1.Rehmanniae Radix Praeparata Improves Neurological Function of Ischemic Stroke Rats by Inhibiting Autophagy and Ferroptosis
Saifei LI ; Peipei YUAN ; Yaxin WEI ; Liyuan GAO ; Panying LI ; Yuan RUAN ; Yi CHEN ; Yang FU ; Xiaoke ZHENG ; Weisheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):26-33
ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation, model, low- and high -dose (3.5 g·kg-1 and 7 g·kg-1) Rehmannia Radix Praeparata, and nimodipine (0.01 g·kg-1) groups. The rat model of middle cerebral artery occlusion (MCAO) was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile, the serum levels of lactate dehydrogenase (LDH), oxidative stress-related indicators superoxide dismutase (SOD), glutathione peroxidase 4 (GPX4), and malondialdehyde (MDA), and the iron (Fe) content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats, Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector (beclin-1), microtubule-associated protein light chain 3 (LC3B), and ubiquitin-binding protein p62 (p62). The ferroptosis-associated proteins included transferrin (TF), transferrin receptor 1 (TFR1), ferritin heavy chain 1 (FTH1), and ferropotin (FPN1). The neurological function injury-associated proteins included brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). ResultCompared with the sham operation group, the model group showed increased neurological function score, cerebral infarction volume, and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition, the model group presented elevated levels of LDH, MDA, and Fe (P<0.01) and lowered levels of SOD and GPX4 (P<0.01). Compared with the model group, Rehmanniae Radix Praeparata decreased the content of LDH, MDA, and Fe (P<0.05, P<0.01) and elevated the levels of SOD and GPX4 (P<0.05, P<0.01). Compared with the sham operation group, the modeling promoted the expression of beclin-1,LC3B Ⅱ/Ⅰ, TF, and TFR1 and inhibited the expression of p62, FTH1, FPN1, BDNF, and TrkB (P<0.01). The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.
2.Association between ulcerative colitis and pancreatitis: a Mendelian randomization study
XU Jun ; XU Yaxin ; GAO Yanan ; YAO Ting ; SUN Suya ; CHEN Yamei
Journal of Preventive Medicine 2024;36(1):26-29, 33
Objective :
To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients.
Methods:
Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method.
Results:
MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one.
Conclusions
Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.
3.Application of auditory verbal learning test-Huashan version in patients with subjective cognitive decline and mild cognitive impairment
Qiumin ZHOU ; Yaxin GAO ; Tong WANG
Chinese Journal of Rehabilitation Medicine 2024;39(2):191-195,209
Objective:To explore the diagnostic value of auditory verbal learning test-Huashan version(AVLT-H)of memo-ry impairment in patients with subjective cognitive decline(SCD)and mild cognitive impairment(MCI). Method:According to the inclusion criteria,the recruited elderly were screened and divided into three groups:normal cognition(NC),SCD and MCI group.The neuropsychological tests including mini-mental state exami-nation(MMSE),Montreal cognitive assessment-Beijing version(MOCA-BJ)and AVLT-H were completed af-ter inclusion.The scores of MMSE,MoCA-B,AVLT-N2,N3,N4,N5,N6 and N7 were recorded and analyzed. Result:There were significant differences in the scores of MMSE,MoCA and AVLT-H among the three groups(P<0.0167).The adjusted Bonferroni test was used to detect significant differences in post-hoc comparison.There were significant difference in MMSE and MoCA scores between SCD and NC(P<0.001)and between MCI and NC(P<0.001).However,no significant difference between MCI and SCD was found.There were sig-nificant difference in N1 score between MCI and NC(P=0.013)and between MCI and SCD(P=0.001),but there was no significant difference between SCD and NC.There were significant difference in AVLT-N2,N3,N4,N5,N6 and N7 scores between MCI and NC(P<0.001)and between MCI and SCD(P<0.001),but there was no significant difference between SCD and NC.The area under the curve of MMSE,MoCA and AVLT-H scores were examined using NC group and SCD group as state variables,respectively.For differentiat-ing MCI and SCD,eAVLT-H scores had a larger area under the curve with higher sensitivity and specificity,N1 and N7 had the highest sensitivity.For distinguishing MCI from NC,AVLT-H and MoCA scores had a larger area under the curve with higher sensitivity and specificity,N4,N6 and N7 had the highest sensitivity. Conclusion:AVLT-H,combined with MMSE and MoCA,can improve the defining diagnostic sensitivity of MCI and SCD from normal cognition.It is recommended to routinely use AVLT-H in a routine assessment for MCI and SCD patients.
