1.Study on the traditional Chinese medicine syndromes in 757 cases of children with hepatolenticular degeneration based on factor analysis and cluster analysis
Daiping HUA ; Han WANG ; Qiaoyu XUAN ; Lanting SUN ; Ling XIN ; Xin YIN ; Wenming YANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):303-311
Objective:
To explore the distribution of traditional Chinese medicine (TCM) syndromes in children with hepatolenticular degeneration (Wilson disease, WD) based on factor analysis and cluster analysis.
Methods:
From November 2018 to November 2023, general information (gender, age of admission, age of onset, course of disease, clinical staging, Western medicine clinical symptoms, and family history) and TCM four-examination informations (symptoms and signs) were retrospectively collected from 757 cases of children with WD at the First Affiliated Hospital of Anhui University of Chinese Medicine, and factor analysis and cluster analysis were used to investigate TCM syndromes in children with WD.
Results:
A total of 757 children with WD were included, of which 483 were male and 274 were female; the median age at admission was 12.58 years, the median age at onset was 8.33 years, and the median course of disease was 24.37 months; clinical typing result indicated 506 cases of hepatic type, 133 cases of brain type, 99 cases of mixed-type, and 19 cases of other type; 36.46% of the children had no clinical symptoms (elevated aminotransferases or abnormalities in copper biochemistry); a total of 177 cases had a definite family history, and 10 cases had a suspected family history. Forty-three TCM four-examination information were obtained, with the top 10 in descending order being feeling listless and weak, brown urine, slow action, inappetence, dim complexion, slurred speech, angular salivation, body weight loss, hand and foot tremors, and abdominal fullness. In children with WD, the syndrome element of disease location was primarily characterized by the liver, involving the spleen and kidney, and the syndrome elements of disease nature were characterized by dampness, heat, and yin deficiency. Based on factor analysis and cluster analysis, five TCM syndromes were derived, which were, in order, syndrome of dampness-heat accumulation (265 cases, 35.01%), syndrome of yin deficiency of the liver and kidney (202 cases, 26.68%), syndrome of liver hyperactivity with spleen deficiency (185 cases, 24.44%), syndrome of qi and blood deficiency (79 cases, 10.44%), and syndrome of yang deficiency of the spleen and kidney (26 cases, 3.43%).
Conclusion
The TCM syndromes of children with WD were primarily syndromes of dampness-heat accumulation, yin deficiency of the liver and kidney, and liver hyperactivity with spleen deficiency. The liver was the main disease location, and the disease nature was characterized by deficiency in origin and excess in superficiality, excess and deficiency mixed. These findings suggest that treating children with WD should be based on the liver while also considering the spleen and kidney.
2.Correlations Between Traditional Chinese Medicine Syndromes and Lipid Metabolism in 341 Children with Wilson Disease
Han WANG ; Wenming YANG ; Daiping HUA ; Lanting SUN ; Qiaoyu XUAN ; Wei DONG ; Xin YIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):140-146
ObjectiveTo study the correlations between traditional Chinese medicine (TCM) syndromes and lipid metabolism in children with Wilson disease (WD). MethodsClinical data and lipid metabolism indicators [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein a (Lpa)] were retrospectively collected from 341 children with WD. The clinical data were compared among WD children with different syndromes, and the correlations between TCM syndromes and lipid metabolism in children with WD were analyzed. Least absolute shrinkage and selection operator (LASSO) regression was used for variable screening, and unordered multinomial Logistic regression was employed to analyze the effects of lipid metabolism indicators on TCM syndromes. ResultsThe 341 children with WD included 121 (35.5%) children with the dampness-heat accumulation syndrome, 103 (30.2%) children with the liver-kidney Yin deficiency syndrome, 68 children with the combined phlegm and stasis syndrome, 29 children with the spleen-kidney Yang deficiency syndrome, and 20 children with the liver qi stagnation syndrome. The liver-kidney Yin deficiency syndrome, combined phlegm and stasis syndrome, and spleen-kidney Yang deficiency syndrome had correlations with the levels of lipid metabolism indicators (P<0.05). Lipid metabolism abnormalities occurred in 232 (68.0%) children, including hypertriglyceridemia (108), hypercholesterolemia (23), mixed hyperlipidemia (67), lipoprotein a-hyperlipoproteinemia (12), and hypo-HDL-cholesterolemia (22). The percentages of hypertriglyceridemia and hypo-HDL-cholesterolemia varied among children with different TCM syndromes (P<0.05). Correlations existed for the liver-kidney Yin deficiency syndrome with TG, TC, and HDL-C, the combined phlegm and stasis syndrome with TG, the spleen-kidney Yang deficiency syndrome with TG, TC, and LDL-C, and the liver Qi stagnation syndrome with TC and LDL-C (P<0.05, P<0.01). ConclusionThe TCM syndromes of children with WD are dominated by the dampness-heat accumulation syndrome and the liver-kidney Yin deficiency syndrome, and dyslipidemia in the children with WD is dominated by hypertriglyceridemia and mixed hyperlipidemia. There are different correlations between TCM syndromes and lipid metabolism indicators, among which TG, TC, LDL-C, and HDL-C could assist in identifying TCM syndromes in children with WD.
