Objective:To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS).Methods:A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children′s Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis method. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the " ACMG guidelines" ). This study has been approved by the Medical Ethics Committee of Hangzhou Children′s Hospital (Ethics No. 2021-06).Results:The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears.The results of Trio-WES showed that he has harbored a NF1 gene c. 3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene child was associated with NFNS, which was an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+ PM2+ PP3+ PP2). No pathogenic variant in genes associated with Noonan syndrome, such as those in PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. Conclusion:The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c. 3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS). METHODS: A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children's Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio-whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the "ACMG guidelines"). This study has been approved by the Medical Ethics Committee of Hangzhou Children's Hospital (Ethics No. 2021-06). RESULTS: The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears. The results of Trio-WES showed that the he had harbored the NF1 gene c.3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene was associated with NFNS, which has an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+PM2+PP3+PP2). No pathogenic variant in genes associated with Noonan syndrome, such as PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. CONCLUSION The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c.3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.
Child ; Humans ; Male ; Exome Sequencing ; Mutation ; Neurofibromatosis 1/genetics* ; Neurofibromin 1/genetics* ; Noonan Syndrome/genetics*

Objective:To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS).Methods:A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children′s Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis method. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the " ACMG guidelines" ). This study has been approved by the Medical Ethics Committee of Hangzhou Children′s Hospital (Ethics No. 2021-06).Results:The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears.The results of Trio-WES showed that he has harbored a NF1 gene c. 3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene child was associated with NFNS, which was an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+ PM2+ PP3+ PP2). No pathogenic variant in genes associated with Noonan syndrome, such as those in PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. Conclusion:The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c. 3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.

Objective To observe the effect of pressure-controlled ventilation volume-guaranteed(PCV-VG)mode on respiratory mechanics,lung injury markers and postoperative pulmonary complications(PPCs)in thoracoscopic patients.Methods Fifty-nine patients undergoing elective thoracoscopic lobecto-my,29 males and 30 females,aged 18-64 years,BMI 18.5-26.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using a random number table method:the PCV-VG mode group(group P,n=29)and the volume-controlled ventilation(VCV)mode group(group V,n=30).The PCV-VG mode was used for one-lung ventilation(OLV)in group P,and the VCV mode was used in group V.Anesthesia in-duction and maintenance medications were consistent in all patients.PaO2 was recorded before induction of anesthesia,5 minutes after intubation,15 minutes after OLV,30 minutes after OLV,and 3 days postopera-tively,and oxygenation index(OI)and intrapulmonary shunt rate(Qs/Qt)were calculated.Peak airway pressure(Ppeak),pulmonary dynamic compliance(Cdyn),and driving pressure(DP)were recorded 5 minutes after intubation,15 minutes after OLV,and 30 minutes after OLV.Clara cell secretory protein-16(CC-16)and interleukin-6(IL-6)concentration were measured before induction of anesthesia and after ex-tubation.Recording the occurrence of PPCs within 1 week after surgery.Results Compared with group V,Ppeak and DP were significantly reduced,Cdyn was increased significantly in group P 15 minutes and 30 minutes after OLV(P＜0.05),PaO2 and OI were significantly increased in group P 3 days postoperatively(P＜0.05),CC-16 and IL-6 concentrations were significantly reduced in group P after extubation(P＜0.05).Compared with group V,the incidence of PPCs was significantly reduced in group P(P＜0.05).Conclusion During one-lung ventilation for thoracoscopic surgery,the pressure-controlled ventilation vol-ume-guaranteed mode reduces peak airway pressure and driving pressure,improves pulmonary dynamic compliance and improves oxygenation,reduces the incidence of PPCs.

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity. METHODS: A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic. CONCLUSION The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.
Female ; Humans ; Computational Biology ; East Asian People ; Genetic Counseling ; Genomics ; Mutation ; Obesity, Morbid/genetics* ; Child, Preschool ; Pediatric Obesity/genetics*

Background The health and safety climate of workplace has an important impact on the physical and mental health of workers. There is no available scale for the evaluation of workplace health and safety climate in China at present. Objective This study aims to sinicize and evaluate the reliability and validity of the Health and Safety Climate Survey. Methods The English version of Health and Safety Climate Survey was translated to Chinese and back-translated to English, and followed by expert evaluation to develop a Chinese version. Quota sampling method was used to select 2600 employees from 16 enterprises and public institutions in Pudong New Area of Shanghai and to evaluate the reliability and validity of the Chinese version of the scale. Structural validity, convergent validity, and discriminant validity were included in validity evaluation. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to test structural validity. In EFA, an acceptable factor loading of items on their respective dimensions was > 0.60. In CFA, an acceptable root mean square error of approximation (RMSEA), a standard absolute fitness index, was < 0.05. Comparative fit index (CFI) and parsimony-adjusted non-normed fit index (PNFI), measures of incremental improvement and fit, > 0.90 indicated a good fit. Convergent validity was evaluated by average variance extracted (AVE), and an AVE > 0.50 indicated good convergent validity. Discriminant validity was determined as good by the square root of AVE greater than the correlation coefficient between latent variables. Cronbach’s α coefficient was used to evaluate the internal consistency of the scale; the internal consistency considered was very good with an α > 0.90. Cronbach’s α coefficient may cause underestimation of reliability in the case of error correlation. Therefore, composite reliability (CR) calculated based on structural equation model >0.70 indicated that the CR was good. Results The response rate was 95.69%. The Chinese version of Health and Safety Climate Survey included 22 items belonging to six dimensions which was extracted by the EFA, and the cumulative variance contribution rate was 74.79%. The corrected RMSEA was 0.045, the PNFI was 0.970, and the CFI was 0.975 in the CFA, indicating good fit. The dimensional AVE values were all greater than 0.50, indicating good CV. The square root of AVE was greater than the correlation coefficient between latent variables, indicating good DV. The Cronbach’s α was 0.90 for the total scale and were above 0.70 for all dimensions. The CR was 0.93 for the total scale and were above 0.70 for all dimensions, indicating that the overall reliability of the scale was good. Conclusion The Chinese version of Health and Safety Climate Survey has good reliability and validity, and can be further improved in field application.

