OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. METHODS: A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to "multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands. RESULTS: The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T>G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T>G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T>G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T>G missense mutation resulted in the failure of forming 1 disulfide bond. CONCLUSION The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.
Humans ; Pedigree ; Arthrogryposis/genetics* ; Male ; Female ; Heterozygote ; Phenotype ; Mutation ; Child ; Metalloendopeptidases

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. METHODS: A child presented at the Affiliated Children's Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child's clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001). RESULTS: The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c.790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. CONCLUSION The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c.790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.
Humans ; Female ; Child, Preschool ; Osteosclerosis/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Mutation ; Exome Sequencing ; Retrospective Studies ; Tumor Suppressor Proteins

OBJECTIVE: To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). METHODS: A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. RESULTS: The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. CONCLUSION The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
DNA Copy Number Variations ; Heterozygote ; Pedigree ; Phenotype ; RNA Splicing ; Mutation

OBJECTIVE: To define the nature and origin of a chromosomal aberration in a child with unexplained growth and development retardation, and to analyze its genotype-phenotype correlation. METHODS: A child who had presented at the Affiliated Children's Hospital of Zhengzhou University on July 9, 2019 was selected as the study subject. Chromosomal karyotypes of the child and her parents were determined with routine G-banding analysis. Their genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array). RESULTS: Karyotyping analysis combined with SNP array suggested that the chromosomal karyotype of the child was 46,XX,dup(7)(q34q36.3), whilst no karyotypic abnormality was found in either of her parents. SNP array has identified a de novo 20.6 Mb duplication at 7q34q36.3 [arr[hg19] 7q34q36.3(138335828_158923941)×3] in the child. CONCLUSION The partial trisomy 7q carried by the child was rated as a de novo pathogenic variant. SNP array can clarify the nature and origin of chromosomal aberrations. Analysis of the correlation between genotype and phenotype can facilitate the clinical diagnosis and genetic counseling.
Female ; Humans ; Trisomy/genetics* ; Phenotype ; Genotype ; Karyotyping ; Chromosome Banding

Objective:The decision tree Chi-square automatic interactive detection (CHAID) algorithm and binary Logistic regression analysis were used to construct the risk prediction model of premature ovarian failure (POF) in patients with uterine fibroids complicated with hypertension after surgery, and the results of the risk prediction model were compared and analyzed.Methods:Patients with uterine fibroids complicated with hypertension admitted to Taizhou Hospital of Zhejiang Province from Jan. 2019 to Sep. 2022 were retrospectively analyzed as the research objects. CHAID algorithm and Logistic regression analysis were used to establish risk prediction models, respectively. The area under the curve (AUC) of receiver operating characteristic curve (ROC) was used to compare and evaluate the prediction effects of the two models.Results:A total of 860 patients were collected, including 56 patients with premature ovarian function failure after operation, and the incidence of premature ovarian function failure was 6.51%. CHAID method and Logistic regression analysis showed that uterine myoma surgery, hypertension, smoking or passive smoking, family history of premature ovarian failure, sleep status, physical exercise and history of induced curettage were important influencing factors of premature ovarian failure. The accuracy of risk prediction of decision tree model was 88.2%, and the fitting effect of the model was good. The Logistic regression model Hosmer-Leme-show goodness of fit test showed that the model fit was good. The AUC of Logistic regression model was 0.893 (95% CI: 0.862-0.899), and the AUC of decision tree model was 0.882 (95% CI: 0.856-0.899). The predictive value of the two models was moderate, and there was no significant difference between them ( Z=0.254, P>0.05) . Conclusions:The combination of decision tree and Logistic regression model can find the influencing factors of premature ovarian function failure in patients with uterine fibroids complicated with hypertension after operation from different levels, and the relationship between the factors can be more fully understood. The establishment of a risk model for premature ovarian function failure in patients with uterine fibroids complicated with hypertension after surgery can provide a reference for postoperative intervention in patients with uterine fibroids complicated with hypertension, and more effectively help patients actively prevent and slow down the occurrence and development of POF.

Objective:To explore the safety of laparoscopic antegrade modular pancreatosplenectomy (L-RAMPS) through vascular axis approach in the treatment of pancreatic body and tail adenocarcinoma.Methods:The clinical data of 12 patients with pancreatic body and tail adenocarcinoma undergoing L-RAMPS in Department of Hepatobiliary Pancreatic Surgery, Anhui No.2 Provincial People's Hospital from April 2021 to December 2022 were retrospectively analyzed, including eight males and four females, aged (65.8±11.6) years. Data regarding operative time, intraoperative blood loss, anal exhaust time, postoperative hospital stay, lymph node dissection, pathology, and postoperative complications, and survival were analyzed.Results:The procedures were successfully completed in all 12 patients. Eight patients underwent anterior L-RAMPS, four underwent posterior L-RAMPS. In one patient laparoscopic procedure was almost completed, but eventually conversed to open surgery due to vascular invasion. The operative time was (221.5±21.7) min, the intraoperative blood loss was (224.1±125.3) ml, the anal exhaust time was (3.5±1.0) d, and the postoperative hospital stay was (10.0±3.9) d. All patients underwent R 0 resection, and (15.1±3.7) lymph nodes were dissected. Positive lymph nodes were confirmed in four patients. Six patients had postoperative pancreatic fistula. The patients had been followed up for a median time of 9.5 (3.2-15.0) months, and three patients died. Conclusion:The vascular axis approach could optimize the L-RAMPS surgical approach and improve surgical safety.

ObjectiveTo investigate the effect of entecavir (ETV) alone or combined with interferon (IFN) on the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for 409 patients with CHB who were admitted to Beijing Ditan Hospital from January 2008 to December 2014, and according to their antiviral therapy, they were divided into ETV+IFN group with 169 patients (IFN treatment for ≥6 months) and ETV group with 240 patients (ETV treatment for ≥12 months). The patients were followed up to June 2019, and the development of HCC was the outcome event. The Mann-Whitney U test was used for comparison of continuous variables between two groups, and the chi-square test was used for comparison of categorical variables between two groups. The propensity score matching (PSM) method was used to eliminate baseline differences between groups, the Kaplan-Meier method and the log-rank test were used to compare the incidence rate of HCC between groups, and the Cox proportional-hazards regression model analysis was used to investigate the risk factors for the development of HCC. ResultsThe median follow-up time in this study was 5.4 years (IQR: 4.9-7.9). There was no significant difference in the cumulative incidence rate of HCC between the two groups before and after PSM (before PSM: 1.2% vs 2.8%, χ2=1.423, P=0.233; after PSM: 1.7% vs 4.1%, χ2=1.676, P=0.195), and the subgroup analysis also showed no significant difference in the cumulative incidence rate of HCC between the two groups in the non-high risk population (1.3% vs 1.5%, χ2=0.335, P=0.563). The Cox proportional-hazards regression model showed that age was an independent risk factor for HCC (hazard ratio=1.107, 95% confidence interval: 1.005-1.219, P=0.038). ConclusionFor CHB patients without a high risk of cancer, compared with ETV monotherapy, ETV combined with IFN for at least 6 months does not significantly reduce the risk of HCC.

Clinically, hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of morbidity and mortality. Hepatitis B virus infection is the main cause of hepatocellular carcinoma in China and it is a serious threat to people's health. Antiviral drugs such as nucleos(t)ide analogues and interferon can inhibit viral replication and liver fibrosis progression and reduce the occurrence of hepatitis B-related HCC. This article reviews the effects of different antiviral therapy on the occurrence of hepatitis B-related hepatocellular carcinoma in recent years.

Objective : To explore the effects of“radiotherapy assistant”application on lung cancer patients who receive radiotherapy. Methods : A total of 120 patients with lung cancer who received radiotherapy in Hangzhou Cancer Hospital from March to September 2017 were recruited and randomly divided into a control group and an experimental group. The patients in the control group received the routine health education,while the ones in the experimental group performed the“radiotherapy assistant”application focused on interactive guidance. Before and after the intervention,the scores of treatment-nursing compliance and self-management efficacy between the two groups were compared. Results : After the intervention,the compliance scores of radiotherapy treatment,health behaviors,regular review,moderate exercise,medication and diets in the experimental group were 2.77±0.43,2.67±0.51,2.68±0.50,2.45±0.75,2.77±0.43 and 2.65±0.55;the ones in the control group were 2.62±0.49,2.42±0.59,2.55±0.50,2.37±0.64,2.67±0.48 and 2.37±0.69. The scores of the six items of compliance in the two groups were all improved compared to the ones before the intervention,but the interaction between the groups and intervention time was not statistically significant（P>0.05）. The scores of positive attitude,self-decompression,self-decision and total self- management efficacy in the experimental group were 52.48±7.69,10.51±3.31,36.88±6.15 and 97.62±12.87,respectively;the ones in the control group were 37.38±10.44,5.70±1.51,27.58±9.41,and 92.17±11.19. The scores of the two groups were all improved compared to the ones before the intervention,and the ranges of the scores improved in the experimental group were wider than those in the control group. Conclusion The“radiotherapy assistant”application can significantly improve the self-management efficacy of patients who receive the lung cancer radiotherapy,but its effect on the improvement of treatment compliance requires long-term intervention to verify.

To date, the efficacy of radical surgery (RS) versus conservative surgery (CS) for liver hydatid cysts (LHC) remains controversial. This meta-analysis was conducted to compare the two interventions. PubMed, Embase, and Web of Science were searched from their inceptions until June 2016. Meta-analysis was performed using STATA 12.0 software. We identified 19 eligible studies from 10 countries by retrieval. In total, 1853 LHC patients who received RS were compared with 2274 patients treated by CS. The risk of postoperative overall complication, biliary fistula, and recurrence was significantly lower, and operation time was significantly longer in the RS group. However, no statistically significant differences were found in terms of mortality risk and the duration of hospital stay between RS and CS. No significant publication biases were observed in all the above analyses. In conclusion, RS reduces the rates of postoperative complications and recurrence, whereas no trend toward such a reduction in mortality was observed in LHC patients.
Echinococcosis, Hepatic ; mortality ; surgery ; Humans ; Length of Stay ; statistics & numerical data ; Operative Time ; Postoperative Complications ; epidemiology ; Recurrence ; Treatment Outcome