Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Development and internal validation of a clinical prediction model for osteopenia in Chinese middle-aged and elderly men: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. METHODS: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. RESULTS: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. CONCLUSIONS: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Differentiation of Low- and High-Grade Pediatric Brain Tumors with High b-Value Diffusion-weighted MR Imaging and a Fractional Order Calculus Model.

PURPOSE: To demonstrate that a new set of parameters (D, ß, and µ) from a fractional order calculus (FROC) diffusion model can be used to improve the accuracy of MR imaging for differentiating among low- and high-grade pediatric brain tumors. MATERIALS AND METHODS: The institutional review board of the performing hospital approved this study, and written informed consent was obtained from the legal guardians of pediatric patients. Multi-b-value diffusion-weighted magnetic resonance (MR) imaging was performed in 67 pediatric patients with brain tumors. Diffusion coefficient D, fractional order parameter ß (which correlates with tissue heterogeneity), and a microstructural quantity µ were calculated by fitting the multi-b-value diffusion-weighted images to an FROC model. D, ß, and µ values were measured in solid tumor regions, as well as in normal-appearing gray matter as a control. These values were compared between the low- and high-grade tumor groups by using the Mann-Whitney U test. The performance of FROC parameters for differentiating among patient groups was evaluated with receiver operating characteristic (ROC) analysis. RESULTS: None of the FROC parameters exhibited significant differences in normal-appearing gray matter (P ≥ .24), but all showed a significant difference (P < .002) between low- (D, 1.53 µm(2)/msec ± 0.47; ß, 0.87 ± 0.06; µ, 8.67 µm ± 0.95) and high-grade (D, 0.86 µm(2)/msec ± 0.23; ß, 0.73 ± 0.06; µ, 7.8 µm ± 0.70) brain tumor groups. The combination of D and ß produced the largest area under the ROC curve (0.962) in the ROC analysis compared with individual parameters (ß, 0.943; D,0.910; and µ, 0.763), indicating an improved performance for tumor differentiation. CONCLUSION: The FROC parameters can be used to differentiate between low- and high-grade pediatric brain tumor groups. The combination of FROC parameters or individual parameters may serve as in vivo, noninvasive, and quantitative imaging markers for classifying pediatric brain tumors.

Comparison of immediate and long-term results between the single balloon and inoue balloon techniques for percutaneous pulmonary valvuloplasty.

BACKGROUND: This study was undertaken to compare the immediate and long-term follow-up results of balloon pulmonary valvuloplasty (BPV) between the single balloon and Inoue balloon for isolated pulmonary valve stenosis (PS). METHODS: A retrospective analysis of outcomes following BPV in 38 children using the single balloon and 42 adults using the Inoue balloon at a single institution was performed. RESULTS: The majority of children (76.3%) were asymptomatic while 26 adults (61.9%) presented with symptoms. The ratio of balloon size to pulmonary valve annulus was 1.23 ± 0.12 in the children group and 1.22 ± 0.10 in the adult group (P=0.641). The children group had a right ventricle-pulmonary artery systolic gradient of 52.79 ± 35.08 mmHg that decreased to 22.55 ± 12.92 mmHg following BPV (P<0.001). The adult group had a gradient of 94.79 ± 42.19 mmHg that decreased to 34.02 ± 15.00 mmHg following BPV (P<0.001). Mild pulmonary regurgitation occurred in eight children (21.1%) and 10 adults (23.8%) (P=0.768). During a median follow-up of 15 years, gradients were not significantly different from that obtained at one-month follow-up in children (P=0.280) and adults (P=0.373). CONCLUSIONS: Adults can be treated with BPV using the Inoue balloon with encouraging immediate and long-term follow-up results that are similar to those in children using the single balloon.

EvoVis: A Visual Analytics Method to Understand the Labeling Iterations in Data Programming.

Obtaining high-quality labeled training data poses a significant bottleneck in the domain of machine learning. Data programming has emerged as a new paradigm to address this issue by converting human knowledge into labeling functions(LFs) to quickly produce low-cost probabilistic labels. To ensure the quality of labeled data, data programmers commonly iterate LFs for many rounds until satisfactory performance is achieved. However, the challenge in understanding the labeling iterations stems from interpreting the intricate relationships between data programming elements, exacerbated by their many-to-many and directed characteristics, inconsistent formats, and the large scale of data typically involved in labeling tasks. These complexities may impede the evaluation of label quality, identification of areas for improvement, and the effective optimization of LFs for acquiring high-quality labeled data. In this paper, we introduce EvoVis, a visual analytics method for multi-class text labeling tasks. It seamlessly integrates relationship analysis and temporal overview to display contextual and historical information on a single screen, aiding in explaining the labeling iterations in data programming. We assessed its utility and effectiveness through case studies and user studies. The results indicate that EvoVis can effectively assist data programmers in understanding labeling iterations and improving the quality of labeled data, as evidenced by an increase of 0.16 in the average F1 score when compared to the default analysis tool.

Effects of Zinc Methionine Hydroxy Analog Chelate on Laying Performance, Serum Hormone Levels, and Expression of Reproductive Axis Related Genes in Aged Broiler Breeders.

