Elevated preoperative plasma D-dimer level was an independent prognostic factor for patients with PDAC after curative resection: a retrospective analysis.

OBJECTIVE: In this study, the relationship between preoperative plasma D-dimer level and overall survival and recurrence free survival were evaluated in patients with curative resection of pancreatic ductal adenocarcinoma. METHODS: Preoperative plasma D-dimer level of 573 patients with pancreatic ductal adenocarcinoma were collected. The univariate and multivariate Cox hazard models were used to identify independent variables associated with overall survival and recurrence free survival in this study. The Kaplan-Meier method was used to evaluate overall survival and recurrence free survival, and the differences between survival curves were analyzed using the Log-rank test. Continuous variables were presented as $\overline{x}\pm s$, parametric analysis was performed using t-test. Categorical variables were analyzed by means of the chi-square or Fisher's exact test. RESULTS: Based on the analysis for the whole study, the results showed that patients in the elevated plasma D-dimer levels had a tendency to have an elder mean age (58.69 ± 8.32 years vs. 63.05 ± 8.44 years, P < 0.001), larger tumour size ≥4 cm (P = 0.006), advanced T stage (P = 0.024), N stage (P = 0.041), Tumor, Node and Metastasis (TNM) stage (P = 0.029) and postoperative complications (P = 0.042) was more likely occurred. Besides, according to the results of Cox multivariate analysis, elevated preoperative plasma D-dimer level was an independent prognostic factor not only for overall survival (Hazard Ratio (HR):1.430, 95% Confidence Interval (CI) (1.163-1.759), P = 0.001) but also for recurrence free survival (HR:1.236, 95% CI (1.018-1.500), P = 0.032). CONCLUSION: In our study, the elevated preoperative plasma D-dimer level may act as an independent prognostic factor for overall survival and recurrence free survival in patients with pancreatic ductal adenocarcinoma after curative resection. Pancreatic ductal adenocarcinoma patients with elevated preoperative plasma D-dimer level had a worse prognosis than those with normal plasma D-dimer level; and the elevated preoperative plasma D-dimer level may imply heavy tumour burden and provide supplementary information regarding disease status.

The Role of TAK1 in RANKL-Induced Osteoclastogenesis.

Bone remodelling is generally a dynamic process orchestrated by bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts are the only cell type capable of bone resorption to maintain bone homeostasis in the human body. However, excessive osteoclastogenesis can lead to osteolytic diseases. The receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) has been widely considered to be an important modulator of osteoclastogenesis thereby participating in the pathogenesis of osteolytic diseases. Transforming growth factor ß-activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, is an important intracellular molecule that regulates multiple signalling pathways, such as NF-κB and mitogen-activated protein kinase to mediate multiple physiological processes, including cell survival, inflammation, and tumourigenesis. Furthermore, increasing evidence has demonstrated that TAK1 is intimately involved in RANKL-induced osteoclastogenesis. Moreover, several detailed mechanisms by which TAK1 regulates RANKL-induced osteoclastogenesis have been clarified, and some potential approaches targeting TAK1 for the treatment of osteolytic diseases have emerged. In this review, we discuss how TAK1 functions in RANKL-mediated signalling pathways and highlight the significant role of TAK1 in RANKL-induced osteoclastogenesis. In addition, we discuss the potential clinical implications of TAK1 inhibitors for the treatment of osteolytic diseases.

Generalized pulp canal obliteration in a patient on long-term glucocorticoids: a case report and literature review.

BACKGROUND: The calcification of the tooth pulp is a pathological condition that occurs in response to various factors. A uncommon haematological condition known as paroxysmal nocturnal haemoglobinuria (PNH) is characterized by bouts of haemolysis, and it requires long-term use of glucocorticoids (GCs). CASE PRESENTATION: A female patient who was diagnosed with PNH and had a history of long-term use of GCs came to our department for root canal therapy (RCT) for teeth 25, 26, and 27. The radiographs showed generalized pulp canal obliteration (PCO) in most of the patients. None of these teeth (25, 26, or 27) were sensitive to percussion, and they did not respond to thermal or electrical sensitivity tests. A diagnose of pulp necrosis was made for these teeth. RCT was carried out with the help of an oral microscope, and then a prosthodontic procedure was created for the teeth. CONCLUSIONS: Based on the patient's long history use of GCs and a series of related studies, we conclude that the long-term usage of GCs contributes significantly to the onset of PCO.

Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies.

