Improved Biocompatibility and Angiogenesis of the Bone Titanium Scaffold through ERK1/2 Signaling Mediated by an Attached Strontium Element.

The promotion of early osseointegration is crucial for the success of biomedical titanium implants. Physical and chemical modifications to the material surface can significantly compensate for the lack of biocompatibility and early osseointegration of the implant. In this study, we implanted strontium onto titanium plates and analyzed the effect of strontium-doped materials on angiogenesis and biocompatibility in the human bone structure. Our findings demonstrated that strontium-loaded titanium sheet materials effectively promote human umbilical vein endothelial cell (HUVEC) biocompatibility and vascular differentiation ability, as evidenced by proliferation-apoptosis assays, RT-qPCR for vascular neogenesis markers, ELISA for vascular endothelial growth factor (VEGF) levels, and nitric oxide (NO) analysis. Mechanism studies based on RNAseq and Western blotting analysis revealed that strontium can promote titanium material biocompatibility with HUVEC cells and vascular neovascularization ability by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Meanwhile, blocking the ERK1/2 signaling pathway could reverse the promotional effect of vascular formation. Overall, we have successfully fabricated a multifunctional biocompatible bone implant with better histocompatibility and angiogenesis compared to uncoated implants.

Modelling and analysis of periodic impulsive releases of the Nilaparvata lugens infected with wStri-Wolbachia.

In this paper, we formulate a population suppression model and a population replacement model with periodic impulsive releases of Nilaparvata lugens infected with wStri. The conditions for the stability of wild-N.lugens-eradication periodic solution of two systems are obtained by applying the Floquet theorem and comparison theorem. And the sufficient conditions for the persistence in the mean of wild N.lugens are also given. In addition, the sufficient conditions for the extinction and persistence of the wild N.lugens in the subsystem without wLug are also obtained. Finally, we give numerical analysis which shows that increasing the release amount or decreasing the release period are beneficial for controlling the wild N.lugens, and the efficiency of population replacement strategy in controlling wild populations is higher than that of population suppression strategy under the same release conditions.

Survival analysis of a stochastic impulsive single-species population model with migration driven by environmental toxicant.

Considering the influence of environmental toxicant on population migration between patches, we propose and study a stochastic impulsive single-species population model with migration driven by environmental toxicant in this paper. We first discuss the existence and uniqueness of global positive solutions of the model by constructing the Lyapunov function. Then, we obtain sufficient conditions for extinction, stochastic persistence and persistence in the mean of the single-species population. Finally, we present some numerical simulations to illustrate our results. These results provide insights for the conservation and management of species in polluted environments.

A velocity-guided Harris hawks optimizer for function optimization and fault diagnosis of wind turbine.

Harris hawks optimizer (HHO) is a relatively novel meta-heuristic approach that mimics the behavior of Harris hawk over the process of predating the rabbits. The simplicity and easy implementation of HHO have attracted extensive attention of many researchers. However, owing to its capability to balance between exploration and exploitation is weak, HHO suffers from low precision and premature convergence. To tackle these disadvantages, an improved HHO called VGHHO is proposed by embedding three modifications. Firstly, a novel modified position search equation in exploitation phase is designed by introducing velocity operator and inertia weight to guide the search process. Then, a nonlinear escaping energy parameter E based on cosine function is presented to achieve a good transition from exploration phase to exploitation phase. Thereafter, a refraction-opposition-based learning mechanism is introduced to generate the promising solutions and helps the swarm to flee from the local optimal solution. The performance of VGHHO is evaluated on 18 classic benchmarks, 30 latest benchmark tests from CEC2017, 21 benchmark feature selection problems, fault diagnosis problem of wind turbine and PV model parameter estimation problem, respectively. The simulation results indicate that VHHO has higher solution quality and faster convergence speed than basic HHO and some well-known algorithms in the literature on most of the benchmark and real-world problems.

A Comprehensive Investigation on Potential Risk Factors for NSCL/P in a Rural District of Hebei Province, China.

