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 observe any effect of combining motor imagery therapy (MIT) with repeated transcranial magnetic stimulation (rTMS) for improving upper limb motor functioning after a stroke.Methods:Ninety stroke survivors were randomly divided into a control group, an MIT group and a combination group, each of 30. All received conventional rehabilitation therapy, while the MIT group additionally received MIT and the combination group received the MIT along with 1Hz rTMS applied over the M1 region of the contralateral cortex. Before and after 4 weeks of treatment, everyone′s upper limb functioning was quantified using the Fugl-Meyer assessment scale (FMA) and the Hong Kong version of the hemiplegia upper limb function test (FTHUE-HK). Motor evoked potentials (MEPs), cortical latency (CL) and central motor conduction time (CMCT) were also recorded.Results:After the treatment the average FMA and FTHUE-HK scores of all three groups had improved significantly. The average CL and CMCT were significantly shortened. Compared with the control group, the average upper limb FMA score and FTHUE-HK scores of the treatment group were significantly higher. The combination group showed a significant improvement in its average MEP cortical latency and CMCT values.Conclusions:MIT therapy alone can improve the upper limb motor functioning of stroke survivors, but it is more effective in combination with rTMS.

Objective:To study the quality of life and postoperative complications in patients after laparoscopic cholecystectomy (LC).Methods:The data from 319 patients who were admitted to Nanjing First Hospital Affiliated to Nanjing Medical University and underwent LC from October 2013 to October 2017 were reviewed. These patients were assessed by a questionnaire which was based on the Gastrointestinal Quality of Life Index (GIQLI) before and after surgery.Results:The GIQLI scores on conscious symptoms, physiological function were significantly lower after surgery. The main postoperative complications were diarrhea (53.9%), decline in physical strength (30.1%), abdominal distension (25.4%), fatigue (26.9%) and abdominal pain (11.0%). Among patients with decline in physical strength, fatigue, and abdominal pain, 60.4%, 55.8%, and 51.4% of each of the groups, respectively, were associated with diarrhea. The incidences of severe diarrhea was 0.9%, severe fatigue was 0.3%, severe decline in physical strength 0% and severe abdominal pain 0%.Conclusions:The quality of life of patients declined after LC. The main postoperative complications were diarrhea, decline in physical strength, abdominal distension, fatigue and abdominal pain. However, the incidence of serious complications was small.