1.Analysis of Clinical and Phenomics Characteristics of Patients with Phlegm-Stasis Binding Syndrome and Its Accompanied Patterns in Stable Angina Pectoris of Coronary Heart Disease
Chongchai LI ; Han LI ; Zheng LI ; Zeng LI ; Yushi ZHOU ; Yuhan AO ; Shuang XU ; Xue WANG ; Yaoyao SUN ; Dongning WU ; Hongcai SHANG ; Mingxue ZHANG
Journal of Traditional Chinese Medicine 2026;67(14):1514-1522
ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris (SAP) of coronary heart disease (CHD). MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome, 125 cases of qi deficiency-accompanied syndrome, 38 cases of qi stagnation-accompanied syndrome, and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine (TCM) patterns. Data of patients with different TCM patterns were collected, including general condition, TCM symptoms, blood lipids, coagulation function, immune indicators, and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection (VIP) ≥1 and fold change (FC) ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group, with a relatively high proportion of males. Regarding TCM symptoms, patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse, chest pain, and chest tightness; in patients with qi deficiency-accompanied syndrome, fatigue, chest pain, and weak pulse were most common; in patients with qi stagnation-accompanied sydnrome, wiry-choppy or wiry-slippery pulse, chest pain, and symptoms that increase or decrease with emotional changes, belching, or flatulence were most common; in patients with toxin accumulation-accompanied syndrome, bitter taste in the mouth, chest tightness, irritability, restlessness or manic delirium, and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters (P<0.05), whereas no statistically significant difference was found in blood lipid levels and immune indicators (P>0.05).Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine, leucine, and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin (FC = 3.58) and oxypurinol (FC = 124.50). Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine (FC = 2.62) and D-mannosamine (FC = 2.99). Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine (FC = 7.83) and canrenone (FC = 8.94). ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders, amino acid metabolism abnormalities, and multiple immune indicators activation, which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.
2.Analysis of Clinical and Phenomics Characteristics of Patients with Phlegm-Stasis Binding Syndrome and Its Accompanied Patterns in Stable Angina Pectoris of Coronary Heart Disease
Chongchai LI ; Han LI ; Zheng LI ; Zeng LI ; Yushi ZHOU ; Yuhan AO ; Shuang XU ; Xue WANG ; Yaoyao SUN ; Dongning WU ; Hongcai SHANG ; Mingxue ZHANG
Journal of Traditional Chinese Medicine 2026;67(14):1514-1522
ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris (SAP) of coronary heart disease (CHD). MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome, 125 cases of qi deficiency-accompanied syndrome, 38 cases of qi stagnation-accompanied syndrome, and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine (TCM) patterns. Data of patients with different TCM patterns were collected, including general condition, TCM symptoms, blood lipids, coagulation function, immune indicators, and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection (VIP) ≥1 and fold change (FC) ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group, with a relatively high proportion of males. Regarding TCM symptoms, patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse, chest pain, and chest tightness; in patients with qi deficiency-accompanied syndrome, fatigue, chest pain, and weak pulse were most common; in patients with qi stagnation-accompanied sydnrome, wiry-choppy or wiry-slippery pulse, chest pain, and symptoms that increase or decrease with emotional changes, belching, or flatulence were most common; in patients with toxin accumulation-accompanied syndrome, bitter taste in the mouth, chest tightness, irritability, restlessness or manic delirium, and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters (P<0.05), whereas no statistically significant difference was found in blood lipid levels and immune indicators (P>0.05).Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine, leucine, and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin (FC = 3.58) and oxypurinol (FC = 124.50). Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine (FC = 2.62) and D-mannosamine (FC = 2.99). Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine (FC = 7.83) and canrenone (FC = 8.94). ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders, amino acid metabolism abnormalities, and multiple immune indicators activation, which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.
