Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).
B7-H1 Antigen/genetics* ; Humans ; Immunohistochemistry ; Prognosis ; Triple Negative Breast Neoplasms/pathology*

Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group Ⅰ: 48 cases (18.5%) were sTIL low/LAG-3 low; group Ⅱ: 52 cases (20.0%) were sTIL high/LAG-3 low; group Ⅲ: 39 cases (15.0%) were sTIL low/LAG-3 high; group Ⅳ: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.
Adenocarcinoma/pathology* ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/metabolism* ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/pathology*

ObjectiveTo investigate the efficacy and mechanism of tetramethylpyrazine derivative T-006 on learning and memory function of APP/PS1/Tau transgenic （3×Tg） mice. MethodsEight-month-old 3×Tg mice and their wild-type （WT） littermates were divided into WT group， WT+T-006 （10 mg/kg） group， 3×Tg group， low-dose T-006 group （1 mg/kg）， medium-dose T-006 group （3 mg/kg）， high-dose T-006 group （10 mg/kg）， donepezil group （1.3 mg/kg） and memantine group （5 mg/kg）. Within 4 months， T-006 and donepezil were continuously administered once a day and memantine twice a day. Behavioral tests including novel object recognition， step-down avoidance and morris water maze were performed to evaluate learning and memory function of mice. Immunohistochemistry was used to observe the deposition of amyloid plaques in the hippocampus of mice. Western blotting was employed to detect the protein expression of APP， BACE-1， PSD95， synapsin I， synapsin Ⅱ， synaptophysin， BDNF， CREB and p-CREB. ResultsT-006 treatment reduced the numbers of errors in the step-down avoidance test （P< 0.05）， significantly reduced the APP expression and increased the expression of PSD95， synaptophysin， synapsin I and BDNF （P<0.05）. ConclusionT-006 improves the learning and memory function of 3×Tg mice and reduces the APP expression， which may be explained by the increase of synaptic associated protein expression.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) have been reported to improve wound healing. However, type I collagen secreted by ADMSCs will contribute to scar formation. Therefore, inhibiting type I collagen secretion from ADMSCs will strengthen its clinical application. OBJECTIVE: To investigate the effect of 1,25(OH)2D3on secretion of type I collagen by ADMSCs and its mechanism. METHODS: Human ADMSCs were isolated by collagenase digestion, and identified by flow cytometry. ADMSCs at passage 4 were cultured in DMEM/F12 medium containing different concentrations of 1,25(OH)2D3(10-7, 10-8, 10-9, 10-10and 0 mol/L) respectively for 4 days. Then, the concentration of type I collagen in cell supernatant was measured by ELISA. Real-time PCR and western blot were used to detect the expression of Smad3 at mRNA and protein levels and phosphorylated protein Smad3 level in ADMSCs cultured with and without 1,25(OH)2D3. To analyze the contribution of Smad3 to the effect of 1,25(OH)2D3, Smad3 inhibitor was added to culture medium 30 minutes before adding 1,25(OH)2D3, and type I collagen in cell supernatant was detected by ELISA at 4 days after addition of SMAD3 inhibitor. RESULTS AND CONCLUSION: 1,25(OH)2D3inhibited the secretion of type I collagen by ADMSCs in a dose-dependent manner. The results of real-time PCR and western blot showed that the expression of Smad3 was upregulated by 1,25(OH)2D3, and the results of western blot showed that the phosphorylated Smad3 protein level in ADMSCs was significantly increased by 1,25(OH)2D3. Moreover, the inhibition of type I collagen secretion by 1,25(OH)2D3could be blocked by Smad3 inhibitor. These results indicate that 1,25(OH)2D3can inhibit the secretion of type I collagen from ADMSCs by up-regulating the expression of Smad3.

OBJECTIVETo explore the correlation between resting heart rate (RHR) and blood glucose level in elderly patients with coronary heart disease (CHD) complicated by diabetes mellitus.

METHODSBetween April and July, 2011, a total of 1336 outpatients over 60 years of age recruited from 165 hospitals were asked to complete a questionnaire and received blood glucose and RHR examination. According to baseline RHR, the patients were divided into 3 groups with HRH <70 min-1 (group I, 372 cases), between 70 and 79 min(-1) (group II, 533 cases), and ≥80 min(-1) (group III, 431cases) for analysis of the relationships of RHR with blood glucose control rate.

RESULTSHbA1c levels in the total, male and female patients differed significantly among the 3 groups (F=15.436, 15.436, and 24.270, respectively, P<0.05), and increased in the order from group I to group III. Blood glucose control rate in the total, male and female patients also differed significantly among the 3 groups (χ(2)=13.471, 6.752, and 6.522, respectively, P<0.05), and was significantly lower in group III than in group I (P<0.05). RHR was found to positively correlate with FPG, 2 hPG and HbA1c by Pearson correlation analysis (r=0.058, 0.085, and 0.058, respectively; P<0.05) and multiple linear regression analysis (β=0.075, 0.075, and 0.018, respectively; P<0.05). Multivariable logistic regression equation showed that compared with patients with RHR <70 min-1, the total, male and female patients with RHR ≥80 min(-1) had OR values of blood glucose control failure of 1.99 (95% CI: 1.23-2.37, P<0.05), 1.81 (95% CI: 1.17-2.77, P<0.05), and 2.18 (95% CI: 1.12-3.74, P<0.05), respectively.

CONCLUSIONRHR in elderly CHD patients with MD is positively correlated with their blood glucose level, and an increased RHR is associated with an increased risk of poor blood glucose control. Rigorous RHR control in such high-risk patients may prove beneficial for both blood glucose control and secondary prevention of CHD.

