Interpretation of course conceptual structure and student self-efficacy: an integrated strategy of knowledge graphs with item response modeling.

BACKGROUND: There is a scarcity of studies that quantitatively assess the difficulty and importance of knowledge points (KPs) depending on students' self-efficacy for learning (SEL). This study aims to validate the practical application of psychological measurement tools in physical therapy education by analyzing student SEL and course conceptual structure. METHODS: From the "Therapeutic Exercise" course curriculum, we extracted 100 KPs and administered a difficulty rating questionnaire to 218 students post-final exam. The pipeline of the non-parametric Item Response Theory (IRT) and parametric IRT modeling was employed to estimate student SEL and describe the hierarchy of KPs in terms of item difficulty. Additionally, Gaussian Graphical Models with Non-Convex Penalties were deployed to create a Knowledge Graph (KG) and identify the main components. A visual analytics approach was then proposed to understand the correlation and difficulty level of KPs. RESULTS: We identified 50 KPs to create the Mokken scale, which exhibited high reliability (Cronbach's alpha = 0.9675) with no gender bias at the overall or at each item level (p > 0.05). The three-parameter logistic model (3PLM) demonstrated good fitness with questionnaire data, whose Root Mean Square Error Approximation was < 0.05. Also, item-model fitness unveiled good fitness, as indicated by each item with non-significant p-values for chi-square tests. The Wright map revealed item difficulty relative to SEL levels. SEL estimated by the 3PLM correlated significantly with the high-ability range of average Grade-Point Average (p < 0.05). The KG backbone structure consisted of 58 KPs, with 29 KPs overlapping with the Mokken scale. Visual analysis of the KG backbone structure revealed that the difficulty level of KPs in the IRT could not replace their position parameters in the KG. CONCLUSION: The IRT and KG methods utilized in this study offer distinct perspectives for visualizing hierarchical relationships and correlations among the KPs. Based on real-world teaching empirical data, this study helps to provide a research foundation for updating course contents and customizing learning objectives. TRIAL REGISTRATION: Not applicable.

Serum LncRNA PANDAR may Act as a Novel Serum Biomarker of Diabetic Nephropathy in Patients with Type 2 Diabetes.

BACKGROUND: The current study aims to investigate the expression and significance of lncRNA PANDAR in the serum of patients with type II diabetes mellitus (T2DM) and diabetic nephropathy (DN). METHODS: The expression of PANDAR in 77 T2DM patients, 60 DN patients, and 60 healthy controls was detected by RT-PCR. Pearson's correlation assay was carried out to analyze the correlation between serum lncRNA PANDAR and clinical indicators. Receiver operator characteristic (ROC) analysis was carried out to analyze the diagnostic value of PANDAR in T2DM and DN patients. RESULTS: The expression of PANDAR in T2DM and DN patients was significantly higher than that in the control group. Moreover, the expression of PANDAR in DN patients with massive proteinuria was significantly higher than that in DN patients with microalbuminuria. Further study showed that the expression of PANDAR was positively correlated with the level of proteinuria (r = 0.690, p < 0.001), and negatively correlated with the glomerular filtration rate (r = -0.780, p < 0.001). In T2DM and DN patients, the area under ROC curve (AUC) of PANDAR as serum marker was 0.861 (95% CI: 0.786 - 0.935, p < 0.001), between DN patients and T2DM patients, while the AUC of PANDAR as a marker in diabetic nephropathy was 0.914 (95% CI: 0.828 - 0.980, p < 0.001) between DN patients and healthy controls. CONCLUSIONS: In summary, the high expression of PANDAR is related to the development of DN in T2DM patients, and it is expected to be a biomarker for predicting the prognosis of DN patients.

Clinicopathological and prognostic value of CD24 expression in breast cancer: a meta-analysis.

