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

With the acceleration of aging process and the increase of average life in China, the number of disabled elderly in China is also growing rapidly, which undoubtedly brings a heavy care burden and pressure to families and society.Facing the great challenges brought by aging, the increasing evidences show that only by reducing the incidence of disease and disability from the source, improving the health level of the elderly, prolonging their healthy life and realizing healthy aging, we can fundamentally alleviate the great pressure brought by the aging society.The concept of motor function maintenance and health promotion of the elderly has become an important link and breakthrough to realize healthy aging and active health.Facing the requirements of active health medicine and the development trend of science and technology in the future, it is imperative to deeply study the motion characteristics and function maintenance of the elderly, and promote the development of sports medicine with innovative technologies such as internet, big data and artificial intelligence.In the future, we will continue to improve the assessment and maintenance system for motor function of the elderly, develop and optimize functional maintenance products that meet the exercise needs of the elderly, and actively build an elderly-friendly sports environment support system, thereby promoting the healthy China strategy and realize healthy aging to the greatest extent.

Objective:To understand the quality of life of high risk population of stroke in community and analyze the influencing factors.Methods:Four community health service centers in Huangpu District were randomly selected, and the subjects were included by using convenient sampling method among the high risk groups of stroke found in the community stroke screening and prevention and control project in Shanghai.The World Health Organization quality of life scale-brief form questionnaire(WHOQOL-BREF), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used as the survey tools to study 1200 high-risk stroke subjects.Single sample t-test was used to compare the differences between the scores and the data of 24 centers in the world, and multiple linear stepwise regression were used to analyze the influencing factors. Results:The scores of physical field, psychological field and social relationship field ((13.60±1.86), (14.58±1.97), (13.72±2.10)respectively) of high-risk population of stroke were lower than the scores of general population of 24 centers in the world ( P<0.01), and the scores of environmental field (14.08±1.95) were higher than it ( P<0.01), of which the differences were all statistically significant.The results of multiple linear stepwise regression analysis showed that old age, anxiety and depression were the risk factors influencing the scores of physical field( β=-0.027, -0.056, -0.051), psychological field( β=-0.019, -0.055, -0.050) and environmental field( β=-0.017, -0.040, -0.054); old age and depression were the risk factors influencing the scores of social relationship field( β=-0.026, -0.067); anxiety and depression were the risk factors influencing the self-assessment of quality of life and health ( β=-0.012, -0.014 for quality of life; -0.012, -0.014 for health, all P<0.01). Conclusion:The quality of life of high-risk population of stroke may be related to age, depression, anxiety and other psychological factors.The prevention and treatment of stroke should take both physical and mental measures, take timely intervention for poor psychological status, and gradually improve the quality of life.

Objective To observe the effect and adverse effect of ultrashort wave combined with Etroricox-ib in treatment of periarthritis of shoulder. Methods 80 cases with periarthritis of shoulder from March 2015 to March 2016 were randomly assigned into treatment group and control group. Etroricoxib therapy was provided in control group while ultrashort wave plus Etroricoxib therapy in treatment group. VAS ,ROM and MBI were applied for the evaluation before and after the treatment. The differences of clinical cure rate ,recurrence rate and adverse reactions were observed between 2 groups. Results There were higher cure rates ,lower recurrence rates and less adverse reactions in 2 groups after the treatment. The shoulder joint pain ,rang of should motion and BI of both groups were improved with significant differences after the treatment ,but treatment group witnessed more improve-ment(P<0.05). Conclusions Ultrashort wave combined with Etroricoxib therapy can relieve shoulder pain ,and further improve the function of shoulder joint activity in the treatment of periarthritis of shoulder. It is recommended for clinical application.

One hundred and six patients with hip fracture admitted in hospital from 2011 to 2014 were randomly divided into two groups: 52 patients received celecoxib and parecoxib ( trial group ) and 54 patients received oxycodone hydrochloride and bucinnazine (control group).On d1 and d7 after the surgery, serum levels of C-reactive protein[(26.2 ±5.4) and (10.4 ±2.8) mg/L], tumor necrosis factor-α[(40.6 ±6.1) and (31.8 ±5.3)ng/L], interleukin-6 [(22.3 ±5.7) and (18.3 ±5.2) ng/L] and prostaglandin E2 [(181.1 ± 19.4) and (153.3 ±25.8) ng/L] in trial group were all significantly lower than those in control group [(46.1 ± 14.0) and (22.1 ±5.2)mg/L, (53.2 ±5.3) and (44.6 ±7.4) ng/L, (43.3 ±11.0) and (29.1 ±8.6)ng/L, (354.3 ±105.9) and (251.0 ±37.3)ng/L, all P<005].The length of hospital stay [(11.0 ±2.2) d], rate of lung infections (6/52) and neurological abnormality (3/52) in trial group were significantly lower than those in control group [(15.5 ±1.8) d, 15/54 and 11/54, all P <0.05].The expression of CD4 +CD45 + T cells [(34.9 ±3.7)% vs.(42.5 ±4.3)%] was reduced and CD4 +Foxp3 +T cells [(19.7 ±3.8)% vs.(6.9 ± 1.5)%] was increased at 24 h after surgery in trial group compared with control group( all P<0.05).The results indicates that calecoxib can reduce the inflammatory reaction by promoting CD4 + to Foxp3 + CD4+T cell differentiation and may improve the prognosis of elderly patients with hip fracture.

The effects of different doses of nitric oxide (NO) on the proliferation and apoptosis of the cultured bovine trabecular meshwork (TM) cells were studied. L-arginine and NG-nitro-L-arginine methyl (L-NAME) were incubated with TM cells for 48 h. In the control group, no medicine was given. In the experimental groups, concentrations of L-arginine and L-NAME were 1 x 10(-7) mol/L, 1 x 10(-6) mol/L, 1 x 10(-5) mol/L, 1 x 10(-4) mol/L, 1 x 10(-3) mol/L and 1 x 10(-2) mol/L, respectively. NO2- in supernate, the proliferation and apoptosis of TM cells and mRNA expression of bcl-2 and bax were measured by Griess reagent, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), MTT assay and in situ hybridization, respectively. The results showed that L-arginine with concentration > or = 1 x 10(-4) mol/L could induce apoptosis of the TM cells and inhibit the proliferation of TM cells through increasing the NO levels, down-regulating bcl-2 mRNA expression and up-regulating bax mRNA expression; L-NAME with concentration > or = 1 x 10(-5) mol/L could induce the proliferation of the TM cells through suppressing the production of NO. It was concluded that NO in high level could induce apoptosis of the TM cells and suppress the proliferation of the TM cells.
Animals ; Apoptosis ; drug effects ; Cattle ; Cell Division ; drug effects ; Cells, Cultured ; Culture Media ; Cyclin D1 ; biosynthesis ; genetics ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; pharmacology ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; RNA, Messenger ; biosynthesis ; genetics ; Trabecular Meshwork ; cytology ; bcl-2-Associated X Protein