1.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.
2.Analyses of the epidemiological and clinical characteristics of 21 confirmed monkeypox cases in a district of Chengdu City
Kejun LIAO ; Yawen TIAN ; Shuhua REN ; Yong YUE ; Yunfeng HE ; Caibin YANG ; Xuanji CHEN ; Jiangchao LI ; Wan YANG ; Jie LI
Shanghai Journal of Preventive Medicine 2026;38(3):231-234
ObjectiveTo analyze the epidemiological and clinical characteristics of the 21 confirmed monkeypox cases in a district of Chengdu City, and to provide scientific guidance for the prevention and control of subsequent monkeypox epidemics. MethodsData of confirmed monkeypox cases residing in this district were collected from the Disease Control and Prevention Information System of China. A retrospective descriptive epidemiological analysis was used to analyze the demographic, distributional and behavioral characteristics of the cases. ResultsThe first confirmed case of monkeypox was reported on July 5, 2023. Up to April 30, 2025, a total of 21 confirmed cases of monkeypox have been reported. All cases were male, with a mean age of (30.9±6.2) years. The highest proportion of cases(47.62%) was in the 30‒40 years age group. The majority were men who have sex with men (MSM) population (90.48%, 19/21). The results showed that 19.05% of cases were co-infected with HIV, and 19.05% had a history of syphilis infection. Within 21 days prior to symptom onset, 19 cases (90.48%) self-reported engaging in male-to-male sexual contact, among whom 10 cases (52.63%) reported having taken protective measures, while 9 cases (47.37%) did not take safety precautions. Thirteen cases (61.90%) had no travel history to areas with reported monkeypox cases during the 21 days before symptom onset. The predominant manifestation was exanthem (100%, 21/21), followed by fever (57.14%, 12/21) and lymphadenectasis (47.62%, 10/21). Among febrile cases, 50.00% (6/12) had low-grade fever (37.3‒38.0 ℃). All cases were identified through active medical consultation. The median interval from symptom onset to the first medical visit was 3 (2, 6) days, with a maximum interval of 14 days. The median interval from symptom onset to laboratory confirmation was 7 (5, 9) days. Six cases (28.57%) had two or more visits to the hospital, with bacterial infection being the primary initial diagnosis. ConclusionMonkeypox prevention and control efforts in a district of Chengdu City should prioritize MSM population and young and middle-aged adults aged 30 to <40 years. It is recommended to establish an integrated monkeypox epidemic prevention and control network by leveraging existing HIV/AIDS prevention and control network. Concurrently, accelerating the deployment of the national intelligent infectious disease monitoring and early warning front-end software will strengthen early detection capabilities and be beneficial for the overall effectiveness of epidemic prevention and control efforts.
3.Impacts of combined exposure to PM2.5 and cold spells on non-accidental mortality in Zigong City from 2016 to 2021
Yizhang XIA ; Wei HUANG ; Yang LI ; Yuquan CHEN ; Jie ZHANG ; Haili REN ; Qinglan HUANG ; Xi CHEN
Journal of Environmental and Occupational Medicine 2026;43(1):35-42
Background Amid global climate change, extreme environmental events are occurring more frequently, and it is imperative to investigate the impacts of combined exposure to fine particluate matter (PM2.5) and cold spells (CS) on population mortality. Objective To analyze the association between sequential extreme PM2.5-cold spell (EP-CS) events and non-accidental mortality among residents in Zigong City from 2016 to 2021. Methods Using time-series study design, meteorological data in Zigong were collected from the Zigong Meteorological Bureau for the period from January 1, 2016 to December 31, 2021, while daily non-accidental mortality data were obtained from the mortality surveillance system of the Zigong Center for Disease Control and Prevention. We adopted the percentile method to define extreme PM2.5 events and cold spells. We analyzed the risk effect of EP-CS events on non-accidental mortality among residents in this city and explored the potential amplification of damage resulting from different patterns of consecutive extreme events by using distributed lag nonlinear model (DLNM). We also conducted stratified analyses based on age, gender, education level, and marital status. Results The EP-CS events demonstrated a significant impact on non-accidental mortality among the local residents, exhibiting a certain lagged effect. The effects on the overall residents lasted from lag0 (RR=1.030, 95%CI: 1.013, 1.048) to lag14 (RR=1.035, 95%CI: 1.019, 1.052). Notably, the effects were more pronounced among females, individuals aged 65 years and above, and those who were never married, divorced, or widowed. Different patterns of EP-CS events all associated with adverse effects, the health impact of EP-CS events was significantly greater than that of individual PM2.5 pollution or CS events. The analysis of lag effects across different event patterns revealed that the overall effect of EP-CS events with shorter intervals (0–7 d) had a stronger effect compared to EP-CS with longer intervals (8–14 d), and the RR values of lag14 were 1.034 (95%CI: 1.015, 1.054) and 1.017 (95%CI: 1.007, 1.027), suggesting that the damaging effect of compound events occurring in the short term was more significant. Conclusion All sequential extreme EP-CS events have an impact on non-accidental mortality among residents in this city, with compound events demonstrating a stronger effect. Females, individuals aged ≥65 years, and those who were never married, divorced, or widowed are more sensitive to EP-CS events.