3.Change Law in Material Basis of Rhei Radix et Rhizoma During Nine-time Repeating Steaming and Sun-drying Processing Based on Characteristic Chromatogram and Chemometrics
Xuan AO ; Taotao LIU ; Miao YU ; Lan WANG ; Xiaojie YIN ; Jingyu ZUO ; Li LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):191-198
ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma, and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography(HPLC) was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces, and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside, chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics, the contents and quantity ratio relationships of the glycosides, aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed, and the partial least squares-discriminant analysis(PLS-DA) and cluster analysis of the main components in different steaming times were conducted, the statistically significant differential markers were selected with the variable importance in the projection(VIP) value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma, there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times, the anthraquinone glycosides and aglycones could be roughly divided into three stages, including rapid change stage, fluctuation change stage and stable stage, and the total amount of tannins showed a decreasing trend. However, the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes, while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening, it was found that chrysophanol, emodin, chrysophanol-8-O-β-D-glucoside, rhein, physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb, which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.
4.Study on Kinetic and Static Tasks With Different Resistance Coefficients in Post-stroke Rehabilitation Training Based on Functional Near-infrared Spectroscopy
Ling-Di FU ; Jia-Xuan DOU ; Ting-Ting YING ; Li-Yong YIN ; Min TANG ; Zhen-Hu LIANG
Progress in Biochemistry and Biophysics 2025;52(7):1890-1903
ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.
5.Transcriptome Sequencing on Treatment of Kidney Deficiency and Blood Stasis-thin Endometrium in Rats with Bushen Huoxue Prescription Through Enema
Xuan ZHANG ; Wanting XIA ; Zhixing YIN ; Nana HAN ; Jinzhu HUANG ; Hang ZHOU ; Yi WANG ; Juan LI ; Qian ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):79-90
ObjectiveTo explore the mechanism of Bushen Huoxue enema in treating the rat model of kidney deficiency and blood stasis-thin endometrium (KDBS-TE) by transcriptome sequencing. MethodThe rat model of KDBS-TE was established by administration of tripterygium polyglycosides tablets combined with subcutaneous injection of adrenaline. The pathological changes of rat endometrium in each group were then observed. Three uterine tissue specimens from each of the blank group, model group, and Bushen Huoxue enema group were randomly selected for transcriptome sequencing. The differentially expressed circRNAs, lncRNAs, and miRNAs were screened, and the disease-related specific competitive endogenous RNA (ceRNA) regulatory network was constructed. Furthermore, the gene ontology (GO) functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed for the mRNAs in the network. ResultCompared with the blank group, the model group showed endometrial dysplasia, decreased endometrial thickness and endometrial/total uterine wall thickness ratio (P<0.01), and differential expression of 18 circRNAs, 410 lncRNAs, and 7 miRNAs. Compared with the model group, the enema and estradiol valerate groups showed improved endometrial morphology and increased endometrial thickness and ratio of endometrial to total uterine wall thickness (P<0.05). In addition, 21 circRNAs, 518 lncRNAs, and 17 miRNAs were differentially expressed in the enema group. The disease-related specific circRNA-miRNA-mRNA regulatory network composed of 629 nodes and 664 edges contained 2 circRNAs, 34 miRNAs, and 593 mRNAs. The lncRNA-miRNA-mRNA regulatory network composed of 180 nodes and 212 edges contained 5 lncRNAs, 10 miRNAs, and 164 mRNAs. The mNRAs were mainly enriched in Hippo signaling pathway, autophagy-animal, axon guidance, etc. ConclusionBushen Huoxue enema can treat KDBS-TE in rats by regulating specific circRNAs, lncRNAs, and miRNAs in the uterus and the ceRNA network.
