1.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
2.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
3.Analysis of associations between risk factors for cardiovascular disease and breast cancer
Ruijie NIU ; Jun ZENG ; Zhoutong LI ; Cheng WANG ; Jinquan JIANG
Chinese Journal of Clinical Medicine 2024;31(6):932-938
Objective To explore the associations between risk factors for cardiovascular disease and breast cancer. Methods A total of 300 patients with breast cancer and 300 with benign breast diseases diagnosed by postoperative pathology were included in the Department of Breast Surgery, Huangpu Branch of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from January 2023 to June 2023. The main cardiovascular risk factors in patients between the two groups were compared. Stratification was performed according to menstrual status, and the main cardiovascular risk factors in patients with different menstrual status between the two groups were compared. The logistic regression correlation analysis was used to analyze the risk factors related to cardiovascular disease for breast cancer. Results There were statistically significant differences in clinical data and laboratory indicators between the two groups (P<0.01) . Multivariate logistic regression analysis showed that age (OR=1.03, P=0.029), triglyceride (TG; OR=1.94, P=0.025), C-reactive protein (CRP; OR=2.73, P<0.001), D-dimer (OR=61.19, P<0.001), and homocysteine (Hcy; OR=2.10, P<0.001) were independently associated with breast cancer. The stratified analysis showed age, TG, CRP, D-dimer, and Hcy were independently associated with breast cancer in both premenopausal and postmenopausal patients (P<0.05). Conclusions Among risk factors for cardiovascular disease, advanced age, increased TG, CRP, D-dimer, and Hcy might increase breast cancer risk, which are helpful of screening high-risk individuals for breast cancer.
4.Research status of pharmacological mechanism of PCSK9 inhibitors and discussion of their clinical application
Wen-Hui MO ; Si-Lei XU ; Xia HE ; Niu-Niu BAI ; Meng-Ying YUAN ; Zhi-Min LI ; Jiao ZHANG ; Fei WANG ; Yuan-Kun ZHENG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2438-2441
Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.
5.Pathogenic microorganism monitoring in the food processing of school canteens
NIU Huimin,JIAO Qiang,LI Ruohan,LIU Zhiyong
Chinese Journal of School Health 2024;45(6):895-898
Objective:
To analyze the key control points of pathogenic microbial contamination during the food processing of school canteens, so as to provide a basis for effectively preventing the occurrence of campus food safety incidents.
Methods:
In March 2023, 10 school canteens from Zhengzhou City, Henan Province were selected by convenient sampling method. A total of 300 samples were collected from the storage equipment of raw materials, production tools, staff hands, infrastructure, dining utensils and other facilities in the school canteens during the food processing process.The rapid detection method of foodborne pathogens based on isothermal multiple selfmatchinginitiated amplification (IMSA) technology was used to analyze the possible risk of pathogenic microorganism contamination. Fisher exact probability method was applied for the statistical analysis.
Results:
Among the 300 samples collected, pathogenic microorganisms including Staphylococcus aureus, Salmonella and Listeria monocytogenes were detected in 5 samples, distributed in the food preparation utensils such as cutting boards, operating tables, knives and staff hands, while no pathogenic microorganisms were detected in dining utensils, raw material storage equipment and canteen infrastructure.There was no statistically significant difference between the IMSA rapid detection method and the national standard method for testing Staphylococcus aureus, Salmonella and Listeria monocytogenes(P>0.05). Compared to international method, the positive coincidence of pathogenic microorganism detected by IMSA rapid inspection system was 83.3%(5/6), the negative coincidence was 100%(n=294), and the overall consistency rate was 99.7%.
Conclusions
The key control points of pathogenic microbial contamination in the food processing process of school canteens mainly are the utensils in the food production process, such as cutting boards, operating tables, knives and staff hands in the food processing process of the school canteen, which could be accurately identified by the rapid detection method of pathogenic microorganism established based on IMSA technology. The quality and efficiency campus food safety supervision should be promoted to prevent the food safety events in school canteen.
