1.Safety and efficacy of the Neuroform EZ stent in treating severe symptomatic intracranial atherosclerotic stenosis
Ziang CHEN ; Wenbo LIU ; Dehua GUO ; Yanyan HE ; Mengyue LIU ; Yang ZHAO ; Yukuan PANG ; Tianxiao LI ; Yingkun HE
Chinese Journal of Cerebrovascular Diseases 2025;22(10):721-730
Objective To evaluate the safety and efficacy of the Neuroform EZ self expanding stent for severe symptomatic intracranial atherosclerotic stenosis(sICAS).Methods Retrospectively enrolled consecutive patients with severe sICAS who underwent percutaneous transluminal angioplasty and stenting(PTAS)with a Neuroform EZ stent in the Department of Cerebrovascular Disease,Henan Provincial People's Hospital,from March 2020 to December 2022.Baseline demographic and clinical data were collected,including age,sex,hypertension,diabetes mellitus,coronary artery disease,dyslipidemia,hyperhomocysteinemia,transient ischemic attack(TIA)and ischemic stroke,smoking history,modified Rankin scale(mRS)score at admission,and National Institutes of Health stroke scale(NIHSS)score.Preoperative imaging data included target vessel(basilar artery,intracranial segment of the internal carotid artery,middle cerebral artery,and intracranial vertebral artery),lesion length,degree of stenosis,and vascular morphology according to the Mori classification(type A,lesion length<5 mm with concentric or moderately eccentric stenosis;type B,lesion length<10 mm with severely eccentric stenosis;type C,lesion length>10 mm or arterial angulation>90°).Technical success was defined as accurate delivery and deployment of the stent with complete coverage of the target lesion and immediate post deployment residual stenosis<50%.Postoperative head CT was performed to detect intracranial hemorrhage.Periprocedural complications were recorded,including intracranial hemorrhage,arterial dissection,in stent thrombosis,and perforator occlusion occurring intraoperatively within 72 hours after the procedure.At one-month post-operation,patients were seen through outpatient follow-up for TIA,hemorrhagic or ischemic stroke,and all cause death.At 6 months after surgery,DSA or CT angiography(CTA)was performed to assess in stent restenosis(ISR,defined as>50%stenosis within the stent or within5mm of its edges,or>20%luminal loss).At 1 and 2 years postoperatively,ipsilateral ischemic stroke or TIA recurrence was assessed by outpatient visit or telephone follow up.Results A total of 76 patients with severe sICAS underwent PTAS with a Neuroform EZ stent(56 males,20 females,age 47-80 years,with a mean age of[61±10]years).(1)Within all patients enrolled,40 had middle cerebral artery,16 with basilar artery,6 with intracranial vertebral artery and 14 with intracranial internal carotid artery.The preprocedural lesion length was 2-15 mm,with a mean length of(6.2±2.5)mm,and stenosis severity was70%-99%,the mean severity was(83.2±6.9)%,with Mori type B being the most common type(57.9%[44/76]).(2)PTAS was successfully completed on all patients(technical success 100%).Pre dilation with a conventional balloon was performed in all cases(using balloon with diameter of 1.5-3.5mm,and stent with diameter of 2.5-4.5 mm and length of 15-30 mm).Immediate post procedural residual stenosis was(17.4±9.0)%,significantly lower than baseline(t=52.9,P<0.05),with a mean difference of 65.8%(95%CI63.3%-68.3%).(3)Among all 76patients,one patient developed a flow limiting dissection post balloon angioplasty,which recovered after stent deployment.One patient with basilar artery stenosis experienced recurrent ischemic stroke at 5-day postoperatively,presenting with right sided weakness and coughing on liquids.Imaging showed an acute infarct in the left pons,considered perforator occlusion.The overall periprocedural complication rate was 2.6%(2/76).(4)No deaths occurred within 30 days after surgery.Sixty nine patients(90.8%)underwent 6 month imaging follow up with DSA(52 cases)or CTA(17 cases).ISR occurred in 12 patients(17.4%),including 6 asymptomatic and 6symptomatic cases.The ipsilateral ischemic stroke recurrence rate was 6.6%(5/76)at1 year and13.2%(10/76)at2years.Conclusions Neuroform EZstent assisted PTASappears safe and feasible for the treatment of severe sICAS.The long term effectiveness requires confirmation in large,multicenter,prospective studies.
