AIM:To investigate the integrative treatment of both coenzyme Q 10 ( CoQ10 ) and minocycline in the rats intranigrally intoxicated with 1-methyl-4-phenylpyridinium ( MPP+) .METHODS:The rat model of Parkinson disease ( PD) was established by intranigral microinjection of MPP +.The degree of microglial activation was measured by immuno-fluorescent density of OX-42 ( a microglia marker ) in the substantia nigra ( SN) .The number of viable dopaminergic neurons was determined by counting the tyrosine hydroxylase ( TH) positive neurons in the SN .The behavioral performances were re-vealed with the number of apomorphine-induced rotations , score of forelimb akinesia and vibrissae-elicited forelimb placing a-symmetry.RESULTS:Pretreatment with CoQ10 or intracerebroventricular (icv) posttreatment with minocycline alone pro-vided partial attenuation against MPP +-induced locomotor defects .Integrative therapy provided enhanced beneficial effects , and resulted in a significant attenuation of locomotor disability than any single therapy (all P<0.01).The results of immu-nohistological analysis showed that the TH positive neurons were maximally protected by integrative therapy compared with minocycline group and CoQ 10 group (P<0.01) .CONCLUSION:The integrative therapy of CoQ 10 combined with minocy-cline may offer additional therapeutic benefit to MPP +-induced hemiparkinson rat model .Such neuroprotective strategy of tar-geting different aspect of the neurodegenerative phenotypes may highlight a new therapeutic strategy for future management of PD.

In order to solve the problems of present quartz crystal microbalance ( QCM ) measuring instruments, such as high demand for crystal cutting technology and uncomprehensive measurements for crystal parameters, a modified quadrature demodulation-based method was proposed with broadband adaptive response capacity and high frequency resolution. Moreover, it is also capable of measuring both resonant frequencies and dissipation factor D synchronously and continuously. Experimental results at room temperature indicated that the adaptive frequency range was 1-9 MHz while the frequency resolution was less than 1 Hz, measured resonance frequency shifts of crystals in the range scale linearly with the equal thickness increments of poly acrylic acid ( PAA) membrane on the working electrode, and with the volatilization of different solvent factor D is measured continuously and effectively along the time axis. To sum up, compared with traditional ones, this new method has lower material cost and more obtained parameters.

Objective To investigate the neuroprotective effect of Dengzhan Shengmai capsule (DZSM) in rat cerebral ischemia-reperfusion injury and to explore the mechanism. Methods Rats were divided into Sham group, MCAO group, DZSM group, carbenoxolone (CBX) group and DZSM + CBX group. Each group was assessed for neurological function , infarct volume and the expression of Caspase-3 48 h after reperfusion. Connexin 43 (Cx43) expression of MCAO group was detected 3, 12, 24, 48 h after reperfusion. Results There were lower neurological deficit scores , infarct volume and the expression of Caspase-3 in DZSM , CBX and DZSM + CBX group 48 h after reperfusion when compared with those in MCAO group (P < 0.05) but Cx43 expression level in each group increased after reperfusion at each time point (P < 0.05). Expression of Cx43 was lower in DZSM, CBX and DZSM + CBX group than that in MCAO group (P < 0.05). Lower expression of Cx43 was also seen in CBX and DZSM + CBX group when compared with that in DZSM group (P < 0.05). Conclusion DZSM capsule can improve neurological function , reduce infarct volume and inhibit the expression of Caspase-3. The mechanism may be related to its inhibition of Cx43 expression.

[ ABSTRACT] AIM:To investigate the effect of triptolide on the inhibition of microglial activation in 1-methyl-4-phenyl pyridinium ( MPP+)-induced hemiparkinson disease rats.METHODS:The rat model of Parkinson disease was es-tablished by intranigral injection of MPP +.The rats were randomly divided into sham group, MPP+group, triptolide group and vehicle group.The survival of dopaminergic neurons was detected by the immunofluorescence of tyrosine hydroxylase ( TH) in the substantia nigra ( SN) .The activation of microglia was determined by immunofluorescence of OX-42 ( micro-glia marker) in the SN.The expression of chemokine receptor CX3CR1 in SN was measured by Western blotting.RE-SULTS:Intranigral injection of MPP+increased the fluorescence intensity of the microglial marker, and promoted DA neu-ron degenerative death.Immunohistological analysis showed that the OX-42 density was decreased (P<0.01) and tyrosine hydroxylase (TH) positive neurons were increased in the triptolide group (P<0.01).The expression of CX3CR1 was lower in triptolide group than that in model group (P<0.05).CONCLUSION:Triptolide may improve PA neurons func-tion in MPP+-induced rats through inhibiting CX3CR1 expression and microglial activation.