4.Efficacy and Mechanism of Lutongning Granules in Treatment of Trigeminal Neuralgia Induced by Injection of Talc into Infraorbital Foramen of Model Rats Based on P2X7R-mediated Neuroinflammation
Qiyue SUN ; Shuran LI ; Shuangrong GAO ; Shanshan GUO ; Zihan GENG ; Lei BAO ; Ronghua ZHAO ; Jingsheng ZHANG ; Bo PANG ; Yingli XU ; Yu ZHANG ; Shan CAO ; Yaxin WANG ; Xiaolan CUI ; Bing HAN ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):56-63
ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action, so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group, model group, carbamazepine group (0.06 g·kg-1·d-1), high-dose Lutongning group (2.70 g·kg-1·d-1), and low-dose Lutongning group (1.35 g·kg-1·d-1) according to the stratified basic mechanical pain thresholds, with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin (HE) staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, neuropeptide substance P, and β-endorphins (β-EP) in the serum of rats, and Western blot was used to detect the protein expression levels of IL-1β, purinergic receptor P2X7 (P2X7R), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK). ResultCompared with that in the normal group, the pain threshold of rats in the model group was significantly lower (P<0.01). The absolute value of neutrophils (NEUT#) and the percentage of neutrophils (NEUT) were significantly improved, and the percentage of lymphocytes (LYMPH) was significantly reduced (P<0.01). The serum levels of IL-1, IL-6, IL-8, and TNF-α were significantly increased (P<0.01). SP content in brain tissue was significantly increased, and β-EP content was significantly decreased (P<0.01). The relative protein expression of IL-1β, P2X7R, and p-p38 MAPK was significantly increased (P<0.05). HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration, mild proliferation of microglial cells, reduction in the number of myelinated nerves, and obvious demyelination. The trigeminal nerve fibers of rats were disarranged, and some nerve fibers showed vacuolization. Axons were swollen, and Schwann cells proliferated. Demyelination was observed. Compared with the model group, each administration group significantly increased the pain threshold of rats (P<0.05, P<0.01), reduced NEUT# and NEUT, and elevated LYMPH (P<0.05, P<0.01). The administration group significantly decreased the levels of IL-1, IL-6, IL-8, and TNF-α in serum and SP in brain tissue (P<0.01) and increased the level of β-EP (P<0.01). They significantly down-regulated the protein expression of IL-1β, P2X7R, and p-p38 MAPK(P<0.05, P<0.01) and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats, and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.
5.Correlation analysis between nutritional immune score based on prealbumin and T lymphocyte count and prognosis of critically ill patients
Xiaoxuan NIU ; Yaxin XU ; Hongbin LI ; Jian GAO
Chinese Journal of Clinical Medicine 2024;31(6):925-931
Objective To explore the correlation between the nutritional and immunity score (NIS) based on prealbumin and T lymphocyte count and the prognosis of critically ill patients. Methods A retrospective study was conducted involving patients from the intensive care unit of the First Affiliated Hospital of Zhengzhou University from September 2020 to August 2021. Patients’ basic information, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores within 24 hours of admission, and relevant biochemical indicators were collected. The primary endpoint was all-cause mortality within 28 days. The optimal cut-off values for prealbumin and T lymphocyte count related to mortality risk were determined using X-tile software. Patients were stratified according to these cut-off values and normal reference ranges, and the NIS was calculated. Univariate and multivariate Cox regression analyses were conducted to evaluate the relationship between NIS and mortality. Results The optimal cut-off value for prealbumin was 110 mg/L, and for T lymphocyte count, it was 455/μL, with NIS scores ranging from 0 to 4. After adjusting for confounding factors, patients with NIS scores of 2 (HR=1.87, 95%CI 1.19-2.94, P=0.023), 3 (HR=2.04, 95%CI 1.20-3.19, P=0.007), and 4 (HR=1.68, 95%CI 1.24-3.96, P=0.005) showed a significantly increased risk of mortality. Conclusions NIS≥2 is associated with an increased risk of death in critically ill patients. NIS can serve as an effective tool for early risk stratification and prognostic assessment in critically ill patients.