4.An empirical analysis on the association between sarcopenia and all-cause mortality in Chinese elderly residents
Jie KONG ; Shutie LI ; Pandeng HUANG ; Meihong LIU ; Dongjing REN
Shanghai Journal of Preventive Medicine 2025;37(2):148-155
ObjectiveTo investigate the association between variant degree of sarcopenia and all-cause mortality in Chinese elderly residents, and to provide insights into the prevention and control of sarcopenia in the elderly population. MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 and 2020 were analyzed, and a total of 2 792 subjects aged 65 years or older were selected according to the inclusion and exclusion criteria. Univariate and multivariate Cox proportional hazards regression analysis were performed to explore the potential factors influencing all-cause mortality among the elderly in China, and Kaplan-Meier curves were used to visualize the survival of elderly people with variant degree of sarcopenia. Finally, a multiple-adjusted Cox proportional hazards regression model was used to control the confounding factors and explore the association between sarcopenia and all-cause mortality. ResultsBefore adjusting potential covariates, univariate and multivariate Cox proportional hazards regression models showed that 10-year all-cause mortality was significantly associated with variant degree of sarcopenia, namely possible sarcopenia (HR=1.40, 95%CI: 1.1‒1.68, P<0.001), mild-to-moderate sarcopenia (HR=1.49, 95%CI:1.20‒1.86, P<0.001), and severe sarcopenia (HR=1.68, 95%CI: 1.29‒2.19, P<0.001); after adjusting all confounders, 10-year all-cause mortality remained to be significantly associated with variant degree of sarcopenia, including probable sarcopenia (HR=1.38, 95%CI: 1.15‒1.66, P<0.001), mild-to-moderate sarcopenia (HR=1.48, 95%CI: 1.19‒1.84, P<0.001) and severe sarcopenia (HR=1.71, 95%CI: 1.31‒2.23, P<0.001). ConclusionIn Chinese elderly residents, sarcopenia is positively associated with an increased risk of 10-year all-cause mortality, and the progression of sarcopenia is positively associated with an increased risk of death.
5.Current status and latent profile analysis of nurses'caring behaviors in hospice care
Tiantian WANG ; Jie CHEN ; Nanxiao REN ; Yunrong LI ; Liuliu ZHANG ; Bing WU ; Yun ZHAO
Chinese Journal of Nursing 2025;60(1):90-98
Objective To explore the current situation of caring behavior among hospice nurses,and to analyze its latent profiles and population characteristics,so as to provide ideas for targeted interventions.Methods From August to November 2023,convenience sampling was used to select hospice nurses from 22 secondary and above hospitals in Jiangsu Province,Zhejiang Province,Shanghai City,Shandong Province,Anhui Province,Beijing City,Guangdong Province,and Sichuan Province.The demographic characteristics questionnaire,the Caring Behaviors Inventory,the Empathy Ability Scale for Hospice Nurses,and the Practice Environment Scale were used for investigation.Latent profile analysis was conducted based on 24 items of the Caring Behaviors Inventory as explicit indicators,and the influencing factors of different profiles were analyzed through multivariate logistic regression model.Results A total of 420 questionnaires were collected,of which 393 were valid,with a valid questionnaire response rate of 93.57%.The caring behavior of hospice nurses could be divided into 3 latent profiles,namely high level of care-low respect and connection group(49.62%),high to low caring behavior-overall fluctuation group(30.79%),and medium level of care-high knowledge and skills group(19.59%).The results of multivariate logistic regression showed that age,the dimensions of cognitive and emotional empathy in the Empathy Ability Scale for Hospice Nurses and the dimension of nursing foundations for quality of care in the Practice Environment Scale were the influencing factors of the latent profile of hospice nurses'caring behavior(P<0.05).Conclusion There is significant heterogeneity in the caring behavior of hospice nurses.Nursing managers should develop individualized interventions for hospice nurses according to the influencing factors of different latent profiles to improve their level of caring behavior.