BACKGROUND: A number of studies have been conducted to explore the relationship between CD24 expression and the prognosis of breast cancer; however, the results remain inconsistent. Therefore, we performed this meta-analysis to clarify the impact of CD24 expression on clinicopathological features and prognosis of breast cancer. METHODS: A comprehensive literature search for relevant studies was performed, and statistical analysis was conducted using Stata software. RESULTS: Twenty studies, including 5,179 cases, were included in this meta-analysis. The pooled analysis indicated that CD24 expression was associated with lymph node invasion (odds ratio [OR] = 0.68, for negative vs. positive, 95% confidence interval [95% CI], 0.53-0.87, p = 0.002) and TNM stage (OR = 0.63, for I + II vs. III + IV, 95% CI, 0.49-0.81, p<0.001). The prognosis analysis also suggested CD24 overexpression indicated a poorer 5-year overall survival (OS) rate (relative risk ratio [RR] = 0.93, 95% CI, 0.86-0.99, p = 0.03) and 5-year disease-free survival (DFS) rate (RR = 0.90, 95% CI, 0.83-0.98, p = 0.02). However, CD24 expression had no correlation with tumor size, tumor grade, distance metastasis, estrogen receptor (ER) status, progesterone receptor (PR) status, or HER2 status. CONCLUSIONS: Our results suggest that higher CD24 expression is significantly associated with lower OS rate, lower DFS rate and some clinicopathological factors such as lymph node invasion and TNM stage. This meta-analysis suggested that CD24 is an efficient prognostic factor in breast cancer.

Decreased MiR-155 Level in the Peripheral Blood of Non-Alcoholic Fatty Liver Disease Patients may Serve as a Biomarker and may Influence LXR Activity.

BACKGROUND: Obesity is now a common risk factor for non-alcoholic fatty liver disease (NAFLD). Thus, it is important to explore its underlying mechanisms. METHODS: Total RNA was extracted from peripheral whole blood samples from 50 NAFLD patients and 50 healthy controls. In addition, human liver specimens were obtained through liver biopsies from NAFLD patients and healthy controls. The level of miRNA was studied using real-time PCR. The expression of lipogenic genes was analyzed using western blot, and a dual luciferase reporter assay was conducted to identify the possible target gene. Adenovirus vectors were injected into the tail vein of the high fat diet (HFD)-fed mice to study the role of miR-155 on lipid accumulation in vivo. RESULTS: The level of miR-155 was markedly reduced in the livers and peripheral blood of NAFLD patients compared with healthy controls. Upregulation of miR-155 decreased intracellular lipid content and the SREBP1 and FAS protein levels, while inhibition of miR-155 enhanced the intracellular lipid content. The dual luciferase reporter assay showed that Liver X receptor (LXR)α was the target gene of miR-155, and silencing miR-155 reduced the expression of SREBP1 and FAS. An in vivo study showed that upregulation of miR-155 decreased the hepatic lipid accumulation mainly by suppressing the LXRα-dependent lipogenic signaling pathway. CONCLUSIONS: In summary, decreased expression of miR-155 in the peripheral blood may be utilized as a potential novel biomarker for NAFLD screening mainly by targeting LXRα.

Pseudogene PTENP1 Functions as a Competing Endogenous RNA (ceRNA) to Regulate PTEN Expression by Sponging miR-499-5p.

Increasing evidence has shown that pseudogenes can widely regulate gene expression. However, little is known about the specific role of PTENP1 and miR-499-5p in insulin resistance. The relative transcription level of PTENP1 was examined in db/db mice and high fat diet (HFD)-fed mice by real-time PCR. To explore the effect of PTENP1 on insulin resistance, adenovirus overexpressing or inhibiting vectors were injected through the tail vein. Bioinformatics predictions and a luciferase reporter assay were used to explore the interaction between PTENP1 and miR-499-5p. The relative transcription level of PTENP1 was largely enhanced in db/db mice and HFD-fed mice. Furthermore, the overexpression of PTENP1 resulted in impaired Akt/GSK activation as well as glycogen synthesis, while PTENP1 inhibition led to the improved activation of Akt/GSK and enhanced glycogen contents. More importantly, PTENP1 could directly bind miR-499-5p, thereby becoming a sink for miR-499-5p. PTENP1 overexpression results in the impairment of the insulin-signaling pathway and may function as a competing endogenous RNA for miR-499-5p, thereby contributing to insulin resistance.

Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats.

Seawater drowning-induced acute lung injury (ALI) is a serious clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory responses, and refractory hypoxemia. However, current therapeutic options are largely supportive; thus, it is of great interest to search for alternative agents to treat seawater aspiration-induced ALI. Erythropoietin (EPO) is a multifunctional agent with antiinflammatory, antioxidative, and antiapoptotic properties. However, the effects of EPO on seawater aspiration-induced ALI remain unclear. In the present study, male rats were randomly assigned to the naive group, normal saline group, seawater group, or seawater + EPO group. EPO was administered intraperitoneally at 48 and 24 h before seawater aspiration. Arterial blood gas analysis was performed with a gas analyzer at baseline, 30 min, 1 h, 4 h, and 24 h after seawater aspiration, respectively. Histological scores, computed tomography scan, nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6, IL-10, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde, and superoxide dismutase in the lung were determined 30 min after seawater aspiration. Our results showed that EPO pretreatment alleviated seawater aspiration-induced ALI, as indicated by increased arterial partial oxygen tension and decreased lung histological scores. Furthermore, EPO pretreatment attenuated seawater aspiration-induced increase in the expressions of pulmonary nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, IL-1ß, myeloperoxidase activity, and malondialdehyde when compared with the seawater group. Collectively, our study suggested that EPO pretreatment attenuates seawater aspiration-induced ALI by down-regulation of pulmonary pro-inflammatory cytokines, oxidative stress, and apoptosis.

Elevated Resting Heart Rate Is Associated with Carotid Atherosclerosis in Middle-Aged and Elderly Chinese Population.

BACKGROUND: Elevated resting heart rate predicts poor cardiovascular and cerebrovascular outcomes. Atherosclerosis may be a mediator linking this relationship. In a Chinese population, we investigated whether resting heart rate was associated with carotid atherosclerosis as indicated by elevated carotid intima-media thickness (CIMT) and presence of carotid plaque. METHODS: A total of 1557 participants older than 50 years old from a community-based population without known cardiovascular diseases were included. All participants provided detailed lifestyle and medical information, and blood samples for biochemical measurements. The participants were categorized according to resting heart rate quartiles (<67, 67-73, 74-81, >81 beats per minute [bpm]). CIMT and presence of carotid plaque were determined using B-mode ultrasonography. Elevated CIMT was defined as the upper quartile of CIMT. RESULTS: We observed positively graded associations between resting heart rate quartiles and carotid atherosclerosis. Participants with resting heart rates higher than 81 bpm had an odds ratio of 2.82 (95% confidence interval 1.92-4.13) for elevated CIMT, and an odds ratio of 2.00 (1.36-2.92) for carotid plaque, compared to participants with resting heart rates lower than 67 bmp. Each 10-bpm increase in resting heart rate was associated with an odds ratio of 1.47 (1.29-1.68) for elevated CIMT and an odds ratio of 1.40 (1.23-1.60) for carotid plaque. The associations were independent of conventional cardiovascular risk factors. CONCLUSIONS: Elevated resting heart rate was strongly and independently associated with carotid atherosclerosis in the middle-aged and elderly Chinese population. Atherosclerosis may be a potential mediator between resting heart rate and adverse cardiovascular outcomes.

MiR-499-5p Contributes to Hepatic Insulin Resistance by Suppressing PTEN.