2.Incidence rates and high-risk factors of different typies of patient-ventilator asynchrony under assisted mechanical ventilation
Qimin CHEN ; Jiaoyangzi LIU ; Jia YUAN ; Dehua HE ; Ming LIU ; Caixue PAN ; Ying LIU ; Yan TANG ; Xu LIU ; Xianjun CHEN ; Chuan XIAO ; Shuwen LI ; Wei LI ; Daixiu GAO ; Feng SHEN
The Journal of Practical Medicine 2025;41(10):1509-1516
Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10~15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95%(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76%(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58%,57/453),double triggering(11.92%,54/453),ineffective triggering(9.49%,43/453),flow starvation(5.30%,24/453),and exhalation flow limitation(1.77%,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7%in volume-assist/control ventilation(V-A/C),38.1%in pressure-assist/control ventilation(P-A/C),42.9%in synchronized intermittent mandatory ventilation(SIMV),and 16.7%in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95%CI:2.140~10.263,P<0.001;P-A/C:OR=2.922,95%CI:1.489~5.734,P=0.002;SIMV:OR=4.682,95%CI:1.758~12.466,P=0.002]and actual respiratory rate(OR=1.07,95%CI:1.016~1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.
3.Long-term outcomes of endoscopic papillectomy for duodenal papillary adenomas and risk factors for incomplete resection
Kun LIU ; Xintong ZHANG ; Xiang ZHANG ; Muhan NI ; Peng YAN ; Bei TANG ; Wenting LI ; Dan XU ; Wen LI ; Pin WANG ; Dehua TANG ; Xiaoping ZOU ; Lei WANG ; Shanshan SHEN
Chinese Journal of Digestive Endoscopy 2025;42(7):545-551
Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.
4.Research and application of a new deep learning based strategy for platelet histogram review
Enming ZHANG ; Chao YANG ; Xianchun CHEN ; Yan LIN ; Taixue AN ; Haixia LI ; Yongjian HE ; Zhiwei LIU ; Limei FENG ; Wanying LIN ; Tie XIONG ; Kai QIU ; Ya GAO ; Lizhu HUANG ; Jing HE ; Chunyan WANG ; Dehua SUN ; Bo SITU ; Lei ZHENG
Chinese Journal of Laboratory Medicine 2025;48(9):1201-1206
Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.
5.Safety and efficacy of the Neuroform EZ stent in treating severe symptomatic intracranial atherosclerotic stenosis
Ziang CHEN ; Wenbo LIU ; Dehua GUO ; Yanyan HE ; Mengyue LIU ; Yang ZHAO ; Yukuan PANG ; Tianxiao LI ; Yingkun HE
Chinese Journal of Cerebrovascular Diseases 2025;22(10):721-730
Objective To evaluate the safety and efficacy of the Neuroform EZ self expanding stent for severe symptomatic intracranial atherosclerotic stenosis(sICAS).Methods Retrospectively enrolled consecutive patients with severe sICAS who underwent percutaneous transluminal angioplasty and stenting(PTAS)with a Neuroform EZ stent in the Department of Cerebrovascular Disease,Henan Provincial People's Hospital,from March 2020 to December 2022.Baseline demographic and clinical data were collected,including age,sex,hypertension,diabetes mellitus,coronary artery disease,dyslipidemia,hyperhomocysteinemia,transient ischemic attack(TIA)and ischemic stroke,smoking history,modified Rankin scale(mRS)score at admission,and National Institutes of Health stroke scale(NIHSS)score.Preoperative imaging data included target vessel(basilar artery,intracranial segment of the internal carotid artery,middle cerebral artery,and intracranial vertebral artery),lesion length,degree of stenosis,and vascular morphology according to the Mori classification(type A,lesion length<5 mm with concentric or moderately eccentric stenosis;type B,lesion length<10 mm with severely eccentric stenosis;type C,lesion length>10 mm or arterial angulation>90°).Technical success was defined as accurate delivery and deployment of the stent with complete coverage of the target lesion and immediate post deployment residual stenosis<50%.Postoperative head CT was performed to detect intracranial hemorrhage.Periprocedural complications were recorded,including intracranial hemorrhage,arterial dissection,in stent thrombosis,and perforator occlusion occurring intraoperatively within 72 hours after the procedure.At one-month post-operation,patients were seen through outpatient follow-up for TIA,hemorrhagic or ischemic stroke,and all cause death.At 6 months after surgery,DSA or CT angiography(CTA)was performed to assess in stent restenosis(ISR,defined as>50%stenosis within the stent or within5mm of its edges,or>20%luminal loss).At 1 and 2 years postoperatively,ipsilateral ischemic stroke or TIA recurrence was assessed by outpatient visit or telephone follow up.Results A total of 76 patients with severe sICAS underwent PTAS with a Neuroform EZ stent(56 males,20 females,age 47-80 years,with a mean age of[61±10]years).