6.Effect of abnormal iron metabolism on neurological function in elderly patients with HICH after minimally invasive hematoma clearance
Mingyue LI ; Jie GAO ; Yu YUAN ; Jiaqiang ZHANG ; Jiahui REN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(9):1169-1172
Objective To investigate the effect of abnormal iron metabolism on neurological func-tion in elderly patients with hypertensive intracerebral hemorrhage(HICH)after minimally inva-sive surgical evacuation.Methods A prospective study was conducted on 300 elderly patients with HICH admitted to our hospital from January 2021 to December 2023.At 28 d after surgery,Glas-gow Outcome Scale(GOS)was used to assess the presence of neurological deficits or not,and then they were divided into a good neurological function group(GOS score≥4,175 cases)and a poor neurological function group(GOS score<4,125 cases).Iron deposition in cerebrospinal fluid and serum iron metabolism were compared between the two groups,and the risk factors for neu-rological deterioration were analyzed.Results Compared with the good neurological function group,the poor neurological function group exhibited significantly decreases in Glasgow coma scale(GCS)scores at admission and 7 d after admission and iron ions(P<0.01).Bleeding vo-lume,ferritin,transferrin,and quantitative susceptibility mapping(QSM)values of the thalamus and the hippocampus were obviously increased upon admission(P<0.01).Multi variate logistic regression analysis showed that admission bleeding volume(OR=1.083,95%CI:1.012-1.159,P=0.021),ferritin(OR=1.065,95%CI:1.016-1.116,P=0.009),and thalamic QSM value(OR=4.075,95%CI:2.848-5.830,P=0.000)were risk factors for neurological dysfunction in the HICH patients after minimally invasive surgical treatment,while GCS score(OR=0.430,95%CI:0.259-0.715,P=0.001)and iron ions(OR=0.193,95%CI:0.064-0.581,P=0.003)at 7 d of admission were protective factors.Conclusion Iron deposition in cerebrospinal fluid and abnormal iron metabolism in serum are related to the deterioration of neurological function in eld-erly patients with HICH after minimally invasive hematoma evacuation,and are regarded as po-tential therapeutic targets.
7.The effect of irisin in alleviating mitochondrial damage and oxidative stress in the liver of mice with acute necrotizing pancreatitis
Jie LI ; Yifan REN ; Zhanli WEI ; Yunjie DING ; Xiaopeng LI
Chinese Journal of Pancreatology 2025;25(4):289-293
Objective:To explore the protective effect and mechanism of irisin on liver injury and mitochondrial dysfunction of hepatocytes in mice with acute necrotizing pancreatitis (ANP).Methods:24 mice were randomly divided into the control group, the ANP group, the irisin group and the cilengitide group, with 6 mice in each group. The ANP group was prepared by intraperitoneal injection of 20% L-arginine. The irisin group was injected with 250 μg/kg of irisin intraperitoneally on the basis of the induction of ANP. The cilengitide group was injected with the integrin receptor αVβ3/5 inhibitor cilengitide at 20 mg/kg on the basis of the treatment of the irisin group. The control group was injected with 0.9% normal saline instead of L-arginine. Routine liver histopathological examination and scoring were performed; immunohistochemical staining was used to detect the level of neutrophil infiltration in liver tissue; the ultrastructure changes of mitochondria were observed under transmission electron microscopy; biochemistry was used to detect the ATP content in liver tissue to reflect the changes in mitochondrial function; the total antioxidant capacity of liver tissue was detected by the ferric reducing/antioxidant power (FRAP) method; the DHE fluorescence probe labeling method was used to detect the accumulation degree of oxygen free radicals in liver tissue.Results:The livers of the control group showed no obvious abnormalities. However, the ANP group, the irisin group and the cilengitide group all had liver tissue damage and infiltration of inflammatory cells in the mice. Compared with the ANP group, the liver pathological score, the number of neutrophil infiltration, and the DHE fluorescence staining density in the irisin group were significantly lower [(3.40±0.72) vs (7.26±1.01) points, (14.67±2.51) vs (33.33±3.51) cells, (16.33±5.03) vs (50.33±10.69) cells], while the above indicators in the cilengitide group were all increased [(7.06±1.55) points, (40.33±5.03) cells, (51.00±12.8) cells]; the ATP content [(296.04±64.6), (54.77±18.05), (109.50±56.61), (40.29±11.68) μmol/gprot], and the antioxidant capacity [(0.19±0.01), (0.10±0.01), (0.17±0.02), (0.11±0.01) mmol/g] in the control group, ANP group, irisin group and cilengitide group changed accordingly. The above differences were statistically significant (all P value <0.05). Transmission electron microscopy observation revealed that the abnormal mitophagy of liver cells in the irisin group restored to normal, while the mitophagy abnormality in the cilengitide group was exacerbated. Conclusions:Irisin could improve the disordered mitochondrial function and oxidative stress in liver cells by acting on integrin receptors αVβ3/5, thereby alleviating liver damage and inflammatory responses in ANP mice.