Inorganic zinc (Zn) supplements are commonly used in poultry feeds, but their low utilization results in the increase of Zn excretion. Thus, to provide a new perspective for the substitution of inorganic Zn, a novel Zn methionine hydroxy analog chelate (Zn-MHA) was studied in the present study to evaluate its effects on laying performance, serum hormone indexes and reproductive axis-related genes in broilers breeders. A total of 480 Hubbard breeders (56-week-old) were fed a basal diet (containing 27.81 mg Zn/kg) without Zn addition for 2 weeks, and then allocated to 4 groups with 6 replicates (each replicate consisting of 10 cages and 2 breeders per cage) for 10 weeks. Four treatment diets given to broiler breeders included the basal diet added with 25, 50, and 75 mg/kg of Zn-MHA and 100 mg/kg of Zn sulfate (ZnSO4). The laying rate, egg weight and feed conversation ratio increased in the 75 mg/kg Zn-MHA group compared to the ZnSO4 group. The eggshell thickness was not decreased with the addition of 50 mg/kg and 75 mg/kg Zn-MHA in the diet compared to the 100 mg/kg ZnSO4 group. There was a significant improvement in the reproductive performance of breeders in the 75 mg/kg Zn-MHA group, including the fertility and 1-day-old offspring weight. Besides, serum sex hormone levels including FSH and P4 increased significantly in 75 mg/kg Zn-MHA group. No significant effect on the ovarian weight or the number of follicles in broiler breeders was observed by supplementing Zn-MHA. Compared to the 100 mg/kg ZnSO4 group, dietary supplementation with 75 mg/kg of Zn-MHA showed an up-regulation of the FSHR mRNA in the granular layer of follicles. However, dietary supplementation of Zn-MHA had no effects on mRNA expressions of the ovarian LHR and PRLR genes. These findings reinforce the suggestion that Zn-MHA (75 mg/kg) could replace ZnSO4 (100 mg/kg) as a Zn supplement in diet of broiler breeders, which resulted in better laying and reproduction performances by regulating the expression levels of reproductive axis related genes and serum hormone levels.

Ginger extract enhances antioxidant ability and immunity of layers.

This experiment was to investigate ginger extract on production performance, antioxidant ability and immunity of laying hens. A total of 600 Hy-Line brown laying hens aged at 25 wk old were randomly divided into 2 treatments, 4 replicates per treatment, 75 layers each replicate. The control group hens were fed a basal diet; the experimental group hens were fed basal diets with 0.1% ginger extract. The results were shown as follows: 1) ginger extract significantly enhanced laying rates (P < 0.05) and daily egg weight (P < 0.05), substantially reduced the ratio of feed to egg (P < 0.05) of the hens; 2) ginger extract did not change the activities of glutathione peroxidase (GSH-PX) and total antioxidant capacity (TAOC) but significantly improved plasma superoxide dismutase (SOD) activity (P < 0.05), reduced malondialdehyde (MDA) content (P < 0.05) of the birds; 3) ginger extract did not affect the contents of serum total protein (TP), albumin (ALB), globulin (GLB), but significantly increased lysozyme (LZM) activity (P < 0.05); 4) ginger extract also significantly reduced plasma prostaglandin E2 (PGE2) content (P < 0.05). This study shows that ginger extract not only can improve the birds' antioxidant capacity, enhance immune function, but also has a potential of reducing inflammatory response.

HOXA1 enhances the cell proliferation, invasion and metastasis of prostate cancer cells.

HOXA1, a member of the HOX gene family, has been implicated in tumor progression. However, the role of HOXA1 in prostate cancer is not well-established. In the present study, we found that HOXA1 was highly expressed in prostate cancer cells. We then repressed the expression of HOXA1 by short hairpin RNA (shRNA) to investigate the function of HOXA1 in prostate cancer cells. Our in vitro data showed that knockdown of HOXA1 attenuated the growth, invasion and migration of prostate cancer DU-145 and PC-3 cells. Furthermore, knockdown of HOXA1 resulted in an increased E-cadherin level and decreased Snail and MMP-3 levels in the DU-145 cells. In addition, knockdown of HOXA1 inhibited activation of ERK1/2 and AKT in the DU-145 cells. Our in vivo data revealed that knockdown of HOXA1 suppressed the growth and metastasis of prostate cancer cells. Collectively, our findings suggest that HOXA1 is involved in the regulation of prostate cancer progression, including cell growth, migration, invasion and metastasis. Thus, downregulation of HOXA1 may be a novel approach for the treatment of prostate cancer.

[Influence of PKB on ROS regulation of proliferation in human 7721 hepatoma cells].

