To study the multidrug resistance activity of 1-alkyl-2-acetyl-1, 2, 3, 4-tetrahydroisoquinoline derivatives. Methods: A series of novel tetrahydroisoquinoline derivatives bearing at C-1 position a carbon chain derived from fatty acids were prepared through the Bischler-Napieralski cyclization reaction. Their multidrug resistance (MDR) reversal cancerous multidrug resistance activities were evaluated against K562 and K562/DOX cell lines in vitro by MTT assay with verapamil as a control. Results and Conclusion: The structures of these tetrahydroisoquinolines were confirmed by extensive spectroscopic methods(1H NMR, MS, IR and elemental ana-lyses). MDR results showed that compounds 7 and 10 exhibited moderate reversal activities, and were slightly less potent than those of verapamil against K562 cell line. It is believed that compounds 7 and 10 have MDR activity.

Objective To develop a method for dynamically observing the biological efficacy of botulinum toxin A (BTX-A) and to investigate the dose-effect relationship between BTX-A dosage and muscle strength.MethodsFifty-four male Sprague Dawley rats were randomly divided into 9 groups.Groups 1-7 were injected intramuscularly with 0.1 ml BTX-A (0.01 U to 4.0 U) into the gastrocnemius on the right side.Rats in group 8 were injected intramuscularly with an equal volume of saline solution as the control group,and group 9 was used to determine the location of injection.Gastrocnemius muscle strength was evaluated using a self-made evaluation system before and after the toxin injection and on the 3rd,7th,14th,21st,30th,45th,60th and 75th day following.ResultsMuscle strength reached its lowest level on days 3 to 7,with a significant difference in the decline of muscle strength between the test groups and the control group up to day 60.With the lower BTX-A doses (0.01 U,0.1 U,0.5 U,1.0 U),muscle strength had decreased significantly on the 21st day,but recovered to its initial levels in all groups at the same time.There was no significant difference among the 1.0 U,1.5 U,2.0 U and 4.0 U groups.ConclusionsStandardized gastrocnemius injection combined with neuromuscular functional evaluation can establish a model of BTX-A dosage and muscle paralysis which can be used to assess the evolution of the biological efficacy of BTX-A.

OBJECTIVETo explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats.

METHODSTwenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared.

RESULTSCompared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in the model group (P < 0.05), while that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of Ach in the model group was obviously; lower than that in the control group (P < 0.05), and that in the 7-d treatment group was higher than that in the model group (P < 0.05).

CONCLUSIONElectrical stimulation at auricular vagus nerve combined with sound masking) could regulate the threshold of ABR, especially in the 15-d treatment group. This may be ascribed to modulating the levels of neurotransmitter of γ-GABA, 5-HT and Ach in inferior colliculus.

Acupuncture Points ; Animals ; Brain Stem ; physiopathology ; Electric Stimulation ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Inferior Colliculi ; physiopathology ; Male ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Tinnitus ; physiopathology ; therapy ; Vagus Nerve ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