6.Cytoplasmic linker protein 170 inhibits papillary thyroid cancer cell metastasis through the TGF-β pathway
Ma BINYUAN ; Xu YAXIN ; Pan YUNYAN ; Wu YANI ; Gao HONGWEI
Chinese Journal of Clinical Oncology 2024;51(5):217-223
Objective:To explore whether cytoplasmic linker protein 170(CLIP170)affects papillary thyroid cancer(PTC)cell metastasis and invasion and clarify the underlying mechanisms.Methods:We analyzed CLIP170 expression levels in PTC using GEO and TCGA data and con-structed CLIP170 knockdown(CLIP170KD)cells using lentiviral transfection.Then,we evaluated their functions through Transwell transfer and invasion assays.We assessed how CLIP170 affected the cellular actin structure via immunofluorescence analysis.We detected transforming growth factor-β 1(TGF-β1)release in the cell culture medium using enzyme-linked immunosorbent assay(ELISA).We also assessed epithelial-mesenchymal transition(EMT)and TGF-β signaling pathway molecule expression using immunoblotting and reverse-transcription quantitat-ive fluorescence PCR and validated the results in a nude mouse lung metastasis model.Results:CLIP170 expression level in PTC was lower than that in normal thyroid tissue.Regarding the function,CLIP170KD significantly enhanced PTC cell metastasis both in vitro and in vivo.Re-garding the underlying mechanism,CLIP170KD triggered TGF-β pathway activation,subsequently promoted tumor cell migration and invasion.The inhibitor of TGF-β effectively inhibited TGF-β activation,and this inhibition significantly reversed the CLIP170KD-induced tumor metastasis.Conclusions:CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.
7.Evidence summary of prevention complications for parenteral nutritional support in hospitalized patients
Ting YAO ; Yanan GAO ; Yaxin XU ; Jun XU ; Yamei CHEN
Chinese Journal of Nursing 2024;59(11):1360-1367
Objective To evaluate and summarize the evidence related to the prevention of parenteral nutritional support complications in inpatients,and to provide an evidence-based basis for guiding healthcare professionals to prevent parenteral nutritional support complications in a scientific and standardized manner.Methods Computerized search was conducted in UpToDate,BMJ Best Clinical Practice,Centre for Evidence-Based Health Care database of the Joanna Briggs Institute in Australia,Ontario Registered Nurses Association website in Canada,National Institute for Health and Clinical Excellence website in the United Kingdom,Scottish Intercollegiate Guidelines Network,Guidelines International,New Zealand Guidelines Collaborative,American Society for Parenteral and Enteral Nutrition website,European Society for Clinical Nutrition and Metabolism Society website,International Practice Guidelines Registry Platform China Clinical Guidelines Repository,Medical Pulse,PubMed,Cochrane Library,Web of Science,CINAHL,Embase,China Biomedical Literature Database,CNKI,Wanfang Database,etc.The search period was from the time of database construction to October 2023.After literature screening and quality evaluation,the evidence extraction and integration were carried out.Results A total of 16 papers were included,including 3 clinical decision-making,1 evidence summary,4 guidelines,6 expert consensuses,and 2 systematic evaluations.27 pieces of best evidence were extracted from 3 areas,namely metabolic complications,mechanical complications,and infectious complications.Conclusion This study summarized the evidence related to the prevention and management of complications of parenteral nutrition support in adult inpatients,aiming to provide an evidence-based basis for healthcare professionals to develop scientific and standardized measures for the prevention and management of complications of parenteral nutrition support.
8.Association between Crohn's disease and frailty: a bidirectional Mendelian randomization study
GAO Yanan ; XU Yaxin ; ZHU Yuqian ; XU Jun ; YAO Ting ; CHEN Yamei
Journal of Preventive Medicine 2023;35(11):943-947
Objective :
o evaluate the association between Crohn's disease (CD) and frailty using a Mendelian randomization (MR) approach, so as to provide the evidence for prevention and control strategies.
Methods:
Genetic association data for CD were collected through the International Inflammatory Bowel Disease Genetics Consortium, with 20 883 samples and 12 276 506 single nucleotide polymorphism (SNP), and genetic association data for frailty were collected through a meta-analysis including 175 226 samples and 7 589 717 SNPs. A forward MR analysis was performed using the inverse-variance weighted (IVW) method with 37 CD-associated SNPs as instrumental variables, and frailty as the study outcome, and a reverse MR analysis was performed with 13 frailty-associated SNPs as instrumental variables and CD as the study outcome. The heterogeneity was assessed using the Cochran's Q test, and the horizontal pleiotropy was assessed using the MR-PRESSO global test and MR-Egger regression. In addition, the robustness of the results was verified with the leave-one-out.