BACKGROUND: Type 2 diabetes afflicts 95% of diabetes patients. Recent data suggest that miRNAs play a key role in insulin production, secretion and function. This study aims to explore the specific role of miR-499-5p in hepatic insulin resistance. METHODS: The miRNA expression levels in the livers of db/db mice were analyzed using miRNA chips and were verified by real-time PCR. miR-499-5p mimics and an inhibitor were transfected into NCTC1469 cells. Then, the PI3K/AKT signaling pathway and glycogen level were determined. The target genes of miR-499-5p were predicted by bioinformatics and then confirmed by dual luciferase reporter assay and Western blot. To establish an insulin resistance (IR) animal model, C57BL/6 mice were fed a high-fat diet (HFD). The level of miR-499-5p in the livers of HFD-fed mice was upregulated through tail vein injection of adenovirus vectors (ad) containing miR-499-5p mimics. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to determine glucose tolerance and insulin tolerance, respectively. RESULTS: MicroRNA chips and qPCR showed that miR-499-5p was significantly decreased in the livers of db/db mice. Downregulation of miR-499-5p impaired the insulin signaling pathway and glycogen synthesis, whereas upregulation of miR-499-5p promoted the insulin signaling pathway and glycogen synthesis in NCTC1469 cells. The dual luciferase reporter assay and Western blot demonstrated that PTEN was the target gene of miR-499-5p. Compared with the control group, miR-499-5p was increased 2.1-fold in the livers of HFD-fed mice. By tail vein injection of adenovirus vector containing miR-499-5p mimics, GTT and ITT were improved in HFD-fed mice. CONCLUSION: Downregulation of the miR-499-5p level impaired the PI3K/AKT/GSK signaling pathway and glycogen synthesis by targeting PTEN.

[Effectiveness and related factors of Z-palatopharyngoplasty for treating obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the efficacy and related factors of Z-palatopharyngoplasty for treating severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Thirty four OSAHS patients with graded 1-3 tonsil, posterior airway space (PAS) > or = mm , Friedman II and III oropharyngeal airway were included in this study, all cases had Z-palatopharyngoplasty. The follow up was at least 6 months postoperatively. Measurement parameters of responders and nonresponders were analyzed. RESULTS: According to related criterion of China, cure rate was 35.3%, accumulative total excellence rate 64.7% and accumulative valid rate 70. 6%. The cured and excellence patients were considered as responders, the other as nonresponders. The lowest oxygen saturation (LSaO2), percentage of time with oxyhemoglobin saturation below 0.90 (CT90), mandibular plane angle (MPA), mandibular body length, position of tongue and Friedman clinical stage are statistically significant between responder and nonresponder. The best cut points of LSaO2, CT90 and MPA were 0.72, 22.80% and 29.40 degrees respectively. The logistic regression showed that Friedman stage and MPA entered into equation, which was Y = ln [P/(1-P)] = -122.85 + 31.57X1 + 1.01X2, if setting X1 as Friedman stage, and X2 as MPA. CONCLUSIONS: Z-palatopharyngoplasty is effective surgical approach for OSAHS patients with posterior airway space (PAS) > or = 11 mm. The affective factors of Z-palatopharyngoplasty included LSaO2, CT90, MPA, mandibular body length, position of tongue and Friedman clinical stage. Among them, the mandibular plane angle and Friedman clinical stage were predominant factors.

Genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty for severe OSAHS.

OBJECTIVE: To evaluate the outcome of a comprehensive surgical approach on the treatment of severe obstructive sleep apnea hypopnea syndrome (OSAHS) and find out possible predictors to the effectiveness of this approach. STUDY DESIGN AND SETTING: Eighteen patients received genioglossus advancement with hyoid suspension (GAHM) and uvulopalatopharyngoplasty (UPPP). The multiple logistic regression was used to analyze predictors for the outcome of treatment. RESULTS: Apnea hypopnea index (AHI) showed a reduction in the preoperative vs postoperative polysomnography (63.83 +/- 16.34 vs 21.43 +/- 20.34). With success defined as a final postoperative AHI of less than 20 events per hour, the success rate was 67%. The main differences between responders and nonresponders include age, posterior airway space (PAS), time of oxyhemoglobin saturation below 90% (CT90), and body mass index (BMI). Age and BMI were key predictors for therapeutic effect. CONCLUSION: GAHM plus UPPP may benefit severe OSAHS patients with oropharyngeal and hypopharyngeal obstruction. The success was best predicted by low BMI and younger age. SIGNIFICANCE: This paper provides reference for patient selection of UPPP plus GAHM, and considers that older or morbidly obese patients with OSAHS should be excluded from this operation.

