Methods A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R (version 3.6.3) and its suitable packages. Results Overall, we found that the common cancers differentially expressed between tumor and normal samples and prognostic-associated were BRCA, PRAD, KIRP, and LIHC in terms of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The pan-cancer Spearman analysis showed that the mRNA expression of APOF was negatively correlated with four tumor stemness indexes (DMPss, DNAss, ENHss, and EREG-METHss) with statistical significance for PRAD and was positively correlated for LIHC. In terms of BRCA and PRAD patients, we found negative correlation of APOF with TMB, MSI, neo, HRD and LOH. The mutation frequencies of BRCA and LIHC were 0.3%. APOF expression was negatively correlated with immune infiltration and positively correlated with tumor purity for PRAD patients. The mRNA expression of APOF was negatively associated with most TILs for LIHC, B cells, CD4+ T cells, neutrophils, macrophages and dendritic cells, but was positively associated with CD8+ T cells. Conclusions Our pan-cancer study offered a relatively comprehensive understanding of the roles of APOF on BRCA, PRAD, KIRP, and LIHC.

AbstractBackground The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods.Methods An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis.Results A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18–1.77, p 37.23 ng/mL (OR: 2.11, 95% CI: 1.50–2.97, p 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93–3.30, p 5.7 pmol/L (OR: 1.96, 95% CI: 1.48–2.60, p

In 2018, the concept of 'resuscitation center' was officially introduced in China. The 'resuscitation center' refers to a special system established by medical institutions for cardiac arrest patients, which covers the entire process from prevention to emergency care, monitoring, treatment, and rehabilitation of cardiac arrest. Integrating various medical resources and optimizing the whole process helps provide high-quality care for patients, with the best possible resuscitation outcome. The construction of the resuscitation center is an indispensable need for high-quality emergency medical services, an important initiative for hospitals to promote multidisciplinary development, especially emergency medicine, and an important grasp for hospitals to improve their management capabilities. It aims to deepen and upgrade the traditional emergency medical system, and explore higher quality treatment models and processes for the most urgent emergencies. The construction of a resuscitation center first requires a consensus and active voice from the emergency medicine community before it gradually expands from a regional pilot to a nationwide program with the support of the health administration.

Abstract Background Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. Methods Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Results We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p

Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibit the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

Ten–eleven translocation 3 (TET3) participates in tumorigenesis and malignant transformation by mediating DNA demethylation and specific gene activation in malignances. This study aims to elucidate its molecular function and regulatory mechanism in esophageal squamous cell carcinoma (ESCC). Stable ESCC cells that infected with TET3 overexpression (OE) and knockdown lentiviral vector had been established. The biological behaviors and molecular mechanism of TET3 were demonstrated by cell biology experiments in vitro and in vivo. Tissues from patients with ESCC were used to demonstrate the clinical value of TET3. Our findings revealed that TET3 is highly expressed in ESCC tissues and related to poor prognosis of patients with ESCC. OE of TET3 presented a significant effect on proliferation, metastatic potential, and spheroid formation of ESCC cells by activating the PI3K/AKT/GSK3β/β-catenin axis. Knockdown of TET3 could remarkably reverse these malignant phenotypes. Patients with ESCC with high TET3 expression resulted in a shorter overall survival (OS) and disease-free survival. Based on the multivariate analysis, TET3 could be an independent favorable factor for predicting OS and recurrence. The high expression of TET3 not only aggravates malignant behaviors in vitro and in vivo but also becomes a novel biomarker for clinical monitoring and individualized precision treatment for patients with ESCC.

Abstract Background Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa. Methods We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages. Results We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50–23.93, p

Airway management is a basic skill for emergency doctors. Difficult airways are one of the most important challenges. In 2022, the American Association of anesthesiologists published the fourth edition of guideline on the management of difficult airways, which provided us with the latest evidence-based medicine about the definition, evaluation, preparation, management and extubation of difficult airways. To improve the status of airway management of emergency doctors in China, this paper interprets the key points and updates the contents of the guidelines from the perspective of emergency medicine.

Abstract Although cyanide’s biological effects are pleiotropic, its most obvious effects are as a metabolic poison. Cyanide potently inhibits cytochrome c oxidase and potentially other metabolic enzymes, thereby unleashing a cascade of metabolic perturbations that are believed to cause lethality. From systematic screens of human metabolites using a zebrafish model of cyanide toxicity, we have identified the TCA-derived small molecule glyoxylate as a potential cyanide countermeasure. Following cyanide exposure, treatment with glyoxylate in both mammalian and non-mammalian animal models confers resistance to cyanide toxicity with greater efficacy and faster kinetics than known cyanide scavengers. Glyoxylate-mediated cyanide resistance is accompanied by rapid pyruvate consumption without an accompanying increase in lactate concentration. Lactate dehydrogenase is required for this effect which distinguishes the mechanism of glyoxylate rescue as distinct from countermeasures based solely on chemical cyanide scavenging. Our metabolic data together support the hypothesis that glyoxylate confers survival at least in part by reversing the cyanide-induced redox imbalances in the cytosol and mitochondria. The data presented herein represent the identification of a potential cyanide countermeasure operating through a novel mechanism of metabolic modulation.