6.Exploring the Effect of Shuwei Decoction (舒胃汤) for Rats with Functional Dyspepsia of Liver-Depression and Spleen-Deficiency Syndrome Model on the Ultrastructure of ENS-PDGFRα+ Cell-SMC Network in Gastric Sinusoidal Tissues
Junyao LIANG ; Xuan GUO ; Dexu ZHANG ; Man ZHOU ; Jie XIAO ; Chusen TANG ; Hui FENG ; Yin XU
Journal of Traditional Chinese Medicine 2024;65(12):1269-1278
ObjectiveBased on the ultrastructure of enteric nervous system (ENS)-platelet-derived growth factor receptor α positive (PDGFRα+) cell - smooth muscle cell (SMC) network, the effect and mechanism of Shuwei Decoction (舒胃汤) for rats with functional dyspepsia (FD) of liver-depression and spleen-deficiency syndrome were explored. MethodsFifty SD rats were divided into blank group, model group, low-, medium- and high-dose Shuwei Decoction groups randomly, with 10 rats in each group. The blank group was not set up, and the other 4 groups were set up with the modified composite cause (chronic restraint stress + tail irritation + excessive fatigue + diet disorder) for 21 days, resulting in FD model rats with liver-depression and spleen-deficiency syndrome. After successful modelling, rats in the low-, medium- and high-dose groups were given 3.78, 7.56 and 15.12 g/(kg·d) of Shuwei Decoction by gavage, respectively, while rats in the blank group and the model group were given 10 ml/(kg·d) of saline by gavage; all of them were given gavage once a day for 14 days. Body mass increase were collected before and after gavage, and compared after the experiment; the elevated cross maze experiment was conducted to observe the percentage of staying time and the percentage of times entering the open arm of rats; the gastric emptying rate and small intestinal propulsion rate were measured by black semi-solid paste; HE staining was used to observe histopathology of the gastric antrum; the Western Blotting and RT-qPCR were used to detect the expression levels of PDGFRα, small conductance calcium activated potassium (SK3), and purinergic G protein-coupled receptor P2Y1 (P2Y1 R), and mRNA expression in gastric antrum; immunofluorescence double staining was used to detect the co-localization of PDGFRα with receptor tyrosine kinase (C-kit), protein gene product 9.5 (PGP9.5), Sk3, and smooth muscle cells (SMCs) in gastric sinusoidal tissues; and transmission electron microscopy was used to observe the ultrastructure of the ENS-PDGFRα+ cell-SMC network. ResultsHE staining results showed that the mucosal folds of gastric tissue were clear in all groups, no organic lesions such as bleeding, ulceration and swelling were observed, and the arrangement of gastric glands in the lamina propria of gastric sinusoidal tissues in model group and low-dose Shuwei Decoction group was disordered. The arrangement of gastric glands in lamina propria in medium- and high-dose Shuwei Decoction groups was more orderly, and the lesion degree was less than that in model group and low-dose Shuwei Decoction group. Compared with the blank group, the growth value of body mass, the percentage of open arm retention time, the percentage of times entering the open arm, the small intestine propulsion rate, and the gastric empty rate of rats in the model group significantly decreased after gavage; the expressions of PDGFRα, Sk3, P2Y1 protein and mRNA in gastric sinusoidal tissues decreased; the co-localization expression of PDGFRα with C-kit, Sk3, SMC and PGP9.5 significantly decreased (P<0.05 or P<0.01); the ultrastructure of ENS-PDGFRα+ cell-SMC network was damaged without gap junction. Compared with model group and low-dose Shuwei Decoction group, the growth value of body mass, the percentage of open arm retention time, the percentage of times entering the open arm, the small intestine propulsion rate, and the gastric empting rate of rats in medium- and high-dose Shuwei Decoction groups increased after gavage; the expressions of PDGFRα, Sk3, P2Y1 protein and mRNA in gastric sinusoidal tissues increased; the co-localization expression of PDGFRα with C-kit, Sk3, SMC and PGP9.5 significantly increased (P<0.05 or P<0.01); the ultrastructure of ENS-PDGFRα+ cell-SMC network was intact. Compared with medium-dose Shuwei Decoction group, the protein expressions of PDGFRα, Sk3 and P2Y1, the mRNA expressions of PDGFRα and Sk3, and the co-localization expressions of PDGFRα and C-kit, Sk3, SMC, and PGP9.5 in high-dose Shuwei Decoction group increased (P<0.05 or P<0.01). ConclusionShuwei Decoction can improve the pathological lesion of the gastric antrum in the FD model rats with liver-depression and spleen-deficiency syndrome and increase the gastric emptying rate as well as the small intestinal propusion rate. The mechanism of Shuwei Decoction on FD rats with liver-depression and spleen-deficiency syndrome is related to the protection of the ultrastructural integrity of ENS-PDGFRα+ cell-SMC network.
