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.

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.

Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent proteinuria and progressive decline in renal function, and is one of the microvascular complications of diabetes. With the in-depth understanding of the pathogenesis of DN, the role of intestinal flora imbalance in the disease has been found clinically. This suggests that restoring the host′s healthy gut flora may be a means of improving DN. In fact, recent studies have shown that many of the drugs currently used to treat DN affect gut microbiota composition. In this review, intestinal flora is regarded as one of the main factors affecting the development of DN, and DN therapy targeting intestinal flora is summarized to provide new ideas for the diagnosis and treatment of DN.

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.

Cognitive impairment is one of the adverse outcomes of atrial fibrillation, which can affect patients' treatment compliance and effectiveness. Mild cognitive impairment (MCI) is an unstable clinical transitional stage, considered an early signal of dementia, and intervention during this stage is of great significance for cognitive recovery. This article summarizes the definition of MCI and the incidence, evaluation tools, influencing factors, and non-pharmacological intervention strategies of MCI in patients with atrial fibrillation, providing reference for medical and nursing staff to develop MCI prevention measures for patients with atrial fibrillation.

Objective:To explore the clinical treatment of retinoblastoma (RB) after being treated with vitrectomy (PPV) due to misdiagnosis.Methods:A retrospective case study. From July 2015 to July 2018, 5 cases and 5 eyes of RB children diagnosed by pathological examination at the Eye Center of Beijing Tongren Hospital were included in the study. Among them, there were 3 males with 3 eyes and 2 females with 2 eyes; all of them had monocular disease. The average age was 4.8±1.7 years old. At the first visit, the diagnosis was endophthalmitis in 2 eyes (40%, 2/5); vitreous hemorrhage in 3 eyes (60%, 3/5). All were treated with PPV. All children underwent slit lamp microscopy, orbital MRI and CT, and eye color Doppler ultrasound blood flow imaging. If there was no clear extraocular spread, the eyeball removal combined with artificial orbital implantation was performed; if there was clear extraocular spread, the modified orbital content enucleation operation was performed with part of the eyelid preserved. The average follow-up time after surgery was 34.6±7.9 months.Results:Among the 5 eyes, 2 eyes (40%, 2/5) underwent eyeball enucleation combined with stage I artificial orbital implantation, and 3 eyes (60%, 3/5) with modified orbital content enucleation. There were 2 eyes of endogenous type (40%, 2/5), 1 eye of diffuse infiltration type (20%, 1/5), and 2 eyes of mixed type (40%, 2/5). The orbit spread in 3 eyes, the tumor invaded the optic nerve in 1 eye, and regional lymph node metastasis in 2 eyes. All children received systemic chemical therapy (chemotherapy). During the follow-up period, there were no new metastatic diseases and no deaths.Conclusions:After RB misdiagnosis and PPV, surgical treatment should be performed as soon as possible. If there is no clear extraocular spread, eyeball removal or combined stage I orbital implantation should be performed. If there is clear extraocular spread, the orbital contents should be enucleated; Chemotherapy should be combined after surgery.

Objective:To investigate the prevalence, gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency (VLCADD) in newborns in Henan Province.Methods:From January 2013 to December 2019, 867 103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data, biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given, and their growth and development were followed up.Results:Six neonates were diagnosed as VLCADD, and the prevalence of VLCADD in the Henan Province was 1/144 517.A total of 11 mutations in the ACADVL gene were found, including 5 new variants c. 692-2_692-1delAG, c.753-23_753-22del, c.960delG, c.1361A>G, and c. 1955C>T.The newborns were given a high-carbohydrate, low-fat diet, and followed up for 8-56 months.Except for two deaths, all patients had a good outcome. Conclusions:The prevalence of neonatal VLCADD in Henan Province is 1/144 517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.