Splenic artery aneurysm (SAA) is a rare condition; however, it is one of the most common intra-abdominal aneurysm. In the emergency department (ED), due to an uncommon cause of shock and syncope in SAA, it poses great diagnostic challenge for emergency physicians. Here we reported a case of spontaneous rupturing of SAA. A 47-year-old man presented to the ED for syncope and shock. As he had unstable hemodynamic, we gave him fluid resuscitation and point-of-care ultrasound (POCUS), free intraperitoneal fluid was identified on ultrasound, then hemorrhagic ascites was identified by a diagnostic abdominal paracentesis. The rare but life-threatening diagnosis of spontaneous rupturing of SAA was confirmed by contrast-enhanced Computed Tomography and surgery. Spontaneous SAA rupturing is a rare fatal condition which needs immediate diagnosis and management to achieve a favorable outcome. Though there are no risk factors, emergency physicians should consider SAA in the differential diagnosis of sudden collapse. Also, as an emergency physician, it is very important to be a master of first aid skills such as POCUS and treat patients according to the process.

Since June 2020, the re-emergence of coronavirus disease 2019 (COVID-19) epidemics in parts of China was linked to the cold chain, which attracted extensive attention and heated discussions from the public. According to the typical characteristics of these epidemics, we speculated a possible route of transmission from cold chain to human. A series of factors in the supply chain contributed to the epidemics if the cold chain were contaminated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as temperature, humidity, personal hygiene/protection, and disinfection. The workers who worked in the cold chain at the receiving end faced a higher risk of being infected when they were not well protected. Facing the difficult situation, China put forward targeted and powerful countermeasures to block the cold chain-related risk. However, in the context of the unstable pandemic situation globally, the risk of the cold chain needs to be recognized and evaluated seriously. Hence, in this review, we reviewed the cold chain-related epidemics in China, analyzed the possible mechanisms, introduced the Chinese experience, and suggested coping strategies for the global epidemic prevention and control.

COVID-19 highlights the lack of interdisciplinary medical talents. The international history of medical education shows the urgent need of high-level interdisciplinary medical talents. Anchoring the goal to develop a global center of talents and highland of innovation, this article takes medical education of Zhejiang University as an example, focusing on and exploring the training mode of high-level interdisciplinary medical talents in the new era. It includes: firstly, optimizing the training mode of eight-year program for medical doctors with non-medical bachelor degree followed with complete education for a medical doctorate that innovates the curriculum system of clinical medicine; secondly, creating the training system of postdoctor of clinical medicine and integrating medical resources that include high-quality talents and health care system, in order to build a high-quality teaching staff with a interdisciplinarity background and innovative bases. It not only strengthens the residents' competency and frontier creativity, but also ensures the sustainable development of interdisciplinary medical talents. The reform of training mode, curriculum system, teaching staff and clinical teaching bases all contribute to the goal of building a country with interdisciplinary talents that serve the frontier of science and technology in the world, the major needs of the country and people's health in the new era.

It is of great significance to identify the pest species accurately and control it effectively to reduce the loss of agricultural products. The research results of this project will provide theoretical basis for preventing and controlling the spread of pests and reducing the loss of agricultural products, and have important practical significance for improving the quality of agricultural products and increasing the output of agricultural products. At the same time, it provides a kind of effective prevention and control measures for farmers, so as to ensure the safety and health of crops. Because of the slow speed and high cost of manual identification, it is necessary to establish a set of automatic pest identification system. The traditional image-based insect classifier is mainly realized by machine vision technology, but because of its high complexity, the classification efficiency is low and it is difficult to meet the needs of applications. Therefore, it is necessary to develop a new automatic insect recognition system to improve the accuracy of insect classification. There are many species and forms of insects, and the field living environment is complex. The morphological similarity between species is high, which brings difficulties to the classification of insects. In recent years, with the rapid development of deep learning technology, using artificial neural network to classify pests is an important method to establish a fast and accurate classification model. In this work, we propose a novel convolutional neural network-based model (MSSN), which includes attention mechanism, feature pyramid, and fine-grained model. The model has good scalability, can better capture the semantic information in the image, and achieve more accurate classification. We evaluated our approach on a common data set: large-scale pest data set, PlantVillage benchmark data set, and evaluated model performance using a variety of evaluation indicators, namely, macro mean accuracy (MPre), macro mean recall rate (MRec), macro mean F1-score (MF1), Accuracy (Acc) and geometric mean (GM). Experimental results show that the proposed algorithm has better performance and universality ability than the existing algorithm. For example, on the data set, the maximum accuracy we obtained was 86.35%, which exceeded the corresponding technical level. The ablation experiment was conducted on the experiment itself, and the comprehensive evaluation of the complete MSSN(scale 1+2+3) was the best in various performance indexes, demonstrating the feasibility of the innovative method in this paper.