3.Regulation of signaling pathways related to systemic scleroderma fibrosis by microRNAs
Jingwei XU ; Shuang CHEN ; Kelei GUO ; Li HAN ; Hua BIAN
Chinese Journal of Dermatology 2025;58(8):788-793
Systemic scleroderma (SSc) is a fibrotic disease involving the skin and a variety of internal organs, which is currently thought to be mainly caused by abnormal activation of fibroblasts and excessive secretion of extracellular matrix. Growing evidence has shown signaling cascades associated with SSc fibrosis, including transforming growth factor-β/Smads, Notch, Wnt/β-catenin, rat sarcoma/extracellular regulated protein kinases, etc. MicroRNAs participate in the post-transcriptional regulation of different target genes and control the cell state, determining the changes in transcriptomes and proteomes caused by various cellular signaling cascades. This review summarizes recent research progress in the regulatory role of microRNAs in SSc fibrosis-related signaling pathways and potential therapeutic targets.
4.Establishment and Evaluation of A Remote Medication Treatment Management Model for Elderly Patients with Chronic Diseases Based on Mobile Technology
Lijuan YANG ; Wei ZHANG ; Quanzhi LI ; Tingting ZHENG ; Shuo YANG ; Ping LIN ; Shuang HAN ; Sitong LIU ; Tianjing ZHANG ; Jiancun ZHEN
Herald of Medicine 2025;44(3):486-490
Objective To evaluate the effectiveness and feasibility of a remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology.Methods A convenient and elderly-friendly mo-bile application(hereinafter referred to as Yaoshiyi APP)was developed,and a remote medication treatment management team consisting of clinical pharmacists from tertiary hospitals,community pharmacists,and community physicians was formed.Patients from communities were selected for practical research,led by pharmacists.Based on the Yaoshiyi APP,patients were subjected to 6 months of medication treatment management practice,and the effectiveness and feasibility of the practice were evaluated.Re-sults The Yaoshiyi APP can be integrated with a variety of medical-grade wearable devices to realize the functions of automati-cally uploading monitoring data,abnormal value reminding,medication reminding,medication consultation,and medication sci-ence popularization.A total of 302 elderly patients with chronic disease at home completed the study.The results showed that phar-macists have identified and intervened in 695 cases of medication-related problems.According to the classification of medication-related problems,the top three were 247 cases(35.5%)of additional treatment,97 cases(14.0%)of unnecessary drug treat-ment,and 93 cases(13.4%)of medication compliance problems.The patient's medication adherence score(Morisky medication adherence scale-8,MMAS-8)increased from(5.85±1.57)at enrollment to(6.74±1.23)6 months after enrollment(P<0.01).After 6 months of enrollment,the patient's satisfaction with the pharmacist's work reached a score of(4.99±0.08)out of 5.The average reduction in drug costs for patients caused by pharmacists intervening in irrational medication is(20.9±18.0)%.At the end of follow-up,93.4%of patients were proficient in using the Yaoshiyi APP.Conclusion The remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology constructed in this study can ef-fectively improve patient compliance with disease monitoring and medication,ensure rational drug use,reduce medical resource waste,and receive high patient acceptance.
5.Water extract of Rehmannia glutinosa improves bleomycin-induced pulmonary fibrosis in mice and its metabolic mechanism
Zi-yu ZHANG ; Meng-nan ZENG ; Peng-li GUO ; Yu-han ZHANG ; Xiang-da LI ; Yan-xing WU ; Shuang-ying FU ; Zi-chang LIAN ; Wei-sheng FENG ; Xiao-ke ZHENG
Chinese Pharmacological Bulletin 2025;41(12):2315-2325
Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.
