Objective To identify the clinical features and pathogenic variants in two unrelated families with gna-thodiaphyseal dysplasia(GDD),a rare genetic bone disorder.Methods Facial and limb deformities and skeletal morphology were observed in the probands and their family members.Peripheral blood samples(3-4 mL)were col-lected from the probands and their parents.Genomic DNA was extracted by standard phenol-chloroform method.Whole exome sequencing(WES)was performed to screen for candidate pathogenic gene variants of the probands.PCR-Sanger sequencing was used to validate the candidate pathogenic variants in the probands and their family members.The pathogenic variants responsible for GDD in the target families were determined through co-segregation of the pathogenic variants in the affected families,evolutionary conservation at the mutation sites,population allele frequency analysis and bioinformatics analysis.Results Heterozygous missense variants in the ANO5 gene were identified in both GDD probands.In family 1,the pathogenic variant was c.1 066T＞G located in the exon 11 of the ANO5 gene,while in family 2,the pathogenic variant was c.1 553G＞A located in the exon 15 of the ANO5.These two variants resulted in the substitutions of amino acid cysteine with glycine at position 356(p.Cys356Gly)and amino acid glycine with glutamic acid at position 518(p.Gly518Glu)in the ANO5 protein,respectively.Conclusions This study first identified the pathogenic variant c.1 066T＞G(p.Cys356Gly)in Chinese population,provided important evidence for prediction of disease prognosis and development of potential prenatal genetic diagnosis.

Objective To investigate the risk factors of diabetic retinopathy(DR)in elderly patients with type 2 diabetes mellitus(T2DM)and establish the related prediction model.Methods A total of 426 elderly T2DM patients admitted to the Endocrinology Department of our hospital from January 2021 to March 2023 were enrolled in this study and divided into DR group(n=104)and T2DM group(n=322)according to the occurrence of DR.Results The DM duration≥10 years,hypertension,DPN,smoking,HbA1c,SUA,and high myopia were higher in the DR group than in the T2DM group(P<0.05).Pearson correlation analysis showed that DR was positively correlated with DM duration≥10 years,HbA1c,hypertension,DPN,smoking,SUA and high myopia in elderly T2DM patients(P<0.05).Logistic regression analysis showed that DM duration≥10 years,HbA1c,hypertension,DPN,smoking history,SUA,and high myopia were risk factors for DR in elderly T2DM patients.The analysis of the working characteristic curve of the subjects showed that the area under the curve for the occurrence of DR in elderly T2DM patients was 0.863,with a sensitivity of 78.8%and a specificity of 81.1%.Conclusions The duration of diabetes≥10 years,hypertension,DPN,smoking,HbA1c,SUA and high myopia are risk factors for the occurrence of DR in elderly patients with T2DM.The prediction model of DR has good accuracy in elderly patients with T2DM.

OBJECTIVE: To explore the genetic basis for three Chinese patients with McCune-Albright syndrome (MAS). METHODS: Three children who had respectively presented at Shandong Provincial Hospital in April 2019 and Peking Union Medical College Hospital in August 2020 and May 2021 were selected as the research subjects. Peripheral blood samples of the probands and their family members were taken for the extraction of genomic DNA. Potential variants were screened by whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing of the patients and their family members. RESULTS: The proband from family 1 was found to harbor a heterozygous c.601C>T (p.R201C) missense variant in exon 8 of the GNAS gene, whilst the probands from families 2 and 3 were both found to harbor a heterozygous c.602G>A (p.R201H) missense variant in exon 8 of the GNAS gene. Both variants were known to be pathogenic, and all probands were found to be mosaics for the corresponding variants but with various degrees. CONSLUSION WES can effectively diagnose MAS and other somatic genetic disorders. In this study, the combined WES and Sanger sequencing have verified the degree of mosaicisms of pathogenic variants in the three MAS patients, albeit no apparent correlation was found between the degree of mosaicisms and the phenotype of patients. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the affected families.
Humans ; Mutation ; Fibrous Dysplasia, Polyostotic/genetics* ; East Asian People ; Exons ; Phenotype ; Pedigree

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Congenital heart disease(CHD) in children refers to a group of clinical syndromes in which fetal heart and blood vessels develop abnormally due to various factors, which further affect normal structure and function.The clinical mortality rate of CHD in children ranks the first among non-infectious diseases, which brings great mental pressure and economic burden to the families of children.Most scholars believe that genetic factors and environmental factors alone or both cause CHD.In recent years, with the development of molecular genetics research, the genetic factors of children′s CHD have become the focus of study, mainly including single gene mutation, polygene mutation and chromosome abnormality, these mutations or abnormalities have no absolute one-to-one relationship with clinical phenotypes of CHD in children.Genetic research of CHD can provide theoretical basis for primary prevention of the disease and help prenatal counseling to reduce the occurrence of birth defects.