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids on experimental animals with autoimmune diseases (AIDs). METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO (CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, PubMed, Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases; consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines. RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin (IL)-1ß [standardized mean difference (SMD) = -1.94, 95% confidence interval (CI) (-2.99, -0.90), P = 0.0003], IL-6 [SMD = -1.65, 95% CI (-2.33, -0.97,) P < 0.000 01], IL-17 [SMD = -2.41, 95% CI (-3.61, -1.20), P < 0.0001], tumor necrosis factor (TNF)-α [SMD = -1.84, 95% CI (-2.61, -1.06), P < 0.0001], and interferon (IFN)-γ [SMD = -1.54, 95% CI (-2.43, -0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI (0.15, 2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI (1.39, 2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD = -0.63, 95% CI (-1.82, 0.57), P = 0.30]. CONCLUTIONS: Substances containing saponins, flavones, and alkaloids regulated the changes of immune-related cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice.

Psoriasis is an autoimmune disease, which has a significant impact on the quality of patient's life. And, there is still no cure for psoriasis. The human dental pulp stem cell (hDPSC) possesses the properties of immunoregulation. In this study, we aimed to determine the effect of hDPSC on the imiquimod (IMQ)-induced psoriasis in mice. The psoriasis model was established by topical application of IMQ cream in mice for 7 days. We found that subcutaneous injection of hDPSC could reduce the symptoms of skin lesions in IMQ-induced psoriasis and suppress the expression of keratin 16, S100A8, S100A9, which are associated with abnormal epidermal proliferation. Subepithelial inflammatory cytokines, CD4+ T lymphocytes and CD11c+ dendritic cells infiltrations were significantly inhibited in by hDPSC. The TNF-α, IFN-γ expressions in serum were decreased, and splenomegaly induced by IMQ was improved after hDPSC treatment. In summary, our study demonstrated that hDPSC could reduce the symptoms of skin lesions and suppress local and systemic immune responses of IMQ-induced psoriasis in mice, which might provide a new sight for the treatment of psoriasis.

Nonspecific biochemical changes under different health statuses and a quantitative model based on biological markers to evaluate systemic function in humans.

BACKGROUND: To investigate the markers of systemic function by using laboratory parameters as life parameters. METHODS: Lymphocyte count, albumin, and creatinine levels were measured using automatic analyzers in young, healthy individuals (20-39 years) and senior individuals (80-95 years) as well as in terminally ill patients. We developed a mathematic model and scoring system (indexes of systemic function, ISF) based on the above mentioned biological markers. RESULTS: ISF scores were significantly lower in the senior group (P < 0.05) than those in the young, healthy group. A significant decrease was observed in the ISF of the terminally ill group and that of the senior group (P < 0.05). CONCLUSIONS: Our results suggest that the ISF scoring system of systemic function can be used to objectively evaluate the systemic function in individuals with different health statuses.

Quantificational evaluation of the resolving power of qualitative biomarkers with different cardinal numbers based on a magnitude-standardized index.

Biomarkers are used for clinical diagnostic purposes, but existing indexes exhibit limitations in terms of the resolving power of biomarkers. This paper proposes a new index, the magnitude-standardized index (MSI), to describe the quantitative variations and resolving powers of different biomarkers. In MSI analysis models, variation scales for ratios and differences are considered simultaneously, and a higher MSI value implies a stronger risk or effect for a biological factor. We explain the rationale for the MSI via hybrid and geometric methods and verify its efficacy through simulation experiments. Our results indicate that the MSI is superior to the Youden index and odds ratio for describing resolving power. When two biomarkers with similar Youden index values, odds ratios, or MSI values but different positive test rates (or cardinal numbers) were combined, all three index values increased; however, only the MSI value remained relatively stable. For a very small cardinal number, such as that of a single nucleotide polymorphism, the MSI value is at most half of the maximum value (0.5), allowing comparisons between MSI values for biomarkers with different cardinal numbers. The MSI can thus provide a better quantifiable evaluation of the resolving power of biomarkers with different cardinal numbers.

Therapeutic Effects of CUR-Activated Human Umbilical Cord Mesenchymal Stem Cells on 1-Methyl-4-phenylpyridine-Induced Parkinson's Disease Cell Model.

The purpose of this study is to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) activated by curcumin (CUR) on PC12 cells induced by 1-methyl-4-phenylpyridinium ion (MPP+), a cell model of Parkinson's disease (PD). The supernatant of hUC-MSC and hUC-MSC activated by 5 µmol/L CUR (hUC-MSC-CUR) were collected in accordance with the same concentration. The cell proliferation and differentiation potential to dopaminergic neuronal cells and antioxidation were observed in PC12 cells after being treated with the above two supernatants and 5 µmol/L CUR. The results showed that the hUC-MSC-CUR could more obviously promote the proliferation and the expression of tyrosine hydroxylase (TH) and microtubule associated protein-2 (MAP2) and significantly decreased the expression of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in PC12 cells. Furtherly, cytokines detection gave a clue that the expression of IL-6, IL-10, and NGF was significantly higher in the group treated with the hUC-MSC-CUR compared to those of other two groups. Therefore, the hUC-MSC-CUR may be a potential strategy to promote the proliferation and differentiation of PD cell model, therefore providing new insights into a novel therapeutic approach in PD.