6.Improvement of Core Behavior in Autism Spectrum Disorder Mice by 8-Week Aerobic Exercise
Niu LIU ; Ya-Qi XUE ; Shi-Jiao WANG ; Zhi-Ping ZHEN
Progress in Biochemistry and Biophysics 2024;51(9):2168-2181
ObjectiveTo investigate the effect of 8-week aerobic exercise on the improvement of core behaviors of male and female autistic mice induced by valproic acid (VPA). MethodsExperimental mice were randomly divided into the control group (CTL), VPA-induced autism group (VPA) and VPA+aerobic exercise group (VEX), with 10 mice in each group. The pregnant mice were injected with VPA intraperitoneally at E12.5, and their offspring were used as autistic mice. Pups were weaned 28 d after birth and began an 8-week aerobic exercise intervention. The day after exercise, mice were tested in behavioral experiments to detect exploratory behavior, social skills, repetitive stereotypic behavior, cognitive ability and mood. The mice were tested for social skills, repetitive stereotyped behaviors, cognitive and learning memory abilities, exploratory behaviors, and emotions by behavioral assays on the following day after the exercise. ResultsBoth male and female mice in the CTL group showed a significant decrease in the total distance and percentage of time spent in the interaction zone in the 4th socialization compared to the 1st socialization (P<0.01); the total distance and percentage of time spent in the interaction zone in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01); in VPA group, both male and female mice showed no significant change in the total distance and percentage of time spent in the interaction zone in the 4th and 5th socialization; in the VEX group, the total distance and percentage of time spent in the interaction zone by male mice in the 4th socialization was significantly decreased compared to the 1st socialization (P<0.01, P<0.05); and in the VEX group the total distance and percentage of time spent in the social interaction zone by both male and female mice in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01, P<0.05). The results of the first phase of three-box socialization experiment showed that male and female mice in the CTL group spent more time socializing with their social partners than in contact with the empty cages (P<0.01); there was no difference in the time spent by male and female mice in the VPA group in socializing with their social partners and the empty cages; and male and female mice in the VEX group spent a longer time socializing with their social partners(P<0.01). The results of the second phase of three-box test showed that male and female mice in the CTL group showed a significant tendency to socialize with new social partners (P<0.01), whereas no significant changes were observed in the mice of VPA group; aerobic exercise significantly ameliorated this deficit in male and female mice with autism. Compared with the CTL group, VPA-induced significant decreases were observed in the total distance freely moved in the central area of the open field, the time and percentage of time spent in the open arm of cross maze, and the distance and time spent in the white box in both male and female autistic mice (P<0.01); a significant increase in the number of bead burials and time spent in self-grooming (P<0.01); a significant decrease in the cognitive index (P<0.01); a significantly longer latency to find the platform, and significantly decreased the percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01). Compared with the VPA group, after 8 weeks of aerobic intervention, male and female mice in the VEX group showed a significant increase in total distance, open-arm dwell time, and percentage of free movement in the central area of the empty field (P<0. 05), and a trend toward a decrease in the dwell time of females in the white box was not significant, the number of beads burying and the time of self-combing were significantly lower(P<0.01, P<0.05); and a significant increase in cognitive index (P<0.05), a significantly shorter time to find the platform, and significantly increased percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01), showing excellent learning memory. ConclusionAutistic mice severely suffer from social and cognitive impairments, repetitive stereotyped behaviors, decreased activity level, and the exhibition of anxiety. 8 weeks of aerobic exercise can improve the social and cognitive abilities, alleviate the stereotyped repetitive behaviors, increase the activity level, and positively regulate the anxiety in autistic mice. It is hypothesized that aerobic exercise has an important role in motor rehabilitation of autism, in order to provide a theoretical basis for clinical research.
