OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

The effectiveness and professionalism of hospice care services for children with cancer are of great significance for improving their quality of life and reducing the mental and economic burden on their families. Currently， a relatively complete quality evaluation system for hospice care for children with cancer has been established abroad， while research in this field in China is still in its infancy. By elaborating on the concept and connotation of quality assessment of hospice care for children with cancer in detail， systematically reviewing the research status of quality assessment of hospice care for children with cancer abroad， and addressing the problems and challenges faced by quality assessment of hospice care for children with cancer in China， corresponding inspirations and improvement strategies were proposed， aiming to provide a reference for improving the quality of hospice care for children with cancer in China.

Objective To explore the sex difference in clinical manifestations, echocardiographic features and prognosis of patients with bicuspid aortic valve (BAV) combined with moderate to severe aortic stenosis (AS). Methods The clinical data and echocardiographic follow-up parameters of patients diagnosed with BAV combined with moderate to severe AS at Zhongshan Hospital, Fudan University, from July 30, 2010 to August 1, 2015 were retrospectively collected. The composite endpoint was defined as all-cause mortality or surgical intervention. Kaplan-Meier survival curve and log-rank test were used to compare the risk of composite endpoint events between male and female patients, and Cox regression models were used to analyze independent risk factors for composite endpoint events. Results A total of 144 patients were included, with 69 males and 75 females, and a median age of 60 years. Compared to males, female patients were younger (58[46, 65] years vs 61[54, 67] years, P＝0.046), had a lower proportion of aortic valve calcification (61.1% vs 81.1%, P＝0.009), and a higher peak transvalvular pressure gradient (72[59, 88] mmHg vs 63[55, 72] mmHg, P＝0.002). In terms of left ventricular remodeling types, the proportion of concentric remodeling was higher in females than in males (36.0% vs 15.9%, P＝0.006), while the proportion of eccentric hypertrophy was lower in females than in males (10.7% vs 29.0%, P＝0.006). The proportion of female patients classified as New York Heart Association (NYHA) functional class Ⅲ-Ⅳ was higher than that of males (45.3% vs 17.4%, P＜0.001), and left ventricular ejection fraction was higher in females (68%[65%, 72%] vs 65%[60%, 70%], P＝0.003). With a median follow-up of 49 months, Kaplan-Meier survival analysis showed that the risk of composite endpoint events was higher in females than in males (P＜0.001). Independent risk factors for composite endpoint events included female (HR＝1.74, 95%CI 1.02-2.96, P＝0.042), severe AS (HR＝1.99, 95%CI 1.18-3.36, P＝0.010), and NYHA functional class Ⅲ-Ⅳ (HR＝2.08, 95% CI 1.24-3.47, P＝0.005). Conclusions Sex significantly affects the clinical manifestations, echocardiographic characteristics, and prognosis of patients with BAV combined with moderate to severe AS, suggesting that sex-specific echocardiographic assessment and follow-up monitoring should be conducted for these patients.

OBJECTIVE: To determine the types of genetic variants in six Chinese pedigrees affected with Marfan syndrome (MFS) and analyze their clinical characteristics and molecular pathogenesis. METHODS: Six MFS pedigrees presented at the Taizhou Enze Medical Center (Group) between 2017 and 2022 were selected as the study subjects. Clinical data of pedigrees were retrospectively analyzed. Peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out. Candidate variants of the FBN1 gene were verified by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), pathogenicity of the candidate variants was assessed. AlphaFold3 and PyMOL software were used for homology modeling of the FBN1 protein and analysis of its three-dimensional structure and amino acid sequence conservation. This study was approved by the Medical Ethics Committee of Taizhou Enze Medical Center (Group) (Ethics No. 20231002). RESULTS: Cardiovascular system abnormalities were noted in all pedigrees, ocular abnormalities were present in pedigrees 2 and 5, skeletal system abnormalities were presented in pedigrees 1, and 4 to 6. FBN1 gene mutations were identified in all pedigrees, including c.1957_1958dupGT (p.Asp654fs), c.5014T>A (p.Cys1672Ser), c.8135delC (p.Pro2712fs), c.2302G>T (p.Glu768*), c.3473A>G (p.Glu1158Gly) and c.6169C>T (p.Arg2057*), with each involving a different exon. Four variants were rated as pathogenic, one as likely pathogenic, and one as variant of uncertain significance. Among these, c.5014T>A (p.Cys1672Ser), c.1957_1958dupGT (p.Asp654fs), c.8135delC (p.Pro2712fs), and c.2302G>T (p.Glu768*) were unreported previously. Bioinformatic analysis with SIFT and PolyPhen-2 predicted that the c.5014T>A (p.Cys1672Ser) and c.3473A>G (p.Glu1158Gly) variants were deleterious. Protein homologous sequence alignment analysis revealed that the four novel mutation sites are highly conserved across various species. Homology modeling of the FBN1 protein three-dimensional structure indicated that the six variant sites in the amino acid sequence are all close to hydrogen bonds and may alter the secondary and tertiary structures to varying degrees, thereby confirmed the relationship between the variants and MFS. CONCLUSION Four novel variants of the FBN1 gene have been discovered in this study, which has enriched the mutational and phenotypic spectrum of MFS and provided a basis for disease diagnosis and genetic counseling.
Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China ; East Asian People/genetics* ; Exome Sequencing ; Fibrillin-1/genetics* ; Marfan Syndrome/genetics* ; Mutation ; Pedigree ; Retrospective Studies ; Adipokines

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Hypertrophic cardiomyopathy (HCM) due to a truncating variant of ALPK3 gene. METHODS: A 44-year-old male admitted to Taizhou Hospital of Zhejiang Province on December 29, 2018 was selected as the study subject. Whole-exome sequencing (WES) was carried out, and candidate variant was interpreted by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). For ALPK3 was considered an autosomal recessive gene, the WES results was considered insufficient to explain his phenotype. In April 2023, the proband's WES data were re-analyzed using updated annotation pipelines, and peripheral blood samples were collected from his first-degree relatives (mother and brother) for Sanger sequencing validation. Conservation analysis and protein structural modeling were performed to assess the impact of the variant. Clinical evaluation and genetic counseling were provided to the proband's family members. Relevant literature on ALPK3tv-induced HCM patients were searched in Wanfang Data Knowledge Service Platform, CNKI, and PubMed database using "ALPK3" and "hypertrophic cardiomyopathy" as keywords. Clinical characteristics of HCM patients with heterozygous ALPK3tv variants were summarized and compared with the clinical characteristics of HCM patients with positive sarcomere-associated gene variants (SARC+). This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Ethics No.: K20230314). RESULTS: The proband was a 44-year-old male who was transferred to our institution on December 29, 2018 due to "chest tightness and pain for 6 months, exacerbated for 2 days". Emergency coronary angiography was performed, which led to a preliminary diagnosis of "acute coronary syndrome", and the patient was admitted to the Cardiology Department for treatment. Based on electrocardiogram and echocardiogram findings, the diagnosis was revised as HCM. The patient's condition has stabilized post-coronary angiography, and he was discharged with improved condition. On January 2019, WES was conducted to determine the etiology of the proband's HCM. WES results identified a novel heterozygous c.2156dupC (p.Pro720ThrfsTer53) truncating variant in the ALPK3 gene. At that time, the inheritance pattern could not explain the phenotype. In 2022, a literature indicated that heterozygous ALPK3tv could lead to autosomal dominant HCM. Consequently, in April 2023, the proband's whole-exome data were re-annotated, revealing changes in the transcript and protein versions, with the updated site annotated as ALPK3 (NM_020778.5): c.1550dupC (p.Pro518ThrfsTer53). Sanger sequencing confirmed that the proband's mother and brother also carried this variant. The mother exhibited obstructive HCM, while the brother showed no related phenotype. Bioinformatics analysis demonstrated conservation of this site across multiple species, and the variant has resulted in the loss of a protein domain. Based on ACMG guidelines, the variant was classified as likely pathogenic. Literature review and Bayesian calculation further elevated the pathogenicity rating, indicating that this variant was the cause of HCM in the patient. Literature study revealed distinctions between HCM caused by this variant type and SARC+ HCM. The age of onset among heterozygous ALPK3tv patients was delayed by approximately 10 years compared to SARC+ patients. Both forms of HCM exhibited a male predominance, which was particularly marked in individuals with ALPK3tv. Electrocardiographic left ventricular hypertrophy was more prevalent in heterozygous ALPK3tv patients than in SARC+ patients. The incidence of apical or concentric hypertrophy patterns was higher in heterozygous ALPK3tv patients compared to asymmetric septal hypertrophy, which predominated in SARC+ patients. ALPK3tv patients exhibited lower penetrance and later onset compared to SARC+ patients. A positive correlation between left ventricular wall thickness and age was noted in female patients only. CONCLUSION In this pedigree, the proband has presented with HCM, characterized by echocardiographic evidence of apical left ventricular hypertrophy without significant outflow tract obstruction or extracardiac phenotypes. Although his mother and brother had carried the same heterozygous ALPK3 (NM_020778.5) c.1550dupC (p.Pro518ThrfsTer53), the mother exhibited severe obstructive HCM, while the brother was asymptomatic, suggesting incomplete or age-dependent penetrance within the family. This study has enriched the evidence for the pathogenicity of ALPK3tv among Chinese HCM pedigrees and underscored the importance of periodic literature reviews and genetic re-analysis for unresolved genetic testing results.
Humans ; Male ; Pedigree ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Heterozygote ; Asian People/genetics* ; Exome Sequencing ; Mutation ; China ; Female ; East Asian People

Objective:To systematically evaluate the qualitative research on the decision-making participation experience of parents of terminally ill neonates in neonatal intensive care unit (NICU).Methods:Qualitative research on the decision-making participation experience of parents of terminally ill neonates in NICU were searched from PubMed,Web of Science,Embase,CINAHL,Cochrane Library,Sinomed,China National Knowledge Infrastructure (CNKI),Wanfang,and VIP databases,with the search period from the establishment of the database to August 2023.The quality of the literature was evaluated using the qualitative research quality evaluation standard of the Joanna Briggs Institute (JBI) in Australia,and the literature was summarized using a synthesizing meta-synthesis method.Results:A total of 13 articles of literature were included,as well as 33 results were extracted and classified into 12 new categories and synthesized into 4 integrative outcomes,including participation tendency,role experience,obstacles,and needs on parental decision-making of terminally ill neonates.Conclusion:Parents of terminally ill neonates in NICU face difficult decision-making choices.Medical staff need to work together with parents to determine their ideal role in decision-making and develop personalized communication content.Society,hospitals,and families need to create a supportive social and psychological environment to provide parents with information and emotional support,as well as improve the coping ability of parents of terminally ill neonates in decision-making.

Objective:To explore the effect of cold-strap endoscopic mucosal resection (CS-EMR) in patients with colorectal polyps.Methods:A prospective randomized clinical trial was conducted to 320 selected patients with colorectal polyps diagnosed by Shenzhen Luohu District People′s Hospital from May 2019 to June 2021. The patients were randomly divided into CS-EMR group and HS-EMR group with 160 cases each, using a random number table generated by Excel 2007. The main parameters for statistical analysis contain the process indicators of the two groups of surgical methods, the complete polypectomy rate of patients after surgery, the degree of postoperative pain and the recovery of gastrointestinal function, and the differences in surgical complications.Results:The polypectomy time of CS-EMR group was shorter than that of HS-EMR group: (4.11 ± 1.20) min vs. (4.42 ± 0.98) min, with a statistically significant difference ( P<0.05). The score of visual analogue pain scale (VAS) in CS-EMR group was lower than that in HS-EMR group at 4 and 12 hours after operation: (3.11 ± 0.78) scores vs. (3.48 ± 0.80) scores, (3.38 ± 0.80) scores vs. (3.61 ± 0.92) scores, with a statistically significant difference ( P<0.05). The first anal exhaust time and first defecation time in CS-EMR group were lower than those in HS-EMR group: (27.83 ± 5.01) h vs. (29.66 ± 4.84) h, (43.73 ± 7.80) h vs. (47.28 ± 8.14) h, with a statistically significant difference ( P<0.05). The complications in CS-EMR group were significantly lower than those in HS-EMR group: 5.63% (9/160) vs. 12.50% (20/160), with a statistically significant difference ( P<0.05). Conclusions:The effect of CS-EMR in the treatment of colorectal polyps is not different from that of HS-EMR, but the former has the advantages of short resection time, rapid recovery of gastrointestinal function after operation, light pain and less complications.

Objective:To investigate the cognition and demands of parents of premature infants on family integrated care (FICare) and to provide reference for formulating appropriate FICare programs.Methods:Using the convenient sampling method, a total of 160 parents of premature infants who were followed up in Neonatal Integrated Clinic of Children 's Hospital of Chongqing Medical University from March to July 2021 were selected as the research objects. The parents of premature infants were surveyed using a self-designed Questionnaire on the Cognitive Needs of Parents of Premature Infants on FICare. A total of 160 questionnaires were distributed and 140 valid questionnaires were recovered, with the effective recovery rate of 87.5%. Results:Among 140 parents of premature infants, 135 parents thought FICare was beneficial. 71.9% (97/135) parents chose to participate in 1 to 4 hours of care every day, but 31.1% (42/135) parents lacked confidence in care. Among the FICare providers selected by the parents, 94.1% (127/135) were neonatologists, 88.9% (120/135) were neonatal nurses, 62.2% (84/135) were breast-feeding counselors and 62.2% (84/135) were dietitians. 66.7% (90/135) parents and 58.5% (79/135) parents chose simulation teaching and online course as the ideal training mode. Discharge guidance was the service that parents urgently needed, with a score of 74.5%.Conclusions:Parents of premature infants have multi-level and multi-dimensional demands for FICare, so it is necessary to develop multi-level and all-round FICare services based on parents ' demands in the future to improve the outcomes of families of premature infants.

Objective:To explore the relationship between genotypes and phenotypes in hypertrophic cardiomyopathy(HCM) patients using whole exome sequencing(WES) and three-dimensional speckle-tracking echocardiography(3D-STE).Methods:Twenty patients with apical HCM(ApHCM) and 25 patients with non-apical HCM(non-ApHCM) from June 2018 to January 2019 in Zhongshan Hospital of Fudan University were enrolled. All subjects underwent venous blood sampling and WES. Regular two-dimensional echocardiography was performed to acquire the following parameters: interventricular septum thickness, left ventricular posterior wall thickness, left ventricular end diastolic diameter, left ventricular end systolic diameter, the maximum thickness of left ventricular walls and left ventricular ejection fraction(LVEF). Full volume images were collected and then off-time analyzed with 3D-STE to acquire global longitudinal strain(GLS), global circumferential strain(GCS), twist and torsion. The relationships between above parameters, genotypes and phenotypes of left ventricle were analyzed.Results:Mutations were found in 73% of HCM patients.The two most common genes MYBPC3 and MYH7 accounted for 18% and 15% of mutations respectively. KCNEc.79C>T(p.Arg27Cys) and PRKAG2c.905G>A (p.Arg302Gln) were detected in both ApHCM group and non-ApHCM group. In ApHCM group, 60% of patients carried genetic mutations, which was significantly lower than non-ApHCM group(84%)( P=0.041). Compared with non-ApHCM group, GLS in ApHCM group was significantly higher ( P=0.008). There was no statistical difference of GLS between patients with mutations and without mutations( P=0.068). GLS demonstrated a moderate correlation with morphologic types of HCM(ApHCM and non-ApHCM)( r=0.364, P=0.012). However, there was no correlation between GLS and the condition of mutations( r=0.269, P=0.062). Conclusions:The relationship between genetics and phenotypic expression of HCM appears to be complex and heterogeneous. There are marked differences in gene mutations and systolic functions between ApHCM and non-ApHCM. The value of GLS correlates with the shape of left ventricle but not with genotypes.

Meridian theory plays an important role in the guidance of clinical practice of acupuncture and moxibustion. Since the publication of(), the meridian theory has been developed. In the paper, in view of complex science, the topological properties of acupoint-symptom network were analyzed quantitatively by taking acupoint as node and indication as the connection, such as high clustering coefficient and the small world effect. It was the first time to give the abstraction for the topological proof of the high efficiency information transmission property of acupoint-symptom network meridian system at different times. Its quantitative and digitalized significance was analyzed on the development of meridian theory under the complex scientific background so as to provide a new thought and method for the study of meridian theory and acupuncture modernization.