Genetic and phenotypic analysis of 225 Chinese children with developmental delay and/or intellectual disability using whole-exome sequencing.

Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1-2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups. The phenotype and genomic data of patients with DD/ID were further retrospectively analyzed. There were 96/225 (42.67%; 95% confidence interval [CI] 36.15-49.18%) patients were found to have causative single nucleotide variants (SNVs) and small insertions/deletions (Indels) associated with DD/ID based on WES data. The diagnostic yields among the seven subgroups ranged from 31.25 to 71.43%. Three specific clinical features, hearing loss, visual loss, and facial dysmorphism, can significantly increase the diagnostic yield of WES in patients with DD/ID (P = 0.005, P = 0.005, and P = 0.039, respectively). Of note, hearing loss (odds ratio [OR] = 1.86%; 95% CI = 1.00-3.46, P = 0.046) or abnormal brainstem auditory evoked potential (BAEP) (OR = 1.91, 95% CI = 1.02-3.50, P = 0.042) was independently associated with causative genetic variants in DD/ID children. Our findings enrich the variation spectrums of SNVs/Indels associated with DD/ID, highlight the value genetic testing for DD/ID children, stress the importance of BAEP screen in DD/ID children, and help to facilitate early diagnose, clinical management and reproductive decisions, improve therapeutic response to medical treatment.

Research hotspots and emerging trends in mesenchymal stem/stromal cells in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a prevalent lung disease in neonates that is associated with numerous complications and high mortality. The promising approach to treat BPD is the use of mesenchymal stem cells (MSCs), However, the current treatment of MSCs presents safety concerns, including occlusion of blood vessels and tumorigenicity. In this study, relevant publications from the Web of Science Core Collection were downloaded in January 2023. The acquired data were analyzed and predicted for trends and hotspots in this field using CiteSpace software. Results revealed that in recent years, the focus of co-cited references has been primarily on the clinical studies of MSCs and the application of MSCs derivatives for treating BPD models. The keywords that have gained attention are extracellular vesicles and exosomes. The United States has emerged as the most influential co-authoring country in this field. Among the co-cited journals, the American Journal of Respiratory and Critical Care Medicine holds the highest influence. Thus, this study provides trends in publications, collaboration, research interests, and hotspots, and provides clues for novel ideas and strategies in to further MSCs treatments for BPD.

Risk factors for refracture of the femoral shaft in children after removal of external fixation.

BACKGROUND: External fixation is the primary treatment option in children for femoral shaft fractures, such as open femoral or multiple fractures. One complication is refracture, which is the biggest limitation of fixation devices. This study aims to investigate the risk factors associated with refracture after the removal of external fixation devices and decrease the frequency of refracture. MATERIALS AND METHODS: Retrospectively reviewed clinical data of 165 patients treated at our hospital for fresh femoral shaft fractures with external fixation between May 2009 and February 2018 were included in this study. Patients with pathological fractures, fractures of the femoral neck, fractures that were fixed using plates or elastic stable intramedullary nailing, and old fractures, as well as those who underwent postoperative femoral surgery were excluded. Potential risk factors included: patient age, gender, and weight, fracture sides, open or closed fracture, fracture sites, reduction methods, operation time, perioperative bleeding, number and diameter of the screws, and immobilization time. These factors were identified by univariate and logistic regression analyses. RESULTS: Femoral shaft refracture developed in 24 patients. Univariate analysis revealed that refracture was not statistically significantly associated with any of the above factors, except AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF) classification type 32-D/4.2 and L2/L3 ratio (L2, length of femur fixed by the two screws farthest from the fracture line; L3, the total length from the greater trochanter to the distal end of femur; P < 0.001 and P = 0.0141, respectively). Multivariate analysis showed that PCCF classification type 32-D/4.2 and L2/L3 ratio were also independent risk factors for femoral refracture. CONCLUSIONS: Femoral shaft refracture is relatively common in children treated with external fixation. Because of the limited number of cases in this study, we cautiously concluded that the PCCF classification type 32-D/4.2 and L2/L3 ratio were independent risk factors for femoral shaft refracture in these patients. LEVEL OF EVIDENCE: IV.

Open Reduction of Neglected Supracondylar Humeral Fractures With Callus Formation in Children.

BACKGROUND: The standard treatment for supracondylar humeral fractures (SHFs) in children is closed reduction and percutaneous Kirschner (K)-wire fixation. In patients who present >14 days after injury and show callus formation, this procedure cannot be performed. There are 2 options in these cases: functional exercises with osteotomy performed at a later stage if cubitus varus is present, or immediate open reduction and percutaneous K-wire fixation. This study aimed to evaluate the outcomes of K-wire fixation through an anterior approach in children with neglected SHF and identify factors predicting the outcomes. METHODS: This retrospective study assessed the files of 32 children treated for neglected SHF at our hospital between June 2015 and May 2018. An incision was made along the anterior transverse groove of the elbow. The callus was removed, the fracture was reduced, and K-wire fixation was performed. The outcome evaluation included the radiological Baumann angle, pin fixation construct, carrying angles, and the functional outcome was Mayo Elbow Performance Score and Flynn criteria. Binary regression analysis compared the functional outcome as the dependent variable with age, time from injury to operation, operation time, and the amount of callus. RESULTS: The interval between injury and operation was 14 to 40 days (average, 22.4 d). Patients were followed for 12 to 36 months (average, 21.5 mo). Fracture healing took 5 to 8 weeks (average, 6.6 wk). No patient had a vascular injury or compartment syndrome. Twelve patients were intraoperatively assessed for radial and median nerve injury. No nerve repair was required. All nerve injuries recovered within 3 months. No iatrogenic ulnar nerve injury occurred. One patient had an infected incision. Binary regression analysis showed that the time elapsed between injury and operation (P=0.033) and Gartland type (P=0.008) were inversely correlated with outcomes; the longer the duration, the poorer the outcomes. CONCLUSIONS: The functional outcomes after open reduction and K-wire fixation through an anterior approach were poorer with longer time to surgery and Gartland type. LEVEL OF EVIDENCE: Level III.

The Efficacy and Safety of the Chinese Herbal Formula, JTTZ, for the Treatment of Type 2 Diabetes with Obesity and Hyperlipidemia: A Multicenter Randomized, Positive-Controlled, Open-Label Clinical Trial.

BACKGROUND AND AIM: Studies have shown an increasing number of type 2 diabetes (T2D) patients with concomitant obesity and hyperlipidemia syndromes, resulting from relevant metabolic disorders. However, there are few medications and therapies, which can thoroughly address these issues. Therefore, the current study evaluated the efficacy and safety of using JTTZ, a Chinese herbal formula, to treat T2D with obesity and hyperlipidemia. METHODS: A total of 450 participants with T2D (HbA1c ≥ 7.0%; waist circumference ≥ 90 cm and 80 cm in males and females, resp.; and triglycerides (TG) ≥ 1.7 mmol/L) were randomly assigned, in equal proportions, to two groups in this multicenter randomized, positive-controlled, open-label trial. One group received JTTZ formula, and the other received metformin (MET) for 12 consecutive weeks. The primary efficacy outcomes were changes in HbA1c, TG, weight, and waist circumference. Adverse reactions and hypoglycemia were monitored. RESULTS: HbA1c decreased by 0.75 ± 1.32% and 0.71 ± 1.2% in the JTTZ and MET groups, respectively, after 12 weeks of treatment. TG levels in the JTTZ and MET groups were reduced by 0.64 ± 2.37 mmol/L and 0.37 ± 2.18 mmol/L, respectively. Weight was decreased by 2.47 ± 2.71 kg in the JTTZ group and by 2.03 ± 2.36 kg in the MET group. JTTZ also appeared to alleviate insulin resistance and increase HOMA-ß. In addition, symptoms were significantly relieved in participants in the JTTZ group compared to those in the MET group. One case of hypoglycemia was reported in the MET group. No severe adverse events were reported in either group. CONCLUSIONS: The JTTZ formula led to safe and significant improvements in the blood glucose, blood lipids, and weight levels; relieved symptoms; and enhanced ß cell function for T2D patients with obesity and hyperlipidemia. The JTTZ formula has shown that it could potentially be developed as an alternative medicine for patients with T2D, particularly those who cannot tolerate metformin or other hypoglycemic drugs. This trial was registered with Clinicaltrials.gov NCT01471275.