Objective To analyze the acoustic features of patients with Parkinson's disease (PD),and to explore the correlation between the acoustic features and the severity and course of disease.Methods Fifty-two patients with PD from the Tongji Hospital Affiliated to Tongji Medical University and the Ninth People's Hospital Affiliated to the Medical College of Shanghai Jiaotong University from August to December 2015 were enrolled into this study.Thirty-two age-matched healthy people served as control group.PD patients were tested with Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr (H-Y) staging.And all the patients were tested with Mini-Mental State Examiantion (MMSE) and Voice Handicap Index (VHI).The voice samples of all subjects were collected and the frequency perturbation (jitter),amplitude perturbation (shimmer),and harmonic-to-noise ratio (NHR) were analyzed using a vocal assessment.Fundamental frequency (F0),standard deviation of fundamental frequency (SDF0) and formant ratio (F2i/F2u) were analyzed using a real-time speech measuring instrument.The acoustic parameters of the two groups were compared and the correlation between the parameters of the patients and the disease and course of disease was analyzed.Results Subjective assessment using VHI showed a total of 24 VHI abnormalities (46％) in the PD group,including 13 males (54％),11 females (46％).No VHI abnormalities were found in the control group.Among the parameters analyzed by objective acoustic method,compared with the control group (female/a/1.43(1.19,1.92),/i/3.39(1.49,9.85),/u/1.46(1.23,3.85);male/a/1.06(0.92,1.89),/u/1.30(1.07,1.64)),the SDF0 of the three vowels of the female patients in the PD group (/a/2.99(1.81,4.12),Z=5.429,P＜0.01;/i/10.89(5.47,22.20),Z=8.487,P＜0.01;/u/5.16(3.75,7.80),Z=7.138,P＜0.01) and /a/ and /u/ of the male patients in the PD group (/a/2.16(1.73,2.94),Z=4.858,P=0.002;/u/3.70(2.41,5.43),Z=7.664,P＜0.01) were significantly increased,and the F2i/F2u in the PD group (male 1.96±0.84,female 1.81± 1.14) was lower than that in the control group (male 3.48±0.70,female 4.14± 1.08),and the difference was statistically significant (t=-6.669,-6.844,P＜0.01).There were no statistically significant differences in frequency perturbation,amplitude perturbation,harmonic noise ratio and fundamental frequency.Only the fundamental frequency standard deviation of the sound parameters used in the study was correlated with the disease course of PD patients.After the severity of the disease was assessed by H-Y staging,the frequency perturbation (jitter),amplitude perturbation (shimmer) in the middle and late stage patients were higher than those in the early stage patients,and the difference of frequency perturbation in the three vowels was statistically significant,and the difference of amplitude perturbation in the vowels/i/and/u/was statistically significant.No correlation was found between the acoustic parameters and UPDRS score.Conclusions Consonance disorders are common in PD patients,and the changes in acoustic parameters are mainly manifested as the increase in the SDF0 and the decrease in the F2i/F2u.Acoustic parameters can be used as an effective indicator to evaluate the condition and course of PD patients,and further language tasks need to be added to clarify.

OBJECTIVE: To compare the efficiency of human bone marrow mesenchymal stem cells (hBMSCs) with rat BMSCs (rBMSCs) transfected by modified adenovirus containing fiber 35 (AdF35)-enhanced green fluorescence protein(eGFP). METHODS: We separated hBMSCs and rBMSCs from the bone marrow of humans and rats, respectively, and osteogenesis and adipogenesis were induced. eGFP was carried by modified AdF35, which was transfected to hBMSCs and rBMSCs with different multiplicity of infections (MOIs). Activity of the cells was detected by MTT. The transfected cells were observed under fluorescent microscope. The transfection efficiency was measured by flow cytometer. The expression of coxsackie and adenovirus receptor (CAR) and CD46 mRNA in the cells was inspected by real time PCR. RESULTS: hBMSCs and rBMSCs induced osteogenesis and adipogenesis successfully after being separated from human and rat bone marrow respectively. The activity of the cells was inhibited when MOI was 1,000 PFU/mL. hBMSCs with strong green fluorescence were observed but few rBMSCs were seen under fluorescence microscope 48 h after being transfected by AdF35-eGFP. The transfective efficiency was (84.8±7.1)% and (3.3±1.1)%, respectively. The expression of CD46 was high while that of CAR was low in hBMSCs. The expression of CAR was very high and that of CD46 was low in rBMSCs (P<0.01). CONCLUSION AdF35 may be the ideal vector to carry the target gene to transfect hBMSCs effectively but not to transfect rBMSCs.
Adenoviridae ; genetics ; Animals ; Bone Marrow Cells ; cytology ; metabolism ; Genetic Vectors ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Humans ; Mesenchymal Stem Cells ; cytology ; metabolism ; Rats ; Transfection

Parkinson′s disease is a neurodegenerative disease characterized by bradykinesia, resting tremor, and hypermyotonia. Its pathological features are the loss of nigra dopamine neurons and the abnormal aggregation of α-synuclein, and there is currently no treatment that blocks the progression of the disease. Gene therapy, by increasing the expression of neurotrophic factors and increasing levels of neurotransmitters, may slow, terminate, or even reverse the progression of the disease, so it gets more attention. This article reviews the progress of registered clinical research on gene therapy for Parkinson′s disease.