Non syndromic cleft lip with or without palate (NSCL/P), one of the most common birth defects, is closely related to various risk factors. However, information regarding risk factors for NSCL/P in rural districts in China is very limited thus far. The objective of this study was designed to identify the potential risk factors for NSCL/P in rural districts.A comprehensive retrospective investigation including 435 NSCL/P patients and 402 healthy children was carried out in Hebei Province, China. Multiple logistic regression analysis and transmission disequilibrium test (TDT) were respectively used to identify non-genetic and genetic risk factors for NSCL/P, and then PLINK was used to explore the relationship between non-genetic and genetic risk factors.The results showed that maternal periconceptional exposure to pesticides and herbicides, as well as low parental education level were involved in the increased risk of NSCL/P, whereas maternal folic acid and multivitamin supplementation use during preconception period were associated with the reduced risk of NSCL/P. TDT analysis identified 2 single nucleotide polymorphisms (SNPs) (rs7078160 and rs4752028) in VAX1 and one SNP (rs17563) in BMP4 as the genetic risk factors for NSCL/P. Further analysis showed that the genetic risk factors were closely related with the negative non-genetic risk factors.Our study identified the potential risk factors for NSCL/P in rural districts, thus providing a theoretical basis for the prevention of NSCL/P occurrence.

PARD3 gene variation as candidate cause of nonsyndromic cleft palate only.

Nonsyndromic cleft palate only (NSCP) is a common congenital malformation worldwide. In this study, we report a three-generation pedigree with NSCP following the autosomal-dominant pattern. Whole-exome sequencing and Sanger sequencing revealed that only the frameshift variant c.1012dupG [p. E338Gfs*26] in PARD3 cosegregated with the disease. In zebrafish embryos, ethmoid plate patterning defects were observed with PARD3 ortholog disruption or expression of patient-derived N-terminal truncating PARD3 (c.1012dupG), which implicated PARD3 in ethmoid plate morphogenesis. PARD3 plays vital roles in determining cellular polarity. Compared with the apical distribution of wild-type PARD3, PARD3-p. E338Gfs*26 mainly localized to the basal membrane in 3D-cultured MCF-10A epithelial cells. The interaction between PARD3-p. E338Gfs*26 and endogenous PARD3 was identified by LC-MS/MS and validated by co-IP. Immunofluorescence analysis showed that PARD3-p. E338Gfs*26 substantially altered the localization of endogenous PARD3 to the basement membrane in 3D-cultured MCF-10A cells. Furthermore, seven variants, including one nonsense variant and six missense variants, were identified in the coding region of PARD3 in sporadic cases with NSCP. Subsequent analysis showed that PARD3-p. R133*, like the insertion variant of c.1012dupG, also changed the localization of endogenous full-length PARD3 and that its expression induced abnormal ethmoid plate morphogenesis in zebrafish. Based on these data, we reveal PARD3 gene variation as a novel candidate cause of nonsyndromic cleft palate only.

TRPC1 correlates with poor tumor features, radiotherapy efficacy and survival in tongue squamous cell carcinoma.

Aim: The present study aimed to explore the clinical association of TRPC1 with tongue squamous cell carcinoma (TSCC) tumor features and prognosis. Methods: A total of 246 TSCC patients who underwent surgical resection were retrospectively analyzed, and their tissue specimens were acquired for TRPC1 protein and mRNA detection. Results: TRPC1 protein immunohistochemistry score and mRNA expression were of good value in differentiating TSCC tissue from tumor-adjacent tissue and were positively correlated with pathological grade and tumor node metastasis stage. A high TRPC1 protein score was negatively correlated with overall survival, and this correlation was dramatically obvious in patients who received adjuvant radiotherapy. Conclusion: TRPC1 correlates with poor tumor features and unfavorable survival in TSCC patients.

Castleman's disease with submaxillary lymphadenectasis as the main manifestation: a case report.

