A study of forensic genetics: ITO index distribution and kinship judgment between two individuals.

According to Mendel's law of genetic separation, there must be a certain blood relationship between members of the same family, and two individuals with blood relations must have the following three situations, that is, there are two homologous genes (I denotes), one homologous gene (T denotes), and no homologous genes (O denotes), which is the ITO index for calculating the blood relationship between two individuals. The AGGU Expressmarker 22 kit, ABI 3500 genetic analyzer, and GeneMapper ID-X v1.5 software were used to statistically analyze the ITO index of the gene locus of 5 kinds of samples, 28 pairs of monozygotic twins (MT), 4,000 pairs of parent-offspring (PO), 392 pairs of full sibling (FS), 138 pairs of half-siblings (HS) (including grandchildren, uncles, and nephews) and 3,500 pairs of unrelated individuals (UI). Observing the median distribution of ITO index found that from MT, PO, FS, HS to UI, the more distant the kinship, the smaller the ITO index. Full sibling index (FSI)/half-sibling index (HSI) ≥ 1 can be used as the FS discriminant standard, FSI/HSI < 1 can be used as the HS discriminant standard. According to the distance of kinship, from the direction of MT, PO, FS, HS, and UI, the proportion of the maximum ITO index of the same type of sample in the true kinship index item showed a decreasing trend. ITO index is an important statistical means to identify the kinship between two individuals, according to which the ITO index can accurately determine the kinship between individuals, which has high application value. MT index is not 0 to identify relatives as MT, PO index is an important indicator to distinguish between relatives as PO and FS. The critical values of ITO index discriminant values for UI and HS need to be further studied.

Empagliflozin, a sodium glucose cotransporter-2 inhibitor, ameliorates peritoneal fibrosis via suppressing TGF-ß/Smad signaling.

Sodium glucose cotransporter-2 (SGLT-2) inhibitor has been reported to exert a glucose-lowering effect in the peritoneum exposed to peritoneal dialysis solution. However, whether SGLT-2 inhibitors can regulate peritoneal fibrosis by suppressing TGF-ß/Smad signaling is unclear. We aimed to (i) examine the effect of the SGLT-2 inhibitor empagliflozin in reducing inflammatory reaction and preventing peritoneal dialysis solution-induced peritoneal fibrosis and (ii) elucidate the underlying mechanisms. High-glucose peritoneal dialysis solution or transforming growth factor ß1 (TGF-ß1) was used to induce peritoneal fibrosis in vivo, in a mouse peritoneal dialysis model (C57BL/6 mice) and in human peritoneal mesothelial cells in vitro, to stimulate extracellular matrix accumulation. The effects of empagliflozin and adeno-associated virus-RNAi, which is used to suppress SGLT-2 activity, on peritoneal fibrosis and extracellular matrix were evaluated. The mice that received chronic peritoneal dialysis solution infusions showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and upregulated α-smooth muscle actin and collagen I expression. Empagliflozin treatment or downregulation of SGLT-2 expression significantly ameliorated these pathological changes. Inflammatory cytokines (TNF-α, IL-1ß, IL-6) and TGF-ß/Smad signaling-associated proteins, such as TGF-ß1 and phosphorylated Smad (p-Smad3), decreased in the empagliflozin-treated and SGLT-2 downregulated groups. In addition, empagliflozin treatment and downregulation of SGLT-2 expression reduced the levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6), TGF-ß1, α-smooth muscle actin, collagen I, and p-Smad3 accumulation in human peritoneal mesothelial cells. Collectively, these results indicated that empagliflozin exerted a clear protective effect on high-glucose peritoneal dialysis-induced peritoneal fibrosis via suppressing TGF-ß/Smad signaling.

Polyphyllin I attenuates cognitive impairments and reduces AD-like pathology through CIP2A-PP2A signaling pathway in 3XTg-AD mice.

Polyphyllin I (PPI) is a natural phytochemical drug isolated from plants which can inhibit the proliferation of cancer cells. One of the PPI tumor-inhibitory effects is through downregulating the expression of Cancerous Inhibitor of PP2A (CIP2A), the latter, is found upregulated in Alzheimer's disease (AD) brains and participates in the development of AD. In this study, we explored the application of PPI in experimental AD treatment in CIP2A-overexpressed cells and 3XTg-AD mice. In CIP2A-overexpressed HEK293 cells or primary neurons, PPI effectively reduced CIP2A level, activated PP2A, and decreased the phosphorylation of tau/APP and the level of Aß. Furthermore, synaptic protein levels were restored by PPI in primary neurons overexpressing CIP2A. Animal experiments in 3XTg-AD mice revealed that PPI treatment resulted in decreased CIP2A expression and PP2A re-activation. With the modification of CIP2A-PP2A signaling, the hyperphosphorylation of tau/APP and Aß overproduction were prevented, and the cognitive impairments of 3XTg-AD mice were rescued. In summary, PPI ameliorated AD-like pathology and cognitive impairment through modulating CIP2A-PP2A signaling pathway. It may be a potential drug candidate for the treatment of AD.

Development and Validation of a Radiomic-Based Model for Prediction of Intrahepatic Cholangiocarcinoma in Patients With Intrahepatic Lithiasis Complicated by Imagologically Diagnosed Mass.

