1.Study on the Mechanism of Panax Quinquefolium-Acorus Calamus Ameliorating Diabetic EncepHalopathy in Mice by Mediating Nrf2-Keap1 Signaling Pathway
Dezhi CUI ; You ZHOU ; Jianan LI ; Xu CHEN ; Linan HAN
Chinese Journal of Modern Applied Pharmacy 2024;41(9):1173-1182
OBJECTIVE
To observe the effects of Panax quinquefolium-Acorus calamus on learning and memory abilities in diabetes mellitus(DM) mice and investigate the mechanism of Panax quinquefolium-Acorus calamus in treating diabetic cognitive impairment(DCI) through network pharmacology and animal experiments.
METHODS
Diabetic mouse model was established by intraperitoneal injection of streptozotocin(80 mg·kg−1), followed by 8 weeks of oral administration and assessment of drug efficacy using the Morris water maze. The active ingredients and targets of Panax quinquefolium-Acorus calamus were collected using TCMSP, Swiss Target Prediction, and Gene Cards. The protein-protein interaction network of "Traditional Chinese Medicine-Ingredient-Disease targets" was constructed using the String platform and Cytoscape, visualized, and subjected to enrichment analysis using the Metascape database. The anti-DCI mechanism of Panax quinquefolium-Acorus calamus was examined through ELISA and Western blotting, while changes in hippocampal neurons of diabetic mice were observed using HE staining.
RESULTS
Panax quinquefolium-Acorus calamus reduced the escape latency of diabetic mice(P<0.05), without significant impact on swimming speed. Network pharmacology results indicated that the main components of Panax quinquefolium-Acorus calamus in treating DCI were ginsenoside Re, ginsenoside Rh2, and shanjin phenol, which regulated the Nrf2-Keap1 signaling pathway to treat DCI. Animal experiments demonstrated that Panax quinquefolium-Acorus calamus increased SOD activity(P<0.05), decreased MDA levels(P<0.01), enhanced the expression of HO-1, Keap1, Nrf2 in mouse brain(P<0.01), and alleviated the loosening of granule cell arrangement and nuclear condensation in the hippocampal CA1, CA3, and DG regions.
CONCLUSION
Using animal experiments combined with network pharmacology, this study preliminarily elucidates the potential targets and mechanisms of Panax quinquefolium-Acorus calamus in intervening DCI, and predictes the molecular basis for its intervention in DCI through molecular docking, providing insights for further in-depth research on Panax quinquefolium-Acorus calamus.
2.Clinical profiles of community-acquired Pseudomonas aeruginosa infections in children
Yue QIU ; Daojiong LIN ; Jianan XI ; Yi XU ; Qingwen SHAN ; Chunhui ZHU ; Yibing CHENG ; Fang WANG ; Yiping CHEN ; Mei ZENG
Chinese Journal of Pediatrics 2024;62(8):727-733
Objectives:To investigate clinical characteristics, outcomes and antimicrobial resistance of community-acquired Pseudomonas aeruginosa (CAPA) infections in Chinese pediatric patients. Methods:This retrospective study was conducted at 6 tertiary hospitals in China during January 2016 to December 2018. The clinical and microbiological data of CAPA infected hospitalized children in Hainan and in other regions were collected and compared, and the antimicrobial resistance patterns, clinical characteristics and antibiotic therapy were analyzed. Between different groups were compared using the Chi-square test and Mann-Whitney U test. Results:Among 91 patients, 63 cases were males, 28 cases were females, and 74 cases were from Hainan province, 17 cases were from other regians. The age of consultation was 22.5 (5.4, 44.0) months. Twenty-four cases (26%) had underlying diseases. Fever (79 cases (87%)) and cough (64 cases (70%)) were common initial symptoms. Other concomitant symptoms included wheezing 8 cases (9%), diarrhea 3 cases (3%) and vomiting 4 cases (4%). Twenty-eight cases (31%) had organ infections, including pneumonia 22 cases (24%), skin infection 5 cases (5%), meningitis, intra-abdominal infection and upper urinary tract infection each 1 case (1%). The resistance rate of CAPA isolates to cefepime (4% (4/90)), amikacin (1% (1/90)), ciprofloxacin (2% (2/90)) and levofloxacin (1% (1/89)) was low, and to ceftazidime, piperacillin, piperacillin-azobactam, carbapenem was 12% (11/90), 3/16, 18% (10/56) and 6% (5/90), respectively. Antimicrobial combination therapy accounted for 52% (47/91) of empirical therapy and 59% (52/88) of definite therapy. Two cases (2%) were hopeless discharged, and 3 cases (3%) died during hospitalization. The worse prognosis of CAPA infection is significantly different among children in other regions and in Hainan (4/17 vs. 1% (1/74), χ2=9.74, P<0.05). Conclusions:The invasive CAPA-infection has regional difference in incidence and prognosis in China. Clinical symptoms and signs are non-specific. CAPA strains isolated from pediatric patients display low level of resistance to most of the common antipseudomonal antibiotics. The proportion of poor prognostic outcome is lower in Hainan than in other regions.