Castleman's disease is a lymphoproliferative disease that is rare and hard to diagnose. As a result of untypical manifestations, missed diagnosis and misdiagnosis of Castleman's disease are common in clinical practice. In this paper, we report one patient with clinical manifestations of painless submaxillary lymphadenectasis. The patient was finally diagnosed with Castleman's disease by clinical, laboratory, and pathological examinations. This report may promote the understanding and diagnosis of Castleman's disease for clinicians.

Development and Validation of Risk Prediction Model for In-hospital Mortality Among Patients Hospitalized With Acute Exacerbation Chronic Obstructive Pulmonary Disease Between 2015 and 2019.

Background: In patients with chronic obstructive pulmonary disease (COPD), acute exacerbations affect patients' health and can lead to death. This study was aimed to develop a prediction model for in-hospital mortality in patients with acute exacerbations of COPD (AECOPD). Method: A retrospective study was performed in patients hospitalized for AECOPD between 2015 and 2019. Patients admitted between 2015 and 2017 were included to develop model and individuals admitted in the following 2 years were included for external validation. We analyzed variables that were readily available in clinical practice. Given that death was a rare outcome in this study, we fitted Firth penalized logistic regression. C statistic and calibration plot quantified the model performance. Optimism-corrected C statistic and slope were estimated by bootstrapping. Accordingly, the prediction model was adjusted and then transformed into risk score. Result: Between 2015 and 2017, 1,096 eligible patients were analyzed, with a mean age of 73 years and 67.8% male. The in-hospital mortality was 2.6%. Compared to survivors, non-survivors were older, more admitted from emergency, more frequently concomitant with respiratory failure, pneumothorax, hypoxic-hypercarbic encephalopathy, and had longer length of stay (LOS). Four variables were included into the final model: age, respiratory failure, pneumothorax, and LOS. In internal validation, C statistic was 0.9147, and the calibration slope was 1.0254. Their optimism-corrected values were 0.90887 and 0.9282, respectively, indicating satisfactory discrimination and calibration. When externally validated in 700 AECOPD patients during 2018 and 2019, the model demonstrated good discrimination with a C statistic of 0.8176. Calibration plot illustrated a varying discordance between predicted and observed mortality. It demonstrated good calibration in low-risk patients with predicted mortality rate ≤10% (P = 0.3253) but overestimated mortality in patients with predicted rate >10% (P < 0.0001). The risk score of 20 was regarded as a threshold with an optimal Youden index of 0.7154. Conclusion: A simple prediction model for AECOPD in-hospital mortality has been developed and externally validated. Based on available data in clinical setting, the model could serve as an easily used instrument for clinical decision-making. Complications emerged as strong predictors, underscoring an important role of disease management in improving patients' prognoses during exacerbation episodes.

Upregulation of a kinase interacting protein 1 in tongue squamous cell carcinoma correlates with lymph node metastasis and poor overall survival.

ABSTRACT: A kinase interacting protein 1 (AKIP1) is upregulated in cancer cells/tissues and associated with deteriorative tumor features, while it has not been investigated in tongue squamous cell carcinoma (TSCC). The goal of this study was to measure AKIP1 expression and analyze its correlation with clinical feature and prognosis in TSCC patients.We retrospectively reviewed 194 TSCC patients, whose formalin fixed paraffin-embedded (FFPE) tumor tissue specimens and paired adjacent tissue specimens were accessible for AKIP1 detection by immunohistochemistry (IHC). Whereas only 107 patients whose fresh-frozen tumor tissue and paired fresh-frozen adjacent tissue that were still available in storage were included for AKIP1 mRNA detection by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).AKIP1 expression (both the protein detected by IHC and mRNA detected by RT-qPCR) was higher in TSCC tissue than that in adjacent tissue. In addition, both tumor AKIP1 mRNA and protein expressions were correlated with advanced N stage and TNM stage, while they were not correlated with other clinical features in TSCC patients. As for survival, there was a correlation of AKIP1 mRNA with poor overall survival (OS), while the correlation of AKIP1 protein expression with OS was of limited statistical significance.There is an upregulation of AKIP1 in TSCC and it correlates with lymph node metastasis as well as unfavorable prognosis in TSCC patients.

