OBJECTIVE: To explore the clinical features of a child with Lamb-Shaffer syndrome (LAMSHF) due to a variant of SOX5 gene. METHODS: A child who was admitted to Children's Hospital Affiliated to Zhengzhou University in July 2022 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing (WES) was carried out on peripheral blood samples from the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-100). RESULTS: The child, an one-year-and-seven-month-old male, has manifested delayed development in speech and language, intelligence and movement, in addition with mild facial deformities and eye signs. Whole exome sequencing revealed that he has harbored a heterozygous c.1828_1829insGACT (p.Y610fs*1) frameshifting variant of the SOX5 gene. Sanger sequencing confirmed the variant to be de novo in origin. The variant was also unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_supporting). CONCLUSION The c.1828_1829insGACT (p.Y610fs*1) variant of the SOX5 gene probably underlay the pathogenesis of LAMSHF in this child. For children with delayed mental, language, intellectual, and motor development, genetic testing should be conducted to facilitate early diagnosis. Above finding has enriched the mutational spectrum of the SOX5 gene.
Humans ; SOXD Transcription Factors/genetics* ; Male ; Infant ; Exome Sequencing ; Genetic Testing ; Mutation

OBJECTIVE: To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. METHODS: A child diagnosed with 3MS type 1 at the Children's Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020). RESULTS: The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. WES revealed compound heterozygous variants in the CUL7 gene: c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child's father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c.2686G>T (p.E896) was classified as a pathogenic (PVS1+PM2_Supporting+PM3), and c.1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+PM2_Supporting). Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). CONCLUSION The compound heterozygous variants c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.
Humans ; Cullin Proteins/genetics* ; Female ; Child ; Limb Deformities, Congenital/genetics* ; Exome Sequencing ; Mutation ; Child, Preschool ; Dwarfism ; Muscle Hypotonia ; Spine/abnormalities*

Objective:To establish the mouse model with radiation-induced pulmonary fibrosis, and to identify and analyze it from the aspects of function, imaging and pathology.Methods:Thirty C57BL/6 mice were randomly divided into the control group, 16 Gy irradiation group and 20Gy irradiation group. The mice in the irradiation groups received a single 16 Gy or 20 Gy chest X-ray irradiation, and underwent functional examination, imaging examination and pathological examination at 3 and 6 months after irradiation.Results:At 6 months after irradiation, hair on the chest and back of the mice turned white and fell off, and the airway resistance was increased significantly. CT images showed extensive patch shadows and consolidation in the lung. Three dimensional reconstruction suggested that the lung of mice was distorted and deformed, and the volume was decreased significantly. Pathological examination confirmed that there was extensive pulmonary fibrosis.Conclusions:Significant pulmonary fibrosis occurs after 6 months of chest irradiation in mice. The animal model of radiation-induced pulmonary fibrosis in C57BL/6 mice was successfully established.

Objective:To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored.Methods:The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children′s Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively.Results:There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B 6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B 6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions:The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

Objective:To investigate the knowledge level of hospice care and the related influencing factors among health providers in Shanghai.Methods:From November to December 2019,a questionnaire survey on the hospice care knowledge was conducted among 7 074 health providers from 223 registered hospice care clinics or institutions in 16 districts of Shanghai.Results:A total of 7 027 valid questionnaires were recovered, with an effective recovery rate of 99.3%. Among the 7 027 responders, there were 1 460 males (20.8%) and 5 567 females (79.2%) with an mean age of (36.9±9.3) years; 2 682 nurses (38.2%) and 2 442 doctors (34.8%); 5 065 (72.1%) from community health service centers; 2 982 (42.4%) involving in hospice care services and 4 039 (57.5%) willing to work in hospice care. The average score of hospice care knowledge was (8.9±2.6), and the average accuracy for questions was 59.0%. Health providers had the highest awareness rate for the composition of hospice care professional team (93.9%, 6 597/7 027) and the lowest awareness rate for the emotional commitment in hospice care service (16.6%, 1 165/7 027). Health providers with junior colleges degree ( B=-0.429), vocational college degree and below ( B=-0.544), nurses ( B=-0.652), working in suburban areas ( B=-0.278), social office ( B=-0.891), without witness of dying process of end-of-life patients ( B=-0.329), not involving in hospice care services ( B=-0.283), and not willing to participating in hospice care ( B=-0.820) had low knowledge scores ( P<0.05). Conclusions:The overall level of hospice care knowledge of health providers in Shanghai is generally at a medium level, and the training of hospice care knowledge should be strengthened for the better development of hospice care.

Objective: To learn the level of resilience among community health emergency staff in Zhejiang Province and its influencing factors under the epidemic situation of coronavirus disease 2019. Methods: Using stratified cluster sampling method, the community health emergency workers from six counties in Zhejiang Province were recruited in this study. A self-designed questionnaire, a scale for core emergency response capability of medical workers and 10 Items Connor-Davidson Resilience Scale ( CD-RISC-10 ) were employed. The multivariate linear regression model was used to analyze the influencing factors for resilience. Results: A total of 749 people were surveyed, with 699 valid questionnaires ( effective rate 93.32% ). Among the 699 community health emergency staffs, the total scores of resistance and core emergency response capability were 34.97±7.95 and 118.38±27.60. The multivariate linear regression analysis showed that core emergency response capability ( β＇=0.410 ), education background (diploma: β＇=0.158; bachelor: β＇=0.196), position ( top: β＇=0.083 ) and self-rated physical fitness ( not qualified: β＇=-0.152; less qualified: β＇=-0.235; generally qualified: β＇=-0.219; more qualified: β＇=-0.107 ) were the influencing factors for resilience of community health emergency staff. Conclusion The resilience of community health emergency staff in Zhejiang Province is at a medium level, and is associated with education background, physical fitnes and position.

For non-small cell lung cancer (NSCLC) patients with positive surgical margins, the survival rates can be dramatically decreased. However, high-level evidence is lacking in the standard adjuvant treatment for NSCLC patients with positive surgical margins. In this article, consensus and disputes on the adjuvant therapy for NSCLC patients with positive surgical margins were reviewed.

Objective To determine the median effective dose(ED50)of dezocine inhibiting re-sponses to insertion of laryngeal mask airway(LMA)when combined with propofol in the elderly pa-tients.Methods American Society of Anesthesiologists physical statusⅠorⅡ patients, aged 66-75 yr, with body mass index of 20-25 kg∕m2, were included in this study.Anesthesia was induced with dezocine at the initial dose of 0.2 mg∕kg and propofol which was simultaneously administered by target-controlled infu-sion.The initial target plasma concentration of propofol was 1 μg∕ml, and the concentration was increased in increments of 0.5 μg∕ml every 3 min until the target concentration 3 μg∕ml was achieved.LMA was inserted when bispectral index value reached 50-60.The dose of dezocine was determined using the up-and-down method.The response to insertion of LMA was defined as positive when patients developed coughing, laryn-gospasm and∕or body movement during insertion or within 3 min after insertion.The dose of dezocine was in-creased∕decreased in the next patient if the insertion response was positive or negative.The ratio between the two successive doses was 0.8.The ED50and 95% confidence interval of dezocine inhibiting responses to in-sertion of LMA were calculated.Results When combined with propofol, the ED50of dezocine inhibiting re-sponses to insertion of LMA was 0.126 mg∕kg, and the 95% confidence interval was 0.110-0.143 mg∕kg.Conclusion The ED50of dezocine inhibiting responses to insertion of LMA is 0.126 mg∕kg when combined with propofol in the elderly patients.

Objective To explore therapeutic effect of integrated traditional Chinese and western medicine therapy on reynolds syndrome,and to provide effective and reliable operation method for treatment of the disease. Methods 104 cases with reynolds syndrome were randomly divided into observation group (59 cases)and control group (45 cases)by random number table method.The observation group was treated with aspirin,nifedipine combined with traditional Chinese medicine dialectical therapy,the control group was treated with aspirin and nifedipine. The cold water test ,fist test results and hemorheology indexes of the two groups were measured before and after a period of treatment.The therapeutic effects were evaluated after one course.Results After treatment,the fist test, cold water test positive rates of observation group were 32.2%,23.7%,which were lower than 75.6%,57.8% of the control group (χ2 =19.199,12.504,all P <0.05 ).The plasma viscosity (1.25 ±0.11 )mPa · s,erythrocyte aggregation index (2.04 ±0.29),erythrocyte rigidity index (4.20 ±0.58)of the two groups were lower than those before treatment (1.49 ±0.13)mPa·s,(2.27 ±0.30),(4.67 ±0.59),and the deformation index of red blood cell (1.38 ±0.26)was higher than before treatment (1.21 ±0.28)(t =2.704,1.127,9.200,1.687,12.898,5.200, 12.613,5.323,all P <0.05).After treatment,the plasma viscosity,erythrocyte aggregation index and rigidity index of red blood cells were lower than those in the control group,and the deformation index of red blood cells was higher than the control group (t =10.187,3.948,3.195,4.172,all P <0.05).The total effective rate of the observation group was 89.8%(53 /59),which was higher than 71.1%(32 /45 )of the control group,the difference was statistically significant (χ2 =5.991,P <0.05).Drug adverse reaction rate of the observation group was 10.2%(6 /59),that of the control group was 11.1% (5 /45 ),the difference was not statistically significant (χ2 =0.024,P >0.05 ). Conclusion In the treatment of reynolds syndrome,the integrated traditional Chinese and western medicine therapy has better curative effect and low drug adverse reaction rate,with good clinical application value.

Objective To explore the features of coronary artery morphological changes and left ventricular function indicators of resident population in plateau .Methods 50 plateau healthy adults and 50 plain‐and Dalian‐healthy volunteers completed coronary CTA examination .We measured the pipe diameter of left main coronary atery and right coronary artery and their branches ,respec‐tively .Furthermore ,SV and EF value of left ventricular cardiac function indexes and the wall thickening of free ventricular wall at left ventricular end systolic were measured .Results The average diameter of proximal right coronary of plain‐and Dalian‐healthy volun‐teers thicker than plateau group ,with statistical difference ;Other coronary artery branch did not exhibit any significant between‐group differences ;The two groups did not show significant between‐group differences with heart function indexes .Conclusion The body circulation system have adaptability and compensatory changes of resident population in plateau ,and their coronary artery mor‐phology and left ventricular function are as similar as plain people .