OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective To establish a ultra performance liquid chromatography(UPLC)fingerprint of extract of Cuscutae Semen,and analyze the relationship between the UPLC fingerprint and antioxidant activity.Methods The fingerprint of 11 batches of extract of Cuscutae Semen were determined by UPLC method,the antioxidant activity of Cuscutae Semen in vitro was determined by 1,1-diphenyl-2-picrylhydrazine radical,2,2-diazo-bis(3-ethylbenzothiazole-6-sulfonic acid)diamine salt,and the correlation between the fingerprints and antioxidant activity was analyzed by orthogonal partial least squares(OPLS)and gray correlation method.The key substances that contributed greatly to the antioxidant activity were selected.Results The extract of Cuscutae Semen contains 21 common peaks,all of which exhibited a similarity of more than 0.97.By comparing with the reference sample,10 peaks were identified,of which peak 5 was neochlorogenic acid,peak 8 was chlorogenic acid,peak 9 was cryptochlorogenic acid,peak 10 was caffeic acid,peak 12 was coumaric acid,peak 15 was hyperin,peak 16 was isoquercitrin,peak 17 was astragaloside,peak 20 was quercetin,and peak 21 was kaempferol.According to the grey correlation degree and OPLS results,the peaks 8,15,16 and 18 were positively correlated with the antioxidant activity,and were thus considered to be main effective components.Conclusion The antioxidant activity of Cuscutae Semen is the result of the combined effect of multiple components.The fingerprint and antioxidant spectrum analysis can provide evidential reference for further research of Cuscutae Semen.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

OBJECTIVE: To investigate the effects of melatonin on the growth and metastasis of MDA-MB-231 breast cancer cells and explore the mechanism. METHODS: MDA-MB-231 cells were treated with 1, 3 or 5 mmol/L melatonin, and the changes in cell proliferation were examined using CCK-8 assay. Colony-forming assay and wound healing assay were used to assess the effects of melatonin treatmnent on colony-forming ability and migration of the cells. Flow cytometry and immunofluoresnce assay were employed to examine apoptosis and positive staining for autophagy-related proteins in the cells treated with 3 mmol/L melatonin. The effects of melatonin treatment alone or in combination with 3-methyladenine (3-MA) on the expressions of the proteins associated with autophagy (LC3, P62 and Beclin1), apoptosis (Bcl2 and Bax) and epithelial-mesenchymal transition (E-cadherin and Snail) were examined with Western blotting. RESULTS: Melatonin treatment significantly inhibited the proliferation of breast cancer cells in a concentration- and time-dependent manner (P < 0.05), suppressed colony-forming ability and migration (P < 0.01), and promoted apoptosis of the cells (P < 0.01). Melatonin treatment alone significantly increased the expressions of Bax (P < 0.05), E-cadherin, LC3-II/LC3-I, and Beclin1 and lowered the expressions of Bcl2 (P < 0.05), Snail, P62 (P < 0.05), and Bcl2/Bax ratio (P < 0.01) in the cells, and caused enhanced positive staining of Beclin1 protein and attenuated staining of P62 protein. Compared with melatonin treatment alone, melatonin treatment combined with 3-MA significantly decreased the expressions of Beclin1 (P < 0.001), LC3-II/LC3-I (P < 0.05), Bax (P < 0.01), and E-cadherin (P < 0.001) and increased the expressions of Bcl2 (P < 0.05), Snail, and Bcl2/Bax ratio (P < 0.01). CONCLUSION Melatonin can induce autophagy of MDA-MB-231 breast cancer cells to inhibit cell proliferation and metastasis and promote cell apoptosis, and suppressing autophagy can weaken the inhibitory effect of melatonin on the growth and metastasis of breast cancer cells.
Autophagy ; Autophagy-Related Proteins/metabolism* ; Breast Neoplasms ; Cell Line, Tumor ; Female ; Humans ; Melatonin/pharmacology*

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism. METHODS: A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected. RESULTS: After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment ( CONCLUSION Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.
Acupuncture Points ; Aged ; Dopamine ; Electroacupuncture ; Humans ; Melatonin ; Sleep Initiation and Maintenance Disorders/therapy*

The high failure rate of the new drug development has been well recognized. Relying on the pre-clinical data obtained from animal experiments will inevitably cause a low concordance with human clinical trials, which will eventually lead to new drug development failure. Employing human induced pluripotent stem cells (iPSCs) or adult stem cells to simulate disease models can not only provide an unlimited cell materials, but also faithfully represent the genetic background of a certain disease, when iPSCs or adult stem cells derived from patients with a specific disease genetic variation are applied. In addition, gene editing methods can be used to introduce genetic variants of interest into stem cells to generate disease models. Furthermore, by establishing a cell bank with a population of iPSCs in petri dish, in vitro human genetic studies can be carried out in these cells, with GWAS and QTL studies applied to identify genetic variants that are associated with drug sensitivity or cytotoxicity. These efforts may offer valuable information for the recruitment of suitable patients for clinical trials. Therefore, stem cell-derived disease models can provide valuable resources for the pathophysiological studies of diseases as well as the drug development. In this review, we will briefly introduce the development of the liver disease models derived from stem cells and their applications in disease study and drug development.
Animals ; Cell Differentiation ; Drug Development ; Gene Editing ; Humans ; Induced Pluripotent Stem Cells ; Liver