[Application of preoperative serum CYFRA 21-1 level in the prognosis of colorectal cancer].

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.

Fluoride induced down-regulation of IKBKG Gene expression inhibits hepatocytes senescence.

BACKGROUND: Accumulating evidences have confirmed that liver is one of the more severely damaged organs during chronic fluorosis. However, the detail mechanism is unclear to data. At present, the objective of this study was to investigate the relationship between down-regulation of IKBKG gene expression and hepatocyte senescence induced by sodium fluoride (NaF). METHODS: Chronic fluorosis rats and NaF-exposure human liver L02 cells were reproduced the model of hepatocyte senescence in vivo and in vitro. The mRNA and protein levels of p16, p21 and IKBKG, the IL-8 level were determined. The role of IKBKG in fluoride-induced senescence of hepatocytes was explored by knock down in hepatocytes in vivo and in vitro. RESULTS: The number of senescence-positive cells in rat liver tissues was increased as well as the level of IL-8 and the expression levels of p16, p21 and IKBKG in fluoride exposure to rat depending on the fluoride concentration. The similar results were obtained in NaF treated liver L02 cells, and the number of cells that stagnated in the G2 phase increased significantly. Further, our results confirmed that decreasing the expression of IKBKG in hepatocytes could reduce fluoride-induced hepatocyte senescence and the changes of senescence-related indicators both in vivo and in vitro. CONCLUSION: These results indicated that the elevated expression of IKBKG was positive relation with the fluoride-induced senescence in hepatocytes, suggesting the hepatocyte senescence might have a special relationship with fluoride-caused liver damage. Because of the present results limitation, the mechanism of fluoride induced senescence in hepatocytes should be concentrated in the future in detail, especially the novel targets for fluoride induced liver injury.

Aortic dissection with acute non-st-segment elevation myocardial infarction as the first manifestation.

Acute chest pain caused by aortic dissection or acute myocardial infarction (AMI) is one of the most serious medical emergencies and requires very quick differential diagnosis to seize the best time for treatment. Aortic dissection and acute myocardial infarction are manifested with similar symptoms, making it difficult to differentially diagnose these two conditions. The present case was initially misdiagnosed as an acute non-ST-segment elevation myocardial infarction (NSTEMI) with left aortic disease, and then diagnosed by coronary angiography examination as type A aortic dissection (AAD). This case points to the need to collect and analyze as much patient clinical data as possible, including medical history and the results of auxiliary examination which would help to avoid misdiagnosis or treatment delay and reduce mortality among patients with type AAD when they manifest symptoms of chest pain and an ECG pattern of NSTEMI.

Double-edged-sword effect of IL-1ß on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-κB, MAPK and BMP/Smad signaling pathways.

Microenvironmental conditions can interfere with the functional role and differentiation of mesenchymal stem cells (MSCs). Recent studies suggest that an inflammatory microenvironment can significantly impact the osteogenic potential of periodontal ligament stem cells (PDLSCs), but the precise effects and mechanisms involved remain unclear. Here, we show for the first time that interleukin-1ß (IL-1ß) has dual roles in the osteogenesis of PDLSCs at concentrations ranging from physiologically healthy levels to those found in chronic periodontitis. Low doses of IL-1ß activate the BMP/Smad signaling pathway to promote the osteogenesis of PDLSCs, but higher doses of IL-1ß inhibit BMP/Smad signaling through the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, inhibiting osteogenesis. These results demonstrate that crosstalk between NF-κB, MAPK and BMP/Smad signaling mediates this dual effect of IL-1ß on PDLSCs. We also show that the impaired osteogenesis of PDLSCs results in more inflammatory cytokines and chemokines being released, inducing the chemotaxis of macrophages, which further clarifies the role of PDLSCs in the pathogenesis of periodontitis.

Lysine-specific demethylase 1 promotes the stemness and chemoresistance of Lgr5(+) liver cancer initiating cells by suppressing negative regulators of ß-catenin signaling.

