1.Comparative efficacy of two hemopurification filters for treating intra-abdominal sepsis: A retrospective study.
Ye ZHOU ; Ming-Jun LIU ; Xiao LIN ; Jin-Hua JIANG ; Hui-Chang ZHUO
Chinese Journal of Traumatology 2025;28(5):352-360
PURPOSE:
To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis.
METHODS:
We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included.
EXCLUSION CRITERIA:
pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA.
RESULTS:
Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24 h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score.
CONCLUSIONS
In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.
Humans
;
Retrospective Studies
;
Female
;
Male
;
Middle Aged
;
Sepsis/mortality*
;
Aged
;
Adult
;
Continuous Renal Replacement Therapy/methods*
;
Intraabdominal Infections/mortality*
;
APACHE
;
Organ Dysfunction Scores
;
Intensive Care Units
;
Treatment Outcome
2.Study on the characteristics of lymphocyte-specfic protein-tyrosine kinase methylation in the peripheral blood circulation of patients with rheumatoid arthritis
Lingxia XU ; Cen CHANG ; Ping JIANG ; Kai WEI ; Jia′nan ZHAO ; Yixin ZHENG ; Yu SHAN ; Yiming SHI ; Hua Ye JIN ; Yi SHEN ; Shicheng GUO ; Dongyi HE ; Jia LIU
Chinese Journal of Rheumatology 2024;28(3):155-161
Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.
3.Study on the Substance Benchmark Characteristic Chromatogram and Multi-Component Content Determination of Classical Formula Fuzi Decoction
Zhen-Zhen PAN ; Yu-Jie XU ; Jia-Hui LIU ; Hui-Min YE ; Zhen-Hua WANG ; Chang-Qing LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2442-2451
Objective To establish a high performance liquid chromatography(HPLC)characteristic chromatogram and multi-component content determination method for the substance benchmark of Fuzi Decoction.Methods The characteristic chromatogram method of Fuzi Decoction substance benchmark was established,and the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition)was used to analyze the characteristic chromatograms of 15 batches of Fuzi Decoction substance benchmark samples.The HPLC content determination methods of 1 1 components in the Fuzi Decoction substance benchmark samples were established respectively,and the dry extract rate of 15 batches of Fuzi Decoction substance benchmark samples was determined.Results The similarity of characteristic chromatograms of 15 batches of Fuzi Decoction substance benchmark samples was greater than 0.9,and 12 common peaks were selected and eight of them were identified.The results showed that the contents of benzoylmesaconine,benzoylhypaconine,atractylenolide Ⅲ,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,gallic acid,albiflorin,paeoniflorin,1,2,3,4,6-penta-galloyl glucose and benzoyl paeoniflorin were 0.050 3-0.191 1,0.026 7-0.047 0,0.043 0-0.127 6,0.554 6-1.006 8,0.568 7-0.979 5,0.929 9-1.726 1,1.058 9-2.118 4,1.430 3-4.965 5,6.882 9-9.511 1,0.056 1-0.262 5,0.160 6-0.369 0 mg/g,respectively.The average dry extract rate of the 15 batches of Fuzi Decoction substance benchmark samples was 29.54%.Conclusion The established characteristic chromatogram and multi-index content determination method are accurate and stable,which provides a basis for the quality control of the substance benchmark and related preparations of Fuzi Decoction.
4.Comparison of anterior lateral ligament reconstruction and anterior lateral complex repair in the treatment of anterior cruciate ligament combined with anterior lateral ligament injury with high-grade pivot shift.
Xue-Feng JIA ; Qing-Hua WU ; Tong-Bo DENG ; Xiao-Zhen SHEN ; Jian-Ping YE ; He FANG ; Rong-Chang ZHOU ; Yang CAO ; You-Fen CHEN ; Qi-Ning YANG ; Guo-Hong XU
China Journal of Orthopaedics and Traumatology 2024;37(11):1101-1106
OBJECTIVE:
To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift.
METHODS:
From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared.
RESULTS:
A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05).
CONCLUSION
Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans
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Male
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Female
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Adult
;
Anterior Cruciate Ligament Reconstruction/methods*
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Anterior Cruciate Ligament Injuries/surgery*
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Young Adult
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Retrospective Studies
;
Anterior Cruciate Ligament/surgery*
;
Range of Motion, Articular
5.Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles.
Zhan Yi ZHANG ; Fan ZHANG ; Ye YAN ; Cai Guang CAO ; Chang Jian LI ; Shao Hui DENG ; Yue Hao SUN ; Tian Liang HUANG ; Yun He GUAN ; Nan LI ; Min LU ; Zhen Hua HU ; Shu Dong ZHANG
Journal of Peking University(Health Sciences) 2023;55(5):843-850
OBJECTIVE:
To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats.
METHODS:
A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures.
RESULTS:
Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion.
CONCLUSION
The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Male
;
Rats
;
Animals
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Prostate/diagnostic imaging*
;
Paraffin
;
Indocyanine Green
;
Rats, Sprague-Dawley
;
Fluorescent Dyes
6. Treatment advice of small molecule antiviral drugs for elderly COVID-19
Min PAN ; Shuang CHANG ; Xiao-Xia FENG ; Guang-He FEI ; Jia-Bin LI ; Hua WANG ; Du-Juan XU ; Chang-Hui WANG ; Yan SUN ; Xiao-Yun FAN ; Tian-Jing ZHANG ; Wei WEI ; Ling-Ling ZHANG ; Jim LI ; Fei-Hu CHEN ; Xiao-Ming MENG ; Hong-Mei ZHAO ; Min DAI ; Yi XIANG ; Meng-Shu CAO ; Xiao-Yang CHEN ; Xian-Wei YE ; Xiao-Wen HU ; Ling JIANG ; Yong-Zhong WANG ; Hao LIU ; Hai-Tang XIE ; Ping FANG ; Zhen-Dong QIAN ; Chao TANG ; Gang YANG ; Xiao-Bao TENG ; Chao-Xia QIAN ; Guo-Zheng DING
Chinese Pharmacological Bulletin 2023;39(3):425-430
COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
7.Analysis of the pollution status of paralytic shellfish poisons in shellfish sold in Hainan Province, 2018-2021
LI Cheng ; XIAO Wen-lin ; YE Hai-mei ; LAI Xuan-cheng ; SHI Hui ; HE Chang-hua
China Tropical Medicine 2023;23(5):484-
Abstract: Objective To investigate the pollution of paralytic shellfish poisons (PSP) in shellfish sold in Hainan Province from 2018 to 2021. Methods From 2018 to 2021, the content of 10 paralytic shellfish poisons including saxitoxin (STX), neosaxitoxin (neoSTX), gonyautoxins 1 (GTX1), gonyautoxins 2 (GTX2), gonyautoxins 3 (GTX3), gonyautoxins 4 (GTX4), gonyautoxins 5 (GTX5), decarbamoylsaxitoxin (dcSTX), decarbamoylgonyau toxins 2 (dcGTX2) and decarbamoylgonyau toxins 3 (dcGTX3) in 7 kinds of shellfish commonly sold in 13 cities and counties in Hainan province was analyzed. Results The detection rate of PSP in 360 shellfish samples was 10.3%. Among them, the highest detection rate of STX was 5.83%, followed by GTX2 detection rate of 4.17%; the detection rate of neoSTX and GTX3 were both 1.67%; the detection rate of GTX1 was 1.39%. None of the five PSP, GTX4, GTX5, dcSTX, dcGTX2 and dcGTX3, were detected. Four types of PSP were detected in fanscallops, two were detected in oysters, mussels and Scapharca subcrenata, only one was detected in scallops, and no toxin contamination was detected in clams and razor clams. A single sample of fanscallops detected a maximum of 4 PSP, and a single sample of oysters, scallops, mussels and Scapharca subcrenata detected a maximum of 1 PSP. The equivalence of PSP in all samples was ND-155.6 μg/kg.The annual detection rate of PSP from high to low was: 20.0% in 2020, 15.6% in 2019, 5.3% in 2018, and 2.0% in 2021, and none of the samples tested exceeded the standard. Continuously detectable STX in 2018-2020, all PSP that could be detected in 2018 were STX. In 2019, in addition to STX detected in scallops and Scapharca subcrenata, neoSTX was also detected in oysters, mussels and Scapharca subcrenata. In 2020, PSP was only detected from scallops, and GTX2 could be detected in all positive specimens, while 5 STX, 5 GTX1 and 6 GTX3 were detected. Only GTX2 detected from scallops in 2021. STX was detected in shellfish sold in 12 cities and counties, GTX2 can be detected in 10 cities and counties, neoSTX can be detected in 5 cities and counties, GTX1 and GTX2 were detected in 4 cities and counties respectively. Shellfish sold in Wenchang and Lingshui markets can detect 5 types of PSP. Conclusion Some types of shellfish on the market in Hainan are contaminated with some kind of PSP pollution risks, and it is necessary to strengthen the supervision of PSP in marketed shellfish.
8.Clinical implications of the concentration of alveolar nitric oxide in non-small cell lung cancer.
Xiaodan CHANG ; Hua LIAO ; Lingyan XIE ; Yuehua CHEN ; Liying ZHENG ; Jianpeng LIANG ; Weiwei YU ; Yuexian WU ; Yanmei YE ; Shuyu HUANG ; Haijin ZHAO ; Shaoxi CAI ; Hangming DONG
Chinese Medical Journal 2023;136(18):2246-2248
9.Metabolomic Profiling of Mice Exposed to α-amanitin Using Ultra-performance Liquid Chromatography Quadrupole Time-of-flight Tandem Mass Spectrometry.
Lei LI ; Chong ZHENG ; Jian Fang YE ; Kai ZHU ; Yi Bing ZHOU ; Jia LIU ; Ming GAO ; Yu Tian WU ; Yong Ting LIU ; Li Ya LIU ; Ye LIN ; Hai Chang LI ; Quan ZHANG ; Hua GUO
Biomedical and Environmental Sciences 2023;36(3):289-294
10.Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants.
Ling ZHOU ; Fang FANG ; Jie DENG ; Shuang Jun LIU ; Chun Hong CHEN ; Hua LI ; Chang Hong REN ; Ye WU
Chinese Journal of Pediatrics 2023;61(5):453-458
Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.
Male
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Female
;
Humans
;
Child
;
Infant
;
Epilepsy/genetics*
;
Retrospective Studies
;
Drug Resistant Epilepsy
;
Uridine
;
Evoked Potentials, Visual
;
Anemia
;
Electroencephalography/adverse effects*
;
Neurodegenerative Diseases

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