Objective: To compare the efficacy of induction chemotherapy with or without autologous hematopoietic stem cell transplantation (auto-HSCT) for newly diagnosed young diffuse large B cell lymphoma (DLBCL) patients. Methods: The retrospective study was performed in 90 cases of young patients (≤60 years) with newly diagnosed DLBCL and an age-adjusted International Prognostic Index (aa-IPI) score of 2 or 3. All of them were treated with R-CHOP (32 cases, rituximab combined with CHOP), dose-intensive regimens (DA-EPOCH, Hyper CVAD/MA or ESHAP) combined with or without rituximab (25 cases), and consolidated with up-front auto-HSCT (33 cases), respectively. The efficacy and the potential predictors were evaluated. Results: ①The median age of 90 patients was 43 (18-60) years old. The median follow-up time was 42 (3-110) months. ②The 5-year progression-free survival (PFS) for R-CHOP group, dose-intensive chemotherapy group and auto-HSCT group were (33.5±10.7) %, (55.3±10.1) % and (65.8±13.6) % (P=0.012), the 5-year overall survival (OS) were (49.7±9.0) %, (61.6±10.2) % and (78.6±7.8) % (P=0.035), respectively. There was no significant difference in 5-years PFS and OS between the R-CHOP group and dose-intensive chemotherapy group (P=0.519, P=0.437) compared with that of the dose-intensive chemotherapy group, auto-HSCT group has higher 5-year PFS (P=0.042). ③ When stratified with IPI score, the high-risk group treated with auto-HSCT (26 cases) showed similar 5-years PFS and 5-years OS to those in the low-risk group with chemotherapy alone (12 cases were in R-CHOP group and 8 cases were in dose-intensive chemotherapy group) [5-years PFS were (62.3 ±14.3)%, (58.3 ±18.6)% and (51.4±18.7)%, respectively, P=0.686; 5-years OS were (69.2±13.9)%, (62.5±15.5)% and (58.3±18.6)%, respectively, P=0.592]. ④However, the high-risk group treated with auto-HSCT (26 cases) showed superior 5-years PFS (P=0.002) and 5-years OS (P=0.019) compared to the high-risk group with chemotherapy alone (20 cases were in R-CHOP group and 17 cases were in dose-intensive chemotherapy group) [5-years PFS were (62.3±14.3)%, (41.1±13.5)% and (21.9±11.6)%, respectively; 5-years OS were (69.2±13.9)%, (51.5%±14.0)% and (35.4±13.6)%, respectively]. ⑤In the univariate analysis, as a whole, patients diagnosed with GCB subtype had higher 3-years PFS (P=0.022) and 3-years OS (P=0.037) compared to non-GCB subtype patients; in subgroup analysis, patients diagnosed with GCB subtype had higher 3-years PFS and 3-years OS compared to non-GCB subtype both in R-CHOP group (P=0.030, P=0.041) and dose-intensive chemotherapy group (P=0.044, P=0.047), but not in auto-HSCT group (P=0.199, P=0.093). ⑥In the multivariate analysis, different molecular classification (GCB/non-GCB) was an independent predictor for PFS and OS both in R-CHOP group [HR=0.274 (95% CI 0.094-0.800), P=0.018; HR=0.408 (95% CI 0.164-1.015), P=0.045] and dose-intensive chemotherapy group [HR=0.423 (95% CI 0.043-1.152), P=0.048; HR=5.758 (95% CI 0.882-6.592), P=0.035]. However, there was no significant difference in PFS and OS for auto-HSCT group between GCB/non-GCB patients. Conclusion Induction chemotherapy followed by up-front auto-HSCT has significant effect on efficacy for young and untreated patients with high risk DLBCL. Combined with induction chemotherapy followed by up-front auto-HSCT could improve the prognosis of non-GCB patients.

Objective To explore the relevance between 18F-FDG PET-CT imaging features and laboratory parameters of multiple myeloma (MM) and its prognostic value. Methods The clinical data of 75 MM patients who received 18F-FDG PET-CT examination at the time of initial diagnosis in Tianjin Medical University Cancer Institute & Hospital from September 2008 to August 2016 were retrospectively analyzed, including their clinical features, survival time, PET-CT imaging and laboratory results. The correlation between imaging changes and laboratory results was analyzed. Kaplan-Meier method and log-rank test were used to make survival analysis. Results Of 75 patients, there were 48 patients (64.0%) who had lytic bone lesions everywhere of the bodies, especially in axial skeleton. Twenty-six patients (34.7%) had pathological fracture, which were either rib or spinal pathologic fracture. PET-CT at initial diagnosis showed that the osteolytic lesions were associated with anemia (χ2＝ 0.455, P ＝ 0.032), while pathological fractures were associated with C-reactive protein levels (χ 2 ＝ 0.976, P ＝ 0.007). The existence of pathologic fracture or lytic bone lesions showed no relevance to abnormal cytogenetics, extramedullary lesion, lactic dehydrogenase, albumin or β2-macroglobulin (β2-MG) levels as well as the survival time (all P＞0.05). Twenty-eight patients (37.3%) with