Kawasaki disease is an acute, self-limited vasculitis, which mainly affects infants and children under the age of 5 years.The main complication is coronary artery disease.Untreated Kawasaki disease leads to varying degrees of coronary artery damage in about 15%-25% of patients.The incidence of Kawasaki disease is increasing year by year, which has become one of the main causes of acquired heart disease in children and has a serious impact on the quality of life for children and adults.The cause of Kawasaki disease is not clear.In recent years, it has become a hot topic for pediatric cardiomyovasculopathy.With the development of molecular biology and gene technology, more and more sensitive biomarkers of Kawasaki disease have been found.This article will review the sensitive biomarkers of Kawasaki disease.

Objective To calculate Z-score for mitral and tricuspid color blood flow widths in normal fetuses and fetuses with dilated coronary sinuses ( CS ) using fetal echocardiography ,and explore the application value of Z-score of the color flow widths of atrioventricular valves in normal fetuses and fetuses with dilated CS . Methods Two hundred and thirty-eight normal fetuses (control group) with a gestational age of 16 to 38 weeks were studied by color Doppler echocardiography . Gestational age ( GA ) ,biparietal diameter (BPD) ,femoral length (FL) ,aortic inner diameter (AOd) ,pulmonary artery diameter (PAd) ,and heart area ( HA) were measured as independent variables ,and mitral and tricuspid valve color flow widths were measured as the dependent variables . Z-score models were established by regression analysis . Thirty fetuses with dilated CS (dilated CS group) from 22 to 33 weeks'gestation were involved . The Z-score of the CS fetus was calculated based on the established Z-score models and were compared with those of the normal fetuses . Results The independent sample t-test showed that there were no significant differences in the Z-scores of the blood flow width of the fetal mitral and tricuspid valves between dilated CS group and control group ( P >0 .05) . Conclusions The simple dilated CS does not affect the mitral valve diastolic blood flow ,so there is no significant effect on the filling of left ventricular blood flow .

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

Objective To validate the performance of six enzymatic glycated albumin reagents and evaluate their clinical application.Methods The performance of six enzymatic glycated albumin reagents(labled as A,B,C,D,E,F) from Beijing Jiuqiang Co, Beijing Lideman Co,Ningbomeikang Co, Beijing Haomai Co, Sichuan Maike Co and Asahi Kasei Co were assessed on Olympus AU5800 automatic biochemistry analyzer.According to the standard of CLSI,the precision,interference and linear correlation of these reagents were assessed.To assess the accuracy of GA% ,we used GA standard material whose value had been assigned using ID-LC/MS method provided by ReCCS.To do the method comparison and determine the consistency of assay, 50 fresh serum samples of T2DM outpatient and 80 fresh serum samples of apparently healthy people in Jan 2016 were tested using six kits.According to the EP28-A3C protocol, the reference range for GA%was validated in 122 apparently healthy individuals undertaking medical examination from January to February 2016 in PUMC.Results The precision,and the ability of anti-interference of the six reagents were good.The accuracy percentage deviation of six reagents was-19.3%-9.2%.The correlation coefficient of domestic reagents A to E and imported reagents F in the determination of GA% was 0.966-0.999, the average absolute bias was 7.0%-10.4%.The coincidence rate of A-E and F in determining abnormal GA% was between 88.5% and 96.9%.The coincidence rate was increased after switching to the reference range for preliminary clinical evaluation.Conclusion Six GA enzymatic kits used in automatic biochemical analyzer have high precision and strong anti-interference ability.Accuracy still needs to be improved.

OBJECTIVETo identify deletion of large fragment in COL1A1/2 genes among patients with osteogenesis imperfecta (OI).

METHODSGenomic DNA was extracted from peripheral blood samples by a standard SDS-proteinase K-phenol/chloroform method. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect gross deletions of the COL1A1/2 genes among 46 patients affected with OI, in whom no mutation was detected in the sequences of the COL1A1/2 genes.

RESULTSHeterozygous deletions of the entire COL1A1 gene and exon 20 of the COL1A2 gene were detected in probands A and B, respectively, and no gross deletion was found in the remaining 44 samples. The MLPA result of proband A was confirmed by fluorescence quantitative PCR (Q-PCR) in his family. A further conjunction point analysis through gap-PCR and DNA sequencing revealed deletion of exons 17 to 23 in the COL1A2 gene, and a 637 bp-insertion from chromosome 5 in the proband B.

CONCLUSIONTwo gross deletions have been found in the genes coding for collagen type I in the Chinese OI population, and the deletion of exons 17 to 23 in the COL1A2 gene is a novel mutation. This work not only has expanded the mutation spectrum of the COL1A1/2 gene, but also provided a support for prenatal genetic diagnosis for the families.

Adolescent ; Adult ; Child ; Child, Preschool ; Collagen Type I ; genetics ; Female ; Gene Deletion ; Humans ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Osteogenesis Imperfecta ; genetics