OBJECTIVE: To evaluate the effect of chronic nicotine on contextual fear memory in rats. METHODS: Rats were subcutaneously injected saline or nicotine for 14 days continuously to induce nicotine dependence. Somatic signs of spontaneous nicotine withdrawal were assessed on day 1 and 14 after the last injection. Locomotor activity was tested 13 days after the last injection. Contextual fear conditioning task was run 14 days after the last injection, which included 3 phases: habituation, fear conditioning, and test. Percent freezing was used as an index for fear memory during the conditioning and test phases. Finally, footshock sensitivity test was conducted. RESULTS: Compared with the saline group, the global withdrawal scores significantly increased in the nicotine group when the somatic signs were assessed 1 day after the nicotine injection, while there was almost no difference in the 2 groups 14 days after the last injection. In the contextual task, the nicotine group showed a significant increase in the level of freezing response during the test phase but not in the conditioning phase. There was no significant difference in the locomotor activity and footshock sensitivity between the 2 groups. CONCLUSION Chronic nicotine enhances the contextual fear memory in rats. This effect is not attributed to the change of somatic signs, locomotor activity or footshock sensitivity.
Animals ; Brain ; drug effects ; Conditioning, Classical ; drug effects ; Electric Stimulation ; Fear ; drug effects ; Freezing Reaction, Cataleptic ; drug effects ; Learning ; drug effects ; Male ; Memory ; drug effects ; Nicotine ; pharmacology ; Nicotinic Agonists ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE： To observe the efficacy and safety of fluorouracil combined with paracetamol in the treatment of knee osteoarthritis and its effects on related indexes. METHODS： Totally 115 patients with knee osteoarthritis admitted to our hospital from March 2015 to March 2018 were divided into control group （57 cases） and observation group （58 cases） according to medication plan. Control group was given Paracetamol tablets 0.3 g orally， 3 times a day， for consecutive 8 weeks. Observation group was additionally given intra-articular injection of Fluorouracil injection 0.075 g on the basis of control group， once a week， 4 times as a treatment course， for 2 courses in total. Clinical efficacies， VAS scores， Lysholm knee scores， Fugl-Meyer Assessment （FMA） scores， Barthel indexes， WHO QOL-BREF scores before and after treatment and the occurrence of ADR of 2 groups were observed. RESULTS： The total response rate of observation group was 94.83％， which was significantly higher than 78.95％ of control group （P＜0.05）. Before treatment， there was no statistical significance in VAS score， Lysholm knee scores， FMA scores， Barthel index or QOL-BREF scores between 2 groups （P＞0.05）. After treatment， VAS scores of 2 groups were significantly lower than before treatment， and the observation group was lower than the control group； Lysholm knee scores， FMA scores， Barthel indexes and QOL-BREF scores were significantly higher than the same group before treatment， and observation group was significantly higher than control group （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups （P＞0.05）. No severe ADR was found in 2 groups during treatment. CONCLUSIONS： Fluorouracil combined with paracetamol can significantly improve therapeutic efficacy of patients with knee osteoarthritis， and can significantly improve knee function， motor function， self-care ability and quality of life without increasing the occurrence of ADR.

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Objective: To investigate the effect of elective neck dissection on the 5-year survival rate of patients with early oral squamous cell carcinoma. Methods: The data of 100 patients with early oral squamous cell carcinoma (cT1-2N0M0) were retrospectively analyzed. In 61 cases, the primary tumor was subjected to elective neck dissection (END). Neck observation and follow-up (NOF) were performed in 39 cases with enlarged resection of primary lesions. Clinicopathological data such as pT staging, pathology classification,the rate of cervical lymph node metastasis and the 5-year survival rate of the patients were statistically analyzed. Results: The 5-year survival rates of the END and NOF groups were 86.9% and 69.2%, respectively, and the difference was statistically significant (P=0.028). END treatment was significantly better than NOF in controlling cervical lymph node metastasis in early oral squamous cell carcinoma (P=0.009). After stratified analysis of histopathological features, the 5-year survival rate of patients with pathological T2 (pT2) stage OSCC in the END group was significantly higher than that in the NOF group (P=0.020). The 5-year survival rate of patients with moderate and poorly differentiated pathological grade OSCC in the END group was significantly higher than that in the NOF group (P=0.013). Conclusion END is effective for the management of the cervical lymph node metastasis rate in early OSCC patients. For patients with pT2 stage or low differentiation pathological grade, active END can significantly improve the 5-year survival rate.