Anatomic and spiral computed tomographic study of the genial tubercles for genioglossus advancement.

OBJECTIVE: To measure and compare Chinese mandibular genial tubercles measured anatomically and with computed tomography (CT). STUDY DESIGN AND SETTING: Spiral CT scans were taken of 40 adult human skulls; the superior genial spines were measured using anatomic and CT methods. RESULTS: The height and width of the superior genial spines, mandible thickness, and distance from the menton to the inferior and superior margins of the superior genial spines were 5.82 +/- 0.71, 6.98 +/- 1.35, 11.95 +/- 1.59, 11.08 +/- 2.05, and 16.91 +/- 2.30 mm from anatomic measurements and 6.17 +/- 0.71, 7.01 +/- 1.13, 12.19 +/- 1.64, 10.41 +/- 1.55, and 15.73 +/- 2.12 mm using spiral CT, respectively. The anatomic and CT measurements were correlated. CONCLUSION: Spiral CT of the genial tubercles can help locate the osteotomy in genioglossus advancement. SIGNIFICANCE: This study acquired reference data on Chinese genial tubercles demonstrating that CT measurements of the genial tubercles reflect their anatomy, which should allow accurately locate the osteotomy.

[Effectiveness of combined surgery for treating severe obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the efficiency of a comprehensive surgical approach of genioglossus advancement and hyoid suspension (GAHM) plus uvulopalatopharyngoplasty (UPPP) for treating severe obstructive sleep apnea hypopnea syndrome (OSAHS) and to evaluate related factors on surgery outcomes. METHODS: Eighteen patients with severe OSAHS (apnea hypopnea index, AHI > 40/h) confirmed with polysomnography received genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty. The obstruction in both the oropharynx and the hypopharynx were evaluated by preoperative physical examination, fiberoptic pharyngolaryngoscopy, cephalometry, and computed tomography of the upper airway. The follow up was at least 6 months postoperatively. The Wilcoxon signed rank test was used to compare the preoperative and postoperative results by SPSS 11.0 for windows. The Mann-Whitney test was used to analyze the difference between responders and nonresponders. RESULTS: The follow up time ranges from 6 to 24 months, there were statistically significance in all but body mass index (BMI) between preoperative and postoperative measurements. Mean AHI was reduced from preoperative (x +/- s, 63.8 +/- 16.3)/h to postoperative (23.6 +/- 19.5)/h, lowest mean oxygen saturation increased from 0.72 +/- 0.07 to 0.81 +/- 0.13(x +/- s). According to criterion at home, the 6-month rate of responder is 83%, if AHI <20/h and decreased by at least 50% as success, the rate of success is 67%. The age, posterior airway space (PAS) and percentage of time with oxyhemoglobin saturation below 0.90 (CT90) were (39.1 +/- 7.4) years, (8.3 +/- 0.9) mm, (18.5 +/- 10.9)% in responder, while (52.5 +/- 9.4) years, (6.8 +/- 1.3) mm, (37.7 +/- 23.6) % in nonresponder, and there are statistically significant between responder and nonresponder. CONCLUSIONS: GAHM plus UPPP is effective surgical approach for patients with severe OSAHS who suffer from oropharyngeal and hypopharyngeal obstruction. Age, PAS and CT90 were possible affective factors on surgical outcomes.

Expression of bioactive recombinant GSLL-39, a variant of human antimicrobial peptide LL-37, in Escherichia coli.