Cancer initiating cells (CICs) are responsible for the unrestrained cell growth and chemoresistance of malignant tumors. Histone demethylation has been shown to be crucial for self-renewal/differentiation of stem cells, but it remains elusive whether lysine-specific demethylase 1 (LSD1) regulates the stemness properties of CICs. Here we report that the abundant expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is associated with the progression of hepatocellular carcinoma (HCC). Lgr5(+) HCC cells behave similarly to CICs and are highly tumorigenic and resistant to chemotherapeutic agents. Importantly, Lgr5(+) cells express higher levels of LSD1, which in turn regulates Lgr5 expression and promotes the self-renewal and drug resistance of Lgr5(+) CICs. Mechanistically, LSD1 promotes ß-catenin activation by inhibiting the expression of several suppressors of ß-catenin signaling, especially Prickle1 and APC in Lgr5(+) CICs, by directly regulating the levels of mono- and di-methylation of histone H3 lysine-4 at the promoters of these genes. Furthermore, LSD1-associated activation of the ß-catenin signaling is essential for maintaining the activity of Lgr5(+) CICs. Together, our findings unravel the LSD1/Prickle1/APC/ß-catenin signaling axis as a novel molecular circuit regulating the stemness and chemoresistance of hepatic Lgr5(+) CICs and provide potential targets to improve chemotherapeutic efficacies against HCC.

Frozen shoulder: correlation between the response to physical therapy and follow-up shoulder arthrography.

OBJECTIVE: To study the correlation between improvement of shoulder motion and shoulder joint space capacity determinated by arthrography. DESIGN: Case series. SETTING: General community hospital. PATIENTS: Twelve patients with clinically diagnosed frozen shoulder without rotator cuff tear. All subjects were divided as "primary" and "secondary" according to spontaneous onset or not, and "acute" or "chronic" depending on whether duration of disease was less than 2 months or longer. INTERVENTIONS: Outpatient rehabilitation programs, including physical modalities, exercise intervention, and regular weekly outpatient clinic follow-up. MAIN OUTCOME MEASURES: Shoulder range of motion (ROM) and joint space capacity in shoulder arthrography. RESULTS: In acute patients, the joint space capacity increased significantly after treatment (t = 2.82; p < .05). Increased joint space capacity was most significantly correlated with improvement in external rotation (r = .77, p < .05), followed by abduction (r = .43, p > .05), but was poorly correlated with flexion and internal rotation. In chronic patients, both primary and secondary groups, there was no obvious joint space capacity increase despite significant shoulder motion improvement. Follow-up arthrograms showed the reappearance and/or enlargement of the axillary recess and smoother capular margins in all the patients except one chronic case (disease duration for 1 year). These findings were more obvious in acute than in chronic patients. CONCLUSIONS: For frozen shoulder, generally described as "adhesive capsulitis," the adhesion was reversible in the acute stage. The increase of joint space capacity was significant and was correlated with improvement of external rotation. In chronic patients, ROM restoration occurred independent of change in joint space capacity, which increased slightly. The stretching of other contracted soft tissues around the shoulder, in addition to the adhesive capsule, may contribute to the recovery of chronic frozen shoulder.

A retrospective study on diagnosis and treatment of severe acute pancreatitis.

Severe acute pancreatitis is highly controversial on its diagnostic criteria, the optimum time for surgery, the selection of surgical procedures, and the prevention and treatment of complications. We treated 40 patients with severe acute pancreatitis from July 1983 to July 1988. The comparison of clinical and laboratory data of severe acute pancreatitis and mild acute pancreatitis showed that in some patients neither Ranson's nor Bank's criteria are reliable in classifying or predicting the severity of the disease. The coexistence of acute peritonitis and bloody ascites with elevated amylase level is very helpful to identify the local conditions of pancreatic necrosis and hemorrhage. We suggest early operation (within 48 hours) be applied in severe acute pancreatitis. In our series, five types of surgical procedures were used. We consider that proper treatment of acute respiratory distress syndrome (ARDS) is most important in the management of severe pancreatitis.

[Diagnosis and treatment of severe pancreatitis: analysis of 40 cases].

Forty cases of severe pancreatitis confirmed and treated by surgery were studied. In order to have a retrospective observation, we compared the clinical and laboratory data of 28 severe cases with that of 72 mild cases treated conservatively and found that in some cases neither Ranson nor Bank criteria were reliable in predicting the severity. We also found that frank peritonitis and bloody ascites with elevated amylase level were very good indication of pancreatic necrosis and hemorrhage. It was the author's opinion to explore early within 48 hrs after onset, using both drainage and open lesser sac lavage in most severe cases of pancreatitis.