Association between WNT-1-inducible signaling pathway protein-1 (WISP1) genetic polymorphisms and the risk of gastric cancer in Guangxi Chinese.

BACKGROUND: WNT1-inducible signaling pathway protein 1 (WISP1) is a member of the CCN protein family and a downstream target of ß-catenin. Aberrant WISP1 expression may be involved in carcinogenesis. To date, no studies have investigated the association between single-nucleotide polymorphisms (SNPs) of WISP1 and gastric cancer. Therefore, we conducted this study to explore their relationship. METHODS: Polymerase chain reaction-restriction fragment length polymorphism assay was used to analyze three SNPs of WISP1 in 204 gastric cancer patients and 227 controls. RESULTS: Overall, we could not identify a significant association between WISP1 SNPs and gastric cancer risk. However, the subgroup analysis demonstrated that the presence of the rs7843546 T allele was associated with a significantly decreased risk of gastric cancer in those of Han Chinese ethnicity (CT vs. CC: OR = 0.33, 95%CI 0.14-0.78; TT vs. CC: OR = 0.29, 95%CI 0.11-0.76; CT + TT vs. CC: OR = 0.32, 95%CI 0.14-0.74). In addition, patients with the rs7843546 TT genotype display a 0.34-fold lower risk of developing stage I/II gastric cancer than those with the CC genotype Furthermore, individuals ≥ 50 years old who carried the rs10956697 AC genotype had a significantly decreased risk of gastric cancer (OR = 0.58, 95%CI 0.35-0.98). Smokers with the rs10956697 AC and AC + AA genotypes exhibited a 0.28-fold lower and 0.32-fold lower risk of gastric cancer, respectively. CONCLUSIONS: The WISP1 SNPs rs7843546 and rs10956697 were, for the first time, found to reduce susceptibility to gastric cancer in various subgroups of Guangxi Chinese.

A digital approach for 1-step formation of the supraimplant emergence profile at the time of immediate implant placement.

An optimal soft tissue profile is essential for obtaining optimal esthetics in anterior implant-supported restorations. Commercially available cylindrical healing abutments do not mimic the shape of natural teeth and may create a poor peri-implant emergence. This article introduces a digital protocol to improve the formation of the supraimplant emergence profile with an individualized healing abutment fabricated by computer-aided design and computer-aided manufacture (CAD-CAM) at the time of implant placement. A benefit of this technique is obtaining optimal morphology of the peri-implant soft tissues, especially for teeth with increased horizontal overlap.

Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

[Effect of Fuxin Mixture on The 01-AR-cAMP-PKA Pathway of Rats with Heart Failure].

Objective To observe the effect of Fuxin Mixture(FXM) on the ß,-AR(adrenergic receptor) -cAMP(cyclic adenosine monophosphate, cAMP) -PKA ( protein kinase A, PKA) pathway of rats with heart failure. Methods Male Wistar rats were randomly divided into blank control group, captopril group, FXM low dose group, FXM high dose group and model group.Models of CHF were established. After drug intervention for 6 weeks, the left ventricular mass index (LVMI) was analysed, the expression of ß1 - AR mRNA in myocardial tissue was measured,the level of cAMP in rat plasma,the OD value PKA content of spleen tissue homogenate were detected. Results Compared with the blank control group, the LVMI and the cAMP in plasma of model group were increased (P <0. 05), the expression of ß1,-AR mRNA, the OD value of spleen tissue homogenate and PKA were decreased (P <0. 01). Compared with the model group, the LVMI were decreased,and the expression of ß1-AR mRNA were increased in FXM high dose group and captopril group (P <0. 01 , P <0. 05) ; the level of cAMP in plasma of each drug group were decreased (P <0. 01) , the OD value of spleen tissue homogenate and PKA were increased (P <0. 01). Compared with the captopril group, the expression of ß1-AR mRNA, the OD value of spleen tissue homogenate and PKA were decreased, and the LVMI and the cAMP were increased in the FXM low dose group (P <0. 01 , P <0. 05). Compared with the FXM low dose group, the LVMI and the cAMP of FXM high dose group were decreased (P <0. 05), the expression of ß1-AR mRNA, the OD value of spleen tissue homogenate and PKA were increased (P <0. 01). Conclusion FXM could play the role of anti-heart fail- ure through regulating P1-AR-cAMP-PKA pathway.

A Bayesian three-parameter logistic model for early- and late-onset DLTs in oncology Phase I studies.