(1)Within all patients enrolled,40 had middle cerebral artery,16 with basilar artery,6 with intracranial vertebral artery and 14 with intracranial internal carotid artery.The preprocedural lesion length was 2-15 mm,with a mean length of(6.2±2.5)mm,and stenosis severity was70%-99%,the mean severity was(83.2±6.9)%,with Mori type B being the most common type(57.9%[44/76]).(2)PTAS was successfully completed on all patients(technical success 100%).Pre dilation with a conventional balloon was performed in all cases(using balloon with diameter of 1.5-3.5mm,and stent with diameter of 2.5-4.5 mm and length of 15-30 mm).Immediate post procedural residual stenosis was(17.4±9.0)%,significantly lower than baseline(t=52.9,P<0.05),with a mean difference of 65.8%(95%CI63.3%-68.3%).(3)Among all 76patients,one patient developed a flow limiting dissection post balloon angioplasty,which recovered after stent deployment.One patient with basilar artery stenosis experienced recurrent ischemic stroke at 5-day postoperatively,presenting with right sided weakness and coughing on liquids.Imaging showed an acute infarct in the left pons,considered perforator occlusion.The overall periprocedural complication rate was 2.6%(2/76).(4)No deaths occurred within 30 days after surgery.Sixty nine patients(90.8%)underwent 6 month imaging follow up with DSA(52 cases)or CTA(17 cases).ISR occurred in 12 patients(17.4%),including 6 asymptomatic and 6symptomatic cases.The ipsilateral ischemic stroke recurrence rate was 6.6%(5/76)at1 year and13.2%(10/76)at2years.Conclusions Neuroform EZstent assisted PTASappears safe and feasible for the treatment of severe sICAS.The long term effectiveness requires confirmation in large,multicenter,prospective studies.
6.Cross-cultural adaptation, reliability, and validity of the Birth Satisfaction Scale-Revised
Xiaoying ZHONG ; Martin Colin R. ; Xixi LI ; Xiujing GUO ; Dehua LI ; Bangjun WANG ; Xiuping LIU
Chinese Journal of Practical Nursing 2025;41(17):1330-1337
Objective:To translate the Birth Satisfaction Scale-Revised (BSS-R) into Chinese and assesses the psychometric properties of this tool.Methods:Following the Beaton cross-cultural adaptation guidelines, the Chinese version of BSS-R was formed through forward translation, back translation, expert consultation, and pre-testing. The present study was conducted in a sample of 347 women took part between 6-8 weeks postpartum, from the postpartum clinics of two tertiary hospitals in Sichuan province.Results:Totally 340 questionnaires were effectively collected with a majority of respondents aged 30-39 accounting for 64.7% of the total. The Chinese version of BSS-R comprises 10 items, which were classified into three domains as stress experienced during labour, women′s personal attributes, and quality of care provision. The Cronbach α coefficient was 0.745 for the total scale and ranged from 0.523 to 0.738 for sub-scales. The split-half reliability was 0.746 for the total scale, and ranged from 0.523 to 0.733 for sub-scales. Exploratory factor analysis revealed the presence of three components with eigen values greater than 1, explaining a total variance of 58.868%. The fit indices showed that the original correlated three factor model of Chinese version of BSS-R was adequate.Conclusions:The Chinese version of BSS-R can be considered a clear, easily understandable and convenient tool for assessing the women′s birth satisfaction in Chinese cultural context.