8.Predictive value of nutritional risk related indicators in the prognosis of elderly esophageal squamous cell carcinoma patients undergoing radical radiotherapy
Yajuan WU ; Jie WANG ; Qi LI ; Yaqiong REN ; Fei CHEN ; Xiaomin LI
Cancer Research and Clinic 2025;37(1):19-26
Objective:To investigate the predictive value of nutritional risk related indicators in the prognosis of elderly esophageal squamous cell carcinoma (ESCC) patients undergoing radical radiotherapy.Methods:A retrospective case series study was conducted. The clinical data of ESCC patients aged ≥ 70 years who received radical radiotherapy in Shanxi Province Cancer Hospital from January 2015 to December 2019 were retrospectively analyzed. According to the radiotherapy planning system, the maximum transverse diameter of gross tumor volume of primary tumors (GTVt) and GTVt volume in the esophagus were calculated. The nutritional risk related indicators of ESCC patients before and after radiotherapy were calculated and recorded, including body mass index (BMI), geriatric nutritional risk index (GNRI), and neutrophil-to-lymphocyte ratio (NLR); Kaplan-Meier method was used for survival analysis, and log- rank test was performed; Cox proportional risk model was used to analyze the factors influencing the prognosis of patients. The overall survival (OS), progression-free survival (PFS), short-term efficacy, and adverse reactions of patients with different clinicopathological characteristics were compared.Results:The last follow-up time was 30 December, 2023. The 1-year, 3-year, and 5-year OS rates of 161 elderly patients with ESCC were 79.5%, 33.9%, and 16.1% respectively, with a median OS time of 25.8 months (95% CI: 20.11-31.49 months); the 1-year, 3-year, and 5-year PFS rates were 65.8%, 28.9%, and 14.8%, respectively, with a median PFS time of 20.0 months (95% CI: 16.31-23.69 months). There were statistically significant differences in the median OS time of patients with different age, lesion contrast length, maximum transverse diameter of GTVt, GTVt volume, short-term efficacy, BMI before radiotherapy, BMI after radiotherapy, GNRI after radiotherapy, NLR before radiotherapy, and NLR after radiotherapy (all P < 0.05); there were statistically significant differences in the median PFS time of ESCC patients with different age, maximum transverse diameter of GTVt, GTVt volume, short-term efficacy, BMI before radiotherapy, BMI after radiotherapy, GNRI after radiotherapy, and NLR before radiotherapy (all P <0.05). The results of multivariate Cox regression analysis showed that the maximum transverse diameter of GTVt was an independent influencing factor of the patients' OS ( P < 0.05); GTVt volume, short-term efficacy, GNRI after radiotherapy, and NLR before radiotherapy were independent influencing factors for OS and PFS of the patients (all P < 0.05). Among 161 elderly patients with ESCC, 45 achieved complete remission (CR), 111 achieved partial remission (PR), and 5 achieved stable disease (SD). There were statistically significant differences in the proportions of patients with different maximum transverse diameter of GTVt, GTVt volume, BMI after radiotherapy, GNRI after radiotherapy, and NLR before radiotherapy reaching CR and PR+SD (all P < 0.05). Among the 161 patients, grade 0, 1, 2, and 3 radiation-induced esophagitis (RE) occurred in 59, 54, 42, and 6 cases, respectively during treatment and within 3 months after treatment; among them, ≥ grade 2 RE occurred in 48 cases (29.8%); grade 0, 1, 2, and 3 radiation pneumonitis (RP) occurred in 95, 38, 25, and 3 cases, respectively; among them, ≥ grade 2 RP occurred in 28 cases (17.4%). Conclusions:Nutritional risk related indexes GNRI and NLR may be predictive indicators for the prognosis of elderly ESCC patients undergoing radical radiotherapy.
