ObjectiveTo investigate the association of tuberous sclerosis gene 1/2 (TSC1/2) mutation with disease severity and prognosis in patients with hepatocellular carcinoma (HCC), and to provide a feasible basis for the diagnosis and treatment of HCC. MethodsA total of 492 patients with HCC who were admitted to The Affiliated Hospital of Jiangsu University from January 2012 to January 2020 were enrolled, among whom 59 had TSC1/2 mutations (20 with TSC1 mutations, 41 with TSC2 mutations, and 2 had both TSC1 and TSC2 mutations). The clinical features of patients with TSC1/2 mutations were analyzed, and the association of TSC1/2 mutations with the clinical stage of HCC was analyzed. The 35 patients in the mutation group and 35 in the non-mutation group were followed up for 3 years to observe the effect of TSC1/2 mutations on the prognosis of HCC. The chi-square test was used for comparison of categorical data between groups; the Kruskal-Wallis H test was used for comparison of ranked data between groups; a multivariate logistic regression analysis was used to investigate association; the Kaplan-Meier survival analysis was used to analyze follow-up data. ResultsFor the 492 patients with HCC, the overall TSC1/2 mutation rate was 11.99%. There were no significant differences in sex, age, Child score, and tumor size between the TSC1/TSC2 mutation group and the non-mutation group (all P＞0.05), while there were significant differences in tumor number, extrahepatic metastasis, and PS score between the two groups (all P＜0.05). The logistic regression analysis showed that TSC1/TSC2 gene mutation was positively correlated with the severity of HCC (odds ratio=1.706, P＜0.05). The follow-up results showed that the TSC1/2 mutation group had a significantly lower survival rate than the non-mutation group, and there was a significant difference in 3-year mortality rate between the TSC1/2 mutation group and the non-mutation group (60.3% vs 38.6%, χ2=3.923,P＜0.05). ConclusionTSC1/TSC2 gene mutation may predict the malignant progression of HCC in the early stage, and patients with TSC1/2 mutation tend to have poor prognosis. Targeted drug therapy for gene mutations may have a certain effect in delaying the progression of HCC.

OBJECTIVEThe aim of this study was to explore the effect of SPARC on the anti-cancer effect of gemcitabine and underlying mechanism in pancreatic cancer.

METHODSAfter treating with gemcitabine, the proliferation rate of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells was detected by MTT assay. The cell cycle distribution and cell apoptosis in each group were examined by flow cytometry, and the capability of clone formation was tested by adhesion-dependent clone formation assay. The apoptosis-related proteins were analyzed by Western blot.

RESULTSThe growth of pancreatic cancer cells was inhibited by gemcitabine in a time-dependent and dose-dependent manner. Its IC50 at 24, 48, and 72-h was (40.1 ± 2.5) µmol/L, (15.0 ± 0.5) µmol/L and (6.6 ± 0.1) µmol/L, respectively. The overexpression of SPARC increased the inhibitory effect of gemcitabine on growth of pancreatic cancer MIA PaCa2/SPARC69 cells, presenting a dose- and time- dependent manner. Its IC50 at 24, 48, 72 h was (24.3 ± 1.5) µmol/L, (7.7 ± 0.3) µmol/L and (4.8 ± 0.2) µmol/L, respectively. The clone formation assay showed that before gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (2350 ± 125), (2130 ± 120) and (1567 ± 11), respectively. After gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 1674 ± 79) , (1587 ± 94) and (557 ± 61), respectively. The overexpression of SPARC enhanced the chemosensitivity of MIA PaCa2 cells to gemcitabine chemotherapy. After treating with 10 µmol/L gemcitabine for 48 h, the ratio of G0/G1 cells in MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (56.0 ± 5.5)%, (55.0 ± 4.5)% and (68.0 ± 7.0)%, respectively. The cells arrested at G0/G1 phase were significantly increased in the MIA PaCa2/SPARC69 cells. The apoptosis rates of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (22.4 ± 2.5)%, (19.9 ± 2.0)% and (37.7 ± 3.9)%, respectively, indicating that overexpression of SPARC enhanced the gemcitabine-induced apoptosis in MIA PaCa2 cells. The Western blot analysis showed that, compared with MIA PaCa2 and MIA PaCa2/V cells, the expression of caspase-2, -8, -9 and cleaved PARP protein was significantly increased, while the expression of Bcl-2 was not changed significantly in the MIA PaCa2/SPARC69 cells.

CONCLUSIONSPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins.

Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Caspase 2 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cysteine Endopeptidases ; metabolism ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Osteonectin ; metabolism ; Pancreatic Neoplasms ; metabolism ; pathology ; Poly(ADP-ribose) Polymerases ; metabolism ; Time Factors

