Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Objective : To explore the nucleotide variation and protein amino acid changes of E4 and L2 genes of Human Papillomavirus 16 (HPV16) , and to analyze the evolutionary characteristics of HPV16 virus. Methods : 40 HPV16 infection⁃positive cervical exfoliated cells samples and tissue cell samples were collected from hospital , viral DNA was extracted , Sanger sequencing perform in cervical exfoliated cells DNA and high⁃throughput sequencing technology sequenced in cervical tissues DNA for E4 and L2 genes of HPV16 , HPV16 E4 and L2 gene phylogenetic evolution trees were constructed , and variation of HPV16 E4 and L2 genes were analyzed. Results : There were 72 HPV16 E4 variant samples with nucleotide variants (4 missense mutations and 7 synonymous mutations) at 10 sites , HPV16 L2 gene variants in 74 samples , and nucleotide variants (23 missense mutations and 18 synonymous mutations) at 40 sites. The variation frequency of T4177C , A4288C and A4654C in cervical cancer was significantly higher than that in non⁃cervical cancer, and the difference was statistically significant (P < 0. 05) . Conclusion ① The main HPV16 virus strains in Xinjiang are European strains , and a few are Asian strains. ② The mutation frequency of T4177C , A4288C and A4654C in HPV16 L2 gene is higher than that in non⁃cervical cancer, and G4181A is related to the Asian strain.

AIMS: This study focused on the newest evidence of the relationship between forest environmental exposure and human health and assessed the health efficacy of forest bathing on the human body as well as the methodological quality of a single study, aiming to provide scientific guidance for interdisciplinary integration of forestry and medicine. METHOD: Through PubMed, Embase, and Cochrane Library, 210 papers from January 1, 2015, to April 1, 2019, were retrieved, and the final 28 papers meeting the inclusion criteria were included in the study. RESULT: The methodological quality of papers included in the study was assessed quantitatively with the Downs and Black checklist. The methodological quality of papers using randomized controlled trials is significantly higher than that of papers using non-randomized controlled trials (p < 0.05). Papers included in the study were analyzed qualitatively. The results demonstrated that forest bathing activities might have the following merits: remarkably improving cardiovascular function, hemodynamic indexes, neuroendocrine indexes, metabolic indexes, immunity and inflammatory indexes, antioxidant indexes, and electrophysiological indexes; significantly enhancing people's emotional state, attitude, and feelings towards things, physical and psychological recovery, and adaptive behaviors; and obvious alleviation of anxiety and depression. CONCLUSION Forest bathing activities may significantly improve people's physical and psychological health. In the future, medical empirical studies of forest bathing should reinforce basic studies and interdisciplinary exchange to enhance the methodological quality of papers while decreasing the risk of bias, thereby raising the grade of paper evidence.