3.Changes in serine metabolism and inflammation in CD4+T cells of cows with ketosis
Jingjing WANG ; Ming LI ; Jianan WEN ; Shuang WANG ; Chuang XU ; Wei YANG ; Bing-Bing ZHANG
Chinese Journal of Veterinary Science 2024;44(11):2445-2451
To investigate the expression of serine metabolism related genes and inflammatory relat-ed genes in CD4+T cells of healthy and cows with ketosis.Firstly,CD4+T cells in peripheral blood of dairy cows were isolated by magnetic bead sorting.Second,expression of serine metabolism re-lated genes PHGDH,PAST1,PSPH,SHMT1,SHMT2,SDS,SFXN1 and inflammation related genes IL-6,IFN-γ,IL-17A,FOXP3,IL-10,TGF-β in CD4+T cells in healthy and ketosis cows was detected by fluorescence quantitative PCR.The transcription levels of PHGDH,PAST1 and PSPH in CD4+T cells of ketosis cows were significantly increased compared with healthy cows(P<0.01),the transcription level and translation level of SDS were significantly increased(P<0.01).The transcription levels of SHMT2 were significantly decreased(P<0.05).Transcription and translation levels of SFXN1 were significantly decreased(P<0.05).The transcription level of SHMT1 was decreased but not significantly.Compared with healthy cows,the transcription levels of IL-6,IFN-γ and IL-17A in CD4+T cells of ketosis cows were significantly increased(P<0.01),the transcription levels of IL-10,TGF-β and FOXP3 were significantly decreased(P<0.05).The results showed that the expression of genes related to serine synthesis increased,the expression of genes related to serine decomposition decreased,the expression of pro-inflammatory factors increased,and the expression of anti-inflammatory factors decreased,suggesting that serine metab-olism plays an important role in the inflammatory process of dairy cows.
4.Characterization of 19 novel gene mutation sites associated with autosome-dominant polycystic kidney disease
Junlan YANG ; Siqi PENG ; Zhiyuan WEI ; Jianan JIANG ; Bin WANG ; Fengmei WANG ; Xiaotong XIE ; Tian XU ; Xiaoliang ZHANG
Chinese Journal of Internal Medicine 2024;63(9):866-873
By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.
5.Prediction Model for Unfavorable Outcome in Spontaneous Intracerebral Hemorrhage Based on Machine Learning
Shengli LI ; Jianan ZHANG ; Xiaoqun HOU ; Yongyi WANG ; Tong LI ; Zhiming XU ; Feng CHEN ; Yong ZHOU ; Weimin WANG ; Mingxing LIU
Journal of Korean Neurosurgical Society 2024;67(1):94-102
Objective:
: The spontaneous intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. The purpose of this retrospective study is to develop multiple models for predicting ICH outcomes using machine learning (ML).
Methods:
: Between January 2014 and October 2021, we included ICH patients identified by computed tomography or magnetic resonance imaging and treated with surgery. At the 6-month check-up, outcomes were assessed using the modified Rankin Scale. In this study, four ML models, including Support Vector Machine (SVM), Decision Tree C5.0, Artificial Neural Network, Logistic Regression were used to build ICH prediction models. In order to evaluate the reliability and the ML models, we calculated the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR).
Results:
: We identified 71 patients who had favorable outcomes and 156 who had unfavorable outcomes. The results showed that the SVM model achieved the best comprehensive prediction efficiency. For the SVM model, the AUC, accuracy, specificity, sensitivity, PLR, NLR, and DOR were 0.91, 0.92, 0.92, 0.93, 11.63, 0.076, and 153.03, respectively. For the SVM model, we found the importance value of time to operating room (TOR) was higher significantly than other variables.
Conclusion
: The analysis of clinical reliability showed that the SVM model achieved the best comprehensive prediction efficiency and the importance value of TOR was higher significantly than other variables.
6.Rice bran oil supplementation protects swine weanlings against diarrhea and lipopolysaccharide challenge.