Abstract Cellular senescence is a stable cell cycle arrest that normal cells undergo after a finite number of divisions, in response to a variety of intrinsic and extrinsic stimuli. Although senescence is largely established and maintained by the p53/p21WAF1/CIP1 and pRB/p16INK4A tumour suppressor pathways, the downstream targets responsible for the stability of the growth arrest are not known. We have employed a stable senescence bypass assay in conditionally immortalised human breast fibroblasts (CL3EcoR) to investigate the role of the DREAM complex and its associated components in senescence. DREAM is a multi-subunit complex comprised of the MuvB core, containing LIN9, LIN37, LIN52, LIN54, and RBBP4, that when bound to p130, an RB1 like protein, and E2F4 inhibits cell cycle-dependent gene expression thereby arresting cell division. Phosphorylation of LIN52 at Serine 28 is required for DREAM assembly. Re-entry into the cell cycle upon phosphorylation of p130 leads to disruption of the DREAM complex and the MuvB core, associating initially to B-MYB and later to FOXM1 to form MMB and MMB-FOXM1 complexes respectively. Here we report that simultaneous expression of MMB-FOXM1 complex components efficiently bypasses senescence with LIN52, B-MYB, and FOXM1 as the crucial components. Moreover, bypass of senescence requires non-phosphorylated LIN52 that disrupts the DREAM complex, thereby indicating a central role for assembly of the DREAM complex in senescence.

Abstract De novo transcriptome assembly from billions of RNA-seq reads is very challenging due to alternative splicing and various levels of expression, which often leads to incorrect, mis-assembled transcripts. BayesDenovo addresses this problem by using both a read-guided strategy to accurately reconstruct splicing graphs from the RNA-seq data and a Bayesian strategy to estimate, from these graphs, the probability of transcript expression without penalizing poorly expressed transcripts. Simulation and cell line benchmark studies demonstrate that BayesDenovo is very effective in reducing false positives and achieves much higher accuracy than other assemblers, especially for alternatively spliced genes and for highly or poorly expressed transcripts. Moreover, BayesDenovo is more robust on multiple replicates by assembling a larger portion of common transcripts. When applied to breast cancer data, BayesDenovo identifies phenotype-specific transcripts associated with breast cancer recurrence.

Abstract In quantitative PCR research, appropriate reference genes are key to determining accurate mRNA expression levels. In order to screen the reference genes suitable for detecting gene expression in tissues of the reproductive axis, a total of 420 (males and females = 1:5) 3-year-old Magang geese were selected and subjected to light treatment. The hypothalamus, pituitary and testicular tissues were subsequently collected at different stages. Ten genes including HPRT1, GAPDH, ACTB, LDHA, SDHA, B2M, TUBB4, TFRC, RPS2 and RPL4 were selected as candidate reference genes. The expression of these genes in goose reproductive axis tissues was detected by real-time fluorescent quantitative PCR. The ΔCT, geNorm, NormFinder and BestKeeper algorithms were applied to sort gene expression according to stability. The results showed that ACTB and TUBB4 were the most suitable reference genes for the hypothalamic tissue of Magang goose in the three breeding stages; HPRT1 and RPL4 for pituitary tissue; and HPRT1 and LDHA for testicular tissue. For all three reproductive axis tissues, ACTB was the most suitable reference gene, whereas the least stable reference gene was GAPDH. Altogether, these results can provide references for tissue expression studies in geese under light treatment.

In recent years, many researchers have devoted themselves to the application of photodynamic therapy (PDT) in root canal disinfection, as conventional root canal disinfection methods have failed to achieve the optimal effect. Some clinicians have also applied PDT to root canal disinfection. PDT is expected to have a better effect than traditional root canal disinfection. This paper reviews the research progress on the mechanism, effect, influencing factors and limitations of PDT in root canal disinfection. Current research suggests that differences in the type and status of the bacteria, photosensitizers, light sources, operating environment and methods all affect the efficacy of root canal disinfection of PDT. Most of the research into PDT for root canal disinfection finds that it is effective, nontoxic, advantageous to dental pulp regeneration and comfortable for the patient, as well as lacking an excitant; however, its bactericidal effect is inferior to that of sodium hypochlorite. At present, it cannot replace traditional chemical washing but is a promising auxiliary method. The design of the photosensitizer, the energy dose of the light source and the optimal irradiation time need to be determined by further experiments, and more clinical verification is needed before its application in root canal therapy.

With the rapid development of implant technology, implant restoration is a conventional treatment option for adult patients with tooth loss. Severe dental lesions, trauma, tumors, abnormal development and other reasons can cause dental defects and even dentition loss in children and adolescents. There has been hesitation to perform implant therapy for growing children because of the growth period; thus, little is known about the outcomes of the osseointegration procedure in young patients. Therefore, this article reviews the current literature to discuss the use of dental implants in children and adolescents. According to current studies, orthodontic treatment or transitional restoration should be undertaken based on the characteristics of the children and adolescents. Implant surgery should be performed after the end of the peak growth period. For patients with severe dentition defects, relevant criteria should be established before implant surgery to evaluate the effect of implant therapy in children and adolescents. The patients should be treated with a multidisciplinary, staged and long-term treatment approach. Most of the recent literature consists of case reports and short-term studies. There is an urgent need for more studies in this field with long-term follow-up.