Objective The aim of this study was to explore the effect of SPARC on the anti-cancer effect of gemcitabine and underlying mechanism in pancreatic cancer . Methods After treating with gemcitabine, the proliferation rate of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells was detected by MTT assay .The cell cycle distribution and cell apoptosis in each group were examined by flow cytometry, and the capability of clone formation was tested by adhesion-dependent clone formation assay . The apoptosis-related proteins were analyzed by Western blot .Results The growth of pancreatic cancer cells was inhibited by gemcitabine in a time-dependent and dose-dependent manner .Its IC50 at 24, 48, and 72-h was (40.1 ±2.5) μmol/L, (15.0 ±0.5) μmol/L and (6.6 ±0.1) μmol/L, respectively.The overexpression of SPARC increased the inhibitory effect of gemcitabine on growth of pancreatic cancer MIA PaCa2/SPARC69 cells, presenting a dose-and time-dependent manner .Its IC50 at 24, 48, 72 h was (24.3 ±1.5) μmol/L, (7.7 ±0.3) μmol/L and (4.8 ±0.2) μmol/L, respectively.The clone formation assay showed that before gemcitabine treatment , the clone numbers of MIA PaCa 2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 2350 ±125 ) , ( 2130 ±120 ) and ( 1567 ±11 ) , respectively . After gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 1674 ±79) , (1587 ±94) and (557 ±61), respectively.The overexpression of SPARC enhanced the chemosensitivity of MIA PaCa 2 cells to gemcitabine chemotherapy .After treating with 10 μmol/L gemcitabine for 48 h, the ratio of G0/G1 cells in MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (56.0 ±5.5)%, (55.0 ±4.5)% and (68.0 ±7.0)%, respectively.The cells arrested at G0/G1 phase were significantly increased in the MIA PaCa 2/SPARC69 cells.The apoptosis rates of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (22.4 ±2.5)%, (19.9 ±2.0)% and (37.7 ± 3.9)%, respectively, indicating that overexpression of SPARC enhanced the gemcitabine-induced apoptosis in MIA PaCa2 cells.The Western blot analysis showed that , compared with MIA PaCa2 and MIA PaCa2/V cells, the expression of caspase-2,-8,-9 and cleaved PARP protein was significantly increased , while the expression of Bcl-2 was not changed significantly in the MIA PaCa 2/SPARC69 cells.Conclusion SPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins .

Objective The aim of this study was to explore the effect of SPARC on the anti-cancer effect of gemcitabine and underlying mechanism in pancreatic cancer . Methods After treating with gemcitabine, the proliferation rate of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells was detected by MTT assay .The cell cycle distribution and cell apoptosis in each group were examined by flow cytometry, and the capability of clone formation was tested by adhesion-dependent clone formation assay . The apoptosis-related proteins were analyzed by Western blot .Results The growth of pancreatic cancer cells was inhibited by gemcitabine in a time-dependent and dose-dependent manner .Its IC50 at 24, 48, and 72-h was (40.1 ±2.5) μmol/L, (15.0 ±0.5) μmol/L and (6.6 ±0.1) μmol/L, respectively.The overexpression of SPARC increased the inhibitory effect of gemcitabine on growth of pancreatic cancer MIA PaCa2/SPARC69 cells, presenting a dose-and time-dependent manner .Its IC50 at 24, 48, 72 h was (24.3 ±1.5) μmol/L, (7.7 ±0.3) μmol/L and (4.8 ±0.2) μmol/L, respectively.The clone formation assay showed that before gemcitabine treatment , the clone numbers of MIA PaCa 2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 2350 ±125 ) , ( 2130 ±120 ) and ( 1567 ±11 ) , respectively . After gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 1674 ±79) , (1587 ±94) and (557 ±61), respectively.The overexpression of SPARC enhanced the chemosensitivity of MIA PaCa 2 cells to gemcitabine chemotherapy .After treating with 10 μmol/L gemcitabine for 48 h, the ratio of G0/G1 cells in MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (56.0 ±5.5)%, (55.0 ±4.5)% and (68.0 ±7.0)%, respectively.The cells arrested at G0/G1 phase were significantly increased in the MIA PaCa 2/SPARC69 cells.The apoptosis rates of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (22.4 ±2.5)%, (19.9 ±2.0)% and (37.7 ± 3.9)%, respectively, indicating that overexpression of SPARC enhanced the gemcitabine-induced apoptosis in MIA PaCa2 cells.The Western blot analysis showed that , compared with MIA PaCa2 and MIA PaCa2/V cells, the expression of caspase-2,-8,-9 and cleaved PARP protein was significantly increased , while the expression of Bcl-2 was not changed significantly in the MIA PaCa 2/SPARC69 cells.Conclusion SPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins .

ObjectiveTo analyze the current status and correlation of occupational commitment and job burnout in nurses. MethodsOccupational commitment scale and Maslach Burnout Inventory General Survey （MBI-GS） were used to survey 695 nurses in 4 hospitals in Nanchong， and the assessment results were compared among nurses with different demographic characteristics， thereafter， Pearson correlation analysis was conducted to discuss the correlation between occupational commitment and job burnout in nurses. ResultsThe total scores of occupational commitment scale and MBI-GS of nurses were （78.38±12.33） and （37.05±9.61）， respectively. The total occupational commitment scale score showed significant differences among nurses of different hospitals， departments， working years and genders （P<0.05 or 0.01）， and the total MBI-GS score showed statistical differences among nurses of different hospitals， departments， ages， professional titles， working years， educational level and marital status （P<0.05 or 0.01）. Pearson correlation analysis showed that the total score and each dimension score of MBI-GS were negatively correlated with the total score of occupational commitment scale， as well as the scores of affective commitment， normative commitment and economic cost commitment （r=-0.517~-0.075，P<0.05 or 0.01）. The emotional cost commitment score was negatively correlated with the the total MBI-GS score， along with the scores in professional efficacy and depersonalization dimensions （r=-0.172~-0.098， P<0.01）. The score of opportunity commitment was positively correlated with the score of professional efficacy （r=0.106， P<0.01）， and negatively correlated with the score of emotional exhaustion and depersonalization （r=-0.156， -0.123， P<0.01）. ConclusionThe hospital， department and working years of the nurses are the common factors influencing occupational commitment and job burnout. The occupational commitment is higher in female nurses than that in male nurses， and the job burnout is more severe in the unmarried than that in the married， moreover， the job burnout of the nurses is negatively correlated with occupational commitment.