Objective·To explore the effects and potential mechanisms of emodin on Alzheimer's disease(AD).Methods·Wild-type C57BL/6J mice and 3×Tg-AD mice were divided into 6 groups:Control group(C57BL/6J mice),AD group(3×Tg-AD mice),Emodin 25 mg/kg group(3×Tg-AD mice+Emodin 25 mg/kg),Emodin 50 mg/kg group(3×Tg-AD mice+Emodin 50 mg/kg),Emodin 100 mg/kg group(3×Tg-AD mice+Emodin 100 mg/kg)and Donepezil group(3×Tg-AD mice+Donepezil 3 mg/kg).The Morris water maze test was used to evaluate the learning and memory abilities of mice.The expression of glial fibrillary acidic protein(GFAP),glucose-regulated protein 78kDa(GRP78),and inositol-requiring enzyme 1α(IRE1α)was detected by immunohistochemistry.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in brain tissue were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of NF-κB p65,p-NF-κB p65,p38,and p-p38 proteins.Results·Compared with the control group,mice in the AD group showed impaired cognition,increased GFAP expression,elevated levels of TNF-α,IL-1β and IL-6,and increased expression of GRP78 and IRE1α,along with enhanced phosphorylation of NF-κB p65 and p38.Compared with the AD group,emodin improved cognitive impairment of AD mice,inhibited astrocyte overactivation and neuroinflammation,and decreased the expression of GRP78,IRE1α,phosphorylated NF-κB p65,and phosphorylated p38 in brain tissue.Conclusion·Emodin can effectively improve cognitive impairment in AD mice,which may be related to the inhibition of endoplasmic reticulum stress-mediated neuroinflammation in astrocytes.

ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective·To explore the effects and potential mechanisms of emodin on Alzheimer's disease(AD).Methods·Wild-type C57BL/6J mice and 3×Tg-AD mice were divided into 6 groups:Control group(C57BL/6J mice),AD group(3×Tg-AD mice),Emodin 25 mg/kg group(3×Tg-AD mice+Emodin 25 mg/kg),Emodin 50 mg/kg group(3×Tg-AD mice+Emodin 50 mg/kg),Emodin 100 mg/kg group(3×Tg-AD mice+Emodin 100 mg/kg)and Donepezil group(3×Tg-AD mice+Donepezil 3 mg/kg).The Morris water maze test was used to evaluate the learning and memory abilities of mice.The expression of glial fibrillary acidic protein(GFAP),glucose-regulated protein 78kDa(GRP78),and inositol-requiring enzyme 1α(IRE1α)was detected by immunohistochemistry.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in brain tissue were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of NF-κB p65,p-NF-κB p65,p38,and p-p38 proteins.Results·Compared with the control group,mice in the AD group showed impaired cognition,increased GFAP expression,elevated levels of TNF-α,IL-1β and IL-6,and increased expression of GRP78 and IRE1α,along with enhanced phosphorylation of NF-κB p65 and p38.Compared with the AD group,emodin improved cognitive impairment of AD mice,inhibited astrocyte overactivation and neuroinflammation,and decreased the expression of GRP78,IRE1α,phosphorylated NF-κB p65,and phosphorylated p38 in brain tissue.Conclusion·Emodin can effectively improve cognitive impairment in AD mice,which may be related to the inhibition of endoplasmic reticulum stress-mediated neuroinflammation in astrocytes.

Objective: To analyze the survival time of people living with HIV/AIDS and related influencing factors in Sichuan province during 1991-2017. Methods: A retrospective cohort study was conducted to analyze the data of 143 988 HIV/AIDS cases. The data were collected from Chinese HIV/AIDS Comprehensive Information Management System. Life table method was used to calculate the survival proportion of the cases, and Cox proportion hazard regression model was used to identify the factors related with survival time. Results: Among 143 988 HIV/AIDS cases a total of 30 420 cases died of AIDS related diseases (21.1%) and the average survival time was 11.51 years (95%CI: 11.39-11.64). Multivariate Cox regression analysis showed that the influencing factors for the survival of HIV/AIDS cases were gender (male vs. female, HR=1.35, 95%CI: 1.32-1.40), education level (primary school or below vs. junior middle school: HR=1.15, 95%CI: 1.12-1.18), ethnic group (Han vs. other ethnic groups, HR=1.46, 95%CI: 1.41-1.52), occupation (farmer vs. other occupations: HR=1.26, 95%CI: 1.22-1.29), age (≥55 years old vs. 15-24 years old: HR=3.18, 95%CI: 3.02- 3.36), disease phase (AIDS vs. HIV infection: HR=1.44, 95%CI: 1.39-1.48), antiretroviral therapy (ART) (receiving ART vs. receiving no ART: HR=0.20, 95%CI: 0.19-0.20), and CD₄⁺T cell counts at diagnosis (>500 cells/μl vs.<200 cells/μl: HR=0.42, 95%CI: 0.40-0.45). Conclusions The average survival time of HIV/AIDS cases was 11.51 years in Sichuan during 1991- 2017. The risk factors for the survival of the cases were male, education level of primary school or below, Han ethnic group, farmer, old age at diagnosis, disease phase, The protective factors for the survival of HIV/AIDS cases were receiving ART and higher CD₄⁺ T cell counts at diagnosis.