The crown-root ratio (C/R) theory of natural teeth has been widely recognized in the field of stomatology,and has important clinical significance in predicting and assessing the prognosis of natural teeth as well as for abutment selection during denture restoration. In the past few decades, scholars have advocated for the implantation of implants as long in length as possible to improve the success rate according to the theory of crown-root ratio of natural teeth. However, with the application of short implants, our philosophy of implantation has changed, and the relationship between the crown-implant (C/I) ratio and complications has become one of the current research hotspots. In this paper, the concept of the crown-implant ratio, the research progress of the C/I ratio, the implant survival rate and clinical complications of implant restoration were reviewed and summarized, and the following suggestions were put forward: although most studies have shown no significant correlation between the C/I ratio and implant survival or marginal bone loss, this relationship may increase the risk of mechanical complications. A C/I < 3 and a crown length < 15 mm are recommended in implant restoration; when ultra-short implants are applied, the implant system can increase the bone-to-implant contact area, and splint prostheses such as crown or bridge are recommended.

Schizophrenia is a common disease characterized by thinking obstructions and accompanied by cognitive, emotional and behavioral disorders. Under the control of psychiatric symptoms, patients with schizophrenia may self-injure or impulsively wound others, resulting in public risk and increase in the burden of family and society. In recent years, many studies have shown that the violent behavior of patients with schizophrenia is related to genetic factors. This article reviews the research progress on the relationship between genetic polymorphism and violent behavior of patients with schizophrenia, analyzes the possible mechanism of the correlation between the two, puts forward the limitations of current research and the directions of future research, and provides scientific basis for risk assessment and prevention of violent behavior of patients with schizophrenia.

Posttreatment disease is a difficult clinical problem. Periradicular surgery is an important and effective method for cases that cannot be resolved by root canal therapy. In recent years, with the application of microscope for oral surgery and the development of microsurgical instruments, microsurgery in endodontics has reduced treatment trauma compared to traditional periradicular surgery and further improved the success rate of clinical treatment. However, as an invasive surgical method, the indications and timing of microsurgery in endodontics should be strictly defined for clinical applications. This paper reviews the literature on this important issue and discusses it with regard to the clinical experience of the author′s team. Explaining the effective root canal retreatment and good coronary closure are the primary considerations when posttreatment disease occurs. When root canal retreatment fails or cannot be completed after the initial treatment, the anatomical factors, lesion extent and periodontal lesion combination should be fully considered, and the microsurgery treatment strategy should be carefully formulated.

Background: Spleen tyrosine kinase (SYK) is frequently upregulated in recurrent ovarian carcinomas, for which effective therapy is urgently needed. SYK phosphorylates several substrates, but their translational implications remain unclear. Here, we show that SYK interacts with EGFR and ERBB2, and directly enhances their phosphorylation. Methods: We used immunohistochemistry and immunoblotting to assess SYK and EGFR phosphorylation in ovarian serous carcinomas. Association with survival was determined by Kaplan-Meier analysis and the log-rank test. To study its role in EGFR signaling, SYK activity was modulated using a small molecule inhibitor, a syngeneic knockout, and an active kinase inducible system. We applied RNA-seq and phosphoproteomic mass spectrometry to investigate the SYK-regulated EGF-induced transcriptome and downstream substrates. Findings: Induced expression of constitutively active SYK130E reduced cellular response to EGFR/ERBB2 inhibitor, lapatinib. Expression of EGFRWT, but not SYK non-phosphorylatable EGFR3F mutant, resulted in paclitaxel resistance, a phenotype characteristic to SYK active ovarian cancers. In tumor xenografts, SYK inhibitor reduces phosphorylation of EGFR substrates. Compared to SYKWT cells, SYKKO cells have an attenuated EGFR/ERBB2-transcriptional activity and responsiveness to EGF-induced transcription. In ovarian cancer tissues, pSYK (Y525/526) levels showed a positive correlation with pEGFR (Y1187). Intense immunoreactivity of pSYK (Y525/526) correlated with poor overall survival in ovarian cancer patients. Interpretation: These findings indicate that SYK activity positively modulates the EGFR pathway, providing a biological foundation for co-targeting SYK and EGFR. Fund: Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, NIH/NCI, Ovarian Cancer Research Foundation Alliance, HERA Women's Cancer Foundation and Roseman Foundation. Funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript and eventually in the decision to submit the manuscript.