BACKGROUND: This study was conducted with the intent to develop and validate a radiomic model capable of predicting intrahepatic cholangiocarcinoma (ICC) in patients with intrahepatic lithiasis (IHL) complicated by imagologically diagnosed mass (IM). METHODS: A radiomic model was developed in a training cohort of 96 patients with IHL-IM from January 2005 to July 2019. Radiomic characteristics were obtained from arterial-phase computed tomography (CT) scans. The radiomic score (rad-score), based on radiomic features, was built by logistic regression after using the least absolute shrinkage and selection operator (LASSO) method. The rad-score and other independent predictors were incorporated into a novel comprehensive model. The performance of the Model was determined by its discrimination, calibration, and clinical usefulness. This model was externally validated in 35 consecutive patients. RESULTS: The rad-score was able to discriminate ICC from IHL in both the training group (AUC 0.829, sensitivity 0.868, specificity 0.635, and accuracy 0.723) and the validation group (AUC 0.879, sensitivity 0.824, specificity 0.778, and accuracy 0.800). Furthermore, the comprehensive model that combined rad-score and clinical features was great in predicting IHL-ICC (AUC 0.902, sensitivity 0.771, specificity 0.923, and accuracy 0.862). CONCLUSIONS: The radiomic-based model holds promise as a novel and accurate tool for predicting IHL-ICC, which can identify lesions in IHL timely for hepatectomy or avoid unnecessary surgical resection.

Nestin Promotes Peritoneal Fibrosis by Protecting HIF1-α From Proteasomal Degradation.

BACKGROUND: Peritoneal dialysis (PD) is a treatment for end stage renal disease patients, but it can also cause peritoneal fibrosis. Nestin is known as a neural stem cell marker and it has many functions. The hypoxia induced factor (HIF) signaling pathway can be activated under hypoxia conditions, leading to the overexpression of some angiogenesis related genes. The aim of our study is to demonstrate Nestin's role in the development of peritoneal fibrosis (PF), and to provide a new target (Nestin) to treat PF. METHODS: PD mice models were constructed by an intraperitoneal administration of PDS at 10 ml/100g/d for 4 weeks. Nestin-positive cells were isolated from peritonea of Nestin-GFP mice by flow cytometry. The relationship of Nestin and HIF1-α-VEGFA pathway was detected by Nestin knockdown, Co-immunoprecipitation and immunofluorescence. Also, proteasomal activity was demonstrated by CHX and MG132 application, followed by Western blotting and Co-immunoprecipitation. RESULTS: In our experiments, we found that Nestin expression resulted in PF. Also, HIF1-α/VEGFA pathway was activated in PF. Nestin knockdown reduced the level of HIF1-α. Nestin directly bound to HIF1-α and protected HIF1-α from proteasomal degradation. Overexpression of HIF1-α reverts the fibrosis levels in Nestin-knockdown cells. In brief, Nestin inhibited the degradation of HIF1-α by mitigating its ubiquitination level, leading to the activation of HIF1-α signaling pathway, and eventually promoted PF. CONCLUSION: We found a novel mechanism of PF that Nestin promotes by protecting HIF1-α from proteasomal degradation. Taken together, our key findings highlight a novel mechanism by which the silencing of Nestin hinders HIF1- α -induced PF.

An updated comparison of high- and low-viscosity cement vertebroplasty in the treatment of osteoporotic thoracolumbar vertebral compression fractures: A retrospective cohort study.

OBJECTIVE: This study mainly aimed to evaluate complications of cement leakage for osteoporotic thoracolumbar vertebral compression fractures by PVP using HVC, and access the clinical efficacy. METHODS: Between May 2013 and June 2015, 66 patients with osteoporotic thoracolumbar vertebral compression fractures, who underwent PVP (36 HVC and 30 LVC) in our hospital, were enrolled. Cement leakage, Visual Analog Scale (VAS), Oswestry Disability Index (ODI), refracture of the cemented vertebrae, and adjacent vertebral fractures were evaluated. The follow-up time was 1 year. RESULTS: The overall cement leakage rate was 30.55% in the HVC group, lower than 77.77% obtained in the LVC group (P = 0.00). The incidence rates of cement leakage into paravertebral area (P = 0.02) and vein (P = 0.04) in the HVC group were significantly lower than those of the LVC group; however, no differences were found for disc space (P = 0.72) and intraspinal space (P = 0.58). There were no differences in VAS, ODI, refracture of cemented vertebrae, and adjacent vertebral fracture between the two groups (P > 0.05). CONCLUSIONS: PVP using HVC not only can reduce cement leakage, especially in the paravertebral area and peripheral vein, but also has satisfactory clinical effect.

Updated association of tea consumption and bone mineral density: A meta-analysis.

BACKGROUND: Current studies evaluating the association of tea consumption and bone mineral density (BMD) have yielded inconsistent findings. Therefore, we conducted a meta-analysis to assess the relationship between tea consumption and BMD. METHODS: The PubMed, Embase, and Cochrane Library databases were comprehensively searched, and a meta-analysis performed of all observational studies assessing the association of tea consumption and BMD. Forest plots were used to illustrate the results graphically. The Q-test and I statistic were employed to evaluate between-study heterogeneity. Potential publication bias was assessed by the funnel plot. RESULTS: Four cohort, 1 case-control, and 8 cross-sectional studies including a total of 12,635 cases were included. Tea consumption was shown to prevent bone loss [odds ratio (OR): 0.66; 95% confidence interval (CI), 0.47-0.94; P = 0.02], yielding higher mineral densities in several bones, including the lumbar spine [standardized mean difference (SMD): 0.19; 95% CI, 0.08-0.31; P = 0.001], hip (SMD: 0.19; 95% CI, 0.05-0.34; P = 0.01), femoral neck [mean difference (MD): 0.01; 95% CI, 0.00-0.02; P = 0.04], Ward triangle (MD: 0.02; 95% CI, 0.01-0.04; P = 0.001), and greater trochanter (MD: 0.03; 95% CI, 0.02-0.04; P < 0.00001), than the non-tea consumption group. CONCLUSION: This meta-analysis provided a potential trend that tea consumption might be beneficial for BMD, especially in the lumbar spine, hip, femoral neck, Ward triangle, and greater trochanter, which might help prevent bone loss.