Objective To evaluate the relationship of serum cystatin C (Cys C) levels and the severity of coronary artery diseases (CAD).Methods A total of 194 patients underwent coronary angiography were divided into two groups (102 CAD patients) and control group (non-CAD group,92 cases).To study the relationship of the level of serum cystatin C and the severity of CAD,the serum cystatin C of all enrolled patients was detected by immune-enhancing latex turbidimetry and the serum cystatin C level of CAD group was compared to control group.Results The serum levels of cystatin C of CAD were significantly higher than the control group (P ＜ 0.05).With the increased levels of serum Cys C,CAD severity average score was increased; logistic regression analysis showed that Cys C was one of the risk factors of CAD.Cystatin C concentration was significantly correlated with CAD severity score.A cut-off value of 0.79 mg/L for cystatin C predicted incident CAD with a sensitivity of 76.60％ and specificity of 82.60％,respectively.Conclusions Serum Cys C levels are valuable clinical predictors and closely related to CAD.With the increasing levels of serum Cys C,CAD becomes more severe.

Objective To investigate the effect of glycosylphosphatidylinositol specific phospholipase D (GPI-PLD) on artherosclerosis.Methods The GPI-PLD activities and mononuclear cells GPI-PLD gene mRNA expression was detected in 102 patients with coronary artery disease and 121 healthy adult.The GPI-PLD highly expressing cell model was constructed and induced by ox-LDL,the HUVEC and HUVEC transfected with pcDNA3.1(+) as blank and control group,respectively.Before and after the induction,the change of cellular function and biological features was detected.Results The peripheral blood GPI-PLD activity of patients with coronary heart disease and normal control were 31.80±4.21 and 44.32±4.50,and the IA ratio of GPI-PLD mRNA expression of mononuclear cells were 0.92±0.16 and 1.53±0.14,respectively.The activity of GPI-PLD and mRNA expression in patients with coronary artery disease were decreased up to 28.2％ (t=21.31,P＜0.01) and 39.9％ (t=30.36,P＜0.01) as compared with healthy control.The adhesion cells,ET-1,reactive oxygen,malondialdehyde (MDA) and the apoptosis rate of GPI-PLD overexpressing HUVEC were lower as compared with blank [29.59=1.40,3.51 ± 0.45,(50.63 ±4.22) ng/L,0.043±0.011,(3.32±0.44) nmol/L vs.41.39±2.15,10.57±1.12,(59.35±4.45)ng/L,0.052±0.011,(5.01±0.69) nmol/L],and as compared with control [42.68±2.45,9.92±1.03,(61.11±4.12) ng/L,0.051±0.007,(4.89±0.71) nmol/l] after inducing by ox-LDL; while the level of nitrogen noxidium (NO) was higher than blank [(29.88± 1.37)μmol/L vs.(21.76±1.02)μmol/L] and control(23.43±0.85)μmol/L groups.Conclusions The expression and activity of GPI-PLD in patients with coronary artery disease are lower than health people.Stable high expression of GPI-PLD is beneficial to vascular endothelial cell injury repairment and prevent the occurrence and development of atherosclerosis.

Objective To investigate the differential metabolites of lymph node metastasis in pancreatic ductal carcinoma (PDAC) and provide new ideas for the pathogenesis, early diagnosis and treatment of metastatic pancreatic cancer. Methods Forty serum specimens of patients with pancreatic ductal carcinoma were collected and divided into lymph node metastasis group (18 cases) and non-metastasis group (22 cases). Thirty-one serum specimens were also collected from the healthy control group. Liquid chromatographytandem mass spectrometry was used to analyze the differential metabolites and metabolic pathways between patients with PDAC and healthy controls as well as between lymph node metastasis and non-metastasis groups. Results Principal component analysis and partial least squares-discriminant analysis revealed statistically significant differences in metabolites and metabolic pathways between patients with PDAC and the healthy controls and between lymph node metastasis and non-metastasis groups. The differences in profiles were also statistically significant. Seventy-six different metabolites and 11 metabolic pathways were screened between patients with PDAC and the healthy controls, among which phenylalanine metabolism and histidine metabolism were the two most influential metabolic pathways. Four different metabolites were screened between lymph node metastasis and non-metastasis groups, and the expression of ethopropazine and phenylalanine were upregulated but the expression of tetrahydrodeoxycorticosterone and oxprenolol were downregulated. Conclusion Metabolites are significantly altered in the lymph node metastasis group of patients with PDAC compared with the non-metastasis group. Ethopropazine, phenylalanine, tetrahydrodeoxy corticosterone, and oxprenolol are potential biomarkers of lymph node metastasis in patients with PDAC.