Effect of tumor necrosis factor-alpha on resistin expression in 3T3-L1 adipocytes and its mechanism.

In order to investigate the effect of tumor necrosis factor-alpha (TNFalpha) on resistin expression in 3T3-L1 adipocytes, and further explore its mechanisms, the differentiated 3T3-L1 adipocytes were incubated with 0, 1, 10, 100 ng/mL TNFalpha respectively for 24 h, and then the expression of resistin was determined. The differentiated 3T3-L1 adipocytes were incubated with 100 ng/ mL TNFalpha for 3, 6, 24 h respectively, and then the expression of resistin mRNA was analyzed. 3T3-L1 adipocytes were induced to differentiate into mature adipocytes. The cells were randomly divided into 4 groups for culture. In the control group, no drugs were added. Cells of TNFalpha group were treated with 100 ng/mL TNFalpha. In Ro-31-8220 group, 5 micromol/L protein kinase C inhibitor Ro-31-8220 was added. With TNFalpha+Ro-31-8220 group, 100 ng/mL TNFalpha were added 1 h after the addition of 5 micromol/L Ro-31-8220. All adipocytes were cultured for 24 h. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to detect the expression of resistin gene. Our results showed that resistin protein and mRNA in 3T3-L1 adipocytes were inhibited by TNFalpha at different concentrations (P<0.01), and the inhibitory effect increased with the concentration (P<0.01). At the same concentrations, the inhibitory effect increased with time (P <0.01). Ro-31-8220 could inhibit its expression and the inhibitive effect remained unchanged with addition of TNFalpha (P>0.05). It was concluded that TNFalpha could inhibit the expression of resistin in 3T3-L1 adipocytes. The mechanism may be that the expression of resistin is partly controlled by protein kinase C signal conduction pathway.

Quantitatively plotting the human face for multivariate data visualisation illustrated by health assessments using laboratory parameters.

OBJECTIVE: The purpose of this study was to describe a new data visualisation system by plotting the human face to observe the comprehensive effects of multivariate data. METHODS: The Graphics Device Interface (GDI+) in the Visual Studio.NET development platform was used to write a program that enables facial image parameters to be recorded, such as cropping and rotation, and can generate a new facial image according to Z values from sets of normal data (Z > 3 was still counted as 3). The measured clinical laboratory parameters related to health status were obtained from senile people, glaucoma patients, and fatty liver patients to illustrate the facial data visualisation system. RESULTS: When the eyes, nose, and mouth were rotated around their own axes at the same angle, the deformation effects were similar. The deformation effects for any abnormality of the eyes, nose, or mouth should be slightly higher than those for simultaneous abnormalities. The facial changes in the populations with different health statuses were significant compared with a control population. CONCLUSIONS: The comprehensive effects of multivariate may not equal the sum of each variable. The 3Z facial data visualisation system can effectively distinguish people with poor health status from healthy people.

Candesartan attenuates fatty acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells.

Angiotensin II receptor blockers (ARBs) have been shown to decrease insulin resistance in obese diabetic animal models and reduce the risk of new-onset diabetes in hypertensive patients. In the present study, we studied whether candesartan, an ARB, can exert a direct effect against fatty acid-induced oxidative stress in pancreatic beta-cells. The effect of candesartan on lipotoxicity was evaluated using mouse insulin-secreting clonal cell, MIN6 and isolated mouse pancreatic islets. Intracellular insulin and triglyceride content, uncoupling protein-2 (UCP-2) mRNA expression, reactive oxygen species, protein kinase C (PKC) and NAD(P)H oxidase activity were examined. Candesartan recovered decreased insulin content in MIN6 exposed to 25mM glucose with 0.5mM palmitate (P<0.01). Candesartan tended to decrease intracellular triglyceride accumulation in cells exposed to 25mM glucose with 0.5mM palmitate. Palmitate-induced up-regulation of UCP-2 mRNA levels was suppressed by candesartan in a dose-dependent manner. Candesartan decreased palmitate-induced reactive oxygen species accumulation in MIN6 cells by 23% and in mouse islets by 59%. Candesartan also decreased palmitate-induced PKC activity by 21% and NAD(P)H oxidase activity by 37% in MIN6 cells. These findings indicated that candesartan attenuated fatty acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells.