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 explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (MEDHSIL). METHODS: Two children who had visited the Ningbo Women and Children's Hospital on October 15, 2021 were selected as the study subjects. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were verified by Sanger sequencing of their family members. RESULTS: The two children were respectively found to harbor a heterozygous c.138delC (p.Ile47Serfs*42) variant and a c.833del (p.L278*) variant of the MEF2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION The c.138delC and c.833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children. Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.
Child ; Humans ; Family ; Genetic Counseling ; Language ; MEF2 Transcription Factors/genetics* ; Muscle Hypotonia/genetics* ; Neurodevelopmental Disorders

Escherichia coli is a highly adaptable opportunistic pathogen bacterium that can form biofilms on the surface of implants and generates persistent cells,leading to life-threatening infections that are difficult to treat with antibiotics alone.Therefore,there is a need for an effective E.coli biofilm inhibitor to combat this public health threat.Indole is a novel quorum-sensing signaling molecule of E.coli discovered in recent years,which is of great significance in regulating bacterial growth and biofilm formation,and is a potential target for future research on new anti-biofilm preparations.This article reviews the research progress on the formation of Escherichia coli biofilms,the microbial metabolism of indole and its regulation of Escherichia coli biofilm formation,in order to provide information for clinical treatment and drug development.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Objective To observe the effect of dexmedetomidine combined with goal-directed fluid therapy(GDFT)on hemodynamics and cerebral oxygen supply of patients undergoing cerebral aneurysm clipping.Methods A total of 78 patients undergoing cerebral aneurysm clipping surgery in Jinhua Municipal Central Hospital from January 2021 to December 2022 were selected and divided into control group and observation group according to random number table method,with 39 cases in each group.The patients in control group received conventional fluid therapy,and the patients in observation group received dexmedetomidine pump +GDFT.Mean arterial pressure(MAP),heart rate(HR),cardiac index(CI),brain metabolic markers,neuron specific enolase(NSE),S100β levels and mini mental status examination(MMSE)scores at different time points[before anesthesia induction(T0),immediately after tracheal intubation(T1),beginning of surgery(T2),opening meninges(T3),immediately after aneurysm clipping(T4),end of surgery(T5),24h after surgery(T6),72h after surgery(T7)],and fluid intake and outflow of two groups were compared.Results MAP at T1-T4 and CI at T1-T3 in observation group were significantly higher than those in control group(P<0.05).The colloid volume,total infusion volume and urine volume in observation group were significantly higher than those in control group(P<0.05).The serum levels of NSE and S100β at T5-T7 were significantly higher than those at T0 in both groups(P<0.05).The levels of serum NSE and S100β at T5 and T6 in observation group were significantly lower than those in control group(P<0.05).The oxygen content in jugular venous blood(CjvO2)at T1-T4 was significantly lower than that at T0 in control group(P<0.05).Cerebral oxygen extraction ratio at T1 was significantly higher than that at T0 in both groups(P<0.05).CjvO2 at T3-T4 in observation group were significantly higher than those in control group(P<0.05).At T6 and T7,MMSE scores in two groups were significantly lower than at T0 in this group(P<0.05).MMSE score at T6 of observation group was significantly higher than that of control group(P<0.05).Conclusion Dexmedetomidine combined with GDFT can effectively improve preload and brain function,stabilize intraoperative circulatory function,and improve early postoperative cognitive function in patients undergoing cerebral aneurysm clipping.

OBJECTIVE: Through a retrospective large sample analysis of copy number variants in single center, we explored the technical standards for the interpretation and reporting of constitutional copy-number variants (CNVs) jointly proposed by the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) in 2019, analyzing its impact on CNVs ratings and the improvement in the consistency of the classification of CNVs in clinical laboratories. METHODS: 236 CNVs that assessed as pathogenic, uncertain significant (including likely pathogenic, uncertain and likely benign) by the 2011 ACMG guidelines between August 2018 and December 2019 in our center were re-analyzed. Four working group members of the center reclassified and evaluated 235 CNVs according to 2019 ACMG guidelines. RESULTS: The consistency of clinical significance classification of CNVs was 91% and the α test coefficient was 0.98 among four working group members. Compared with the 2011 and 2019 ACMG technical standards for the CNVs classification, evaluation of pathogenicity and uncertain significant is basically consistent. 90% (45/50) of likely pathogenic and likely benign CNVs were Re-evaluated as variants of uncertain significance, and the difference is significant. CONCLUSION The new version ACMG/ClinGen guidelines for the evaluation of CNVs developed semi-quantitative point-based scoring system and help to improve the consistency in clinical classifications. It can also make the interpretation of CNVs more standardized and transparent.
DNA Copy Number Variations ; Genetic Testing ; Genetic Variation ; Genome, Human ; Humans ; Mutation ; Retrospective Studies

Objective:To explore the value of transrectal multimodal ultrasound parameters in monitoring and evaluating the efficacy of endocrine therapy for prostate cancer.Methods:Thirty patients with prostate cancer confirmed by pathology and treated with endocrine therapy in Inner Mongolia Autonomous Region People′s Hospital from November 2019 to May 2021 were selected. The levels of serum prostate specific antigen (PSA), prostate volume, color Doppler parameters, elasticity index and contrast-enhanced ultrasound parameters were measured and recorded before treatment, 1 month and 3 months after treatment. The parameters before and after treatment were statistically analyzed. The correlation between the changes of each index and PSA was analyzed by Spearman correlation analysis.Results:Total prostate specific antigen, free prostate specific antigen, and prostate volume were significantly different before treatment, and 1 month and 3 months after treatment( P<0.05), and the values showed a downward trend with increase of treatment time. There was no significant difference in resistance index before and 1 month after treatment( P>0.05), but decreased significantly 3 months after treatment( P<0.05). The values of elasticity index, peak intensity, area under curve and gradient at 1 month and 3 months after treatment were lower than those before treatment, while the arrival time and rising time at 1 month and 3 months after treatment were significantly higher than those before treatment( P<0.05). Spearman correlation analysis showed that there was no correlation between the changes of quantitative parameters and PSA value before and after treatment( P>0.05). Conclusions:Prostate volume, color Doppler parameters, elasticity index, and contrast-enhanced ultrasound parameters change in the early stage of endocrine therapy for prostate cancer, which can be used as a useful supplement to PSA for prostate cancer, and can be used to evaluate the efficacy of clinical prostate cancer endocrine therapy.

Objective:To investigate the characteristics and evolution of mild motor symptoms (MMS) in patients with prodromal Parkinson′s disease (pPD).Methods:Based on the pPD cohort screened by Parkinson′s Disease Prodromal Clinical Assessment Scale in Nanjing community from July 2018 to December 2020, the clinical data of 30 patients with pPD who completed the baseline assessment and were followed up for at least 1 year were analyzed. According to the Unified Parkinson Diease Rating Scale Ⅲ (UPDRS-Ⅲ) score, the patients were divided into MMS group (UPDRS-Ⅲ score>3) and non-MMS group (NMMS group, UPDRS-Ⅲ score≤3). The differences and evolution characteristics of clinical characteristics between the 2 groups were compared. Multivariate linear regression was used to analyze the risk factors of motor symptom progression in pPD patients.Results:Among the 30 patients with pPD, 7 of 23 patients in the MMS group were converted to PD at the end of follow-up, 1 of 7 patients in the NMMS group were converted to PD at the end of follow-up. The UPDRS-Ⅲ score [10.00 (7.00, 17.00)], Montreal Cognitive Assessment Scale (MoCA) score [25.50 (24.75, 28.00)] and the Hamilton Anxiety Scale (HAMA) score [9.00 (5.00, 13.00)] at the end of follow-up of pPD patients were significantly higher than those at baseline [7.00 (4.00, 12.00), 24.00 (22.75, 25.25) and 8.00 (2.00, 11.00)], and the differences were statistically significant ( Z=-3.505, P<0.001; Z=-2.956, P=0.003; Z=-2.427, P=0.015).Subgroup analysis showed that UPDRS-Ⅲ score [11.00 (7.00, 18.00)], MoCA score [25.00 (24.00, 27.00)] and HAMA score [ 9.00 (6.00, 15.00)] at the end of follow-up in the MMS group were higher than those at baseline [8.00 (6.00, 12.00), 24.00 (22.00, 25.00) and 9.00 (3.00, 11.00)], and the difference was statistically significant (Z=-2.768, P=0.006; Z=-2.457, P=0.014; Z=-2.250, P=0.024). The Non-Motor Symptoms Questionnaire score at the end of follow-up in the MMS group (8.96±5.20) was significantly lower than that in the baseline (11.04±4.41), and the difference was statistically significant ( t=2.441, P=0.023).There was no significant difference in Mini-Mental State Examination (MMSE), Hamilton Depression Scale (HAMD), Rapid Eyes Movement Sleep Behavior Disorder Questionnaire-Hong Kong (RBDQ-HK) and Sniffin′ sticks olfactory test score at the end of follow-up in the MMS group. Only UPDRS-Ⅲ score in the NMMS group was increased at the end of follow-up [7.00 (5.00, 8.00)] compared with the baseline [4.00 (1.00, 4.00)], and the difference was statistically significant ( Z=-2.375, P=0.018). There was no significant difference in MoCA, MMSE, HAMA, HAMD, RBDQ-HK, and Sniffin′ sticks olfactory test score between the NMMS group and the baseline at the end of follow-up. Conclusion:The clinical conversion rate of pPD patients with MMS is high,and screening of this population should be paid attention.