Objective To explore the clinical effect of the alveolar crest approach in the treatment of odontogenic maxillary sinusitis and the repair of edentulous implants in this area.Methods This was a retrospective case series of 20 patients with odontogenic sinusitis. The pathogenesis in each case was investigated. After elimination of the dental origin, each patient was treated with flushing, drainage and anti-inflammatories through the alveolar crest approach. Postoperative CBCT reexamination was performed to evaluate the therapeutic effect. Maxillary sinus elevation surgery with simultaneous or delayed implantation was performed after maxillary sinusitis healing was confirmed. The patients were followed postoperatively.Results Twenty patients with odontogenic sinusitis were treated by the alveolar crest approach, and 17 were cured, for a cure rate of 85%. Among them, 17 of the maxillary sinusitis patients were followed for 1 year, with good results.Conclusion The alveolar crest approach is feasible for the treatment of odontogenic maxillary sinusitis and can serve as a minimally invasive method for the repair of edentulism in this area and implantation.

Objective To investigate the effect of a laser⁃etched pure titanium surface on proliferation of the human osteosarcoma cell line MG63 and to provide a basis for study of implant surface modification. Methods The pure tita⁃ nium plate was cut into titanium pieces by a numerical control machine tool and divided into smooth surface and laser etching groups. The titanium surface of the laser etching group was etched with an Nd:YAG continuous wave laser using predetermined parameters, and the surfaces were observed by scanning electron microscopy (SEM). The surface micro⁃ morphology of each titanium sheet was evaluated. The relative element content of the titanium surface was measured by energy dispersive X⁃ray spectroscopy (EDS). The Ra value of each surface was determined using the Veeco roughness tester. MG63 cells were inoculated on 2 sets of titanium tablets. At 1, 3, and 6 h postinoculation, cell adhesion to the two groups of titanium sheets was observed under the microscope. At 24 h after inoculation, cellular F⁃actin was directly stained using immunofluorescence, and the morphology of the cytoskeleton was observed by laser confocal microscopy.Cell proliferation was examined at 1, 3, and 5 d using a MTS kit, and the data were analyzed with SAS 9.4. Results The surface of the smooth surface group was smooth and flat, the element composition was pure titanium, and the rough⁃ ness Ra was 179.23 nm. The surface of the laser⁃etched group formed a regular and uniform pore structure. The compo⁃ sition was mainly Ti, O, C, etc, and the surface roughness Ra was 14.11 μm. A large number of cells were uniformly dis⁃ tributed on the two titanium sheets in the observations at 1, 3, and 6 h. At 24 h postinoculation, MG63 cells were com⁃ pletely stretched on the two sets of titanium sheets and had extended a large number of pseudopods and microfilaments to cross ⁃ link with peripheral cells; moreover, the cell division phase was observed. The cell proliferation of the two groups at 1, 3, and 5 d showed a significant increase with time, indicating that no cytotoxicity occurred on the surfaces of the two groups. However, the cell proliferation in the laser ⁃ etched group was superior to that in the mechanical smooth surface group. Conclusion The surface morphology of titanium can be controlled by laser etching, which is conductive to increase the microstructure of implants without cytotoxicity and promoting osteoblast proliferation in the early stage.

Objective To explore the role of apoliprotein D (APOD) in the proliferation and migration of human dental pulp cells (DPCs) and to provide a basis for the use of APOD to promote pulp regeneration. Methods APOD ex⁃ pression in human dental pulp cells was inhibited by siRNA. The inhibition effect of APOD was confirmed by qPCR and Western blot. After APOD inhibition, colony formation experiments and CCK8 assays were employed to confirm the proliferation ability of dental pulp cells. Transwell assays were used to verify the cell migration ability after the inhibi⁃ tion of APOD expression. Results After inhibiting APOD expression, the colony formation rate in the si⁃apod group was reduced compared with the NC group, and the difference was statistically significant (t＝7.624, P＝0.002). The CCK8 experiment showed that the OD value in the si⁃apod group decreased at 3, 5 and 7 d compared with that in the NC group (P < 0.05). Transwell results showed that the number of cell divisions was 57.25 ± 4.03 in the si⁃apod group and 154.50 ± 8.39 in the NC group, and the difference was statistically significant (t＝10.45, P < 0.001). Conclusion Inhibition of APOD expression in dental pulp cells inhibits their proliferation and migration ability.

Background: Hepatic stellate cell (HSC) activation induced by transforming growth factor β1 (TGF-β1) plays a pivotal role in fibrogenesis, while the complex downstream mediators of TGF-β1 in such process are largely unknown. Methods: We performed pharmacoproteomic profiling of the mice liver tissues from control, carbon tetrachloride (CCl4)-induced fibrosis and NPLC0393 administrated groups. The target gene MAT2A was overexpressed or knocked down in vivo by tail vein injection of AAV vectors. We examined NF-κB transcriptional activity on MAT2A promoter via luciferase assay. Intracellular SAM contents were analyzed by LC-MS method. Findings: We found that methionine adenosyltransferase 2A (MAT2A) is significantly upregulated in the CCl4-induced fibrosis mice, and application of NPLC0393, a known small molecule inhibitor of TGF-β1 signaling pathway, inhibits the upregulation of MAT2A. Mechanistically, TGF-β1 induces phosphorylation of p65, i.e., activation of NF-κB, thereby promoting mRNA transcription and protein expression of MAT2A and reduces S-adenosylmethionine (SAM) concentration in HSCs. Consistently, in vivo and in vitro knockdown of MAT2A alleviates CCl4- and TGF-β1-induced HSC activation, whereas in vivo overexpression of MAT2A facilitates hepatic fibrosis and abolishes therapeutic effect of NPLC0393. Interpretation: This study identifies TGF-β1/p65/MAT2A pathway that is involved in the regulation of intracellular SAM concentration and liver fibrogenesis, suggesting that this pathway is a potential therapeutic target for hepatic fibrosis. Fund: This work was supported by National Natural Science Foundation of China (No. 81500469, 81573873, 81774196 and 31800693), Zhejiang Provincial Natural Science Foundation of China (No. Y15H030004), the National Key Research and Development Program from the Ministry of Science and Technology of China (No. 2017YFC1700200) and the Key Program of National Natural Science Foundation of China (No. 8153000502).