Factors associated with inpatient length of stay among hospitalised patients with chronic obstructive pulmonary disease, China, 2016-2017: a retrospective study.

OBJECTIVES: To identify factors associated with length of stay (LOS) in chronic obstructive pulmonary disease (COPD) hospitalised patients, which may help shorten LOS and reduce economic burden accrued over hospital stay. DESIGN: A retrospective cohort study. SETTING: This study was performed in a tertiary hospital in China. PARTICIPANTS: Patients with COPD who were aged ≥40 years and newly admitted between 2016 and 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: LOS at initial admission was the primary outcome and health expenditures were the secondary outcome. To identify factors associated with LOS, we collected information at index hospitalisation and constructed a conceptual model using directed acyclic graph. Potential factors were classified into five groups: demographic information, disease severity, comorbidities, hospital admission and environmental factors. Negative binomial regression model was fitted for each block of factors and a parsimonious analysis was performed. RESULTS: In total, we analysed 565 patients with COPD. The mean age was 69±11 years old and 69.4% were men. The median LOS was 10 (interquartile range 8-14) days. LOS was significantly longer in patients with venous thromboembolism (VTE) (16 vs 10 days, p=0.0002) or with osteoporosis (15 vs 10 days, p=0.0228). VTE ((rate ratio) RR 1.38, 95% CI 1.07 to 1.76), hypoxic-hypercarbic encephalopathy (RR 1.53, 95% CI 1.06 to 2.20), respiratory infection (RR 1.12, 95% CI 1.01 to 1.24), osteoporosis (RR 1.45, 95% CI 1.07 to 1.96) and emergence admission (RR 1.08, 95% CI 1.01 to 1.16) were associated with longer LOS. In parsimonious analysis, all these factors remained significant except emergency admission, highlighting the important role of concomitant morbidities in patients' hospital stay. Total hospitalisation cost and patients' out-of-pocket cost increased monotonically with LOS (both ptrend <0.0001). CONCLUSION: Patients' concomitant morbidities predicted excessive LOS in patients with COPD. Healthcare cost increased over the LOS. Quality improvement initiatives may need to identify patients at high risk for lengthy stay and implement early interventions to reduce COPD economic burden.

Dynamics of an SEIR model with infectivity in incubation period and homestead-isolation on the susceptible.

In this paper, we present an SEIR epidemic model with infectivity in incubation period and homestead-isolation on the susceptible. We prove that the infection-free equilibrium point is locally and globally asymptotically stable with condition R 0 < 1 . We also prove that the positive equilibrium point is locally and globally asymptotically stable with condition R 0 > 1 . Numerical simulations are employed to illustrate our results. In the absence of vaccines or antiviral drugs for the virus, our results suggest that the governments should strictly implement the isolation system to make every effort to curb propagation of disease during the epidemic.

NTN1 gene was risk to non-syndromic cleft lip only among Han Chinese population.

OBJECTIVE: Genome-wide association studies (GWAS) found NTN1, NOG and the region between CREBBP and ADCY9 were risks to non-syndromic cleft lip with or without cleft palate (NSCL/P). However, the association of single nucleotide polymorphisms (SNPs) in these genes with NSCL/P in Western China is unknown. SUBJECTS AND METHODS: We selected seven SNPs in NTN1, NOG and between CREBBP and ADCY9, and then performed transmission disequilibrium test (TDT), parent-of-origin effect and sliding window haplotype analysis to test the associations among 302 NSCL/P case-parent trios from Western Han Chinese. RESULTS: We found allele G at rs4791774 in NTN1 was significantly overtransmitted among non-syndromic cleft lip only (NSCLO) (p = 0.0067, OR = 1.79, 95% CI: 1.17-2.74); rs4791774 and rs9915089 tightly linked with each other among NSCL/P (D' = 0.87, r2  = 0.67) and haplotypes carrying the risk allele G at rs4791774 were always found to be overtransmitted from parents to cases. Motif analysis indicated that allele G at rs4791774 could greatly alter the affinity of Myc_disc7, so allele G at rs4791774 in NTN1 might modulate C-MYC transcription to participate in the aetiology of NSCLO. CONCLUSIONS: Our study suggested allele G at rs4791774 in NTN1 gene is risk of NSCLO, which could greatly increase the risk to have a baby with cleft.