6.Study on the effect of differently automatic normal tissue objective weights of Eclipse planning system on intensity modulated radiation therapy for abdominal tumor
Weijie DONG ; Chunqiang WANG ; Linni WANG ; Shuang HAN ; Ye ZHANG ; Yixin LI
China Medical Equipment 2025;22(2):9-14
Objective:To compare the effects of different automatic normal tissue objective(NTO)weights(WNTO)of Eclipse planning system on intensity modulated radiation therapy(IMRT)of fixed field for abdominal tumor.Methods:Twenty patients with rectal cancer and twenty patients with cervical cancer who received radiotherapy in The Second People's Hospital of Huludao from September 2022 to January 2024 were selected.5 groups of different plans[WNTO20,40,60,80 and 100]were respectively formulated for each patient.Among of them,the WNTO20 plan was control group,and other 4 groups were respectively WNTO40 group,WNTO60 group,WNTO80 group and WNTO100 group.Then,the differences in dosimetry and monitor units(MU)among 5 groups of plans were compared.Results:In the WNTO 80 and 100 groups of patients with rectal cancer,the conformation index(CI)values of target regions of them were respectively 1.02±0.04 and 1.00±0.03,all of which approached to 1,and the CI values of two groups were lower than that of control group,and the differences were statistically significant(t=15.986,18.422,P<0.05).The homogeneity index(HI)of WNTO 80 and 100 groups were respectively 0.09±0.12 and 0.10±0.14,which were higher than that of control group,and the differences were statistically significant(t=-1.371,-1.463,P<0.05).The 52Gy dose volume(Vmax52)of small intestine of the two groups were respectively(4.48±14.49)and(4.77±10.47)cm3,which were higher than that of control group,and the differences were statistically significant(t=-1.360,-2.005,P<0.05).The 30 Gy dose volume percentage(V30 Gy)values of the right femoral heads of the two groups were respectively(12.28±4.57)%and(10.96±4.17)%,which were lower than that of control group,and the differences were statistically significant(t=6.893,6.75,P<0.05).The 30 Gy dose volume percentage(V30 Gy)values of the left femoral head of the two groups were respectively(11.57±4.41)%and(10.17±3.78)%,which were lower than that of control group,and the differences were statistically significant(t=6.782,5.963,P<0.05).The MU value of WNTO100 group was(1254±93)MU,which was higher than that of control group,and the difference was statistically significant(t=-3.741,P<0.05).In the WNTO 80 and 100 groups of patients with cervical cancer,the CI values of target regions of them were respectively 1.03±0.32 and 1.02±0.03,all of which approached to 1,and the CI values of the two groups were lower than those of control group,and the differences were statistically significant(t=20.069,19.475,P<0.05).The HI values of them were respectively 0.07±0.05 and 0.08±0.01,which were higher than that of control group,and the differences were statistically significant(t=-12.445,-19.478,P<0.05).The V30 Gy values of the right femoral heads of the two groups were respectively(16.11±4.71)%and(14.90±4.56)%,which were lower than that of control group,and the differences were statistically significant(t=7.875,8.020,P<0.05).The V30 Gy values of the left femoral head of the two groups were respectively(15.21±3.71)%and(13.93±3.77)%,which were lower than that of control group,and the differences were statistical significance(t=7.617,7.436,P<0.05).The Vmax52 of small intestine of the two groups were respectively(0.82±1.10)and(4.47±8.81)cm3,which were higher than that of control group,and the difference was statistically significant(t=-2.985,-2.388,P<0.05).Conclusion:The WNTO80 is recommended for IMRT plan of radiotherapy on abdominal tumor,which can more quickly and better meet the assessment conditions of IMRT plan.
7.Construction and validation of predictive model for surgical site infections following spinal surgery in Chinese population
Hongxin WEI ; Yan REN ; Shuang LIU ; Jiao SHAN ; Hui CHEN ; Xiao HAN ; Zhiwei CHEN ; Lin YANG ; Yue LIU ; Luyao LI ; Hong LI
Chinese Journal of Nosocomiology 2025;35(16):2465-2470
OBJECTIVE To construct a predictive tool for surgical site infections(SSIs)in spinal surgery for Chi-nese population to provide evidence support for reducing SSIs.METHODS A systematic review of Chinese and English database literature was conducted for Meta-analysis to obtain pooled risk values for influencing factors,and a risk prediction scoring tool was constructed based on the logistic regression model.Patients who underwent spinal surgery and completed postoperative follow-up in a tertiary hospital in Beijing from Jan.to Dec.2021 were selected to validate the predictive effect of the tool.RESULTS The predictive model for SSIs in Chinese spinal sur-gery patients was Logit(P)=—3.47+0.63(age 60 years)+0.31 ×(patient with cardiovascular disease)+0.69 ×(rheumatoid arthritis)+1.07 ×(diabetes)+1.06 ×(operation duration>3 h)+1.17 ×(preopera-tive albumin<35 g/L)+0.71 ×(history of spinal surgery)+0.67 ×(carrying internal implants)+0.73 ×(blood transfusion).The total score of the predictive tool was 92,with a cutoff score of≥24.50 indicating high-risk individuals.The area under the curve was 0.733,with the sensitivity 58.30%and the specificity 79.60%.CONCLUSION The established predictive model for SSIs in Chinese spine surgery demonstrates good predictive performance and can be used as a reference assessment tool in clinical practice.
8.Risk factors and their predictive efficacy for early postoperative complications in elderly patients with hip fracture
Deen WAN ; Yongzhou YAN ; Feng SHUANG ; Hao LI ; Zhi ZENG ; Mudan HUANG ; Lu HAN ; Xiang PENG ; Di YANG ; Ming CHEN ; Qixin LIU
Chinese Journal of Trauma 2025;41(3):274-281
Objective:To investigate the risk factors and their predictive efficacy for early postoperative complications in elderly patients with hip fracture.Methods:A retrospective cohort study was conducted on the clinical data of 203 elderly patients with hip fracture admitted to the 908th Hospital of the Joint Logistics Support Force of the PLA and the First Affiliated Hospital of Nanchang University from January 2022 to December 2023, including 54 males and 149 females, aged 65-100 years [(80.5±7.7)years]. There were 96 patients with femoral neck fracture and 107 patients with intertrochanteric fracture. According to the AO/OTA classification, the fracture was classified as type 31A in 107 patients and type 31B in 96. Among them, 81 patients were treated with proximal femoral nail antirotation (PFNA), 65 with semi-hip arthroplasty, 52 with total hip arthroplasty (THA), and 5 with closed reduction and cannulated nail internal fixation. The patients were divided into complication group ( n=65) and non-complication group ( n=138) according to whether complications (mainly including delirium, lung infection, stress ulcer, and deep vein thrombosis of the lower limbs) occurred within 15 days after surgery. The gender, age, age stage, educational level, cause of injury, associated underlying diseases before surgery, AO/OTA classification, American Society of Anesthesiologists (ASA) classification, 5-factor modified frailty index (mFI-5) score, prognostic nutritional index (PNI), anesthesia method, operation method, operation time, intraoperative blood loss, length of hospital stay, etc., were recorded in the two groups. Univariate analysis and multivariate binary logistic regression analysis were used to evaluate the correlation between the above indexes and the occurrence of early postoperative complications in elderly patients with hip fracture and to determine their independent risk factors. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of each risk factor for the occurrence of early postoperative complications in elderly patients with hip fracture. Results:Univariate analysis showed a certain correlation between age, age stage, associated underlying diseases before surgery, AO/OTA classification, ASA classification, mFI-5 score, PNI, operation method, and length of hospital stay and the occurrence of early postoperative complications in elderly patients with hip fracture ( P<0.05), while gender, educational level, cause of injury, anesthesia method, operation time, and intraoperative blood loss were not correlated with the occurrence of early postoperative complications in elderly patients with hip fracture ( P>0.05). The results of multivariate binary logistic regression analysis showed that the associated underlying diseases before surgery ( OR=5.46, 95% CI 1.33, 22.39, P<0.05), mFI-5 score ( OR=15.90, 95% CI 5.36, 47.15, P<0.01), and PNI ( OR=0.70, 95% CI 0.60, 0.81, P<0.01) were significantly correlated with the occurrence of early postoperative complications in elderly patients with hip fracture. The results of ROC curve analysis showed that mFI-5 score (AUC=0.85, 95% CI 0.80, 0.91) and PNI (AUC=0.87, 95% CI 0.82, 0.93) had moderate predictive efficacy, while the early warning efficacy of associated underlying diseases was low (AUC=0.54, 95% CI 0.45, 0.62). The combination of the above risk factors was more effective in predicting early postoperative complications in elderly patients with hip fracture (AUC=0.95, 95% CI 0.92, 0.98). Conclusions:The mFI-5 score, PNI, and associated underlying diseases before surgery are independent risk factors for early postoperative complications in elderly patients with hip fracture. The mFI-5 score and PNI have a higher predictive efficacy than associated diseases before surgery on the occurrence of early postoperative complications in elderly patients with hip fracture, while the combination of the above risk factors provides a significantly better predictive performance.
