Clinical analysis of immunotherapy rechallenge in advanced gastric cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.

Comparison of differential metabolites in urine of the middle school students with chronic fatigue syndrome before and after exercise / 中国应用生理学杂志

OBJECTIVE@#To study the differential metabolites in urine and the characteristics of metabolic pathway of middle school students with chronic fatigue syndrome (CFS) before and after exercise, and then explain the metabolic mechanism of CFS.@*METHODS@#Eight male middle school students (age:17-19) with CFS were selectedas the CFS group according to CFS screening criteria of the U.S. centers.At the same time, 8 male health students of the same age from the same school were selected as the control group. They were administrated to do one-time exercise on the improved Harvard step (up and down steps 30 times/min for 3minutes). Their urinewascollected before and after exercise, and the differential metabolitesin urine were detected by liquid chromatography-mass spectrometry (LC-MS). The multidimensional statistical methods were used to analyze the metabolites by principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Finally, MetPA database was used to analyze the metabolites and to construct the correlativemetabolic pathways.@*RESULTS@#Compared with the control group, the creatine, indoleacetaldehyde, phytosphingosine and pyroglutamic acid were selected as differential metabolites and the contents of those were decreased significantly (<0.05 or <0.01) in CFS groupbefore the step movement. However, 11 differential metabolitesin CFS group were selected out after exercise, which were nonanedioic acid, methyladenosine, acetylcarnitine, capric acid, corticosterone, creatine, levonorgestrel, pantothenic acid, pyroglutamic acid, xanthosine and xanthurenic acid in sequence, the contents of methyladenosine and creatinewere significantly increased (<0.05) and the contents of the other 9 differentialmetabolites were significantly decreased (<0.05 or <0.01)compared with the control group.The 15 differential metabolites mentioned above were input MetPA database in order to analyze the metabolic pathways weighted score.The results showed that the arginine-proline metabolism pathway disordersweredetected in theCFS group before exercise, the marker metabolite wascreatine. And 3 metabolic pathwaysdisorder weredetectedin the CFS groupafter exercise, which were arginine-proline metabolism, biosynthesis of pantothenic acid and CoA, steroid hormone biosynthesis, and the marker metabolites, in turn, werecreatine, pantothenic acid and corticosterone.@*CONCLUSIONS@#The disorder of arginine-proline metabolic pathway is detected in CFS middle school students before exercise intervention. After exercise, it can be detected that the steroid hormone biosynthetic metabolic pathway, pantothenic acid and CoA metabolic pathways also have metabolic disorders.

Single and combined effects of estrone and 17β-estradiol on male goldfish / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the single and combined effects of estrone (E1) and 17β-estradiol (E2) on goldfish (Carassius auratus).</p><p><b>METHODS</b>Batch tests were conducted. Serum levels of vitellogenin (VTG) and E2, gonadosomatic indices (GSI), gonadal DNA damage and liver 7-ethoxyresorufin-O-deethylase (EROD) activity were measured after exposure for 14 days.</p><p><b>RESULTS</b>The VTG level increased significantly in a concentration-dependent manner. The serum E2 level was significantly higher and the GSI level was significantly lower in goldfish after exposed to the 3 drugs. DNA damage occurred in treated samples and EROD activity was significantly suppressed 7 days after exposure. The joint effect of E1 and E2 was additive with regard to VTG induction.</p><p><b>CONCLUSION</b>The results of our study highlight a series of effects of steroidal estrogens on goldfish. Further study is needed to confirm their effect as a whole.</p>