We introduce a three-parameter logistic model to analyze the dose limiting toxicity (DLT) as a time-to-event endpoint in oncology Phase I trials. In the proposed model, patients are allowed to stay on trial without the constraint of a maximum follow-up time. Our model accommodates late-onset DLT as well as early-onset DLT, by both of which the dose recommendation is informed. A Bayesian approach is used to incorporate prior knowledge of the test treatment into dose recommendation. Simulation examples show that our proposed model has good operating characteristics in assessing the maximum tolerated dose (MTD).

Enhancing targeted tumor treatment by near IR light-activatable photodynamic-photothermal synergistic therapy.

For several decades, cancer has been one of the most life-threatening diseases. For enhancing anticancer efficiency with minimum side effects, combination therapy is envisioned. The current manuscript reports for the first time the development of a methylene blue (MB) bound nanoplatform, which is capable of delivering targeted diagnostic and combined synergistic photothermal and photodynamic treatment of cancer. Experimental data found that, once the nanoparticle binds with the target cell surface, it can detect LNCaP human prostate cancer cell selectively using fluorescence imaging. Our result shows that the therapeutic actions can be controlled with external NIR light. No cytotoxicity was observed in the absence of NIR light. Targeted photodynamic and photothermal treatment using 785 nm NIR light indicates that the multimodal treatment enhances the possibility of destroying LNCaP prostate cancer cells in vitro dramatically. We discuss the operating principle for the targeted imaging and possible mechanisms for combined therapeutic actions. Our experimental data show that NIR light activated combined therapy for cancer may become a highly effective treatment procedure in clinical settings.

Mini Self-Retrieval Practices of Skeletal Muscles in the Human Gross Anatomy Course.

Students in health professional studies are often faced with the daunting task of memorizing large volumes of information in a limited time. Gross anatomy is usually the first course students may take in their curriculum, and the volume and complexity of anatomical information students must memorize, including muscle names, become overwhelming. Here, we outline a teaching method and pedagogical application of self-retrieval in gross anatomy courses, where students were provided with a number system that served as goals and cues for easy retrieval of muscle names for different anatomical regions.

Evaluation of soil erosion in the Changhua River Basin on Hainan Island based on the Chinese soil loss equation model.

Soil erosion is one of the most serious ecological and environmental problems facing southern China. The Changhua River Basin on Hainan Island is affected by soil erosion, which is causing the soil environment to become more fragile. Compared with the Revised Soil Erosion Equation (RUSLE), the Chinese Soil Loss Equation (CSLE) is based on a large amount of Chinese local data and research results, which more accurately reflect the actual situation of soil erosion in China and therefore have better accuracy and applicability in the Chinese region. By combining GIS and RS technologies, this study establishes the CSLE model of the Changhua River Basin, quantifies the soil erosion data via image elements from 2020 to 2022 using the spatial interpolation method, classifies the erosion intensity, and analyzes the spatial and temporal change characteristics of soil erosion. The statistical results show that, during the period from 2020 to 2022, the area of slight erosion in the Changhua River Basin increased by 553.25 km2, with a rate of change of 15.83 %, and the areas of mild erosion, moderate erosion, intense erosion, very intense erosion, and severe erosion decreased by 446.42 km2, 64.4 km2, 25.73 km2, 11.25 km2, and 5.45 km2, respectively, with rates of change of -31.05 %, -30.08 %, -36.58 %, -18.02 %, and -13.85 %, respectively. Slight erosion is defined as soil erosion less than the permissible soil loss and is not regarded as soil erosion, and the other erosion intensities showed a yearly decreasing trend, indicating that the soil erosion control was effective during this three-year period. In the work of soil and water conservation, it is especially necessary to determine the main factors influencing soil erosion and predict the areas that may be prone to such erosion. Therefore, on the basis of establishing a characteristic model using land use type, slope and soil type, and through superposition analysis, we obtained the spatial and temporal change characteristics of soil erosion. The research results are as follows: (1) slight erosion is mainly concentrated in forested areas, and forested land has a better capacity for soil and water conservation; (2) mild, moderate, and strong erosion mainly occur in cultivated areas and areas with a slope of 0-5°; (3) areas of built land and areas with a slope of 8°-15° are more prone to intense erosion, although they cover a smaller area; (4) when the slope is greater than 15°, the overlap range with the forest area is larger and the slope is no longer the main factor leading to soil erosion. Thus, it can be seen that forest land significantly reduces the impact of soil erosion. (5) among the different soil types, Technosol, Ferralsol and Fluvisol all have less than 55 per cent uneroded area and are generally less erosion-resistant, while Lixisol and Acrisol are relatively more susceptible to a high degree of erosion hazard (Extremely strong erosion, severe erosion).

