OBJECTIVE Toinvestigatethedifferenceofcytotoxiceffectsofhydroxycamptothecin(HCPT)onhuman lungcancercelsA549andhumanembryolungfibroblastcelsMRC-5.METHODS A549celsandMRC-5celswere treated with HCPT 20-200 μmol·L-1 for 24,48 and 72 h,or pulse treated with HCPT 50-400 μmol·L-1 for 24 h along with 5 d release.cellsurvival was detected by MTT assay.Morphological changes for both types of cells were observed under an inverted phase-contrast microscope.cellcycle and apoptosis in both cells treated with HCPT 50 μmol·L-1 for 48 h weredeterminedbyflowcytometry.RESULTS HCPT20-200μmol·L-1inhibitedthesurvivalofbothcelsinaconcen-tration-dependent manner and more cytotoxicity was observed in A549 cells for 48 h.The concentration-effect correlation coefficient(r)of HCPT in A549 and MRC-5 cells for 48 h was 0.898 (P=0.015)and 0.996 (P=2.56E-5)respectively. The inhibition rates were significantly different between A549 and MRC-5 cells with treatment of HCPT 20,50,80,1 00, 1 60 and 200 μmol·L-1 for 48 h (P<0.05).The IC50 of HCPT on A549 and MRC-5 cells was (24.00 ±0.69)μmol·L-1 and (1 23.63 ±3.89)μmol·L-1 respectively,indicating that A549 cells were 5-fold more sensitive to HCPT than MRC-5 cells at 48 h.After exposure to HCPT 50 μmol·L-1 for 48 h,some A549 cells were rounded up and shrank dramatical y, and some cells underwent membrane blebbing or lysing while MRC-5 cells had no obvious changes.cellcycle and apop-tosis analysis showed that A549 cells were arrested at both S and G2/M phases and apoptosis occurred but MRC-5 cells were just arrested at S phase.In the recovery growth curve,the growth of A549 cells was inhibited to a larger extent than MRC-5 cells and the growth retardation stil existed for 24 h in both cells.The survival of MRC-5 cells was faster than that ofA549cels,althoughtherewasnocompleterecoveryineithercel.CONCLUSION A549celsaremoresensitiveto HCPT than MRC-5 cells due to the fact that HCPT induces cellcycle arrest at both S and G2/M phases and apoptosis in A549 cells,but only triggers S phase arrest in the MRC-5 cells.

Objective To study the effect of deep brain stimulation of subthalamic nucleus (STN-DBS) on non-motor symptoms (NMSs) in patients with Parkinson's disease (PD).Methods Seventeen PD patients,admitted to and accepted bilateral STN-DBS in our hospital from 2012 to 2018,were chosen in our study.Unified Parkinson's Rating Scale (UPDRS) Ⅲ and Non-motor Symptoms Scale (NMSS) were used to evaluate the motor symptoms and non-motor symptoms one week before and 12 months after surgery.The correlations of motor symptoms and non-motor symptoms with age and gender were analyzed.Results The UPDRS Ⅲ total scores of 17 patients were 33.48+10.00 one week before DBS and 10.59±6.70 one year after DBS,with statistically significant difference (P＜0.05).The NMSS total scores were 144.47±51.31 one week before DBS and 86.35±40.23 one year after DBS,with statistically significant difference (P＜0.05).There were statistically significant differences in scores of sleep and fatigue,mental and behavioral abnormalities,sensory abnormality,cognitive impairment and constipation between one week before and one year after surgery (P＜0.05).NMSS scores showed no significant correlation with gender,but showed significant correlations with age,course of disease and Hoehn-Yahr grading (P＜0.05).Conclusion Bilateral STN-DBS can significantly improve some non-motor symptoms to a certain degree.

Objective:To explore how electrical stimulation of the sciatic nerve affects learning and memory in cases of chronic cerebral hypoperfusion and its mechanism.Methods:Thirty-two Sprague-Dawley rats were randomly divided into a normal group, a sham-operation group, a model group and a stimulation group, each of 8. In the model and stimulation groups a chronic cerebral hypoperfusion model was established using the modified 2-VO method. The stimulation group then received electrical stimulation of the sciatic nerve for 4 weeks. Afterward all of the rats′ learning and memory were tested using the Morris water maze. HE staining and immunohistochemistry were used to observe any morphological change in the hippocampus and the expression of neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF).Results:The model and stimulation groups demonstrated significantly longer escape latency, fewer platform crossing times and shorter target quadrant times than the normal and sham-ope-ration groups before the intervention. All of these indicators had improved after the intervention. According to the HE staining, neuronal damage in the hippocampus was aggravated significantly in the model group compared with the normal and sham-operation groups, while the degree of damage was reduced in the stimulation group. Moreover, the immunohistochemistry results suggested that the expressions of NSE and VEGF were reduced significantly in the model group compared with the normal and sham-operation groups, while in the stimulation group they had increased significantly compared with the model group.Conclusions:Electrical stimulation of the sciatic nerve can improve learning and memory in cases of chronic cerebral hypoperfusion, at least in rats. It is probably related to the increased expression of VEGF in the hippocampus.

It was generally believed that muscular atrophy of paralyzed limbs after stroke was due to disuse. However, recent studies have found that secondary lesions of motor neurons in the contralateral anterior horn of the spinal cord and the decrease of motor units lead to denervation, which plays an essential role in muscular atrophy and muscle fiber type transition. This article reviews the phenomenon and mechanism of muscular atrophy and denervation of paralyzed limbs after stroke, to provide a reference for clinical evaluation and experimental research.

Objectives : To investigate the effect of sciatic nerve electrical stimulation ( SNES) on motor function recovery in rats with incomplete spinal cord injury (SCI) and its possible mechanism. Methods : The incomplete SCI model was constructed by modified Allen ′s method. Forty⁃five Sprague⁃Dawley (SD) rats were randomly divided into three groups : Sham , SCI , and SNES. Electrical stimulation parameters were 1 ms pulse width and 100 Hz , with 20 mins each time , once a day for 21 days. The motor function was assessed by Basso⁃Beattie⁃Bresnahan (BBB) locomotor function scale , and the action potential conduction was detected by electrophysiology. Hematoxy⁃lin⁃eosin (HE) staining was used to observe the pathological changes in the spinal cord and the average cross⁃sectional area (CSA) of biceps femoris muscle fibers. The number of brain⁃derived neurotrophic factor (BDNF) and tropomyosin⁃related kinase B (TrkB) positive cells , relative mRNA and protein expression were analyzed by immunohistochemistry , reverse transcription polymerase chain reaction (RT PCR) and Western blot separately. Results: On 21 d , the BBB score and average amplitude of action potential of SNES group were higher than those of SCI group , and the difference was statistically significant (P < 0. 05) . Compared with SCI group , the pathological injury of spinal cord tissue in SNES group was significantly improved , and the average CSA of biceps femoris muscles had a statistical difference (P < 0. 05) . The number of BDNF and TrkB positive cells in SNES group was higher than that in SCI group , and there were statistical differences (P < 0. 05) . The relative mRNA and protein expressions of BDNF and TrkB in SNES group were higher than those in SCI group , with statistical differences ( P <0. 05) . The relative mRNA and protein expressions of BDNF and TrkB in SNES group were higher than those in SCI group , with statistical differences ( P <0. 05) . Conclusion These results show that SNES contributes to alleviating spinal cord tissue injury , promoting the recovery of motor function and delaying the atrophy of muscles below the injury level. The possible mechanism is related to the increased expression of BDNF⁃TrkB proteins.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.