An 82-year-old female patient received monotherapy with nivolumab (240 mg by an IV infusion on the firsr day, 14 days as a cycle) because of multiple metastases of central adenocarcinoma in the right upper lobe of the lung. After 8 cycles of immunotherapy (about 4 months), the patient developed severe nausea and vomiting. Laboratory tests showed random blood glucose 43.2 mmol/L and β-hydroxybutyric acid 5.3 mmol/L. Blood gas analysis showed pH 7.01, bicarbonate root 4.0 mmol/L, alkali residual -22.4 mmol/L, serum potassium 6.1 mmol/L, and lactic acid 2.9 mmol/L. The patient had no previous history of diabetes mellitus. Fulminant type 1 diabetes mellitus due to nivolimab was considered. Nivolumab was stopped and rehydration, hypoglycemia, acidosis correction, and other symptomatic treatments were given. Two days later, her symptoms were improved obviously. Laboratory tests showed fasting plasma glucose 15.8 mmol/L and β-hydroxybutyric acid 0.2 mmol/L. Blood gas analysis showed pH 7.39, bicarbonate root 21.2 mmol/L, alkali residual -3.8 mmol/L, serum potassium 4.3 mmol/L, and lactic acid 1.0 mmol/L.

An 82-year-old female patient received monotherapy with nivolumab (240 mg by an IV infusion on the firsr day, 14 days as a cycle) because of multiple metastases of central adenocarcinoma in the right upper lobe of the lung. After 8 cycles of immunotherapy (about 4 months), the patient developed severe nausea and vomiting. Laboratory tests showed random blood glucose 43.2 mmol/L and β-hydroxybutyric acid 5.3 mmol/L. Blood gas analysis showed pH 7.01, bicarbonate root 4.0 mmol/L, alkali residual -22.4 mmol/L, serum potassium 6.1 mmol/L, and lactic acid 2.9 mmol/L. The patient had no previous history of diabetes mellitus. Fulminant type 1 diabetes mellitus due to nivolimab was considered. Nivolumab was stopped and rehydration, hypoglycemia, acidosis correction, and other symptomatic treatments were given. Two days later, her symptoms were improved obviously. Laboratory tests showed fasting plasma glucose 15.8 mmol/L and β-hydroxybutyric acid 0.2 mmol/L. Blood gas analysis showed pH 7.39, bicarbonate root 21.2 mmol/L, alkali residual -3.8 mmol/L, serum potassium 4.3 mmol/L, and lactic acid 1.0 mmol/L.

A 13-year-old male patient presented with skin abnormalities for more than 10 years and slow growth in body height for more than 5 years. Since the age of 6 months, erythema and scales had occurred on the extremities, and gradually spread to the trunk and face; brown pigmentation and punctate depigmentation appeared after subsidance of the erythema and scales, accompanied by dental caries, thickened palms and soles, nail thickening and peeling. Since the age of 6 years, the patient had presented with slow growth in body height, gonadal dysgenesis, sparse eyebrows and eyelashes, flat cheekbones and lameness in walking. In the past 10 years, neutrophil count had been found to be continuously lower than the normal reference value. Blood routine examination showed a neutrophil count of 1.1 × 10 9/L and a neutrophil proportion of 0.345; serum level of testosterone in the patient (< 0.087 nmol/L) was lower than normal levels. DNA was extracted from the peripheral blood of the patient and his parents, and gene mutation analysis was carried out by using whole-exome sequencing technology. Genetic testing showed compound heterozygous mutations in the USB1 gene of the patient, including the c.450-2A>G mutation inherited from his mother and the c.335de1G mutation inherited from his father, and the c.335de1G mutation had not been reported in China and other countries.

Objective? To explore the effect of empowerment-based intervention model on self-efficacy and self-acceptance of patients undergoing permanent enterostomy. Methods? By purposive sampling, a total of 100 colorectal cancer patients undergoing permanent enterostomy operation in the First Affiliated Hospital of Zhengzhou University from January to December of 2018 were selected as the research objects. The 50 patients admitted from January to June of 2018 were taken as the control group while the other 50 patients admitted from July to December of 2018 were taken as the experimental group. During intervention, there were 7 patients lost in the control group and 43 valid questionnaire retrieved; in the experimental group, 2 patients were lost and 48 valid questionnaires were retrieved. The control group was given conventional nursing care while the experimental group was given the nursing intervention formulated based on the empowerment theory. Stoma Self-Efficacy Scale(SSES) and Self-Acceptance Questionnaire(SAQ) were used to assess the patients. Results? After intervention, the total score of SSES, the dimension scores of "stoma care efficacy" and "social self-efficacy"of the experimental group were higher than those of the control group, with statistical significances (P＜0.05). After intervention, the total score of SAQ and the score of "self-acceptance" dimension in the experimental group were higher than those in the control group, and the differences were statistically significant (P＜0.05). Conclusions? The intervention based on empowerment theory can improve the self-management efficacy and self-acceptance level of patients with permanent enterostomy. It is suggested that it should be popularized in clinical practice.