Preoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratioin predicting survival for patients with stage Ⅰ-Ⅱgastric cancer

Background:The preoperative neutrophil-to-lymphocyte ratio(NLR) and the platelet-to-lymphocyte ratio(PLR) are associated with poor prognosis of gastric cancer.We aimed to determine whether the combination of NLR and PLR(NLR-PLR) could better predict survival of patients after curative resection for stage Ⅰ-Ⅱ gastric cancer.Methods:We collected data from the medical records of patients with stage Ⅰ-Ⅱ gastric cancer undergoing curative resection between December 2000 and November 2012 at the Sun Yat-sen Cancer Center.The preoperative NLRPLR was calculated as follows:patients with both elevated NLR(≥2.1) and PLR(≥ 120) were given a score of 2,and patients with only one or neither were given a score of 1 or 0,respectively.Results:Kaplan-Meier analysis and log-rank tests revealed significant differences in overall survival(OS) among patients with NLR-PLR scores of 0,1 and 2(P < 0.001).Multivariate analysis showed that OS was independently associated with the NLR-PLR score[hazard ratio(HR) = 1.51,95%confidence interval(CI) 1.02-2.24,P = 0.039]and TNM stage(HR = 1.36,95%CI 1.01-1.83,P= 0.041).However,other systemic inflammation-based prognostic scores,including the modified Glasgow prognostic score,the prognostic nutritional index,and the combination of platelet count and NLR,were not.In TNM stage-stratified analysis,the prognostic significance of NLR-PLR was maintained in patients with stage Ⅰ(P < 0.001) and stage Ⅱ cancers(P= 0.022).In addition,the area under the receiver operating characteristic curve for the NLR-PLR score was higher than those of other systemic inflammation-based prognostic scores(P = 0.001).Conclusion:The preoperative NLR-PLR score is a useful predictor of postoperative survival in the patients with stage l-ll gastric cancer and may help identify high-risk patients for rational therapy and timely follow-up.

Prognostic value of programmed death.1, programmed death-ligand 1, programmed death-ligand 2 expression, and CD8(+) T cell density in primary tumors and metastatic lymph nodes from patients with stage T1.4N+M0 gastric adenocarcinoma

Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.

Component Analysis of Shuanghuanglian Freeze-dried Powder and Its Effects on Human Hepatocyte Function when Combined with Cefradine

[Objectives]To detect the contents of components in Shuanghuanglian freeze-dried powder and to explore the effects of Shuanghuanglian freeze-dried powder and its components on human hepatocytes(HL-7702)alone or in combination with cefradine.[Methods]High performance liquid chromatography(HPLC)was used to detect the contents of baicalin,wogonin,chlorogenic acid and forsythin,the main components of Shuanghuanglian freeze-dried powder.HL-7702 cells were cultured with Shuanghuanglian freeze-dried powder and the main components of Shuanghuanglian freeze-dried powder alone or in combination with cefradine.Enzyme linked immunosorbent assay(ELISA)was used to detect the contents of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the cell supernatant after culture,and HPLC was used to detect the expression level of adenosine diphosphate(ADP)and adenosine triphosphate(ATP);agarose gel electrophoresis was used to detect the expression of cyclooxygenase 2(COX-2)and heme oxygenase-1(HO-1)in HL-7702 cells.[Results]In Shuanghuanglian freeze-dried powder for injection,the content of baicalin was the highest,and the content of wogonin was the lowest.Compared with the control group,the expressions of AST and ALT in human hepatocytes(HL-7702)in high-dose baicalin group,forsythin group and wogonin group decreased(P<0.05,P<0.01),while the expression of ALT in chlorogenic acid+cefradine group(0.046 mg/mL)and forsythin+cefradine group(0.046 mg/mL)increased(P<0.05,P<0.01),and the expression of AST had no significant difference(P>0.05);the results in the low-dose group were similar to those in the high-dose group.Compared with the control group,ATP expression in chlorogenic acid group,chlorogenic acid+cefradine group(0.046 mg/mL)and forsythin+cefradine group(0.046 mg/mL)in the high-dose group decreased(P<0.05,P<0.01),and ADP expression was not significantly different(P>0.05);in the low-dose group,the expression of ATP and ADP increased in baicalin group(P<0.05),but decreased in wogonin group,baicalin+cefradine group(0.046 mg/mL)and wogonin group+cefradine group(0.046 mg/mL)(P<0.05,P<0.01).Compared with the control group,the expressions of COX-2 and HO-1 in HL-7702 cells in the cefradine group showed no significant difference(P>0.05).The expression of HO-1 and COX-2 in the different dose groups of Shuanghuanglian and the group combined with cefradine increased,and the difference was significant(P<0.05,P<0.01).[Conclusions]The components of Shuanghuanglian freeze-dried powder for injection had effects on hepatocytes,of which baicalin had a significant effect,and the effect of cefradine on hepatocytes was increased when used in combination with cefradine.

