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.

3D printing technology customized medical devices can accurately adapt to the complex anatomical structure of the human body, and have become a new meaning to promote the development of precision medicine. In order to ensure the safety and effectiveness of the clinical use of 3D printed customized medical devices and standardize the management process of such products, a tertiary hospital had started the file-record management of 3D printed customized medical devices since March 2021, covering access approval management, production verification, surgical process management and postoperative traceability management. This practice had achieved standardized management of 3D printed customized medical devices and achieved good results. The 3D printed bone fixation fusion used by the hospital was officially approved as a medical device product registration certificate in March 2023; 109 orthopedic patients recorded the use of 3D printed custom medical devices in 2023, with a significant increase compared to 54 patients in 2022. This practice could provide references for other hospitals to carry out standardized management of the use of customized medical devices. In the future, hospital should further balance regulation and innovation, promote multi-party collaboration, strengthen data integration, ensure data security, and enhance the level of refined management of medical devices.

Objective To investigate the relationship between the mean platelet volume(MPV)to platelet count(PLT)ratio(MPV/PLT),blood urea nitrogen(BUN)to lipoprotein a[Lp(a)]ratio[BUN/Lp(a)]and the prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 106 patients with acute exacerbation of COPD admitted to the hospital from January 2021 to January 2024 were selected as the research objects.According to the prognosis,they were divided into sur-vival group(72 cases)and death group(34 cases).The results of routine laboratory tests,blood lipid and lipo-protein levels were compared between the two groups.Multivariate Logistic regression was used to analyze the influencing factors of death in patients with acute exacerbation of COPD.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of MPV/PLT and BUN/Lp(a)for the prognosis of pa-tients with acute exacerbation of COPD.Results Compared with the survival group,the invasive ventilation rate,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,C reactive protein(CRP),white blood cell count(WBC),MPV,BUN,MPV/PLT and BUN/Lp(a)were significantly increased in the death group(P＜0.05).The non-invasive ventilation rate,lymphocyte count,PLT and Lp(a)levels were signifi-cantly decreased(P＜0.05).Multivariate Logistic regression analysis showed that APACHE Ⅱ score,CRP,WBC,lymphocyte count,MPV,PLT,MPV/PLT,BUN,Lp(a)and BUN/Lp(a)were the influencing factors of death in patients with acute exacerbation of COPD(P＜0.05).ROC curve results showed that the sensitivity and specificity of MPV/PLT combined with BUN/Lp(a)for predicting the prognosis of patients with acute exacerbation of COPD were 88.2％and 84.7％,respectively,and the area under curve was 0.887.Conclusion MPV/PLT and BUN/Lp(a)are closely related to the prognosis of patients with acute exacerbation of COPD.The combination of MPV/PLT and BUN/Lp(a)has a high predictive value for the prognosis of patients.

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 ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

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.

3D printing technology customized medical devices can accurately adapt to the complex anatomical structure of the human body, and have become a new meaning to promote the development of precision medicine. In order to ensure the safety and effectiveness of the clinical use of 3D printed customized medical devices and standardize the management process of such products, a tertiary hospital had started the file-record management of 3D printed customized medical devices since March 2021, covering access approval management, production verification, surgical process management and postoperative traceability management. This practice had achieved standardized management of 3D printed customized medical devices and achieved good results. The 3D printed bone fixation fusion used by the hospital was officially approved as a medical device product registration certificate in March 2023; 109 orthopedic patients recorded the use of 3D printed custom medical devices in 2023, with a significant increase compared to 54 patients in 2022. This practice could provide references for other hospitals to carry out standardized management of the use of customized medical devices. In the future, hospital should further balance regulation and innovation, promote multi-party collaboration, strengthen data integration, ensure data security, and enhance the level of refined management of medical devices.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Objective:To investigate the correlation between preterm infants with brain injury and the proportion of lymphocyte subsets, especially γδ-T cells in the postnatal peripheral blood, and to determine the predictive potential of γδ-T cells in the early peripheral blood in brain injury.Methods:It was a prospective study involving 106 preterm infants with gestational age less than 34 weeks who were delivered in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University from January 1, to June 1, 2021.Relative levels of γδ-T , CD4 + T, CD8 + T, CD3 + T and total lymphocyte subsets in peripheral blood collected within the first 24 hours after birth were measured by flow cytometry.Recruited infants were divided into brain injury group (36 cases) and non-brain injury group (70 cases) according to serial cranial ultrasound and magnetic resonance imaging(MRI) at the corrected gestational age of 36-37 weeks.Differences in general conditions and the proportion of lymphocyte subsets between groups were compared by the t-test or Chi- square test.Patients in brain injury group were further divided into intracranial hemorrhage(ICH) group(8 cases), periventricular leukomalacia (PVL) group (6 cases)and diffuse white matter damage (WMD) group(22 cases). The proportion of lymphocyte subsets among the different groups was compared by One- Way ANOVA, followed by the LSD- t test. Results:The proportion of γδ-T cells in postnatal peripheral blood of preterm infants at 24 hours after birth in brain injury group was significantly lower than that of non-brain injury group [(0.09±0.12)% vs.0.15±0.13)%, t=-2.445, P=0.016]. No significant differences in the proportion of the CD4 + and CD8 + T cell subsets were found between them.Both preterm infants in PVL group and WMD group had a significantly lower proportion of γδ-T cells at 24 hours after birth compared to that of the non-brain injury group [(0.03±0.05)%, (0.07±0.09)% and (0.15±0.13)%], respectively, ( t=-2.190, -2.659, all P<0.05). Conclusions:γδ-T cells in early postnatal peripheral blood may be involved in the development of brain injury in preterm infants and they had early predictive value for preterm infants at high risk of brain injury, especially the leukomalacia and diffuse white matter injury.

Objective:To investigate the effect of peer support-based narrative therapy on postoperative self-image and stigma of patients with head and neck cancer, to provide reference for clinical nursing.Methods:A total of 78 head and neck cancer patients from August 2018 to August 2020 in Fudan University Shanghai Cancer Center were divided into experimental group and control group by random digits table method, each group were 39 cases. The control group was given conventional nursing, while the experimental group implemented support-based narrative therapy on the basis of routine nursing. The intervention time was 4 weeks. The self-image and stigma of the two groups before and after intervention were assessed by Body Image Scale (BIS) and Social Impact Scale (SIS), respectively.Results:Finally, 37 cases were included in the experimental group and 38 cases in the control group. There was no significant difference in BIS, SIS dimension scores and total scores between the two groups before intervention ( P>0.05). After intervention, the emotional demension scores, behavior dimension scores, cognitive dimension scores and total scores in BIS were 4.41 ± 1.04, 1.95 ± 0.51, 3.81 ± 0.63 and 10.16 ± 2.05 in the experimental group, significantly lower than in the control group 5.08 ± 1.08, 2.82 ± 0.60, 5.42 ± 0.76 and 13.32 ± 1.93, the differences were statistically significant ( t values were 2.76-6.86, all P<0.01); the social exclusion scores, internal shame scores, social isolation scores and total stigma scores in SIS were 17.57 ± 2.67, 9.08 ± 1.55, 12.14 ± 3.73 and 46.14 ± 4.95 in the experimental group, significantly lower than in the control group 19.18 ± 3.70, 10.68 ± 1.61, 14.18 ± 3.83 and 51.68 ± 6.09, the differences were statistically significant ( t values were 2.16-4.38, all P<0.05). Conclusions:Peer support-based narrative therapy can effectively alleviate the postoperative self-image problems and stigma of patients with head and neck cancer, which is worthy of clinical application.