Association between genotype and phenotype of virulence gene in Van der Woude syndrome families.

Members from two Van der Woude syndrome (VWS) families were screened to determine the prevalence of interferon regulatory factor 6 (IRF6) as a disease­causing gene and to analyze the interrelationships between patient genotype and phenotype. The peripheral blood of 24 members from two VWS families and 200 control samples were collected. The family members were interviewed for medical histories and other clinical abnormalities using questionnaires. Polymerase chain reaction was directly performed on the peripheral blood to screen for the coding region of the IRF6 gene. Of the 24 family members, a total of 6 patients had mutations of IRF6 gene. c.1234C>T (p.R412X) heterozygous mutation was detected in 3 members of family 1. In families 2 and 3, members carried the c.1210G>A (p.E404K) heterozygous mutations. The other members of the families, were wild type (wt/wt) for IRF6. Genetic testing demonstrated that the disease mutations c.1234C>T and c.1210G>A co­segregated with the two families' pathogenic mutations. The existence of genetic heterogeneity and the complexity of the clinical phenotype was demonstrated in Chinese VWS patients.

Impulsive vaccination and dispersal on dynamics of an SIR epidemic model with restricting infected individuals boarding transports.

To understand the effect of impulsive vaccination and restricting infected individuals boarding transports on disease spread, we establish an SIR model with impulsive vaccination, impulsive dispersal and restricting infected individuals boarding transports. This SIR epidemic model for two regions, which are connected by transportation of non-infected individuals, portrays the evolvement of diseases. We prove that all solutions of the investigated system are uniformly ultimately bounded. We also prove that there exists globally asymptotically stable infection-free boundary periodic solution. The condition for permanence is discussed. It is concluded that the approach of impulsive vaccination and restricting infected individuals boarding transports provides reliable tactic basis for preventing disease spread.

Harvesting on a stage-structured single population model with mature individuals in a polluted environment and pulse input of environmental toxin.

In the natural world, there are many species whose individual members have a life history that they take them with two distinct stages: immaturity and maturity. In particular, we have in mind mammalian populations and some amphibious animals. We improve the assumption of a single population as a whole. It is assumed that the immature individuals and mature individuals are divided by a fixed period. This paper concentrates on the study of a stage-structured single population model with mature individuals in a polluted environment and pulse input of environmental toxin at fixed moments. Furthermore, the mature individuals are harvested continuously. We show that the population goes extinct if the harvesting rate is beyond a critical threshold. Conditions for the extended permanence of the population are also examined. From the biological point of view, it is easy to protect species by controlling the harvesting amount, impulsive period of the exogenous input of toxin and toxin impulsive input amount, etc. Our results provide reasonable tactics for biological resource management.

Pest management through continuous and impulsive control strategies.

In this paper, we propose two mathematical models concerning continuous and, respectively, impulsive pest control strategies. In the case in which a continuous control is used, it is shown that the model admits a globally asymptotically stable positive equilibrium under appropriate conditions which involve parameter estimations. As a result, the global asymptotic stability of the unique positive equilibrium is used to establish a procedure to maintain the pests at an acceptably low level in the long term. In the case in which an impulsive control is used, it is observed that there exists a globally asymptotically stable susceptible pest-eradication periodic solution on condition that the amount of infective pests released periodically is larger than some critical value. When the amount of infective pests released is less than this critical value, the system is shown to be permanent, which implies that the trivial susceptible pest-eradication solution loses its stability. Further, the existence of a nontrivial periodic solution is also studied by means of numerical simulation. Finally, the efficiency of continuous and impulsive control policies is compared.