9.18F-FDG PET/CT metabolic parameters for prediction of treatment response to neoadjuvant immunochemotherapy in locally advanced gastric cancer
Peng LI ; Shuang LU ; Weiwei ZHAO ; Yanmei LI ; Xianhua HAN ; Xiaofeng ZHANG ; Jianwei YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(11):648-653
Objective:To investigate the value of midtreatment 18F-FDG PET/CT metabolic parameters for predicting the pathological response in patients with locally advanced gastric cancer (LAGC) after neoadjuvant immunochemotherapy (NICT). Methods:Twenty-five LAGC patients (19 males, 6 females, age: (64.8±8.6) years) who underwent 18F-FDG PET/CT after NICT in Henan Cancer Hospital from August 2019 to June 2024 were retrospectively analyzed. The lesion′s ROI was delineated, then the SUV max and metabolic tumor volume (MTV) were measured, and the SUV max was divided by SUV mean of the descending aorta to obtain the tumor-to-background ratio (TBR). Patients underwent surgery after PET/CT imaging. Based on the tumor regression grade (TRG) system by the American Joint Committee on Cancer (AJCC) criteria on surgical specimen, patients were divided into responders (TRG0+ 1) and non-responders (TRG2+ 3). Independent-sample t test, Mann-Whitney U test, one-way analysis of variance, and Kruskal-Wallis rank-sum test were used to compare the differences of data. The predictive efficacy of PET/CT metabolic parameters was assessed by the ROC curve analysis. Results:Postsurgical pathology showed that 9 patients were responders and 16 were non-responders. The SUV max (3.10±1.95) and TBR (2.44±1.54) of primary lesions in responders were lower than those in non-responders (7.40±4.68, 5.85±3.74; t values: -2.61, -2.59, both P<0.05), while the MTV of primary tumors and short diameter and metabolic parameters of positive lymph nodes were not significantly different between those 2 groups ( t=-1.50, Z values: -1.09 to -0.75, all P>0.05). No significant relation was found between PET/CT parameters and pathological differentiation or Lauren classification, or other pathological features ( t values: -1.55 to 1.38, Z values: -1.84 to 0, F values: 0.12-2.43, H values: 0.13-0.98, all P>0.05). ROC curve showed that the cut-off value of SUV max for predicting postoperative TRG was 5.40, and the AUC reached 0.77 (95% CI: 0.56-0.91), with the sensitivity and specificity of 9/16, 9/9, respectively. With TBR=3.54 as the cut-off value, its AUC reached 0.77 (95% CI: 0.56-0.91), and the sensitivity and specificity were 11/16, 8/9, respectively. The sensitivity and specificity of PET/CT for predicting lymph node positivity of patients were 8/12 and 13/13, respectively. Conclusion:Interim 18F-FDG PET/CT metabolic parameters can accurately predict the pathological response of LAGC patients after NICT.
10.Clinical and genetic analysis of RARS2-related pontocerebellar hypoplasia
Xiaoli ZHANG ; Mengyue WANG ; Jialin LI ; Yichao MA ; Junling WANG ; Xiaoli LI ; Rui HAN ; Dan XU ; Shuang JIN ; Tianming JIA ; Shujin LI ; Xianjie HUANG ; Yueqin LI
Chinese Journal of Medical Genetics 2025;42(9):1096-1105
Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

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