Objective To examine the characteristics of spontaneous activity of brain regions in bipolar Ⅱ depression patients by using resting state fMRI technology, and explore the pathogenesis of bipolarⅡdepression.Methods In total 21 bipolarⅡdepression patients(BD group)and 21 gender-,age-and education-matched healthy controls(HC group)were recruited.The patients were diagnosed according to the DSM-Ⅳ criteria, and the symptoms were evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), HAMD17and HAMA. The resting-state data was collected via a 3.0 T GE MRI, and was analyzed using an amplitude of low-frequency fluctuation(ALFF)approach,and two-samples t test was used to analyze the difference between BD group and HC group.Correlation analysis was used between the mean value of ALFF in brain regions which were significantly different from the other regions and the depression severity. The brain areas that were significantly different from the other brain regions were regarded as regions of interest,and were made functional connectivity with the whole brain.The functional connectivity was compared between the two groups to explore the impaired emotional network in bipolar Ⅱdepression. Results The ALFFs of left paracentral lobule(t=3.80),right precuneus(t=3.54)and right precentral gyrus(t=3.66) in BD group were significantly higher than HC group(all P<0.05, GRF correction). In BD group, the ALFFs of the left orbital frontal gyrus (r=0.75) and right orbital frontal gyrus (r=0.80) were positively correlated with the HAMA score.The ALFFs of bilateral gyri rectus(r=0.73)and brain regions near the left insular lobe (r=0.74) were positively correlated with the HAMD17score. The ALFF of region 2 of right cerebellar peduncles (r=-0.65) was negatively correlated with the MADRS score(all P<0.05). The functional connectivity between paracentral lobule, precuneus, precentral gyrus and left middle frontal gyrus, left anterior cingulate gyrus together with its lateral gyrus in BD group was significantly increased relative to HC group (t=4.47,4.07; both P<0.05), while the functional connectivity between the right rectangular shape crack and the cortex around was decreased in BD group (t=4.54,P<0.05). Conclusion In bipolar Ⅱ depression patients, the brain function of left paracentral lobule, right precuneus and right precentral gyrus may be impaired and correlated with severity of depressive.

Objective To examine the characteristics of spontaneous activity of brain regions in bipolar Ⅱ depression patients by using resting state fMRI technology, and explore the pathogenesis of bipolarⅡdepression.Methods In total 21 bipolarⅡdepression patients(BD group)and 21 gender-,age-and education-matched healthy controls(HC group)were recruited.The patients were diagnosed according to the DSM-Ⅳ criteria, and the symptoms were evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), HAMD17and HAMA. The resting-state data was collected via a 3.0 T GE MRI, and was analyzed using an amplitude of low-frequency fluctuation(ALFF)approach,and two-samples t test was used to analyze the difference between BD group and HC group.Correlation analysis was used between the mean value of ALFF in brain regions which were significantly different from the other regions and the depression severity. The brain areas that were significantly different from the other brain regions were regarded as regions of interest,and were made functional connectivity with the whole brain.The functional connectivity was compared between the two groups to explore the impaired emotional network in bipolar Ⅱdepression. Results The ALFFs of left paracentral lobule(t=3.80),right precuneus(t=3.54)and right precentral gyrus(t=3.66) in BD group were significantly higher than HC group(all P<0.05, GRF correction). In BD group, the ALFFs of the left orbital frontal gyrus (r=0.75) and right orbital frontal gyrus (r=0.80) were positively correlated with the HAMA score.The ALFFs of bilateral gyri rectus(r=0.73)and brain regions near the left insular lobe (r=0.74) were positively correlated with the HAMD17score. The ALFF of region 2 of right cerebellar peduncles (r=-0.65) was negatively correlated with the MADRS score(all P<0.05). The functional connectivity between paracentral lobule, precuneus, precentral gyrus and left middle frontal gyrus, left anterior cingulate gyrus together with its lateral gyrus in BD group was significantly increased relative to HC group (t=4.47,4.07; both P<0.05), while the functional connectivity between the right rectangular shape crack and the cortex around was decreased in BD group (t=4.54,P<0.05). Conclusion In bipolar Ⅱ depression patients, the brain function of left paracentral lobule, right precuneus and right precentral gyrus may be impaired and correlated with severity of depressive.