In the present study, the relationship between PKB signaling and reactive oxygen species (ROS) during the course of exogenous and endogenous ROS or antioxidants regulating human 7721 hepatoma cell proliferation was studied. To change endogenous ROS levels, 7721 cells were transfected with human manganese superoxide dismutase (MnSOD) construct containing sense or antisense MnSOD cDNA. Low level of exogenous ROS H2O2(1-10 mumol/L) significantly stimulated PKB activity and c-fos/c-jun expression and cell growth, which could be abolished by antioxidant danshensu (40 mg/L). It was observed that overexpression of MnSOD inhibited 7721 cell growth by inhibiting PKB activity and c-fos/c-jun expression; the PKB activity and c-fos/c-jun expression, however, were stimulated by down-regulated MnSOD expression. In addition, PKB-7721 cells (transfected with sense PKB cDNA) promoted c-fos/c-jun expression by stimulating PKB activity. These results suggest that the redox state stimulated hepatoma cell growth through PKB pathway, which modulates AP-1 expression.

Comparison of immediate results and mid-term follow-up of surgical and percutaneous closure of ruptured sinus of Valsalva aneurysm.

BACKGROUND: The past decade has witnessed considerable improvement in implantation techniques for percutaneous closure of ruptured sinus of Valsalva aneurysm. This study was undertaken to compare the immediate results and mid-term follow-up of traditional surgery and percutaneous closure of ruptured sinus of Valsalva aneurysm in China. METHODS: Between January 1993 and January 2013, a total of 35 patients with ruptured sinus of Valsalva aneurysm were enrolled for attempted closure in our institution. Twenty patients (57.1%) underwent surgical repair and the other 15 patients (42.9%) underwent percutaneous closure. RESULTS: Nineteen patients (95.0%) in the surgical group had complete closure and 14 patients (93.3%) in the percutaneous closure group were treated successfully (p=0.681). Twelve patients with ruptured sinus of Valsalva aneurysm combined with subarterial ventricular septal defect (VSD) underwent surgical repair concomitantly. Two patients in the percutaneous closure group were treated for ruptured sinus of Valsalva aneurysm and perimembranous VSD using occluders concomitantly. One case of severe hemolysis developed 8h after the procedure in the percutaneous closure group. One death and one case of patch leak occurred in the surgical group during hospitalization. The time of hospital stay in the percutaneous closure group was shorter than that in the surgical group (p=0.004). The total medical cost of isolated ruptured sinus of Valsalva aneurysm in the percutaneous closure group was lower compared with that in the surgical group (p=0.046). During a median follow-up of 15 months (2-240 months), there were no deaths, infective endocarditis, device embolization, or malposition. CONCLUSIONS: Percutaneous closure is an attractive alternative to surgery in selected patients with ruptured sinus of Valsalva aneurysm for the better clinical advantages and economic benefits.

PPM1D as a novel biomarker for prostate cancer after radical prostatectomy.

Protein phosphatase magnesium-dependent 1 delta (PPM1D) is involved in several types of cancer. The current study examined the role of PPM1D expression in prostate cancer (PCa) tissues and in PCa cell lines. Expression of PPM1D was evaluated using immunohistochemistry in 234 PCa tissues after radical prostatectomy and 80 benign prostatic hyperplasia (BPH) tissues. The associations of PPM1D expression with clinicopathological parameters and survival were analyzed. In vitro, tumor cells were transfected with small interfering RNA targeting PPM1D (siPPM1D) or si-Scramble, and the cell proliferation, migration and invasion were determined. We found that PPM1D expression was significantly higher in PCa tissues than that in BPH tissues. PPM1D expression was positively correlated with Gleason score (p=0.022), T stage (p=0.015) and lymph node status (p=0.016). Kaplan-Meier curve analysis showed that patients with positive PPM1D expression had shorter biochemical recurrence-free survival and overall survival. Furthermore, multivariate analyses showed that PPM1D expression was an independent predictor of both biochemical recurrence-free (hazard ratio=3.437, 95% confidence interval=1.154-6.209, p=0.016) and overall survival (hazard ratio=5.026, 95% confidence interval=2.545-8.109, p=0.007). Knockdown of PPM1D inhibited the proliferation, migration and invasion capabilities of PC-3 and LNCaP cells. PPM1D expression may predict for both overall and biochemical recurrence-free survival in patients after radical prostatectomy for PCa. Elevated PPM1D expression plays a key role in progression of PCa.

Strong cellular and humoral immune responses induced by transcutaneous immunization with HBsAg DNA-cationic deformable liposome complex.

Transcutaneous immunization presents a major challenge on account of poor permeability of antigens through the skin barrier. To overcome this limitation, the deformable liposome could be a better method for transcutaneous delivery of these antigens. In this study, hepatitis B surface antigen (HBsAg) plasmid DNA-cationic complex deformable liposome was utilized as a mode for enhanced immunity against the antigen. Deformable liposome was prepared by conventional rotary evaporation method and characterized for various parameters such as vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity and stability. The immune stimulating activity was studied by measuring serum anti-HBsAg titre and cytokines level (interleukin-4 and interferon-gamma) following topical application of liposome in BALB/c mice and results were compared with deformable liposome encapsulated DNA applied topically as well as naked DNA and pure recombinant HBsAg, administered intramuscularly. It was observed that deformable liposome elicited a comparable serum antibody titre and endogenous cytokines levels compared to other vaccinations. The study signifies the potential of deformable liposome as DNA vaccine carriers for effective transcutaneous immunization.