1.Association between random urine electrolytes and hypertension in children and adolescents
Chinese Journal of School Health 2026;47(3):314-318
Objective:
To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions.
Methods:
In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension.
Results:
At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ).
Conclusion
The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.
2.Safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction for elderly hip arthroplasty
Jiangjing WANG ; Na ZHAO ; Xiaona HU ; Na ZHAO
Chinese Journal of Tissue Engineering Research 2026;30(3):612-619
BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P<0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P<0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P<0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P<0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P<0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.
3.Effects and mechanism of short-acting exenatide on improving diabetic cognitive dysfunction
Xin LING ; Deming WANG ; Qi LU ; Jinyue HUANG ; Xian ZHENG ; Xiaona ZHU
China Pharmacy 2026;37(5):589-594
OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group (normal saline) and exenatide group (50 μg/kg), with db / m mice as the normal control group (normal saline), with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) ] , cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group (25 mmol/L glucose), high glucose group (125 mmol/L glucose), high glucose+exenatide group (125 mmol/L glucose+20 nmol/L exenatide), high glucose+exenatide+H89 (PKA inhibitor) group (125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89), and high glucose+H89 group (125 mmol/L glucose+10 μmol/L H89). After 48 h of intervention with corresponding solutions/culture medium, the levels of oxidative stress indicators, cAMP and PKA, the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ, and the phosphorylation level of dynamin-related protein 1 (Drp1) were measured. RESULTS Animal experiments showed that compared with the normal control group, the model group exhibited significantly increased body weight, fasting blood glucose and MDA level in the hippocampus ( P <0.05), as well as significantly prolonged escape latency ( P <0.05); swimming speed significantly slowed down, the time spent in the target quadrant, the number of platform crossings, and the levels of SOD, GSH, cAMP and PKA in the hippocampus were significantly decreased ( P <0.05). Compared with model group, all the above indicators (except for swimming speed) in the exenatide group were significantly reversed ( P <0.05). Cell experiments showed that compared with high glucose group, the high glucose+exenatide group had significantly decreased MDA level ( P <0.05), and significantly increased levels of SOD, GSH, cAMP and PKA, the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ, and phosphorylation level of Drp1 ( P <0.05). Compared with high glucose+exenatide group, the above indicators in the high glucose+exenatide+H89 group were significantly reversed ( P <0.05). CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway, promote Drp1 phosphorylation, and increase the activities of mitochondrial respiratory enzymes, thereby maintaining mitochondrial stability, reducing oxidative stress injury, and ultimately improving diabetic cognitive dysfunction.
4.Association between obesity and six minute walk test distance among children and adolescents
ZHANG Hang, NA Xiaona, YUAN Yuxing, WANG Jinghui, CHEN Lanling, CHEN Lijing, LI Tao, LIANG Xiaohua
Chinese Journal of School Health 2026;47(5):619-623
Objective:
To investigate the associations between childhood obesity and performance of six minute walk test (6MWT), providing evidence for exercise tolerance assessment and exercise intervention strategies for children and adolescents.
Methods:
From March 2021 to December 2023, a cohort study was conducted among students recruited from a primary and secondary school in Chongqing, a total of 709 valid samples were included. The 6MWT was used to assess exercise tolerance, with vital signs measured before and after the test. Anthropometric indicators, including height, weight, and waist circumference, were measured using standardized procedures. Generalized additive models (GAM) and restricted cubic spline (RCS) regression were employed to analyze the nonlinear relationships between obesity related indicators and six minute walk distance (6MWD).
Results:
The mean 6MWD of participants was (602.59±70.73)m. GAM showed that after adjusting for confounding factors, body mass index (BMI) and weight had non linear relationships with 6MWD [effective degrees of freedom were 1.55 and 7.13 respectively], and overweight/obesity was associated with a decrease in 6MWD ( β =-18.65) (all P <0.01). Further RCS regression analysis showed that both BMI and weight showed an "inverted U shaped" non linear relationship with 6MWD in the overall population and sex stratified subgroups; the 6MWD of females was lower than that of males, and it showed a significant downward trend with the increase of BMI or weight (all P <0.05).
Conclusion
Body weight and BMI in children and adolescents have an important impact on 6MWD, and obesity in children and adolescents is markedly associated with decline in exercise tolerance.
5.Safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction for elderly hip arthroplasty
Jiangjing WANG ; Na ZHAO ; Xiaona HU ; Na ZHAO
Chinese Journal of Tissue Engineering Research 2026;30(3):612-619
BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P<0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P<0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P<0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P<0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P<0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.
6.The efficacy and safety of zanubrutinib combined with BR regimen in B-cell chronic lymphoproliferative disorder
Danxia LIN ; Zhihong JIANG ; Xiaona WANG ; Yating JIANG ; Yangyang WANG ; Yuxin ZHANG ; Zheng WEI
Chinese Journal of Clinical Medicine 2026;33(4):651-660
Objective To explore the efficacy and safety of a zanubrutinib-based combination regimen as first-line treatment for patients with B-cell chronic lymphoproliferative disorder (B-CLPD). Methods A retrospective analysis was performed on 26 patients with B-CLPD, including indolent B-cell non-Hodgkin lymphoma (B-iNHL), mantle cell lymphoma (MCL), and other unclassifiable B-CLPD, who were newly diagnosed and treated at the Department of Hematology, Zhongshan Hospital (Xiamen), Fudan University between January 2021 and January 2025. Patients were divided into two groups according to the treatment regimen: BR (bendamustine plus rituximab) and ZBR (zanubrutinib combined with BR regimen). Baseline characteristics, treatment responses, and the incidence of treatment-related adverse events (TRAE) were compared between the two groups. Results No statistically significant differences in baseline characteristics were observed between the two groups. All patients completed at least four cycles of treatment. There were no significant differences between the BR and ZBR groups in partial response rate (46.2% vs 53.8%), complete response rate (53.8% vs 15.4%), overall response rate (100.0% vs 84.6%), or TRAE incidence. After the first cycle, the lymphocyte count was higher in the ZBR group than in the BR group (P=0.002); no other statistically significant differences in other hematologic parameters were observed at any treatment cycle. Conclusions In patients with B-iNHL, MCL, and other unclassifiable B-CLPD, the ZBR regimen demonstrates similar safety and response rates to the BR regimen. These findings support further investigation into the clinical value of ZBR as first-line treatment regimen in a limited course for indolent lymphoid malignancies.
7.Current application status and ethical challenges of artificial intelligence in hospice care
Menglan ZHONG ; Miaomiao ZHAO ; Xiaoqi LIU ; Shilin WANG ; Xiaona QI
Chinese Medical Ethics 2026;39(9):1206-1211
ObjectiveTo review the current application status, practical challenges, and ethical issues of artificial intelligence (AI) in the field of hospice care, and to conduct a critical evaluation, with a view to offering a reference for promoting the deep integration of AI into clinical hospice care practice in China. MethodsRelevant domestic and international literature was retrieved to comprehensively analyze the application scenarios of AI in hospice care, the practical barriers encountered, and the ethical controversies, and to explore clinical optimization pathways. ResultsAI is gradually transforming the traditional service model of hospice care, with its applications primarily focusing on patient monitoring, symptom management, predictive analytics, clinical decision support, and other aspects. However, its development faced significant practical constraints and complex ethical challenges. ConclusionWhile AI holds immense potential to enhance the quality of hospice care, its application must be grounded in a core ethical framework centered on dignity, empathy, and patient autonomy. Relevant international explorations have been relatively extensive, whereas domestic studies remain in their infancy. Future research urgently warrants an in-depth exploration of the ethical and practical challenges to find localized integration pathways suited to China’s national context.
8.Oral Herombopag Olamine and subcutaneous recombinant human thrombopoietin after haploidentical hematopoietic stem cell transplantation
Dai KONG ; Xinkai WANG ; Wenhui ZHANG ; Xiaohang PEI ; Cheng LIAN ; Xiaona NIU ; Honggang GUO ; Junwei NIU ; Zunmin ZHU ; Zhongwen LIU
Chinese Journal of Tissue Engineering Research 2025;29(1):1-7
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.