7.Effects of Electroacupuncture at "Neiguan" (PC6) - "Zhongwan" (RN12) for Rats with Functional Dyspepsia on Gastric Motility and Metabolites of Antral Tissue
Jingying ZHOU ; Hongzhi YIN ; Qian LIU ; Xuan XU ; Yitian LAI ; Guoshan ZHANG ; Huan ZHONG ; Mi LIU
Journal of Traditional Chinese Medicine 2024;65(14):1478-1487
ObjectiveTo investigate the possible mechanism of electroacupuncture at "Neiguan" (PC6) and "Zhongwan" (RN12) in the treatment of functional dyspepsia (FD). MethodsSPF male SD rats were randomly divided into model group, Neiguan (PC6) group, Zhongwan (RN12) group, and Neiguan-Zhongwan (PC6-RN12) group, with 8 rats in each group. Except for the normal group, the other groups of rats were cogavaged with 0.1% sucrose iodoacetamide solution combined with small platform standing training to establish FD rat models. After successful modeling, the rats in the normal group and model group were tied up for 30 min/d for 7 days; the Neiguan group, Zhongwan group, and Neiguan-Zhongwan group were treated with electroacupuncture intervention at "Neiguan" (PC6), "Zhongwan" (RN12), and "Neiguan" - "Zhongwan" (PC6-RN12) acupoints, respectively, using continuous wave, frequency of 2 Hz, current intensity of 1 mA, 30 min/d, and continuous intervention for 7 days. The general condition of rats in each group was observed. After treatment, the body weight and food intake of rats were measured, and the gastric emptying rate was calculated; HE staining was performed on the gastric antrum tissue of rats to observe the histopathologic changes; the expressions of calcitonin gene-related peptide (CGRP) and Ghrelin protein in gastric antrum were detected by Western Blot; the metabolites in gastric antrum tissues were detected by liquid chromatography-mass spectrometry (LC-MS), and differential metabolites were screened by correlation analysis, then Metabo Analyst 5.0 and KEGG databases were used for metabolic pathway analysis. ResultsUnder light microscope, the gastric antrum structure was complete and the glands were abundant. No obvious inflammation and edema were found in gastric mucosa. Compared with the normal group, the body weight, food intake, and gastric emptie rate of rats in model group decreased, the expression of Ghrelin protein decreased and the expression of CGRP protein increased in gastric antrum tissue (P<0.01). Compared with model group, the body weight, food intake, and gastric emptance rate of rats in Neiguan group, Zhongwan group and Neiguan-Zhongwan group all increased, CGRP protein expression decreased in Neiguan group, and Ghrelin protein expression increased and CGRP protein expression decreased in Zhongwan group and Neiguan-Zhongwan group (P<0.01 or P<0.05). Compared with Neiguan-Zhongwan group, Ghrelin protein expression decreased and CGRP protein expression increased in Neiguan group and Zhongwan group (P<0.05 or P<0.01). Metabolomics results showed that compared with normal group, the content of metabolites adenosine diphosphate ribose, adenosine monophosphate and adenosine diphosphate in gastric antrum tissue of model group decreased; compared with model group, the contents of adenosine diphosphate, adenosine diphosphate and citicoline in Neiguan group increased, the contents of nicotine adenine dinucleotide, cytidine diphosphate ethanolamine and citicoline in Zhongwan group increased, and the contents of adenosine diphosphate, cytidine diphosphate and citicoline in Neiguan-Zhongwan group increased (P<0.05 or P<0.01). Compared with model group, the main metabolic pathways of different metabolites in PC6-RN12 group were glycerophospholipid metabolism, taurine and hypotaurine metabolism, purine metabolism, starch and sucrose metabolism. ConclusionElectroacupuncture at “Neiguan” and “Zhongwan” acupoints can effectively regulate gastrointestinal motility and improve FD symptoms in FD rats, and the effect is better than that of "Neiguan" or "Zhongwan" acupoints alone. The mechanism may be related to the influence of related metabolites on energy metabolism, glucose metabolism and nucleotide metabolism, thereby regulating gastrointestinal motility hormones.