Purpose: Chronic stress and related hormones are key in cancer progression. Peroxisome proliferator-activated receptor γ (PPARγ) and its agonists was reported that inducing anti-tumor effect. However, the function of PPARγ in pro-tumorigenic effects induced by chronic stress in breast cancer remains unknown. Herein, we have characterized a novel role of PPARγ and vascular endothelial growth factor (VEGF)/fibroblast growth factor 2 (FGF2) signals in breast cancer promoted by chronic stress. Materials and Methods: We performed experiments in vivo and in vitro and used bioinformatics data to evaluate the therapeutic potential of PPARγ in breast cancer promoted by stress. Results: Chronic stress significantly inhibited the PPARγ expression and promoted breast cancer in vivo. VEGF/FGF2-mediated angiogenesis increased in the chronic stress group compared to the control group. PPARγ agonist pioglitazone (PioG) injection offset the pro-tumorigenic effect of chronic stress. Moreover, specific β2-adrenergic receptor (β2R) antagonist ICI11-8551 inhibited the effect of chronic stress. In vitro, norepinephrine (NE) treatment had a similar tendency to chronic stress. The effect of NE was mediated by the β2R/adenylate cyclase signaling pathway and suppressed by PioG. PPARγ suppressed VEGF/FGF2 through reactive oxygen species inhibition. Bioinformatics data confirmed that therewas a lowPPARγ expression in breast invasive carcinoma. Lower PPARγ was associated with a significantly worse survival. Conclusion β2R activation induced by chronic stress and related hormones promotes growth and VEGF/FGF2-mediated angiogenesis of breast cancer by down-regulating PPARγ. Our findings hint that β receptor and PPARγ as two target molecules and the novel role for their agonists or antagonists as clinical medicine in breast cancer therapy

To explore the process management strategies of standardized residency training based on the development of information management platform, combining with the management practices, this study has sorted out and analyzed process management contents, and integrated process management concepts and contents into the development of information management platform. The development of information management platform taking the process management as the core has contributed to the update and implementation of standardized residency training policies, building of a multi-role interactive bridge, guarantee of information accuracy, and promotion of the construction of quality assurance system, thus providing an effective tool to ensure the quality of training, which is of great significance to cultivate outstanding physicians.

Objective To investigate the expression types of protease-activated receptors (PAR) in human gingival fibroblasts(HGF) and the functions of PAR in periodontitis.Methods Primary HGF were cultured.Reverse transcription PCR(RT-PCR) was used to detect the expression of PAR in HGF.Recombinant gingipain R (rRgp) was applied to HGF.The change of PAR expression on the cell surface was analyzed by real-time quantitative RT-PCR,and enzyme-linked immunosorbent assay (ELISA) was used to detect the change of the interleukin(IL)-6 production from HGF.The results of RT-PCR and ELISA were statistically analyzed using the two independent samples t-test of SPSS10.0 software.Results HGF expressed PAR-1 and PAR-3.The expression of PAR-1 and PAR-3 changed after two rRgp treatment with HGF cells.The relative expression of PAR-1 was decreased from 1.04 ± 0.31 to 0.67 ± 0.11 and 0.31 ±0.11.The relative expression of PAR-3 was decreased from 1.01 ±0.44 to 0.79 ±0.13 and 0.44 ± 0.12 (P ＜ 0.05).The level of IL-6 was increased after rRgp treatment for 8 h.The control group was (18.77 ±4.09) μg/L,the rRgp treatment groups were (179.36 ± 15.81) and (320.56 ± 26.19) μg/L respectively.Conclusions HGF expressed PAR-1 and PAR-3 and were involved in periodontal inflammation.

Objective To explore the characteristics of trunk muscle activity in persons with Parkinson's disease (PD) in search of better treatments for abnormal posture.Methods Ninety persons with PD of different severity and 8 normal controls were studied using surface electromyography (sEMG).A sixteen-lead sEMG instrument was used to collect sEMG amplitudes from the bilateral thoracic erector spinae,lumbar erector spinae,external oblique and rectus abdominis muscles when the subjects were lying,standing and walking.Results Compared with the control group,a significant increase was observed in the sEMG amplitude of the lumbar erector spinal muscle [(18.56±14.57) μV] and rectus abdominis muscles [(24.00±18.80)μV] of the PD group when lying.Significant relative increases in (P＜0.05),of the external oblique muscles were observed [(27.87± 11.49)μV] when standing (P＜0.05),and in the thoracic erector spinae muscle [(58.74±29.69)μV] and external oblique muscles [(59.01± 25.20) μV] increased when walking (P＜0.05).Compared with the control group,the sEMG activity of the external oblique muscles was significantly elevated in PD patients at Hoehn and Yahr stage 1 to 1.5 when walking.One or more of the trunk muscle groups showed significantly greater activity in the PD patients in Hoehn and Yahr stage 2 or 3 in all three positions.Conclusions The sEMG activities of the extensor and flexor muscles increase simultaneously in PD patients.More trunk muscles are involved in PD patients with higher H-Y grades.These findings provide a neurophysiological basis for the customizaton of rehabilitation therapy for patients with Parkinson's disease and for the precise selection of muscles for botulinum toxin injection.