Objective To explore the diagnostic value of carcinoembryonic antigen(CEA),adiponectin combined with leptin in colorectal cancer.Methods The case control study was adopted.Forty cases newly diagnosed as colorectal cancer were selected.Forty cases of non-colorectal cancer were selected according to 1 ∶ 1 matching proportion.Serum levels of CEA,adiponectin and leptin were measured in the study subjects.The ROC curve was used to evaluate the diagnostic value of adiponectin combined with leptin for colorectal cancer.Results Serum level of adiponectin in the experimental group was lower than that in the control group,while the CEA and leptin levels were higher than those in the control group,the difference between the two groups was statistically significant(P＜0.05).The area under the curve of adiponectin combined with leptin reached 0.714±-0.058,its specificity and sensitivity were 77.5 ％ and 65.7 ％ respectively.The area under the curve of adiponectin,leptin combined with CEA reached 0.818 ±-0.048,its specificity and sensitivity were 82.5 ％ and 89.5 ％ respectively.The cut-off values of leptin and adiponectin were 11.53 μg/mL and 9.08μg/mL respectively.Conclusion The combined screening of CEA,adiponectin and leptin can significantly improve the detection rate of colorectal cancer.

INTRODUCTIONRetinitis pigmentosa (RP) is the most prevalent group of inherited retinopathies and demonstrates considerable clinical and genetic heterogeneity, with wide variations in disease severity, progression, and gene involvement. We studied a large family with RP to determine the pattern of inheritance and to identify the disease-causing gene/locus.

MATERIALS AND METHODSOphthalmic examination was performed on 35 family members to identify affected individuals and carriers and to characterise the disease phenotype. Genetic linkage analysis was performed using short tandem repeat (STR) polymorphic markers encompassing the known loci for Xlinked RP (xlRP) including RP2, RP3, RP6, RP23, and RP24. Mutation screening was performed by direct sequencing of PCR-amplified genomic DNA of the RP2 and RPGR genes of the affected individuals.

RESULTSA highly penetrant, X-linked form of RP was observed in this family. Age of onset was from 5 to 8 years and visual acuity ranged from 20/25 in children to light perception in older adults. Linkage analysis and direct sequencing showed that no known loci/genes were associated with the phenotype in this kindred.

CONCLUSIONA novel disease gene locus/loci is responsible for the xlRP phenotype in this family.

Adolescent ; Adult ; Age of Onset ; Child ; Child, Preschool ; Chromosome Mapping ; DNA Mutational Analysis ; Eye Proteins ; genetics ; Female ; Genetic Diseases, X-Linked ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Lod Score ; Male ; Membrane Proteins ; genetics ; Pedigree ; Phenotype ; Retinitis Pigmentosa ; genetics

Objective To study H.pylori infection and the changes of muco sal inflammation， atrophy and intestinal metaplasia in the different histolog ical types of gastric polyps. Methods Two hundred and seventy－ eight cases of gastric polyps(12.6％ ) from 2 203 gastric mucosal biopsy cases were histologic ally classified and examined for the presence of Helicobacter pylori,for degree and type of inflammation,mucosal atrophy and intestinal metaplasia. Results 53. 9％ gastric polyps were infected with H.pylori,in which faveolar polyp was the highest with an infective rate of 73.1％ .The changes of active inflammation,atr ophy and metaplaisa in gastric mucosa were frequently accompanied with H.pylori positive faveolar polyps almost as same as those in adenoma.The fundic gland pol yps were usually with low rate of H.pylori infection,and the changes of mucosal active inflammation,atrophy and metaplasia were seldom observed. Conclusions Fav eolar polyps,which are different from fundic gland polyp,may caused by H.pylori infection and are usually with the changes of mucosal active inflammation,atroph y and metaplasia.