Endoplasmic reticulum(ER)stress can be caused by disturbances in the function of the ER with the accumulation of misfolded proteins.The ER response is characterized by unfolded protein response(UPR)causing translational attenuation,induction of ER chaperones and degradation of misfolded proteins.In case of prolonged or aggravated ER stress,cellular signals leading to apoptosis are activated.ER stress has been suggested to be involved in human neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,as well as other disorders.Here we will discuss the neurotoxic effect of ER stress in these three major neurodegenerative diseases,and highlight current knowledge in this field that may reveal novel insight into disease mechanisms and help to design better therapies for these disorders.

Objective To explore the manifestations of chest multi-slice spiral CT in patients with initial infection of swine-origin influenza A (H1N1) virus (S-OIV). Methods The chest multi-slices spirals CT images of 19 firstly diagnosed patients with swine-origin influenza A (H1N1) in our institution were retrospectively studied. CT manifestations were evaluated by three experienced radiologists. Location, appearance of lung abnormalities, abnormal distribution, pleural effusion and others (pericadiaum, lymphadenopathy and pleural thickening) were observed and quantitatively analyzed. The correlation of ground-glass and consolidation CT scores with the fever time was studied. Results The abnormal CT findings were observed bilaterally in 18 of 19 subjects including ground-glass (n= 3), consolidation (n=3 ), consolidation accompanied with ground-glass (n=12). Most of these lesions were distributed diffusively (n=14) while the others located in the middle and low lobes (n= 4). Unilateral (n=3) or bilateral (n=2) pleural effusion were observed. Lymphadenopathy (n=2), effusion of pericadium (n=1), pleural thickening (n=1) and cardiac enlargement (n=2) were also found in patients with H1N1. CT scores of ground-glass were 4. 25(n=2),3.75 (n=1),2.25(n=1),1.75(n=1),1.00(n=6),0.75(n=2), 0.50(n=2),0(n=4).CT scores of consolidation were4.25(n=1),4.00(n=1),3.75 (n=1), 2.75(n=1),1.25(n=3),1.00(n=2),0.75(n=2),0.50(n=1),0.25(n=3),0(n=4). CT scores of ground-glass were significantly correlated with the fever time (r= 0.776, P < 0.01), CT scores of consolidation had no correlation with the fever time(r=0.322,P > 0.01). Conclusions The most common CT findings in patients with S-OIV infection are diffuse distribution of bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. The increasing of ground-glass's range could be the marker of progression of H1N1 pulmonary infection at initial stage.

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.

OBJECTIVE:To optimize the extraction technology of total saponins from Coreopsis tinctoria. METHODS:Etha-nol leaching technology was adopted. Based on single factor test,the extraction technology was optimized by orthogonal test using extraction temperature,ethanol volume fraction,extraction time,solid-liquid ratio as factors,extraction rate of total saponins as in-dex. The optimized technology was validated. RESULTS:The optimal technology was that ratio of solid to liquid was 1:30 (C. tinctoria-60% ethanol),extracting for 2 h at 50 ℃. Validation test showed that average extraction rate of total saponins was 6.8%(RSD=0.85%,n=3). CONCLUSIONS:The optimized technology can be used for the extraction of total saponins from C. tinc-toria and keep stable.

ObjectiveTo study the potential of using temporal clustering analysis(TCA)technique in localizing an epileptogenic zone.MethodsTwelve patients with epilepsy were examined using resting functional MRI(fMRI). The patients had detectable focal lesions on cranial MRI.TCA was performed to analyze resting fMRI data in order to identify the timing of interictal epileptiform discharges (IEDs).Standard event-related fMRI analysis in SPM99 was used to generate maps of the activation induced by epileptic brain activities.Comparisons were made between TCA Resultsand SPM motion trochoid.ResultsEight of the twelve subiects showed activations in the brain regions that were consistent with those lesions determined on anatomic MRI.The remaining four subiects showed no clear activation in the areas of detectable lesions. In addition, correlation was found between TCA Resultsand motion trochoids.ConclusionsTemporal cluster analysis,an exploratory data-driven technique,may provide the timing information about interictal epileptiforill discharges.However,the Resultsfrom this novel fMRI analytical technique need to be interpreted with caution as it is vulnerable to motion artifact.

[ 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 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.