Objective To investigate the effects of leptin on the proliferation of stem cells from human stem cells from the apical papilla (hSCAPs) and the expression of osteogenic/dentinogenic genes in vitro to provide an experimen⁃ tal basis for the sustainable development of young permanent teeth. Methods The tissue block method was used to iso⁃ late and culture hSCAPs from the apical papilla of the immature third permanent molar. The expression of leptin and OBRb in hSCAPs was detected using immunocytofluorescence staining, western blotting and reverse transcription poly⁃ merase chain reaction (RT⁃PCR) analysis. The hSCAPs was treated with 0.1 μg/mL of leptin (0.1 μg/mL group) or 1.5 μg/mL of leptin (1.5 μg/mL group) at different time points. The control group was treated with alpha⁃MEM medium. Cell proliferation was measured using the CCK8 assay and cell cycle analysis. QRT⁃PCR was used to detect the expres⁃ sion of related osteoblast/odontogenic genes for alkaline phosphatase (ALP), dentin matrix protein ⁃1 (DMP⁃1), dentin si⁃ alophosphoprotein (DSPP), and osteocalcin (OCN) mRNA. The differences between the treatment groups and the control group were analyzed statistically using one⁃way ANOVA followed by Bonferroni analysis. Results The expression of both leptin and OBRb were found in hSCAPs. Compared with the control group, the cell proliferation capacity and S phase cells in the treatment groups were higher than those in the control group, with the 1.5 μg /mL group displaying higher levels than 0.1 μg /mL group, and the treated hSCAPs demonstrated a higher proliferation rate and a higher ex⁃ pression of ALP, DSPP, and DMP⁃1 from day 3 to day 7, with the 1.5 μg /mL group displaying higher levels than 0.1 μg /mL group , and the difference was statistically significant (P < 0.05), at day 7. The treated hSCAPs demonstrated a lower expression of ALP, DSPP, and DMP⁃1. Compared with the control group, the treated hSCAPs demonstrated a high⁃ er expression of OCN from day 7 to day 14, with significantly higher expression in the 1.5 μg /mL group compared to the 0.1 μg /mL group. Conclusion Leptin may promote cell proliferation and upregulate the expression of relative os⁃ teogenic/dentinogenic genes.

Recent advances in proteomic technologies have made high-throughput profiling of low-abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across 2 large longitudinal cohorts (n = 2839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic, and clinical data from humans to nominate 1 specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Furthermore, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz, and NTR domain–containing protein 2 (WFIKKN2) was, in turn, associated with fasting glucose, hemoglobin A1c, and HOMA-IR measurements in humans. In addition to identifying potentially novel disease markers and pathways in T2DM, we provide publicly available data to be leveraged for insights about gene function and disease pathogenesis in the context of human metabolism.

COVID-19 has had a substantial impact on clinical care and lifestyles globally. The State of Michigan reports over 80,000 positive COVID-19 tests between March 1, 2020 and July 29, 2020. We surveyed 8,041 Michigan Medicine biorepository participants in late June 2020. We found that 55% of COVID-19 cases reported no known exposure to family members or to someone outside the house diagnosed with COVID-19. A significantly higher rate of COVID-19 cases were employed as essential workers (45% vs 19%, p = 9x10-12). COVID-19 cases reporting a fever were more likely to require hospitalization (categorized as severe; OR = 4.4 [95% CI: 1.6-12.5, p = 0.005]) whereas respondents reporting rhinorrhea was less likely to require hospitalization (categorized as mild-to-moderate; OR = 0.16 [95% CI: 0.04-0.73, p = 0.018]). African-Americans reported higher rates of being diagnosed with COVID-19 (OR = 4.0 [95% CI: 2.2-7.2, p = 5x10-6]), as well as higher rates of exposure to family or someone outside the household diagnosed with COVID-19, an annual household income < $40,000, living in rental housing, and chronic diseases. During the Executive Order in Michigan, African Americans, women, and the lowest income group reported worsening health behaviors and higher overall concern for the potential detrimental effects of the pandemic. The higher risk of contracting COVID-19 observed among African Americans may be due to the increased rates of working as essential employees, lower socioeconomic status, and exposure to known positive cases. Continued efforts should focus on COVID-19 prevention and mitigation strategies, as well as address the inequality gaps that result in higher risks for both short-term and long-term health outcomes.