Influence of connection design and material properties on stress distribution and fatigue lifetime of zygomatic implants: A finite element analysis.

Zygomatic implants (ZIs) were developed as a graftless alternative to rehabilitate severely reabsorbed maxillae. This study aims to employ three-dimensional finite element analysis (FEA) to simulate the impact of external hexagonal implant connection (EHC) and internal hexagonal implant connection (IHC) on the stress distribution and fatigue lifetime within the ZI systems using parameters defined in ISO 14801:2016. Two ZI assemblies (Nobel Biocare and Noris Medical) were scanned in a micro-CT scanner and reconstructed using Nrecon software. Three-dimensional models were generated by Simpleware ScanIP Medical software. All models were exported to FEA software (ABAQUS) and subsequently to a fatigue analysis software (Fe-safe). A compressive 150 N load was applied at a 40° angle on the cap surface. A 15 Hz frequency was applied in the in silico cyclic test. The implant components had material properties of commercially pure grade 4 titanium (CPTi) and Titanium-6Aluminum-4Vanadium alloy (Ti64). Von Mises stress data, contour plots, and fatigue limits were collected and analyzed. EHC models exhibited higher peak stresses in implant components for both materials compared to IHC models. However, simulated bone support results showed the opposite trend, with higher stresses on IHCthan EHC models. The fatigue analysis revealed that assemblies with both designs exceeded ISO 14801:2016 number of cycles limits using Ti64, while CPTi groups exhibited comparatively lower worst life-repeats. In conclusion, ZIs with IHC were found to have a more homogeneous and advantageous stress distribution within both materials tested. Ti64 demonstrates a prolonged service life for both design connections.

[Application of quality function deployment technology in extracorporeal membrane oxygenation treatment of patients with critical cardiopulmonary disease].

OBJECTIVE: To accurately and effectively identify the most critical needs of extracorporeal membrane oxygenation (ECMO) treatment for patients with severe cardiopulmonary diseases, and to better carry out continuous improvement of medical service quality an patients' satisfaction. METHODS: Patients who underwent ECMO and transferred from 56 medical institutions in the Henan Provincial People's Hospital Critical Care Medicine Specialist Alliance [the patients who were transported before applying quality function deployment (QFD) from June 2017 to May 2018 were enrolled as the control group, and patients who were transported after applying QFD from June 2018 to May 2019 were the observation group], medical staff in the alliance hospitals, ECMO transfer teams and transfer driver teams were enrolled as the subjects of the survey. QFD was applied to convert the collected requirements into quality improvement elements for targeted improvement measures. RESULTS: A total of 125 questionnaires were distributed in this survey, and 116 valid questionnaires were collected, including 91 from patients (including 27 from the control group and 64 from the observation group), 10 from the medical staff of the alliance hospitals, 10 from the ECMO transport teams and 5 from the transport driver teams. The questionnaire recovery rate was 92.8%. The improvement elements of ECMO treatment for patients with critical cardiopulmonary diseases were ranked according to the importance, and the top five were as follows: the accuracy of the first diagnosis, the specialization of ECMO team, the guarantee of vehicle safety, the seamless responses, and the smooth coordinated rescue protocol. CONCLUSIONS: The top five improvement elements should be prioritized in ECMO treatment of patients with critical cardiopulmonary disease in all hospitals of the Alliance to ensure more accurate and timely treatment.

Collaborative calculation and application of interreal and real interval relations to protect privacy.

The determination of the relation between a number and a numerical interval is one of the core problems in the scientific calculation of privacy protection. The calculation of the relationship between two numbers and a numerical interval to protect privacy is also the basic problem of collaborative computing. It is widely used in data queries, location search and other fields. At present, most of the solutions are still fundamentally limited to the integer level, and there are few solutions at the real number level. To solve these problems, this paper first uses Bernoulli inequality generalization and a monotonic function property to extend the solution to the real number level and designs two new protocols based on the homomorphic encryption scheme, which can not only protect the data privacy of both parties involved in the calculation, but also extend the number domain to real numbers. In addition, this paper designs a solution to the confidential cooperative determination problem between real numbers by using the sign function and homomorphism multiplication. Theoretical analysis shows that the proposed solution is safe and efficient. Finally, some extension applications based on this protocol are given.