OBJECTIVE: To reported on two fetuses diagnosed with 17q12 microdeletion syndrome. METHODS: The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography. Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array (SNP-array) analysis. After 17q12 microdeletion was found in the first fetus, SNP-array was carried out on peripheral blood samples of the parents to determine its origin. With the medical history of the parents taken into consideration, the father underwent high-throughput sequencing for 565 urinary system-related genes to exclude pathogenic or likely pathogenic variants associated with congenital malformations of the urinary and reproductive systems. RESULTS: In both fetuses, SNP-array has revealed a 1.42 Mb deletion at 17q12, or arr[hg19]17q12 (34 822 465-36 243 365) × 1. In both cases the microdeletion was inherited from the father, in whom no urinary disease-related pathogenic or likely pathogenic variants was identified. CONCLUSION Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios. SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.
Chromosome Deletion ; Chromosome Disorders ; Chromosomes, Human, Pair 17 ; Female ; Fetus ; Genetic Counseling ; Genetic Testing ; Humans ; Polyhydramnios/genetics* ; Pregnancy ; Prenatal Diagnosis

Objective:To investigate the role of coupler perfusion in transrectal ultrasound in the diagnosis of preoperative T staging of rectal cancer.Methods:A retrospective analysis of the preoperative clinical data of 132 patients with rectal cancer in the People′s Hospital of Inner Mongolia Autonomous Region from June 2015 to November 2020. According to whether or not the patients agreed to coupler perfusion before ultrasound examination, they were divided into 2 groups, namely the perfusion group 69 cases and the non-perfusion group of 63 cases, with postoperative pathology as the gold standard, and compared with magnetic resonance imaging(MRI) to evaluate the accuracy of the 2 groups and MRI in the T staging of rectal cancer.Results:The total coincidence rates of the coupling agent perfusion group, non-perfusion group and MRI group for the diagnosis of rectal cancer T staging were 89.9%, 76.2% and 87.9%, respectively, and the difference among the three methods was statistically significant (χ 2=6.096, P=0.047). The diagnostic sensitivity of the coupling agent perfusion group for T1 stage was 96.0%, which was higher than 61.5% of the non-perfusion group and 92.3% of the MRI ( P=0.010). The specificity of the perfusion group for the diagnosis of T2 stage was 95.7%, higher than the non-perfusion group and MRI ( P=0.037), the positive predictive value of the perfusion group for T2 stage was 90.9%, which was higher than the non-perfusion group and MRI ( P=0.035). The diagnostic accuracy of the perfusion group for T2 stage was 94.2%, higher than the non-perfusion group and MRI (χ 2=7.070, P=0.029). There were no statistically significant differences in diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy among the perfusion group and the non-perfusion group and the MRI for T3 and T4 (all P>0.05). Conclusions:Coupled-agent perfusion makes it convenient and fast for intracavity ultrasound to diagnose T staging of rectal cancer, and the diagnostic efficiency is comparable to MRI. In particular, it can be used as a highly reliable imaging method for T1 and T2 rectal cancer.