Recently, some global cases of 2019 novel coronavirus (COVID-19) pneumonia have been caused by second- or third-generationtransmission of the viral infection, resulting in no traceable epidemiological history. Owing to the complications of COVID-19pneumonia, the first symptom and imaging features of patients can be very atypical and early diagnosis of COVID-19 infectionsremains a challenge. It would aid radiologists and clinicians to be aware of the early atypical symptom and imaging featuresof the disease and contribute to the prevention of infected patients being missed.

Objective To analyze the clinical value of immature granulocytes in peripheral blood for prediction of persistent systemic inflammatory response syndrome (SIRS) in patients with acute pancreatitis (AP). Methods 1 973 patients with AP in Hunan People's Hospital from 2012 to 2017 were retrospectively enrolled and divided by SIRS duration into the persistent SIRS group, temporary SIRS group and non-SIRS group. The independent risk factor for persistent SIRS in AP patients was evaluated by Logistic regression analysis, and predictive value of immature granulocytes for persistent SIRS in AP patients was analyzed by the receiver operating characteristic (ROC) curve. Results These 1 973 AP patients (1 165 males, 59.0%) with an average age of 49 (40, 60) years old, including 288 persistent SIRS, 189 temporary SIRS and 1 496 non-SIRS cases. There was no significant difference in gender, age and etiology among three groups. Compared with non-SIRS group, more severe symptoms were observed in the temporary and persistent SIRS groups. Moreover, The acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), CT severity index (CTSI), multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS) incidence, mortality and C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT) and immature granulocytes in persistent SIRS group were further higher than those in the temporary SIRS group [APACHEⅡ: 9 (6, 12) vs. 5 (3, 7), CTSI: 6 (4, 6) vs. 4 (3, 6), MOF incidence: 92.0% vs. 32.8%, ARDS incidence: 39.9% vs. 10.1%, morbidity: 11.1% vs. 4.2%, CRP (mg/L): 25.00 (0.80, 212.25) vs. 0.80 (0.80, 123.50), WBC (×109/L): 15.17±6.78 vs. 14.84±5.86, PCT (μg/L): 0.23 (0.10, 1.76) vs. 0.10 (0.10, 0.31), immature granulocytes: 1.95 (0.90, 4.95) % vs. 0.80 (0.40, 2.10) %, all P < 0.05]. Logistic regression analysis showed that besides pancreatic necrosis, WBC and CRP, immature granulocyte was an independent risk factor for persistent SIRS associated with AP [odds ratio (OR) = 1.844, 95% confidence interval (95%CI) = 1.372-2.220]. ROC curve showed that immature granulocytes had better predictive value for persistent SIRS, the area under the curve (AUC) was 0.806, which was significantly higher than the APACHEⅡ (AUC = 0.783), CTSI (AUC = 0.752), PCT (AUC = 0.676), CRP (AUC = 0.677), WBC (AUC = 0.644). The cut-off value of immature granulocyte was 0.65%, the sensitivity was 84.0%, the specificity was 66.3%, the positive predictive value was 62.4%, and the negative predictive value was 76.3%. Conclusion Immature granulocyte in peripheral blood is a potential indicator for persistent SIRS in AP patients.

Objective:To study the risk factors of axillary lymph node metastasis by analyzing the acoustic image characteristics of the automated breast volume scanner (ABVS) of breast cancer masses.Methods:The imaging features of ABVS of 212 patients with breast cancer, unilaterally and singly, confirmed by pathological examination admitted in Hangzhou First People’s Hospital from Jan. 2016 to Dec. 2018 were retrospectively analyzed. There were 83 cases with axillary lymph node metastasis (metastatic group) and 129 cases without (non-metastatic group) . The correlation of clinical and the imaging features of ABVS with axillary lymph node metastasis was analyzed using univariate analysis and multivariate logistic regression. ROC curve was used to analyze the cut-off value of the maximum diameter of the mass in predicting the breast cancer axillary lymph node metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value of each risk factor were analyzed for predicting breast cancer axillary lymph node metastasis.Results:The retraction phenomenon and micro-calcification of breast cancer in the metastatic group (60.2%, 65.1%) were higher than those in the non-metastatic group (43.4%,37.2%) ( P=0.017 vs P<0.001) . The maximum diameter of the breast cancer in the metastatic group was bigger than in the non-metastatic group ( Z=2.18, P=0.029) . Multivariate logistic regression analysis showed that the micro-calcification of breast cancer ( OR=2.522, P=0.003) was an independent predictor of lymph node metastasis in breast cancer. The area under the curves and the cut-off value of the maximum diameter of the mass in predicting the breast cancer axillary lymph node metastasis were 0.589 and 2.85 cm. The sensitivity was 34.9%, the specificity was 82.9%, the positive predictive value was 56.9%, and the negative predictive value was 66.5%. The sensitivities of micro-calcification and retraction phenomenon to predict the occurrence of axillary lymph node metastasis in breast cancer patients were 65.1% and 60.2%, specificities were 62.8% and 56.6%, positive predictive values were 52.9% and 47.2%, and negative predictive values were 73.6% and 68.9%. Conclusion:The study suggests that the maximum diameter, micro-calcification, and retraction phenomenon of masses are associated with the occurrence of the axillary lymph node metastasis in breast cancer.

Objective:This study aims to explore the pathogenic roles of protein S-nitrosylation modification in the development of severe acute pancreatitis, and provide new insights into the molecular mechanisms driving acute pancreatitis development.Methods:Thirty two Sprague Dawley (SD) rats were randomly divided into sham operation group, mild acute pancreatitis (MAP) group, severe acute pancreatitis (SAP) group and SAP + N-nitro-L-arginine methyl ester (L-NAME) group (treated with nitric oxide synthase inhibitor), 8 rats in each group. All rats were sacrificed to take blood from heart and pancreatic tissues 24 h after model construction. Total protein S-nitrosylation modification level in pancreatic tissues was quantitated by the biotin-switch method, followed by histological evaluation via hematoxylin and eosin (HE) staining. The serum endotoxin, D-lactic acid, diamine oxidase, interleukin-6 and tumor necrosis factor-ɑ(TNF-ɑ), amylase, alanine aminotransferase, urea nitrogen and calcium ions in rat were detected. Pearson correlation analysis was used to analyze the correlation between each index and protein S-nitrosylation.Results:Compared with the sham operation group, the modification level of protein S-nitrosylation in pancreatic tissue of MAP group increased significantly ( P<0.05); Compared with MAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP group increased significantly ( P<0.05); Compared with SAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP + L-NAME group decreased significantly ( P<0.05). HE staining showed that the degree of pancreatic necrosis and inflammatory cell infiltration in SAP + L-NAME group were significantly weaker than those in SAP group. The concentrations of serum endotoxin, diamine oxidase, D-lactic acid, IL-6 and TNF-ɑ, amylase, alanine aminotransferase, and urea nitrogen in the MAP group were significantly higher than those in the sham operation group (all P<0.05); The above indexes in SAP group were significantly higher than those in MAP group and sham operation group (all P<0.05); The above indexes in SAP + L-NAME group were significantly lower than those in SAP group (all P<0.05). The serum IL-6 and TNF-ɑ levels in rats with acute pancreatitis were positively correlated with protein S-nitrosylation in pancreatic tissue (all P<0.05). Conclusions:Protein S-nitrosylation modification plays essential roles in the development and progression of severe acute pancreatitis.

OBJECTIVE: To clarify the effect of glycosylphosphatidylinositol-specific phospholipase D (GPIPLD) on hepatoma cells HepG2 and the possible molecular mechanism. METHODS: MTT, fluorescent staining and Western blot were applied to analyze the effect and molecular mechanism of GPI-PLD on hepatoma cells by transfected high expression GPI-PLD model. We inoculated HepG2 in nude mice models to further clarify the effect of GPI-PLD on hepatoma cells in vivo. RESULTS: Compared with the control groups, PI3K-Akt signaling pathway activity and proliferation of hepatoma cells were significantly inhibited in the GPI-PLD group. Nude mice models showed that the tumor growth and tumor weight [(1.87 ± 0.09) g] of the GPI-PLD group were significantly less than those of the blank control group [(2.20 ± 0.17) g] and the negative control group [(2.15 ± 0.09) g]. AST, ALT and AFP serum concentration in the GPI-PLD group were significantly lower than those of the control groups (P<0.05). CONCLUSION GPI-PLD can inhibit the proliferation of hepatoma cells and growth in vivo, and promote the apoptosis of hepatoma cells by reducing the activity of PI3K-Akt signaling pathway.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line ; Down-Regulation ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Mice ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; Phospholipase D ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; Transfection

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.