9.The effect of low-energy dietary nutrition intervention combined with exercise on children with simple obesity
Wenjuan ZHANG ; Xiaona LIU ; Zhiwei CAO ; Chaoyang WANG
Clinical Medicine of China 2025;41(6):441-446
Objective:To investigate the effects of a low-energy balanced diet combined with exercise intervention on glycolipid metabolism levels in children with simple obesity.Methods:A prospective randomized controlled trial was performed in this study. Forty children with simple obesity who attended the pediatric outpatient department of Tangshan Maternal and Child Health Care Hospital in Hebei Province from January 2022 to January 2024 were selected and randomly divided into two groups using a random number table: an observation group ( n=22) and a control group ( n=18). No weight-loss products were used by any children in either group. The control group received exercise intervention alone, while the observation group received a combined intervention of exercise and a low-energy balanced diet. The intervention lasted for 8 weeks for both groups. The differences in energy intake during the intervention, as well as body weight, body mass index (BMI), waist circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), and adiponectin levels before and after the intervention were compared between the two groups. Measurement data with normal distribution were expressed as Mean±SD, inter-group comparisons were performed by independent samples t-test, and within-group comparisons before and after treatment were performedby paired t-test. Counting data were expressed as case (%), and inter-group comparisons were performed by χ2 test. Results:The energy intake during the intervention was lower in the observation group than in the control group [(1 450±180) kcal/d vs. (1 780±205) kcal/d, t=-5.35, P<0.001]. Before the intervention, there were no statistically significant differences in body weight, BMI and waist circumference between the two groups (all P>0.05). After 8 weeks of intervention, body weight, BMI, and waist circumference decreased significantly compared to pre-intervention levels in both groups [Control group: (62±12) kg vs. (64±13) kg, (26.4±2.9) kg/m 2 vs. (27.9±3.4) kg/m 2, (85±7) cm vs. (91±7) cm, t=7.23, 9.07, 12.31, respectively, all P<0.001; Observation group: (59±16) kg vs. (65 ± 17) kg, (23.3±4.3) kg/m 2 vs. (28.5±4.1) kg/m 2, (82±9) cm vs. (92±10) cm, t=24.90, 17.93, 21.40, respectively, all P<0.001]. Furthermore, the post-intervention values for body weight, BMI, and waist circumference were significantly lower in the observation group than in the control group ( t=-10.89, -18.92, -5.16, respectively, all P<0.001). Before the intervention, there were no statistically significant differences in FBG, FINS, TG, TC, or adiponectin levels between the two groups (all P>0.05). After 8 weeks of intervention, FBG, FINS, TG, and TC levels decreased significantly compared to pre-intervention levels in both groups [Control group: (4.99±0.26) mmol/L vs. (5.22±0.27) mmol/L, (24±6) mU/L vs. (26±8) mU/L, (1.3±0.5) mmol/L vs. (1.5±0.4) mmol/L, (4.3±0.6) mmol/L vs. (4.5±0.6) mmol/L, t=19.75, 6.69, 7.64, 18.27, respectively, all P<0.001; Observation group: (4.64±0.34) mmol/L vs. (5.31±0.26) mmol/L, (16±5) mU/L vs. (21±10) mU/L, (1.0±0.3) mmol/L vs. (1.4±0.5) mmol/L, (4.0±0.8) mmol/L vs. (4.5±0.8) mmol/L, t=19.66, 8.82, 11.26, 22.68, respectively, all P<0.001]. Adiponectin levels increased significantly in both groups [Control group: (8.0±1.2) mg/L vs. (6.8±1.1) mg/L , t=8.38, P<0.001; Observation group: (8.8±1.1) mg/L vs. (6.8±1.2) mg/L, t=23.78, P<0.001], while the improvements in all these glycolipid metabolic parameters were significantly greater in the observation group than in the control group ( t=3.70, 2.76, 2.42, 2.22,2.14, P=0.001, 0.009, 0.020, 0.027, 0.039). Conclusion:The combined intervention of a low-energy balanced diet and exercise can reduce body weight, blood glucose, and blood lipid levels in obese children, thereby improving their glycolipid metabolism.
10.Clinical and genetic analysis of a pedigree affected with Distal arthrogryposis type 5D due to compound heterozygous variants of ECEL1 gene
Weiyu HU ; Baiyun CHEN ; Yang GAO ; Xiaona WANG ; Yuke LI ; Qianying LI ; Huichun ZHANG ; Chao GAO
Chinese Journal of Medical Genetics 2025;42(3):322-329
Objective:To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. Methods:A child (proband) diagnosed with DA5D and his family members (proband′s parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children′s Hospital in July 2022 due to " multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate′s pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants wer annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children′s Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands.Results:The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c. 1742_c.1743insT and maternal c. 2314T>G, for which the father and sister were carriers of the c. 1742_c.1743insT heterozygous variant and the mother was carrier of c. 2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c. 1742_c.1743insT variant was classified as likely pathogenic (PSV1+ PM2_Supporting), and c. 2314T>G was classified as uncertain (PM2_Supporting+ PM3+ PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c. 2314T>G(p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c. 2314T>G missense mutation resulted in the failure of forming 1 disulfide bond.Conclusion:The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.


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