Comparing the Clinical Outcome of Peri-implant Hard and Soft Tissue Treated with Immediate Individualized CAD/CAM Healing Abutments and Conventional Healing Abutments for Single-Tooth Implants in Esthetic Areas Over 12 Months: A Randomized Clinical Trial.

PURPOSE: The purpose of this study was to compare the clinical influence of immediate individualized CAD/CAM healing abutments and conventional healing abutments on peri-implant soft and hard tissue in shaping the emergence profile. MATERIALS AND METHODS: Patients with a single maxillary incisor missing who accepted dental implantation were registered in this study. After implantation, individualized CAD/CAM healing abutments and regular prefabricated abutments were randomly inserted to shape the emergence profile. A radiograph was taken, and the pink esthetic score, papilla height, papilla proportion, and probing depth were recorded at 6 months after implant placement (T1), loading (T2, definitive restoration), and 1 year after loading (T3). Patient self-assessment scores were also evaluated through the visual analog scale. The data were analyzed statistically using the t test or repeated-measurements analysis of variance (ANOVA). RESULTS: Twenty patients were enrolled in this study, including 9 patients using individualized abutments and 11 patients using conventional abutments. The mean total marginal bone level in the individualized abutment group was 1.53 ± 0.65 mm at implant placement, 1.10 ± 0.47 mm at loading, and 0.76 ± 0.47 mm at 1 year after loading. In contrast, the mean total marginal bone level in the conventional abutment group was 0.62 ± 0.39 mm at implant placement, 0.14 ± 0.55 mm at loading, and -0.04 ± 0.53 mm at 1 year after loading. The differences between the individualized abutment group and conventional abutment group were statistically significant for the mesial and distal marginal bone level at three time points, respectively (P ≤ .05). Similarly, there were significant differences in probing depth, papilla height, and pink esthetic score between the two groups. CONCLUSION: This immediately individualized healing abutment protocol may significantly preserve the peri-implant marginal bone and soft tissue. The use of individualized CAD/CAM healing abutments for shaping the emergence profile shows better esthetic outcomes than conventional healing abutments.

Improving Academic Performance Using an Innovative Cranial-Nerve Table.

To facilitate the review and retention of the complicated contents of the Head Block in the Dental Gross Anatomy course, an innovative cranial-nerve table was introduced to first-year dental students using an interactive self-retrieval format. Our analysis of exam data shows the efficacy of this learning tool.

Quantitative reproducibility analysis for identifying reproducible targets from high-throughput experiments.

BACKGROUND: High-throughput assays are widely used in biological research to select potential targets. One single high-throughput experiment can efficiently study a large number of candidates simultaneously, but is subject to substantial variability. Therefore it is scientifically important to performance quantitative reproducibility analysis to identify reproducible targets with consistent and significant signals across replicate experiments. A few methods exist, but all have limitations. METHODS: In this paper, we propose a new method for identifying reproducible targets. Considering a Bayesian hierarchical model, we show that the test statistics from replicate experiments follow a mixture of multivariate Gaussian distributions, with the one component with zero-mean representing the irreproducible targets. RESULTS: A target is thus classified as reproducible or irreproducible based on its posterior probability belonging to the reproducible components. We study the performance of our proposed method using simulations and a real data example. CONCLUSION: The proposed method is shown to have favorable performance in identifying reproducible targets compared to other methods.

Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry.

A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8-21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences.

A predictive model for copper partitioning to suspended particulate matter in river waters.

A chemical equilibrium-based predictive model expressing Cu partitioning as a function of aqueous and solid phase characteristics was developed. The model takes into account only the most important factors that govern Cu partitioning, and therefore results in a relatively simple formulation. It assumes particulate organic carbon (POC) and dissolved organic carbon (DOC) binding sites play the most important role in solid and aqueous phases. The model formulation assumed one-surface site and two dissolved organic matter (DOM) sites, and included the "solids effect". Proton effects were considered for both the particle surface sites and the DOM. The model was calibrated with data for samples collected from the Susquehanna River, and validated with White Clay Creek and Delaware River samples. Copper partitioning in natural water systems with different pH, and concentrations of alkalinity, DOC, POC, total suspended solids (TSS), and total copper was predicted reasonably well.

Nonlinear and competitive sorption of apolar compounds in black carbon-free natural organic materials.