7.Analysis of the timeliness of anti-retroviral therapy among newly reported HIV/AIDS cases
SU Dehua ; CHEN Xiangyang ; LI Jun ; ZHAO Lina ; ZHANG Hemei ; ZHU Tingting ; HU Wenxue ; LAI Jiangyi
Journal of Preventive Medicine 2025;37(8):804-808
Objective:
To analyze the timeliness of antir-etroviral therapy (ART) and its influencing factors among newly reported HIV/AIDS cases in Wenzhou City, Zhejiang Province from 2016 to 2023, so as to provide a reference for improving the ART effect of HIV/AIDS cases.
Methods:
Newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were selected as the research subjects. Demographic information, the situation of the first CD4+ T lymphocyte (CD4 cell) test, baseline CD4 cell count, and ART situation were collected through the Chinese Disease Prevention and Control Information System. The timely rate of ART was analyzed, and the influencing factors for timely ART among HIV/AIDS cases were analyzed using a multivariable logistic regression model.
Results:
A total of 4 500 newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were included, among which 3 679 were males, accounting for 81.76%, and 821 were females, accounting for 18.24%. The median age was 46.24 (interquartile range, 26.23) years. Among these cases, 3 606 received timely ART, with a timely rate of 80.13%. The timely rate of ART increased from 57.54% in 2016 to 91.97% in 2023 (P<0.05). Multivariable logistic regression analysis showed that unmarried/divorced/widowed (OR=0.769, 95%CI: 0.641-0.922), detainees (OR=0.492, 95%CI: 0.269-0.900), untimely first CD4 cell test (OR=0.278, 95%CI: 0.234-0.330), baseline CD4 cell count ≥200 cells/µL (OR=0.709, 95%CI: 0.595-0.843) or undetected (OR=0.131, 95%CI: 0.080-0.213) were associated with a lower timeliness for ART among HIV/AIDS cases.
Conclusion
From 2016 to 2023, the timely rate of ART among newly reported HIV/AIDS cases in Wenzhou City showed an upward trend, which was mainly affected by marital status, case source, timeliness of the first CD4 cell test, and baseline CD4 cell count.
8.Research progress on the dual role of tumor-associated neutrophil heterogeneity in tumor microenvironment
Li RONG ; Li YIQING ; Yan YAPING ; Zhao DEHUA ; Bu ZONGYAO ; Ge XIAOJUN
Chinese Journal of Clinical Oncology 2025;52(18):963-967
Tumor-associated neutrophils(TAN)are key components of the tumor microenvironment(TME)that exert dual regulatory roles in tumor progression through highly heterogeneous functional phenotypes.This review systematically addresses the dynamic balance of TAN in pro-tumor and anti-tumor mechanisms:TAN can directly kill tumor cells or collaborate with immune cells to activate anti-tumor re-sponses;however,in contrast,they can accelerate tumor progression by promoting angiogenesis,remodeling the extracellular matrix,and mediating immune evasion.Studies have shown that the functional heterogeneity of TAN is precisely regulated by multiple signaling net-works within the TME,and that the plasticity transformation of different subsets directly influences tumor progression.In-depth analyses of TAN subset characteristics,transformation mechanisms,and their clinical relevance will provide a theoretical basis for the development of inhibitors targeting pro-tumor neutrophils as well as advance the establishment of precise patient selection strategies for TAN subtype-based immunotherapy.