Objective To study the clinical and pathological manifestations of microsporidian encephalitis.Methods The clinical findings and the brain pathological features of a patient with microsporidian encephalitis hospitalized in 2004 were studied.Results The onset was subacute or chronic. The body temperature was usually normal or below 37.5℃,but it rose when patient's condition deteriorated and coma appeaxed.The patient had hypoimmunity but without human immunodeficiency virus infection. Multifocal lesions in the whole brain,signs of meningeal irritation and infective myelogram were observed. Rheumatoid factor increased in the early stage and indirect bilirubin,proteins in cerebrospinal fluid(CSF), and immunoglobulin IgG,IgA increased in the middle stage.Cytological examination of CSF showed lymphocyte reaction.Blood routine test showed normal eosinophil granulocyte count.The patient was found to have pleurisy,peritonitis and cystitis.Brain magnetic resonance image(MRI)manifested plaque-like isometric T1 weight image and long T2 weight image signal in white matter of bilateral cerebral hemisphere and cerebella where FLAIR sequence showed hyperintensity.No apparent mass was identified.Contrast- enhanced MRI scan showed patchy and ring-like intensification.The neural system impairments were permanent and not improved after treatment.The pathology of brain tissue showed neuronal degeneration, karyopycnosis and Derivasculitis.The infectious agents were observed in the cytoplasm of neurons.Wister rats had muhiple organ inflammatory reaction 2 weeks after intraperitoneal inoculation of the patient's CSF and a large quantity of pathogens were found in the peritoneal lavage fluid.Conclusions The patient was PAS staining method is useful for detecting the pathogen in neurons and the rate can be raised by animal intraperitoneal cultivation

Objective To investigate the effect of modified radiographic position for peripherally inserted central catheter (PICC) on XGray imaging.Methods FiftyGone patients of standard anteriorGposterior radiography (control group)and 50 patients of radiography with the left side of the body tilted 10 to 30 degrees to the right (modified group)were collected retrospectively.The quality of imaging was analyzed between groups.Results The image quality was significantly improved in the modified group (χ2＝ 1 7.27,P＜0.05).Conclusion When the bedside mobile DR is performed on PICC patients,raising the left side of the body and tilting to the right 10 to 30 degrees,known as modified radiographic position,can effectively increase the image quality and improve the identification of PICC,so as to accurately determine the depth of the PICC catheter.

Objective To study the effect of scalp acupuncture plus facilitation technique on the temporal and spatial parameters of gait in spastic cerebral palsy. Method Thirty eligible patients with spastic cerebral palsy were randomized into a treatment group and a control group based on the inter-group balance in age, palsy type, and the Gross Motor Function Classification System (GMFCS), 15 cases in each group. The treatment group was intervened by scalp acupuncture, together with the facilitation technique during the retaining of the needles; the control group was also by scalp acupuncture and facilitation techniques but with over 1 h interval between the two methods. The treatment was given once a day, totally for 3 months. The walking, running, and jumping items (E category) of the Gross Motor Function Measure-66 (GMFM-66), temporal and spatial parameters of gait, and vertical ground reaction force during stance were compared before and after the treatment. Result There were no significant inter-group differences in comparing the rates of E category of the GMFM-66 before the treatment (P>0.05), the rates were significantly changed after the treatment in both groups (P<0.05), and there were significant differences in comparing the rates between the two groups after the intervention (P<0.05);after the intervention, the step length, walking speed, and step frequency were increased significantly in both groups (P<0.05), while the double-stance phase was decreased significantly, and swing phase was increased significantly (P<0.05); after the intervention, the step length, walking speed, and step frequency of the treatment group were significantly better than that of the control group (P<0.05). Conclusion Acupuncture plus facilitation technique can mitigate the spasticity in spastic cerebral palsy, improve the gross motor function, especially the function of standing and walking, enhance the activities, and benefit the improvement of the step length, step width, and walk speed.

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

[Purpose]To analyze the trend of bladder cancer incidence and age at diagnosis in can-cer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The data of bladder can-cer incidence from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province,and quality control indicators of the data were evaluated.The crude rate(CR)of incidence,age-standar-dized incidence rate by Segi world standard population(ASIRW),age-specific incidence rate,mean age at diagnosis,mean standardized age at diagnosis,and age-specific incidence composi-tion ratio were calculated.Incidence trends were analyzed using Joinpoint software and the average annual percentage change(AAPC)was calculated.Birth cohort models were constructed and can-cer incidence rates were calculated for people born from 1929 to 2019 and the incidence trends were analyzed.The linear regression models were used to analyze the relationship of average age at onset,standardized average age of onset with year of onset.[Results]The CR of bladder cancer in Jiangsu Province increased from 4.27/105 in 2009 to 7.04/105 in 2019.The CR and ASIRW showed upward trends(CR:AAPC=4.62％,ASIRW:AAPC=1.92％,both P＜0.001).Sex-specific analysis showed that the incidence rate was higher in male(AAPC=5.32％)than that in female(AAPC=1.98％).Birth cohort results indicated a significant upward trend in incidence rates among age groups of 60 years old above,and the fastest increase was in those aged 80 years old and above(AAPC=3.27％,P=0.007).From 2009 to 2019,the average age of bladder cancer onset in Jiangsu Province showed a significant rising trend,increasing by an average of 0.17 years old annually,but the standardized average age of onset showed no significant change after adjusting for age structure.[Conclusion]The incidence rate of bladder cancer showed an increasing trend from 2009 to 2019 in Jiangsu Province,with a significantly higher incidence rate in male than that in female.

Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.