Numerous studies have reported a spectrum of sorption phenomena in soils, sediments, and organic matter isolates of those materials that are inconsistent with a partition model proposed in the late 1970s and early 1980s, a model predicated on a hypothesis that sorption is linear and noncompetitive. To explain these nonideal phenomena, prior studies have proposed a hard-soft (glassy-rubbery) model for SOM (soil and sediment organic matter), while others have attributed them singularly to BC (black carbon: soot and charcoal) particles present in topsoils and sediments. In this study, we demonstrated nonideal sorption behavior (isotherm nonlinearity, competitive effects) for a group of apolar compounds in a large set of natural and model organic materials, including a commercial lignin and humic acids from different sources. Complete oxidation of samples by an acidic dichromate method was taken to signify the absence of BC. (However, polymethylene units are stable even if functionalized on both ends, making the technique unreliable for quantifying BC.) Other samples were inferred free of BC by their source and method of preparation. Characterization by thermalanalytical methods indicated the glassy character of the organic materials. The origin of the nonideal behaviors appears to be the glassy character of these materials. Sorption nonlinearity increased or decreased by changing temperature, cosolvent content, or degree of cross-linking by metal ions as predicted for organic solids in a glassy state. We conclude that macromolecular humic substances in the environment may exhibit nonideal sorption behavior in soils and sediments, quite apart from any such behaviors attributable to BC.

The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE) on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa.

Correlations between angiotensin-converting enzyme (ACE) genotype (I/I, I/D, D/D), disease severity at baseline and response to enzyme replacement therapy (ERT) were assessed in the Pompe disease Late-Onset Treatment Study (LOTS). No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation.

Differences in the timing and magnitude of Pkd1 gene deletion determine the severity of polycystic kidney disease in an orthologous mouse model of ADPKD.

Development of a disease-modifying therapy to treat autosomal dominant polycystic kidney disease (ADPKD) requires well-characterized preclinical models that accurately reflect the pathology and biochemical changes associated with the disease. Using a Pkd1 conditional knockout mouse, we demonstrate that subtly altering the timing and extent of Pkd1 deletion can have a significant impact on the origin and severity of kidney cyst formation. Pkd1 deletion on postnatal day 1 or 2 results in cysts arising from both the cortical and medullary regions, whereas deletion on postnatal days 3-8 results in primarily medullary cyst formation. Altering the extent of Pkd1 deletion by modulating the tamoxifen dose produces dose-dependent changes in the severity, but not origin, of cystogenesis. Limited Pkd1 deletion produces progressive kidney cystogenesis, accompanied by interstitial fibrosis and loss of kidney function. Cyst growth occurs in two phases: an early, rapid growth phase, followed by a later, slow growth period. Analysis of biochemical pathway changes in cystic kidneys reveals dysregulation of the cell cycle, increased proliferation and apoptosis, activation of Mek-Erk, Akt-mTOR, and Wnt-ß-catenin signaling pathways, and altered glycosphingolipid metabolism that resemble the biochemical changes occurring in human ADPKD kidneys. These pathways are normally active in neonatal mouse kidneys until repressed around 3 weeks of age; however, they remain active following Pkd1 deletion. Together, this work describes the key parameters to accurately model the pathological and biochemical changes associated with ADPKD in a conditional mouse model.

A thermodynamically based method to quantify true sorption hysteresis.

Sorption of organic chemicals to soils and sediments often shows true hysteresis (i.e., nonsingularity of the sorption-desorption isotherm not attributable to known experimental artifacts). Since true sorption hysteresis is fundamentally important to contaminant fate, a way to quantify it is desirable. Previously proposed indices of hysteresis are empirical and usually depend on the isotherm model. True sorption hysteresis to synthetic and natural organic solids has been attributed to irreversible alteration of the solid during the sorption-desorption cycle. Given this mechanism, we propose the Thermodynamic Index of Irreversibility (TII) for quantifying hysteresis in soils where natural organic matter dominates the sorption process. The TII is based on the difference in free energy between the real desorption state and the hypothetical fully reversible state. The index is 0 for completely reversible systems and approaches 1 as the process tends toward complete irreversibility. It does not require any assumptions about the physical properties or molecular composition of the solid, and it does not depend on a specific equilibrium model. A sensitivity analysis of measurement errors provides general recommendations for the setup of sorption-desorption experiments. The TII was applied to sorption of 1,4-dichlorobenzene (DCB) to two high-organic soils, Pahokee peat (PP) and Amherst soil (AS), and a low-rank coal reference material, Beulah-Zap lignite (BZL). Common artificial causes of hysteresis were eliminated. Hysteresis was significant in the peat and the coal. The TII was clearly concentration dependent for both solids; it decreased with concentration for the peat, but increased with concentration for the coal. The TII allows quantification of hysteresis as a function of sorbate-sorbent combination, concentration, time, and other variables.