Background: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes severely afflicting the patients, while there is yet no effective medication against this disease. As Kv2.1 channel functions potently in regulating neurological disorders, the present work was to investigate the regulation of Kv2.1 channel against DPN-like pathology of DPN model mice by using selective Kv2.1 inhibitor SP6616 (ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate) as a probe. Methods: STZ-induced type 1 diabetic mice with DPN (STZ mice) were defined at 12 weeks of age (4 weeks after STZ injection) through behavioral tests, and db/db (BKS Cg-m+/+Leprdb/J) type 2 diabetic mice with DPN (db/db mice) were at 18 weeks of age. SP6616 was administered daily via intraperitoneal injection for 4 weeks. The mechanisms underlying the amelioration of SP6616 on DPN-like pathology were investigated by RT-PCR, western blot and immunohistochemistry technical approaches against diabetic mice, and verified against the STZ mice with Kv2.1 knockdown in dorsal root ganglion (DRG) tissue by injection of adeno associated virus AAV9-Kv2.1-RNAi. Amelioration of SP6616 on the pathological behaviors of diabetic mice was assessed against tactile allodynia, thermal sensitivity and motor nerve conduction velocity (MNCV). Findings: SP6616 treatment effectively ameliorated the threshold of mechanical stimuli, thermal sensitivity and MNCV of diabetic mice. Mechanism research results indicated that SP6616 suppressed Kv2.1 expression, increased the number of intraepidermal nerve fibers (IENFs), improved peripheral nerve structure and vascular function in DRG tissue. In addition, SP6616 improved mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC-1α pathway, repressed inflammatory response by inhibiting Kv2.1/NF-κB signaling and alleviated apoptosis of DRG neuron through Kv2.1-mediated regulation of Bcl-2 family proteins and Caspase-3 in diabetic mice. Interpretation: Our work has highly supported the beneficial of Kv2.1 inhibition in ameliorating DPN-like pathology and highlighted the potential of SP6616 in the treatment of DPN. Funding: Please see funding sources.

Background: COVID-19 has severely affected university students everywhere in the world. Due to fear of infection, government and local authorities in China immediately closed academic institutions and tried to find survival techniques to cope with market turbulence. COVID-19 was present in China at the end of 2019. However, little attention has been paid by researchers to coping strategies during the COVID-19 pandemic, and few measures were taken to assess the coping strategies of university students, specifically following the closure of their institutions. To address this gap, this study attempted to discover the coping strategies of Chinese students during the COVID-19 pandemic in China. Methods: We conducted an online survey using a semi-structured questionnaire with a simple random sampling technique and received 559 responses. The survey questions captured information about students’ lives during the COVID-19 outbreak, actions to control anxiety, and what students care about during the pandemic. The associations between coping strategies used and levels of anxiety were tested using analysis of variance (ANOVA) procedures. SPSS Statistics v27 was used for statistical analysis in this study. Results: The university students reported that coping strategies and survival techniques were required due to high levels of anxiety and psychological pressure during the COVID-19 pandemic. Most of the respondents reported the prompt closure of their academic institutions due to COVID-19. Psychological concerns, such as lack of sleep, emotional support, mental support and social appeal, were also reported. Conclusions: This is one of the very first studies on coping strategies for anxiety in China. The study reveals that university students employ a number of coping strategies in relation to COVID-19, but also suggests a need to strengthen such strategies in this population. However, the study was limited to a small number of provinces in China, which may affect the generalizability of the research.

Objective To investigate the effect of pure titanium surface of large diameter TiO2 nanotubes modified by RGD peptide on the adhesion and proliferation of MG63 osteoblasts. to provide theoretical proof for developing titani⁃ um implants. Methods Commercially pure titanium discs were divided into four groups and treated with SLA to obtain a microrough surface (SLA group). Then, nanotubes were imposed on this microrough surface by anodization (SLA+ 80 group). The surface was then modified by dopamine (DOPA) (DOPA Group), after which bioactive RGD peptide layers were generated on the TiO2 nanotube surfaces via electrochemical and molecular self⁃assembly techniques (RGD group). The titanium surface morphology and elemental composition of each group were characterized by field emission scanning electron microscopy (FE⁃SEM) and X⁃ray photoelectron spectroscopy (XPS). MG63 cells were cultured in vitro to evalu⁃ ate biological activities of titanium before and after treatment, including the evaluation of early⁃stage cell adhesion capac⁃ ity by fluorescence microscopy, proliferation capacity by MTS assay, and mRNA expression of the cell osteoblast⁃related genes alkaline phosphatase (ALP) and osteocalcin (OCN) by qRT⁃PCR. Results FE⁃SEM and XPS showed that hierar⁃ chical micro/nanosurfaces decorated with TiO2 nanotubes were produced on titanium using sandblasting and large grit etching combined with anodization, dopamine was then self⁃polymerized to form a polydopamine film on the TiO2 nano⁃ tube surfaces, and RGD peptides were then conjugated to the polydopamine film, finally forming RGD peptide⁃modified bioactive layers. In vitro experiments showed that compared with the other three materials, the RGD⁃modified material was more conducive to cell adhesion and proliferation (P < 0.05). The expression levels of ALP and OCN mRNA in the RGD group were significantly higher than those in the SLA group and DOPA group (P < 0.05). Conclusion Hierarchi⁃ cal micro/nanosurfaces decorated with TiO2 nanotubes functionally modified with RGD peptides have good biocompatibil⁃ ity and could be used for developing titanium implants and further improving early osseointegration.