9.Clinical effect of hysteroscopic pretreatment combined with LNG-IUS in the treatment of adenomyosis
Jie ZHANG ; Xuhua LI ; Ruofei REN ; Hongye LI ; Rujin LI ; Can YANG ; Jing JIANG
Chinese Journal of Reproduction and Contraception 2025;45(5):503-508
Objective:To explore the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) placed in the uterine cavity after transcervical preparation for the treatment of adenomyosis (AM).Methods:A retrospective study analyzed 219 cases of AM patients treated at Department of Obstetrics and Gynaecology, the Second Hospital of Hebei Medical University from March 2022 to February 2023. Among them, 112 cases were treated with LNG-IUS after hysteroscopy due to abnormal uterine bleeding or abnormal uterine echo suggested by gynecological ultrasound, and were recorded as the hysteroscopy+LNG-IUS group; 107 cases without the above manifestations were treated with LNG-IUS alone, and were recorded as the LNG-IUS group. The two groups were observed for dysmenorrhea severity, menstrual volume, endometrial thickness, anemia, serum CA125 levels, uterine volume, and adverse reactions such as abnormal vaginal bleeding and intrauterine contraceptive device displacement or shedding before and 1, 3, 6, and 12 months after treatment.Results:1) Postoperative pathology of hysteroscopy+LNG-IUS group after hysteroscopy included endometrial polyps [39.3% (44/112)], proliferative endometrium [16.1% (18/112)], uterine leiomyoma [11.6% (13/112)], secretory endometrium [8.9% (10/112)], irregular endometrial hyperplasia [6.2% (7/112)], simple hyperplasia [5.4% (6/112)], AM lesions [4.5% (5/112)], and others [8.0% (9/112)]. 2) The degree of dysmenorrhea and menstrual volume, as well as other indicators, improved after treatment in both groups (all P<0.001). 3) When comparing the two groups, the degree of dysmenorrhea, menstrual volume, endometrial thickness, anemia, and serum CA125 at 1, 3, 6, and 12 months of treatment, the hysteroscopy+LNG-IUS group was significantly better than those in the LNG-IUS group (all P<0.05), the difference of uterine volume at 12 months of treatment between the hysteroscopy+LNG-IUS group [(109.76±32.90) cm 3] and the LNG-IUS group [(120.84±31.30) cm 3] was statistically significant ( P=0.011). 4) The cumulative incidence of adverse reactions of the two groups was statistically significant ( P=0.001) between the hysteroscopy+LNG-IUS group [24.1% (27/112)] and the LNG-IUS group [52.3% (56/107), P=0.001]. The hysteroscopy+LNG-IUS group had lower rates of vaginal irregular bleeding [8.0% (9/112)] and ring displacement or shedding [3.6% (4/112)] than those in the LNG-IUS group [23.4% (25/107), P=0.002; 11.2% (12/107), P=0.030]. Conclusion:After treatment with hysteroscopy, the placement of LNG-IUS and the simple intrauterine placement of LNG-IUS both significantly improve the severity of dysmenorrhea, endometrial thickness, anemia, menstrual volume, CA125, and uterine volume. The treatment effect of the LNG-IUS group after hysteroscopy is better and adverse reactions are milder, and it is expected to become the preferred option for the long-term management of conservative treatment of AM.
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 (Ethics 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 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.
Humans
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Amino Acid Metabolism, Inborn Errors/epidemiology*
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Glutaryl-CoA Dehydrogenase/chemistry*
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Infant, Newborn
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Female
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Neonatal Screening/methods*
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Male
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Brain Diseases, Metabolic/epidemiology*
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China/epidemiology*
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Retrospective Studies
;
Mutation
;
Genetic Variation
;
Glutarates


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