Juncheng HUANG ; Wenxia QIN ; Baoyang XU ; Haihui SUN ; Fanghua JING ; Yunzheng XU ; Jianan ZHAO ; Yuwen CHEN ; Libao MA ; Xianghua YAN
Journal of Zhejiang University. Science. B 2023;24(5):430-441
Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 μg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, β-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.
Male
;
Female
;
Swine
;
Animals
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Lipopolysaccharides/toxicity*
;
Antioxidants/pharmacology*
;
Rice Bran Oil
;
Dysbiosis
;
Dietary Supplements
;
Diarrhea/veterinary*
;
Weaning
;
Body Weight
7.Resveratrol and Sir2 Reverse Sleep and Memory Defects Induced by Amyloid Precursor Protein.
Yuping HAO ; Lingzhan SHAO ; Jianan HOU ; Yan ZHANG ; Yuqian MA ; Jinhao LIU ; Chuan XU ; Fujun CHEN ; Li-Hui CAO ; Yong PING
Neuroscience Bulletin 2023;39(7):1117-1130
Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals
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Alzheimer Disease/metabolism*
;
Amyloid beta-Peptides
;
Amyloid beta-Protein Precursor/metabolism*
;
Drosophila/physiology*
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Drosophila Proteins/metabolism*
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Resveratrol/pharmacology*
;
Sirtuin 1
;
Sleep
8.The reliability and validity of the International Classification of Functioning, Disability and Health′s Rehabilitation Set for multidisciplinary inpatients
Xia ZHANG ; Jiahui LI ; Juan JIN ; Fei PAN ; Yuhong XU ; Weiwei LI ; Jianan LI ; Shouguo LIU
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(6):494-499
Objective:To explore the reliability and validity of the International Classification of Functioning, Disability and Health′s 17-item Rehabilitation Set (ICF-RS-17) when used to evaluate multidisciplinary inpatients.Methods:A total of 359 inpatients in the departments of rehabilitation, orthopedics, neurology, and neurosurgery of three hospitals in Jiangsu province were assessed with the ICF-RS-17 at admission and at discharge, and the internal consistency of the tool was calculated. Inter-rater and intra-rater reliability were quantified using interclass correlation coefficients (ICCs). Structural validity was analyzed using factor analysis.Results:The tool′s Cronbach′s α was 0.945. The overall inter-rater ICC was 0.946 with the ICCs of all of the items except b280 sensation of pain within the range from 0.630 to 0.948. The overall intra-rater ICCs ranged from 0.471 to 0.947. The factor analysis found three factors with eigenvalues greater than 1, accounting for 74% of the variation, without double-loaded items. The three influential factors were exercise ability, sleep perception communication ability and self-care ability.Conclusion:The ICF-RS-17 has good internal consistency, inter-rater and intra-rater reliability and structural validity in the evaluation of multidisciplinary inpatients.
10.Development of the Oral Health Protective Motivation Questionnaire for Adults and the test of its reliability and validity
Xiaodong XU ; Jianan HAN ; Na LI ; Xiuna DING
Chinese Journal of Modern Nursing 2023;29(13):1730-1736
Objective:To develop the Oral Health Protective Motivation Questionnaire for Adults and test its reliability and validity.Methods:This study is a cross-sectional study. The initial version of Oral Health Protective Motivation Questionnaire for Adults was constructed based on the protection motivation theory, referring to the Oral Health Guideline for Chinese Population, through literature review, semi-structured interviews and expert consultation. From March to April 2022, 610 adults from 6 communities in Qingdao were selected by convenient sampling to conduct a questionnaire survey. The questionnaire was initially evaluated by item analysis and reliability and validity testing. A total of 610 questionnaires were distributed, and 599 valid questionnaires were recovered, with a valid recovery rate of 98.20% (599/610) . Results:The Oral Health Protective Motivation Questionnaire for Adults included 35 items. Exploratory factor analysis extracted six common factors, namely severity, susceptibility, internal and external rewards, response cost, response efficacy, and self-efficacy, the explanatory variation of each factor was 60.28% to 74.23%. Confirmatory factor analysis showed that the six factors model fitted well. Cronbach's α coefficient of the total questionnaire was 0.946, and the Cronbach's α coefficient of each dimension was from 0.744 to 0.937. The half-reliability coefficient of the total questionnaire was 0.853.Conclusions:The Oral Health Protective Motivation Questionnaire for Adults has good reliability and validity, and can be used to evaluate the adult oral health protection motivation.


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