9.Survey on the current status and analysis of influencing factors of health management cognition and medical care behaviors of active health-oriented community residents in Shanghai
Wanyu LI ; Xiaolan ZHANG ; Hua JIN ; Fen XU ; Dehua YU
Chinese Journal of General Practitioners 2025;24(3):270-278
Objective:To understand the current status of health management cognition and healthcare behaviors of community residents in Shanghai, and to analyze their related influencing factors, in order to promote the optimization of proactive health-oriented health management strategies.Methods:This study was a cross-sectional survey. From February to May 2023, 1-4 community health service centers were randomly selected from each administrative district in Shanghai by stratified random sampling using the random number table method. Ultimately, 28 community health service centers were selected as research sites. The research team then used convenience sampling method to select at least 50 patients as research subjects from those visiting each selected center. A total of 1 436 community residents were included in this study in the form of on-site completion of questionnaire stars, and the study covered the residents′ level of health management cognition, chronic disease management, intention to seek medical care, physical examination behavior, and handling of abnormal values. Multiple regression analysis was used to assess the correlation between health management cognition and medical consultation behavior and their influencing factors.Results:The results of the health management awareness survey showed that 827 residents (57.6%) had a relatively high level of awareness. Among the 755 residents (52.6%) with chronic diseases, the proportion of self-assessed stable control was significantly higher in the high-cognition group (318 (76.0%)) than that in the low-cognition group (223 (66.2%)), and the difference was statistically significant ( χ2=9.01, P=0.003). Multiple regression analysis showed that females ( OR=1.293, 95% CI: 1.028-1.627),≤44 years old and 45-59 years old ( OR=2.328, 95% CI: 1.648-2.328; OR=1.351, 95% CI: 1.035-1.763), bachelor′s degree or above ( OR=1.784, 95% CI: 1.256-2.534), living in suburban area ( OR=1.577, 95% CI: 1.235-2.014), use of employee health insurance and resident health insurance ( OR=2.294, 95% CI: 1.629-3.232; OR=1.628, 95% CI: 1.149-2.306), suffering from a chronic disease ( OR=3.110, 95% CI: 1.918-5.042), and having a contracted family doctor ( OR=1.870, 95% CI: 1.431-2.442) were all positive correlation with health management perception(all P<0.05). In terms of health care behavior, 908 (63.2%) residents showed a high active intention to seek medical care, and 906 (63.1%) and 796 (55.4%) residents showed active participation in medical check-ups and timely handling of medical check-up abnormal values, respectively. Residents in the high awareness group were significantly better than those in the low awareness group in terms of intention to seek medical care ( χ2=33.26), mode of medical checkups ( χ2=110.71), frequency of medical checkups ( χ2=45.37), and the way of dealing with abnormal values after medical checkups ( χ2=93.14), with the difference being statistically significant(all P<0.05). The results of linear regression analysis of the factors influencing the medical behavior of community residents showed that age≤44 and 45-59 ( B=0.479, 0.167), high school and specialist versus bachelor′s degree and above ( B=0.465, 0.739), use of employee medical insurance and residents′ health insurance ( B=0.604, 0.420), the number of current chronic diseases 1 ( B=0.919) and contracted family doctor ( B=0.134) of community residents′ health care behaviors are better (all P<0.05). Conclusions:The level of community residents′ health management cognition needs to be improved, and high health management cognition can significantly promote proactive healthcare-seeking behavior. However, residents′ medical behavior is still influenced by multidimensional factors. Signing a contract with a family doctor is significantly associated with high cognition and quality healthcare behaviors.
10.Newborn screening, clinical characteristics and genetic variant analysis of Glutaric acidemia type I in Henan Province
Xinyun ZHU ; Dehua ZHAO ; Yizhuo XU ; Jie ZHANG ; Xiaole LI ; Suna LIU ; Min NI ; Yihui REN ; Chong ZHANG ; Yaqing GUO ; Junqi LI ; Shubo LYU ; Chenlu JIA ; Ying SHI
Chinese Journal of Medical Genetics 2025;42(6):641-647
Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.


Result Analysis
Print
Save
E-mail