7.Correlation between initial estimated glomerular filtration rate and all-cause mortality in patients with urgent-start peritoneal dialysis
Xiang LI ; Lingling NIU ; Nana LUO ; Zhanfeng JIAO ; Xia WANG ; Yiming ZHANG
Chinese Journal of Postgraduates of Medicine 2024;47(7):589-594
Objective:To explore the correlation between the initial estimated glomerular filtration rate (eGFR) and all-cause mortality in end-stage renal disease (ESRD) patients undergoing urgent-start peritoneal dialysis (USPD).Methods:The clinical data of 380 ESRD patients undergoing USPD from January 2013 to June 2023 in Affiliated Hospital of Jining Medical University were retrospective analyzed. According to the median initial eGFR of 6.25 ml/(min·1.73 m 2), the patients were divided into low eGFR group with eGFR<6.25 ml/(min·1.73 m 2) and high eGFR group with eGFR ≥6.25 ml/(min·1.73 m 2), with 190 patients in each group. The baseline characteristics and hematological indexes within 48 h before USPD were compared between the two groups. The patients were followed up until death or until June 30, 2023, and all-cause mortality was recorded. The Kaplan-Meier survival curve was used to evaluate the accumulated survival rate. Multivariate Cox regression analyses were used to identify the independent risk factors for all-cause mortality in ESRD patients undergoing USPD, with subgroup analyses based on age, gender and diabetes. Results:The median follow-up time was 40.7 (21.7, 59.0) months, 112 patients died, with a total mortality rate of 29.5% (112/380). The blood potassium, blood phosphorus, urea nitrogen, uric acid, parathyroid hormone and dialysis age in high eGFR group were significantly lower than those in low eGFR group: (4.1 ± 0.7) mmol/L vs. (4.5 ± 0.8) mmol/L, (1.6 ± 0.4) mmol/L vs. (1.9 ± 0.6) mmol/L, (21.8 ± 7.2) mmol/L vs. (29.7 ± 11.0) mmol/L, (359.8 ± 99.4) μmol/L vs. (429.4 ± 116.9) μmol/L, 242.2 (151.5, 398.3) ng/L vs. 281.7 (189.1, 487.2) ng/L and 36.1 (18.8, 54.0) months vs. 43.7 (28.8, 68.2) months, the diabetes rate, hemoglobin, platelet count, blood chloride, fasting blood glucose and mortality rate were significantly higher than those in low eGFR group: 20.0% (38/190) vs. 11.6% (22/190), (100.6 ± 18.2) g/L vs. (96.1 ± 20.0) g/L, (207.7 ± 72.6) × 10 9/L vs. (192.4 ± 65.6) × 10 9/L, (100.6 ± 4.1) mmol/L vs. (99.4 ± 4.7) mmol/L, (5.9 ± 2.3) mmol/L vs. (5.5 ± 1.9) mmol/L and 34.2% (65/190) vs. 24.7% (47/190), and there were statistical differences ( P<0.01 or< 0.05). Kaplan-Meier survival curve analysis result showed that the all-cause mortality rate in high eGFR group was significantly higher than that in low eGFR group, and there was statistical difference (log-rank χ2 = 6.64, P<0.01). After adjusting for gender, age and confounding factors, multivariate Cox regression analysis result showed that elevated eGFR, increased mean corpuscular volume and elevated fasting blood glucose were independent risk factors for all-cause mortality in ESRD patients undergoing USPD ( HR = 1.14, 1.04 and 1.15; 95% CI 1.04 to 1.26, 1.01 to 1.08 and 1.03 to 1.29; P<0.01 or<0.05), while female was an independent protective factor ( HR = 0.59, 95% CI 0.38 to 0.92, P<0.05). Subgroup analysis result showed a consistent effect of eGFR on mortality in ESRD patients undergoing USPD. Conclusions:Higher initial eGFR in ESRD patients undergoing USPD is associated with an increased risk of all-cause mortality.
8.Portable spirometer-based pulmonary function test willingness in China: A nationwide cross-sectional study from the "Happy Breathing Program"
Weiran QI ; Ke HUANG ; Qiushi CHEN ; Lirui JIAO ; Fengyun YU ; Yiwen YU ; Hongtao NIU ; Wei LI ; Fang FANG ; Jieping LEI ; Xu CHU ; Zilin LI ; Pascal GELDSETZER ; Till B?RNIGHAUSEN ; Simiao CHEN ; Ting YANG ; Chen WANG
Chinese Medical Journal 2024;137(14):1695-1704
Background::Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.Methods::We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.Results::A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility ( n = 3304, 43.1%) and a lack of trust in primary healthcare institutions ( n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half ( n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs. Conclusions::Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.