Results:
Forward MR analysis results showed that patients with genetically predicted CD had an increased risk of frailty index relative to those without CD (β=0.018, 95%CI: 0.011-0.026, P<0.05). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Reverse MR analysis showed no association between frailty index and the risk of CD (OR=0.740, 95%CI: 0.206-2.661, P>0.05).
Conclusions
Genetically predicted CD is associated with an increased risk of frailty. It is suggested that screening and prevention of frailty should be reinforced among CD patients.
9.The influence of emotional motivation on instant judgment of learning in middle school students
Huimin FU ; Jianjun ZHONG ; Yaxin GAO ; Jingjing YAO
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(12):1104-1110
Objective:To explore whether emotional motivation affects judgment of learning and its mechanism in short-term memory stage.Methods:Through the preliminary test and using E-Prime software, a set of suitable experimental procedures was compiled, and 134 middle school students were selected as subjects.Taking the instant judgment of learning after emotional video induction as the experimental paradigm, a four-factor mixed experiment of 2(emotional motivation direction: positive approach and negative avoidance) ×2(motivation intensity: high and low) ×2(word pair relevance: high and low) ×2(short-term memory load: more and less) was conducted to observe the subjects' judgment of learning scores.SPSS 23.0 software was used for repeated measurement analysis of variance.Results:Regarding learning judgment level, there was a significant interaction effect between emotional motivation direction and intensity( F=5.177, P=0.025, η2 =0.040). Emotional motivation intensity and direction both significantly interacted with short-term memory load capacity( F=4.778, P=0.031, η2=0.037 ; F=4.302, P=0.040, η2=0.034 ). Furthermore, emotional motivation direction( F=15.256, P<0.001, η2=0.110), motivation intensity( F=7.518, P=0.007, η2=0.057), short-term memory load( F=13.384, P<0.001, η2=0.097), and word pair relevance( F=212.238, P<0.001, η2 =0.631) all showed significant main effects.Regarding learning judgment accuracy, there was a significant interaction effect between emotional motivation direction and intensity( F=5.646, P=0.019, η2 =0.044). Both emotional motivation intensity and direction significantly interacted with short-term memory load capacity( F=4.593, P=0.034, η2 =0.036; F=4.033, P=0.047, η2 =0.031). Additionally, emotional motivation direction( F=15.318, P<0.001, η2=0.110), motivation intensity( F=7.572, P=0.007, η2=0.058), short-term memory load( F=11.119, P=0.001, η2=0.082), and word pair relevance( F=135.814, P<0.001, η2 =0.523) all showed significant main effects.Regarding recall performance, word pair relevance( F=416.326, P<0.001, η2=0.771) and short-term memory load( F=9.609, P=0.002, η2=0.772) showed significant main effects. Conclusion:The direction and intensity of emotional motivation have an impact on judgement of learning, emotional motivation and short-term memory jointly affect the level and accuracy of judgment of learning, and emotional motivation affects judgement of learning through clues related to the learning process in short-term memory stage.
10.Neurofibromatosis Type 1 in a Child with Plexiform Neurofibroma Pressing the Urinary System
Jianing XU ; Yaxin GUO ; Shanshan WANG ; Lei YIN ; Jiaming ZHU ; Wen CHENG ; Hongkun JIANG ; Xinghua GAO ; Xuegang XU
JOURNAL OF RARE DISEASES 2023;2(2):186-190
A 3-year-old male patient was diagnosed with neurofibromatosis type 1(NF1) for two years. The patient has multiple neurofibromas in retroperitoneum, lumbococcygeal paravertebral, lumbosacral spinal canal, and foramina. Due to retroperitoneal mass compression, the child suffered from urological complications such as hydronephrosis, ureterdilation, neurogenic bladder, etc., which seriously affected the urination function and resulted in multiple surgical treatments. Currently, the patient has been treated with mitogen activates extracelluar signal-regulated kinases(MEK) inhibitor selumetinib targeted therapy, and has voluntarily urinated, and his general state is better than before medication. The diagnosis and treatment of this case reflects the importance of multidisciplinary collaboration in the diagnosis and treatment of rare diseases.


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