Objective To analyze the morphology and incidence of middle mesial canal (MM) and isthmus in the mandibular first permanent molar by cone⁃beam computed tomography (CBCT). Methods Statistical analysis was per⁃ formed on images from patients who underwent CBCT examination in the Department of Radiology at Stomatological Hospital, Southern Medical University. Samples exhibiting root canal treatment, root resorption and calcification were ex⁃ cluded. Data regarding sex, age, the presence or absence of isthmus and MM, and the number of roots and root canals were recorded. Results Of the 217 mandibular first molar samples, 8 (3.7%) had an MM, and 2 (0.9%) had an inde⁃ pendent apical foramen. The overall incidence rate of isthmus was 57.1%; this rate was 50.7% in the cervical third of the root canal, 17.5% in the middle third, and 13.4% in the apical third. The incidence rate of isthmus was 61.8% on the left side, 52.3% on the right side, 58.7% in males, and 55.8% in females. No significant difference was found be⁃ tween the left and right sides or between females and males (P > 0.05). The incidence rate of isthmus in people under 60 was greater than 50% but was significantly lower in people older than 60. Conclusion Only a very small propor⁃ tion of MMs have an independent apical foramen in the mandibular first molar. The incidence of isthmus in the mesial root of the mandibular first permanent molar is high, and isthmus usually occurs in the cervical third of the root canal. During root canal treatment or apical surgery, attention should be given to the physical and chemical preparation of the isthmus.

Objective To study the vascularization of the collagen ⁃binding basic fibroblast growth factor (bFGF) ⁃ loaded collagen membranes in soft tissue repair in the hard palates of rats. Methods Ninety⁃six male 6⁃week⁃old Wi⁃ star rats were randomly divided into 4 groups, and 3⁃mm⁃diameter circular soft tissue defects were produced from the distal surface of the third molar to the mesial surface of the first molar in their hard palates. The defects were covered with a collagen⁃targeting bFGF/collagen membrane, a free bFGF/collagen membrane, a collagen membrane or no mem⁃ brane (control group). Every 6th rat was randomly sacrificed at 1, 2, 4 and 8 weeks in every group after surgery. Wound healing and the number of new blood vessels were measured by hematoxylin⁃eosin (HE) staining. Results The num⁃ bers of new blood vessels in the collagen⁃targeting bFGF/collagen membrane group were 8.94 ± 0.61, 17.39 ± 2.08 and 11.22 ± 1.66 at 1, 2 and 4 weeks after surgery, respectively, which were significantly greater than the values in the oth⁃ er groups (P 0.05). Conclusion Collagen⁃targeting bFGF/collagen membranes had a favorable effect on promoting an⁃ giogenesis during wound healing, and promoted wound healing.

Objective The present study investigated the clinical effects of a single complete denture using two ⁃ step fine impression during the restoration of mandibular alveolar ridge atrophy. Methods A back ⁃end window tray that was personalized and adjusted was used to obtain the original impression for a mandibular alveolar ridge case. The individual trays were made with the conception of mandibular occlusal denture, and the final impression was obtained after active edge shaping using different viscous silicones. Results A case of single complete denture with mandibular alveolar ridge atrophy restoration was accomplished using a single complete denture and two⁃step fine impression. The denture was well fixed and functioned well, and the patient was satisfied. Conclusion The application of fine impres⁃ sion into a single complete denture is helpful for the restoration of mandibular alveolar ridge atrophy.

Because nanoparticles have particular characteristics, such as small size and surface effects, nano⁃TiO2 is widely used in air purification, wastewater treatment and self⁃cleaning. In recent years, TiO2 photocatalysis has thorough⁃ ly explored as a new titanium implant surface treatment method. Photocatalytic performance is better for TiO2 nanowires than for nano⁃TiO2 particles. Hence, these nanowires have received widespread attention with regard for their more spe⁃ cific surface area and surface energy, improved charge carrier transport efficiency, and enhanced charge collection effi⁃ ciency. Photon⁃generated carrier transport moves in a one dimensional straight path along a nanowire, and this could de⁃ crease photoelectron loss. In this paper, we summarized the principles underlying, factors that influence, and applica⁃ tions involving TiO2 nanowire photocatalysis. Additionally, we describe its method of preparation and toxicity

Abstract Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/c-Kit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors.