Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.

Objective:To explore the clinical characteristics and genetic etiology of four children with Phelan-McDermid syndrome (PMS).Methods:Four children who had visited the Affiliated Women and Children′s Hospital of Ningbo University between June 2, 2022 and May 8, 2023 were selected as the study subjects. Clinical data of the children were collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and quantitative PCR (q-PCR) analysis. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:All children had presented with speech and language delays and intellectual disability. Children 3 and 4 also presented with autistic behaviors. WES showed that the children 1 and 2 had respectively carried a heterozygous c.731T>C (p.Leu244Pro) and a c.2782_2851del (p.Gly928ArgfsTer4) variant of the SHANK3 gene. Sanger sequencing confirmed that their parents did not carry the same variant, suggesting that they were de novo in origin. Children 3 and 4 had respectively harbored a 121 kb and 52.02 kb heterozygous deletion at chromosome 22q13.33, which had both encompassed the SHANK3 and ACR genes mapped to 22q13.33. q-PCR results showed that the deletion of SHANK3 and ACR genes were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 731T>C and c. 2782_2851del variants were predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PS2_Supporting), respectively. Furthermore, the 52.02 kb and 121 kb heterozygous deletions in 22q13.33 were both predicted to be pathogenic (2D+ 4C, 1.05 in score; 2D+ 4C, 1 in score). Conclusion:The four children were all diagnosed with PMS by genetic testing. Above finding has enriched the phenotypic and mutational spectrum of PMS, and provided a basis for clinical diagnosis and genetic counseling for their families.

Objective:To comprehensively and systematically retrieve domestic and international research on nurse-initiated protocolized weaning in adult mechanically ventilated patients, clarify its outcome indicators and effectiveness in clinical practice, and identify influencing factors in its implementation.Methods:Employing the scoping review methodology of Arksey and O'Malley, databases in both English and Chinese were systematically searched. Literature was selected based on inclusion and exclusion criteria, with two researchers independently screening, organizing, and analyzing the articles.Results:Eighteen publications were included: seven interventional studies, four qualitative studies, two cross-sectional studies, two on instrument development, and three reviews. Nurse-initiated protocolized weaning was found to be safe and effective, with common clinical outcome indicators including mechanical ventilation duration, weaning time, and ICU length of stay. Significant barriers included the professional knowledge level of nurses, team cooperation, nurses' personal characteristics, and the healthcare providers' underestimation of patients' clinical symptoms. Continuous care, patient involvement, a supportive nursing culture, and recognition of the nurse's role were facilitators of this treatment.Conclusions:Future research efforts should standardize and refine the intervention measures of nurse-initiated protocolized weaning and conduct large-sample, high-quality studies to provide references for the implementation of nurse-initiated protocolized weaning in China.

Objective:To evaluate the effect of oral cryotherapy in patients with hematopoietic stem cell transplantation (HSCT) .Methods:Randomized controlled trials on the effect of oral cryotherapy in HSCT patients were retrieved in Cochrane Library, PubMed, Embase, Web of Science, Scopus, China Biology Medicine disc, CNKI, WanFang Data and VIP. The retrieval time limit was from the establishment of the database to August 31, 2022. Two researchers conducted article screening, data extraction and evaluation of article quality, and used RevMan 5.3 software for meta-analysis.Results:A total of 9 articles were included, including 639 HSCT patients. Meta-analysis showed that oral cold therapy could reduce the incidence of severe oral mucositis (OM) (grade 3 to 4) [ OR=0.34, 95% CI (0.18, 0.66), P=0.001]and the use of total parenteral nutrition [ OR=0.34, 95% CI (0.13, 0.88), P=0.03]in patients with HSCT, and reduce the incidence of OM [ OR=0.09, 95% CI (0.04, 0.19), P<0.001], OM severity score [ MD=-0.71, 95% CI (-0.78, -0.64), P<0.001]and use of intravenous painkillers [ OR=0.12, 95% CI (0.04, 0.40), P=0.000 4]in patients with autologous HSCT. The relationship between oral cryotherapy and OM incidence of allogeneic HSCT patients [ OR=1.23, 95% CI (0.57, 2.68), P=0.60], OM severity score [ MD=-0.15, 95% CI (-0.57, 0.27), P=0.48], and the length of hospital stay of autologous HSCT patients [ MD=-0.67, 95% CI (-2.10, 0.76), P=0.36]was not clear. Conclusions:Oral cryotherapy can reduce the incidence of OM in patients with autologous HSCT, the use of intravenous painkillers and total parenteral nutrition, but the effect and safety of oral cryotherapy in patients with allogenic HSCT need to be further verified, which needs to be verified by a large number of high-quality, multi-center, large-sample randomized controlled trials.

OBJECTIVE: To delineate the clinical and genetic features of a fetus with micrognathia, low-set ears, microtia, polyhydramnios and anechoic stomach by ultrasonography. METHODS: Whole exome sequencing (WES) was carried out to detect genetic variant in the fetus, for which routine chromosomal karyotyping and chromosomal microarray analysis (CMA) yielded no positive finding. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: WES revealed that the fetus has carried a de novo nonsense c.2302C>T (p.Q768X) variant in exon 23 of the EFTUD2 gene, which was detected in neither parent. The variant was unreported previously and may lead to premature termination of the translation of EFTUD2 protein at the 768th amino acid. Bioinformatic analysis predicted the amino acid to be highly conserved and may alter the structure and function of the EFTUD2 protein. CONCLUSION The c.2302C>T variant of the EFTUD2 gene probably underlay the mandibulofacial dysostosis Guion-Almeida type in the fetus. Discovery of the novel variant has enriched variant spectrum of the EFTUD2 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.
Female ; Fetus ; Humans ; Mandibulofacial Dysostosis/genetics* ; Mutation ; Peptide Elongation Factors/genetics* ; Phenotype ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/genetics*

Objective:To summarize the clinical characteristics of plastic bronchitis caused by severe mycoplasma pneumoniae pneumonia in children, to find the risk factors for plastic bronchitis, and to provide references for judging the prognosis and comprehensively formulating treatment plans.Methods:We retrospectively analyzed the clinical data(146 cases)of children with severe mycoplasma pneumoniae pneumonia who underwent bronchoscopy in the Department of Pediatric Respiratory Medicine of Shengjing Hospital of China Medical University from January 2017 to December 2019.According to whether it was plastic bronchitis, all patients were divided into plastic bronchitis group(68 cases) and non-plastic bronchitis group(78 cases), and the gender, age, laboratory examination indicators, imaging characteristics and treatment of children were collected under the circumstances.The single factor with clinical significance and statistical significance would be subjected to multivariate Logistic regression analysis.Results:There were no significant differences in gender, age, heat duration, white blood cell count, C-reactive protein value, and interleukin-6 value between the two groups(all P>0.05). The percentage of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, D-dimer, number of cases of pleural effusion, length of hospital stay, and number of endoscopy in the plastic bronchitis group were higher than those in non-plastic bronchitis group, the number of right upper lobe consolidation cases was less than that in the non-plastic bronchitis group, and the differences were statistically significant( P<0.05). Multiple Logistic regression analysis showed that pleural effusion( OR=4.898, 95% CI 2.195-10.926) and lactate dehydrogenase ( OR=1.051, 95% CI 1.003-1.101) were independent predictors of plastic bronchitis in children with severe mycoplasma pneumoniae pneumonia. Conclusion:For children with severe mycoplasma pneumoniae pneumonia, if lung CT shows that the upper lobe of the non-right lung is uniformly compacted and complicated with pleural effusion, lactate dehydrogenase is significantly increased, and attention should be paid to the possibility of plastic bronchitis.Timely improvement of fiberoptic bronchoscopy may shorten the course of the disease and reduce the occurrence of complications.

To investigate cerebral autoregulation(CA)in patients with severe unilateral carotid artery stenosis by near infrared spectroscopy. Thirty patients who underwent general anesthesia in our hospital from January 2015 to February 2017 were enrolled in this study.The stenosis group included 15 patients with severe unilateral internal carotid artery stenosis,and the control group included 15 patients without carotid artery stenosis.Both groups were matched in sex and age.Cerebral tissue oxygenation index(TOI)and mean arterial pressure were recorded continuously under stable general anesthesia.The Pearson correlation coefficient()was calculated to judge the CA status. TOI was not significantly different between the stenosis side and the non-stenosis side in the stenosis group(66.52±6.50 65.23±4.50;=0.93, =0.368)or between the stenosis side in the stenosis group and the stenosis side in the control group(66.52±6.50 64.22±3.87;=1.18, =0.248).The values of stenosis side and non-stenosis side in the stenosis group were 0.36±0.12 and 0.17±0.11,respectively,and the values of the stenosis side in the stenosis group and the stenosis side of the control group were 0.36±0.12 and 0.13±0.08,respectively.In the stenosis group,5 patients had transient ischemic attack and 2 patients had a history of stroke within 3 months before operation.When an value of 0.342 was used as the judgment point of CA abnormality,the sensitivity and specificity were 0.625 and 0.909,respectively. Within the range of normal blood pressure fluctuation,cerebral blood flow is linked to blood pressure at the stenosis side in patients with severe unilateral carotid artery stenosis.
Blood Pressure ; Carotid Stenosis ; Cerebrovascular Circulation ; Homeostasis ; Humans ; Ischemic Attack, Transient

Objective:To explore the clinical characteristics of children with atopic mycoplasma pneumoniae pneumonia and to provide evidence for the diagnosis and treatment of children with atopic mycoplasma pneumoniae pneumonia.Methods:One hundred and eighty cases of children diagnosed with mycoplasma pneumoniae pneumonia in Shengjing Hospital of China Medical University from January 2018 to December 2018 were selected. According to whether they had atopic constitution, they were divided into atopic mycoplasma pneumoniae pneumonia(AMPP)group(84 cases)and non-atopic mycoplasma pneumoniae pneumonia(NAMPP)group(96 cases). The clinical data of age, sex, fever time, hospital stay, application time of macrolides, white blood cells, CRP, LDH, and lung CT were collected from the two groups, and the differences in clinical manifestations, laboratory examinations and imaging manifestations of the two groups were analyzed retrospectively.Results:(1)Both the absolute value of eosinophils and total IgE values in the AMPP group were higher than those in the NAMPP group, and the difference was statistically significant( P<0.05). The incidence of severe mycoplasma pneumoniae pneumonia(SMPP)and/or refractory mycoplasma pneumoniae pneumonia(RMPP)and chest imaging manifestations of interstitial pneumonia in the AMPP group was higher, and the difference was statistically significant( P<0.05). (2)The incidence of wheezing in the AMPP group was 48.81%(41 cases/84 cases), which was significantly higher than that in the NAMPP group 22.92%(22 cases/96 cases). The duration of cough and wheezing in the AMPP group was longer than that in the NAMPP group( P<0.05), with statistically significant differences( P<0.05). (3)In the AMPP group, 36.90%(31 cases /84 cases)of the children received intravenous methylprednisolone treatment, which was significantly higher than the 20.83%(20cases /96 cases)of the NAMPP group. Lung rales absorption time in the AMPP group[(9.73±3.59)d] was significantly longer than that in the NAMPP group[(7.52±2.44)d], and the difference was statistically significant( P<0.05). Lung CT examination showed that the absorption of lung inflammation in the AMPP group was worse than that in the NAMPP group, with a statistically significant difference( P<0.05). The hospitalization time of children in the AMPP group[(10.88±4.17)d] was longer than that in the NAMPP group[(9.68±2.68)d], with a statistically significant difference( P<0.05). Conclusion:The condition of AMPP is more serious than that of NAMPP, and it is more likely to cause incomplete absorption of pulmonary inflammation.

Objective:To investigate the clinical characteristics and imagological changes of atopic children with ADV pneumonia.Methods:One hundred and twenty cases of children with ADV pneumonia selected from Shengjing Hospital of China Medical University Pediatric Respiratory Department from June 2018 to December 2019.According to whether had atopy and severity of pneumonia, the children were divided into atopic group 42 cases (mild pneumonia 30 cases, severe pneumonia 12 cases)and non-atopic group 78 cases(mild pneumonia 50 cases, severe pneumonia 28 cases). The children were treated according to the guidelines of ADV pneumonia diagnosis and treatment.Laboratory examination, clinical manifestations, clinical features during hospitalization, pulmonary imaging changes at admission, at discharge and follow-up 1 month after discharge were statistically analyzed.Results:There were statistically significant differences in the proportion of severe cough and wheezing between the atopic children and non-atopic children with mild pneumonia( P=0.041, P=0.004, respectively). There was no statistically significant difference between the two groups in the proportion of children with small airway changes indicated by lung CT at admission and 1 month after discharge( P>0.05). The risk of wheezing during hospitalization of atopic children was 2.32 times as much as that of non-atopic children with mild pneumonia.The risk of developing severe cough was 1.72 times as much as that of non-atopic children with mild pneumonia.There were statistically significant differences in the proportion of wheezing after admission and after discharge between the atopic children and non-atopic children with severe pneumonia( P=0.002, P=0.034, respectively). There were significant differences in the proportion of small airway changes at admission and at discharge between the two groups( P=0.001, P=0.009, respectively). The risk of wheezing during hospitalization of atopic children was 1.94 times as much as that of non-atopic children with severe pneumonia.The risk of wheezing after discharge was 1.98 times as much as that of the non-atopic children with severe pneumonia.The risk of small airway change on admission in atopic children group was 1.25 times as much as that of non-atopic children with severe pneumonia.The risk of having small airway changes 1 month after discharge in atopic children group was 2.31 times as much as that of non-atopic children with severe pneumonia. Conclusion:Atopic children with ADV pneumonia had severe cough and wheezing, and atopic children with severe pneumonia are prone to small airway changes, long imaging recovery time and regular follow-up, which should be paid attention by clinicians.

Objective:To investigate the positive rates of 2019-nCoV nucleic acid in different specimens from confirmed COVID-19 cases during hospitalization and after discharge.Methods:Patients with confirmed COVID-19 were enrolled from designated hospitals. Nasal swabs, throat swabs, and specimens of stool, urine and blood were collected during hospitalization. After the patients were discharged, nasal swabs, throat swabs and stool specimens were collected during follow-up. Real-time RT-PCR was used to detect 2019-nCoV nucleic acid.Results:This study involved 25 confirmed COVID-19 cases. During hospitalization, all patients tested positive in both nasal and throat swab 2019-nCoV nucleic acid tests, and nine of them (36.00%) were positive in stool specimen test. Urine and blood specimen test results were all negative. Nasal swabs, throat swabs and stool specimens were collected from each patient 7 d and 14 d after discharge. Two patients (8.00%) tested positive for 2019-nCoV nucleic acid again in nasal and throat swab tests on 7 d, while all stool specimen tests were negative. No 2019-nCoV nucleic acid was detected in nasal swabs, throat swabs or stool samples on 14 d.Conclusions:2019-nCoV nucleic acid was detected in stool samples of confirmed COVID-19 cases during hospitalization. Nasal and throat swab nucleic acid tests turned positive again in some patients after discharge.