The human cationic antimicrobial peptide hCAP-18/LL-37 is the unique cathelicidin identified in human to date. It has broad spectrum of antimicrobial activities and LPS-neutralizing activity and is involved in angiogenesis. Both purified and synthetic LL-37 or its derivatives were used in the study on LL-37. However, production of LL-37 in Escherichia coli has not been established. In this study, its precursor instead of the mature peptide was adopted for expression to avoid the lethal effect of recombinant LL-37 on host cells. A thrombin recognition site was introduced between the cathelin-like domain and LL-37 domain by overlap PCR to construct fragment encoding modified precursor (mhCAP-18) to facilitate the final release of the recombinant peptide. Then mhCAP-18 was fused in-frame to thioredoxin gene under the control of inducible T7 promoter to construct expression vector pET-mhCAP-18. The soluble form fusion protein was expressed in E. coli and purified by Chelating Sepharose column chromatography. Thrombin digestion of the fusion protein yielded recombinant GSLL-39, which was then purified by cation-exchange chromatography. Recombinant GSLL-39, which has two extra residues on its N-terminus when compared with its native counterpart, showed similar antimicrobial activities against both Gram-negative and Gram-positive bacteria.

IL-18 increases invasiveness of HL-60 myeloid leukemia cells: up-regulation of matrix metalloproteinases-9 (MMP-9) expression.

Similar to matrix metalloproteinases (MMP-9/-2), IL-18 was overexpressed in some hematologic malignancies such as acute myeloid leukemia (AML), which is associated with a poor clinical outcome. To establish a possible functional relationship between IL-18 and MMPs in myeloid leukemia, we used semi-quantitative PCR and zymographic analysis to examine whether IL-18 stimulates human myeloid leukemia cell line HL-60 to produce MMPs and/or specific tissue inhibitors (TIMPs), and to degrade extracellular matrix (ECM) gel in vitro. In the ECM invasion assay IL-18 significantly up-regulated transmigration of HL-60 cells, which in turn was inhibited by a synthetic MMP inhibitor: O-phenanthroline (o-PE), anti-MMP-9, anti-MMP-2 as well as anti-IL-18 monoclonal antibody (McAb), respectively, suggesting that induction of gelatinases by IL-18 leads to ECM degradation by these cells. Moreover, IL-18 could significantly increase MMP-9 but not MMP-2 production at both mRNA and/or protein level, slightly up-regulate TIMP-1 mRNA, and clearly induce TIMP-2 mRNA secretion. We postulate that IL-18 may in part play a role in the clinical aggressiveness of human myeloid leukemia by stimulating MMP-9 production.

Clone and expression of mutant M-CSF and its receptor from human leukemic cell line J6-1.

Macrophage colony-stimulating factor (M-CSF) plays important roles in hematopoietic and immunologic systems. Some isoforms or mutations have been demonstrated including membrane-bound and cellular M-CSF, which associated with some leukemia, lymphoma and other solid tumors. We previously reported that the M-CSF-like membrane-associated factor (MAF-J6-1) and its receptor was found from human leukemic cell line J6-1. In this report, the cDNA of MAF-J6-1 and its receptor were cloned. The cDNA sequence of MAF-J6-1 shows a 768bp open reading frame (ORF) with 99.2% homology to m-M-CSF, but six site mutations, including two synonymous mutations and four missense mutations. The cDNA of MAF-J6-1-R has a 2916bp ORF shared 99.6% homology with M-CSF-R, but 13 site mutations, including six synonymous mutations and seven missense mutations. At the same time, a 1662bp mutant s-M-CSF cDNA, which has 10 site mutations including three synonymous mutations and seven missense mutations, was cloned from J6-1 cells. The cDNAs of MAF-J6-1 and MAF-J6-1-R were inserted into a mammalian expression plasmid pTARGET and were expressed in COS-7 cells that demonstrated by their specific MAb. COS-7 cells transfected with MAF-J6-1-R show obvious protein tyrosine kinase (PTK) activity. Our present work shows that MAF-J6-1 and its receptor are mutations of M-CSF and its receptor.