Role of the South China Sea Summer Upwelling in Tropical Cyclone Intensity

Tropical cyclones (TCs) can affect the thermal structure in the upper ocean by mixing. In turn, upper-ocean thermal structure also affects the evolution of TCs. Here based on satellite data, in situ temperature and salinity observations and the best-track data of the U.S. Joint Typhoon Warning Center, combined with an ocean mixed layer model, the role of the pre-existing summer upwelling of the northern South China Sea (NSCS) in TCs self-induced sea surface cooling was explored. The modeling results showed that for a given atmospheric thermodynamic condition, TCs self-induced sea surface cooling is quite different when they pass over the regions with pre-existing upwelling and without upwelling. The amplitude of TCs self-induced cooling is larger by more than 50% in the region with pre-existing upwelling than that without. For example, for a slow-moving typhoon with translation speed of 4 m/s and wind speed of 45 m/s, TC self-induced surface cooling is 2.5&#176;C when they pass over the upwelling region, but only 1.5&#176;C when they pass over the region without upwelling. The results suggest that upwelling of the NSCS could amplify TCs self-induced cooling and play a negative role in TCs intensification before they made landfall in Southern China.

Construction and evaluation of a polygenic hazard score for prognostic assessment in localized gastric cancer

To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer(GC),we performed two genome-wide association studies(GWASs)of GC survival in the Jiangsu(N=1049)and Shanghai(N=1405)cohorts.By using a TCGA dataset,we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated loci.Then,we constructed a weighted polygenic hazard score(PHS)and developed a nomogram in combination with clinical variables.We also evaluated prognostic accuracy with the time-dependent receiver operating characteristic(ROC)curve,net reclassification improvement(NRI)and integrated discrimination improvement(IDI).We identified a single nucleotide polymorphism(SNP)of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a P value of 4.12×10^(-8),and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA cohort.The PHS derived from these 26 SNPs(PHS-26)was an independent prognostic factor for GC survival(all P<0.001).The 5-year AUC of PHS-26 was 0.68,0.66 and 0.67 for Jiangsu,Shanghai and their pooled cohorts,respectively,which increased to 0.80,0.82 and 0.81,correspondingly,after being integrated into a nomogram together with variables of the clinical model.The PHS-26 could improve the NRIs by 16.20%,4.90%and 8.70%,respectively,and the IDIs by 11.90%,8.00%and 9.70%,respectively.The 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.

Non-canonical distribution and non-equilibrium transport beyond weak system-bath coupling regime： A polaron transformation approach

The concept of polaron, emerged from condense matter physics, describes the dynamical interac- tion of moving particle with its surrounding bosonic modes. This concept has been developed into a useful method to treat open quantum systems with a complete range of system-bath coupling strength. Especially, the polaron transformation approach shows its validity in the intermediate coupling regime, in which the Redfield equation or Fermi＇s golden rule will fail. In the polaron frame, the equilibrium distribution carried out by perturbative expansion presents a deviation from the canonical distribution, which is beyond the usual weak coupling assumption in thermodynam- ics. A polaron transformed Redfield equation （PTRE） not only reproduces the dissipative quantum dynamics but also provides an accurate and efficient way to calculate the non-equilibrium steady states. Applications of the PTRE approach to problems such as exciton diffusion, heat transport and light-harvesting energy transfer are presented.

Spontaneous decoherence of coupled harmonic oscillators confined in a ring

We study the spontaneous decoherence of coupled harmonic oscillators confined in a ring container, where the nearest-neighbor harmonic potentials are taken into consideration. Without any external symmetry-breaking field or surrounding environment, the quantum superposition state prepared in the relative degrees of freedom gradually loses its quantum coherence spontaneously.This spontaneous decoherence is interpreted by the gauge couplings between the center-of-mass and the relative degrees of freedoms, which actually originate from the symmetries of the ring geometry and the corresponding nontrivial boundary conditions.In particular, such spontaneous decoherence does not occur at all at the thermodynamic limit because the nontrivial boundary conditions become the trivial Born-von Karman boundary conditions when the perimeter of the ring container tends to infinity.Our investigation shows that a thermal macroscopic object with certain symmetries has a chance for its quantum properties to degrade even without applying an external symmetry-breaking field or surrounding environment.

ASTE1 frameshift mutation triggers the immune response in Epstein-Barr virus-associated gastric cancer

Dear Editor,Epstein-Barr virus-associated gastric cancer(EBVaGC)is a subtype of GC that is characterized by the presence of EBV in cancer cells.1 EBVaGC is a relatively rare malignancy,accounting for only 10%of GC cases.Compared to other types of GC,EBVaGC presents a distinct tumor microenvironment with ample immune infiltration and increased expression of immune response genes.This unique microenvironment is assumed to have a better response to immunotherapy.However,the efficacy of immunotherapy in EBVaGC is inconsistent.2,3 In some studies,the PR rates were hardly to exceed 30%.Therefore,to improve efficacy and achieve precise treatment under the background of low response rate,it is urgent to identify the specific subgroup of EBVaGC which could benefit from immune therapy.