9.Effects of PM2.5 and O3 sub-chronic combined exposure on ATP amount and ATPase activities in rat nasal mucosa
Tenglong YAN ; Jiayu XU ; Tian CHEN ; Xin YANG ; Weiwei WANG ; Shupei ZHOU ; Piye NIU ; Guang JIA ; Jiao XIA
Journal of Peking University(Health Sciences) 2024;56(4):687-692
Objective:To evaluate the effects of fine particle matter(PM2.5)and ozone(O3)com-bined exposure on adenosine triphosphate(ATP)amount and ATPase activities in nasal mucosa of Spra-gue Dawley(SD)rats.Methods:Twenty male SD rats were divided into control group(n=10)and exposure group(n=10)by random number table method.The rats were fed in the conventional clean environment and the air pollutant exposure system established by our team,respectively,and exposed for 208 d.During the exposure period,the concentrations of PM2 5 and O3 in the exposure system were moni-tored,and a comprehensive assessment of PM2 5 and O3 in the exposure system was conducted by combi-ning self-measurement and site data.On the 208 d of exposure,the core,liver,spleen,kidney,testis and other major organs and nasal mucosal tissues of the rats were harvested.Each organ was weighed and the organ coefficient calculated.The total amount of ATP was measured by bioluminescence,and the ac-tivities of Na+-K+-ATPase and Ca2+-ATPase were detected by spectrophotometry.The t test of two inde-pendent samples was used to compare the differences among the indicator groups.Results:From the 3rd week to the end of exposure duration,the body weight of the rats in the exposure group was higher than that in the control group(P<0.05),and there was no significant difference in organ coefficients be-tween the two groups.The average daily PM2 5 concentration in the exposure group was(30.68±19.23)μg/m3,and the maximum 8 h ozone concentration(O3-8 h)was(82.45±35.81)μg/m3.The chemi-luminescence value(792.4±274.1)IU/L of ATP in nasal mucosa of the rats in the exposure group was lower than that in the control group(1 126.8±218.1)IU/L.The Na+-K+-ATPase activity(1.53±0.85)U/mg in nasal mucosa of the rats in the exposure group was lower than that in the control group(4.31±1.60)U/mg(P<0.05).The protein content of nasal mucosa in the control group and the exposure group were(302.14±52.51)mg/L and(234.58±53.49)mg/L,respectively,and the ac-tivity of Ca2+-ATPase was(0.81±0.27)U/mg and(0.99±0.73)U/mg,respectively.There was no significant difference between the groups.Conclusion:The ability of power capacity decreased in the rat nasal mucossa under the sub-chronic low-concentration exposure of PM2 5 and O3.
10.Phenotype of infantile epileptic spasm syndrome in pyridoxin-dependent epilepsy
Xianru JIAO ; Pan GONG ; Yue NIU ; Zhao XU ; Zongpu ZHOU ; Zhixian YANG
Journal of Peking University(Health Sciences) 2024;56(5):781-787
Objective:To analyze the clinical diagnosis,treatment,and prognosis of the patients with pyridoxine-dependent epilepsy(PDE)characterized by infantile epileptic spasm syndrome(IESS).Methods:A total of 75 PDE patients with ALDH7A1 variants were diagnosed at the Department of Pediat-rics of Peking University First Hospital and Peking University People's Hospital from July 2012 to June 2024,and five PDE patients with the phenotype of IESS were selected.The clinical manifestations,treat-ment,blood biochemistry,metabolic screening,electroencephalogram(EEG),brain magnetic resonance imaging(MRI),and gene testing results of the five PDE patients were analyzed.Results:Among the five patients diagnosed with PDE,three were female and two were male,and the phenotype was consistent with IESS.The age at the last follow-up was from one year and 3 months to 11 years and 9 months.All the five cases were delivered at term.Two cases had anoxia and asphyxia at birth,and three cases had normal birth history.The onset age of seizure ranged from one day to 4 months after birth.One case presented with epileptic spasms(ES),and three cases presented with focal seizure and ES.The other patient was started with ES,followed by multiple seizure types,including focal seizure and generalized tonic-clonic seizure,and developed epileptic status which caused secondary brain injury.The interictal EEG results showed hypsarrhythmia in three cases,generalized and multifocal discharges in one cases,and multifocal discharges in one case.No abnormalities were found in brain MRI in three cases,and secondary cerebral atrophy and hydrocephalus were observed in two cases during the course of the disease.Gene analysis confirmed that the five patients carried compound heterozygous variants of ALDH7A1,and two of them carried exon deletion variants.High dose pyridoxine treatment started at the end of 2 days,4 years,3 years,4 days.and 2 months after the onset of the disease.Up to the last follow-up,seizures of four cases were controlled,followed by normal EEG.One patient with brain atrophy had uncontrolled seizures and EEG remained abnormal.The neurodevelopment of the three patients were se-verely delayed,and two were mildly delayed.Conclusion:IESS could be a rare phenotype of PDE.High doses of pyridoxine can control or reduce the frequency of seizures.Delayed diagnosis and treatment,secondary brain injury,and the genotype,especially deletions variants,were associated with poor prognosis.


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