8. Distal tibiofibular syndesmosis fibular notch typing and its clinical significance based on CT
Shi-Qin YIN ; Rui-Han WANG ; Gui-Xuan YOU ; Si-Yi YANG ; Ying-Qiu YANG ; Rui-Han WANG ; Lei ZHANG ; Lei ZHANG
Acta Anatomica Sinica 2024;55(1):82-87
Objective To investigate the morphological typing and clinical significance of the distal tibiofibular syndesmosis fibular notch based on CT images. Methods According to the inclusion and exclusion ceiteria‚ the imaging data of patients undergoing ankle joint CT examination were analyzed‚ and the inferior tibiofibular joint fibula notch was classified according to the morphological characteristics. The measurements included 8 distances. There were 123 males and 102 females‚ all of whom were Han nationality‚ aged 18-60 years old. Results Retrospectively analyzed the result of 225 patients from December 2013 to December 2022. The distal tibiofibular syndesmosis fibular notch was divided into four types according to morphological characteristics‚ C-shaped (50. 67%)‚ V-shaped (26. 67%)‚ flat-shaped (15. 11%) and L-shaped (7. 56%). The angle between the anterior and posterior facets of the flat shape (145. 56 ± 9. 25)° was the largest and the angle between the anterior and posterior facets of the L shape (125. 07 ± 13. 54)° was the smallest(P< 0. 05); the depth of the notch in the flat shape (3. 11 ± 0. 83) mm was the smallest and in the L shape (4. 47±1. 11) mm was the largest(P<0. 05);The posterior facet length (13. 06 ± 3. 56) mm and anterior tibiofibular gap (3. 83±1. 49) mm on left were larger than on the right side (P<0. 05); The posterior facet length (13. 36 ± 3. 46) mm‚ fibular notch depth (3. 93 ± 1. 10) mm and vertical distance of tibiofibular overlap (9. 10 ± 2. 55) mm larger in men than in women (P<0. 05). Conclusion In this study‚ the data related to the inferior tibiofibular syndesmosis notch were measured and divided into four types according to the shape. The flat inferior tibiofibular syndesmosis notch is more likely to have chronic ankle instability‚ and the fibula is more likely to move forward during anatomical reduction. The inferior tibiofibular syndesmosis of L-shaped and C-shaped notches is more prone to posterior displacement of fibula or poor rotation reduction during anatomical reduction.
9.Efficacy and adverse reactions of donepezil:a pharmacogenomic study
Hongmei SUN ; Chao LÜ ; Xuan SUN ; Siyu CHEN ; Xiaoxue ZHANG ; Yuxin FENG ; Tong YIN ; Jianjun JIA
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):171-174
Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71%vs 9.09%,P=0.029;42.86%vs 9.09%,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95%CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P>0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.
10.Role of nNOS-NOS1AP coupling in remifentanil-induced hyperalgesia in rats
Ruichen SHU ; Yuan LI ; Xuan ZHANG ; Zengli ZHANG ; Zhenguo SONG ; Yiqing YIN
Chinese Journal of Anesthesiology 2024;44(1):66-70
Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.


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