Aged ; Blood Glucose ; Coronary Artery Disease ; blood ; Diabetes Mellitus ; blood ; Female ; Heart Rate ; Humans ; Logistic Models ; Male ; Middle Aged ; Regression Analysis

The effect of topical propranolol gel on the levels of plasma renin, angiotensin II (ATII) and vascular endothelial growth factor (VEGF) in superficial infantile hemangiomas (IHs) was investigated. Thirty-three consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma renin, ATII and VEGF in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants of the same age from out-patient department. The clinical efficiency of topical propranolol gel at 1st, and 3rd month after application was 45%, and 82% respectively. The levels of plasma renin, ATII and VEGF in patients pre-treatment were higher than those in healthy infants (565.86 ± 49.66 vs. 18.19 ± 3.56, 3.20 ± 0.39 vs 0.30 ± 0.03, and 362.16 ± 27.29 vs. 85.63 ± 8.14, P < 0.05). The concentrations of VEGF and renin at 1st and 3rd month after treatment were decreased obviously as compared with those pre-treatment (271.51 ± 18.59 vs. 362.16 ± 27.29, and 405.18 ± 42.52 vs. 565.86 ± 49.66 P < 0.05; 240.80 ± 19.89 vs. 362.16 ± 27.29, and 325.90 ± 35.78 vs. 565.86 ± 49.66, P < 0.05, respectively), but the levels of plasma ATII declined slightly (2.96 ± 0.37 vs. 3.20 ± 0.39, and 2.47 ± 0.27 vs. 3.20 ± 0.39, P > 0.05). It was indicated that the increased renin, ATII and VEGF might play a role in the onset or development of IHs. Propranolol gel may suppress the proliferation of IHs by reducing VEGF.
Administration, Cutaneous ; Adrenergic beta-Antagonists ; therapeutic use ; Angiotensin II ; blood ; Case-Control Studies ; Female ; Gels ; Hemangioma, Capillary ; blood ; blood supply ; drug therapy ; pathology ; Humans ; Infant ; Infant, Newborn ; Male ; Propranolol ; therapeutic use ; Renin ; blood ; Skin Neoplasms ; blood ; blood supply ; drug therapy ; pathology ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo explore the mechanism of hyperthermia inducing infertility by observing the expression of glial cell line-derived neurotrophic factor (GDNF) in rat Sertoli cells cultured in vitro at different temperatures.

METHODSUsing combination enzyme digestion and selective adhesion, we isolated Sertoli cells from male Wistar rats and cultured them in vitro at different temperatures, followed by observation of the changes in their adhesion and morphology and identification by FasL immunohistochemical staining. We divided the Sertoli cells into a control group (35 degrees C) and four experimental groups (36 degrees C, 37 degrees C, 38 degrees C, and 39 degrees C), measured their proliferation by CCK-8, observed their morphology and structure by HE staining, and determined the expression of GDNF by RT-PCR, immunofluorescence and Western blot.

RESULTSSertoli cells were successfully isolated and in vitro-cultured, with a purity of (95.30 +/- 2.15)% (n = 10). The CCK-8 assay showed that the proliferation of the Sertoli cells was the highest at 36 degrees C, gradually decreasing with the temperature above 36 degrees C, and significantly inhibited at 39 degrees C (P < 0.01). Immunofluorescence revealed the expression of GDNF in the cytoplasm, with the highest fluorescence intensity at 36 degrees C. RT-PCR and Western blot exhibited a decreasing trend of the GDNF expression with the increasing temperature above 36 degrees C. There were statistically significant differences in the expression of GDNF between the control group and the four experimental groups (P < 0.01).

CONCLUSIONThe proliferation and GDNF expression of in vitro-cultured Sertoli cells differ significantly at different temperatures. At > 36 degrees C, the higher the temperature is, the lower the Sertoli cell proliferation and GDNF expression are. Our findings suggest that high temperature above 36 degrees C suppresses the function of Sertoli cells and may also damage spermatogenesis.

Animals ; Cells, Cultured ; Glial Cell Line-Derived Neurotrophic Factor ; metabolism ; Male ; Rats ; Rats, Wistar ; Sertoli Cells ; cytology ; metabolism ; Temperature ; Testis ; cytology

BACKGROUNDMost of endovascular stent-graft modifications to preserve side branch must be customized according to extensive pre-operative assessment, which may not be possible in many hospitals and emergency settings. The study was to develop a novel stent-grafts system that would allow in situ "fenestration", with less reliance on preoperative imaging.

METHODSThe magnitude of pressure difference (PD) between left subclavian artery (LSA) and aortic arch were measured in 12 experimental pigs. Changes of PD before and after LSA was covered were analyzed respectively. The novel stent graft was made by multi-dimensional and multiple textiles forming technology. According to the PD measurement in pigs, we evaluated the feasibility of the stent-graft in a mock circulation system.

RESULTSIn pigs, the blood pressure of aortic arch was significantly higher than that of LSA after it was covered (P < 0.001) and PD was (42.78 ± 5.17) mmHg. After target vessel was covered and when PD between the LSA and aorta reached the magnitude measured in pigs, contrast media oozed from the cranny of graft to the LSA, which was generated by sliding and deformation of yarns of novel stent-graft.

CONCLUSIONSThe study proposes the design of pressure difference-induced perforation aortic stent-grafts system and verifies that the PD between LSA and aortic arch is high enough to allow in situ "fenestration" by stent graft made by multi-dimensional and multiple textiles forming technology.

Animals ; Aorta, Thoracic ; surgery ; Blood Pressure ; physiology ; Blood Vessel Prosthesis ; Blood Vessel Prosthesis Implantation ; Prosthesis Design ; Subclavian Artery ; Swine