Objective To investigate the expression of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor-4 ( FGFR-4 ) in the papillary thyroid carcinomas ( PTC ) and clinical significance . Methods Immunohistochemistry and Western blotting for the expression of FGF-2 and FGFR-4 were performed in 89 cases of PTC and 30 cases of normal thyroid tissues ( NTT) adjacent to the tumors .Results Immunohistochemistry results showed that , FGF-2 and FGFR-4 expressions were high in thyroid carcinoma (P<0.01,P<0.01) in contrast to that in the normal thyroid tissues, and the difference was statistically significant;There was a positive linear correlation between expressions of FGF-2 and FGFR-4 and lymph node metastasis (χ2 =14.798,P<0.01;χ2 =7.27,P<0.01)and differentiation degree (χ2=13.824,P<0.01;χ2 =16.921, P<0.01) in papillary thyroid carcinoma ,while there was no difference in gender ,age and tumor size(P>0.05).Analyzed by Western blotting technique ,FGF-2 and FGFR-4 expressions in thyroid carcinoma were significantly higher than that in normal tissue ,with decrease of cancer degree of tissue differentiation and significantly up regulated expression (P<0.05).Expressions of FGF-2 and FGFR-4 were in a positive linear correlation in the disease (rs=0.434,P<0.01).Conclusion The expressions of FGF-2 and FGFR-4 are correlated with papillary thyroid cancer and they participated in the process of invasion and metastasis , both of which have a positive synergistic effect .The degree of malignancy and biological behavior are meaningful and comprehensive indicators ,which provide a theoretical basis for the subsequent experimental studies of cellular and molecular biology .

OBJECTIVETo investigate the association between non-syndromic cleft lip with or without cleft palate (NSCL/P) and environmental factors in Ningxia population.

METHODSThis case-control study involved 453 NSCL/P patients and 452 normal newborns from Ningxia. A questionnaire focusing on various factors, including family history, pregnancy reaction, drug use during pregnancy, and infections, was used and responses were analyzed through Chi-square test and Logistic regression analysis with SPSS 16.0.

RESULTSThe constituent ratio of different types of NSCL/P was cleft lip∶cleft lip and palate∶cleft palate equal to 1︰2.02︰1.51. Logistic regression analysis revealed that abnormal pregnancy, infection, abortion, drugs, drinking, smoking, and living near factories likely increased the risk of NSCL/P (P<0.05). Single fetus, pregnancy-related nausea, vomiting, parents' moderate tastes, and eating soy foods and fruits decreased the risk of NSCL/P (P<0.05).

CONCLUSIONSThe incidence of NSCL/P should be reduced to enhance the conditions of women during pregnancy by maintaining a balanced diet and avoiding infections, abortion, drugs, and negative habits. 
.

Case-Control Studies ; China ; epidemiology ; Cleft Lip ; epidemiology ; Cleft Palate ; epidemiology ; Diet ; Female ; Humans ; Incidence ; Infant, Newborn ; Parents ; Pregnancy ; Smoking

Objective:To explore the possible role and clinical significance of vitamin D receptor (VDR) in intrahepatic bile duct epithelial cells (IBDECs) in biliary atresia (BA).Methods:A retrospective analysis was performed on expression level of VDR in IBDECs of 38 BA children who underwent Kasai surgery in the Second Affiliated Hospital of Xi′an Jiaotong University and the Children′s Hospital of Xi′an Jiaotong University from January 2015 to December 2019.Expression level of VDR in IBDECs of 38 children with BA was detected by immunohistochemical staining, and that in children with choledochal cysts was detected as negative control.Masson staining was performed to examine the degree of liver fibrosis.The correlation between the expression level of VDR in IBDECs of children with BA, and the degree of liver fibrosis during operation, the incidence of refractory cholangitis after Kasai portoenterostomy and the survival time of autologous liver was analyzed.Human intrahepatic bile duct epithelial cells (HiBECs) were induced with dsRNA virus infection by polyinosinic acid-polycytidylic acid [Poly(I∶C)] in vitro, followed by detection of cell activity, apoptosis and VDR level.The differences between 2 independent groups were analyzed using Student t test.The relationship between the expression of VDR and clinicopathologic characteristics was conducted with χ2 test or Fisher′ s test.The Kaplan- Meier survival curve was used to analyze the differences in the survival time of autologous liver after Kasai in BA children with different VDR expression levels. Results:A total of 38 children with BA were included in this study.Among them, 23 cases showed no significant decrease of VDR protein level in IBDECs, and 15 cases showed a significant decrease in IBDECs.Compared with BA children without a significant decrease in VDR level in IBDECs, much severer liver fibrosis ( P<0.001) and significantly higher incidence of refractory cholangitis after Kasai procedure ( P=0.017) were detected in those with a significant decrease in VDR level.Compared with the control group, BA children with significantly lower VDR expression levels in HiBECs had a shorter autologous liver survival time ( P=0.030). Poly (I∶C) increased the apoptotic rate of HiBECs ( P<0.000 1) and decreased cell activity of HiBECs ( P<0.05), which significantly stimulated the secretion of inflammatory factors (interferon, tumor necrosis factor-α, interleukin-6) in the culture medium of HiBECs ( P<0.001). Poly (I∶C) significantly decreased the expression level of VDR protein in HiBECs ( P<0.001). Conclusions:Poly (I∶C) causes HiBECs damage and decreases VDR expression level in HiBECs of BA children, and the significantly decreased VDR expression level in IBDECs may be a marker of poor prognosis of BA.