Identification and validation of CCR5 linking keloid with atopic dermatitis through comprehensive bioinformatics analysis and machine learning.

There is sufficient evidence indicating that keloid is strongly associated with atopic dermatitis (AD) across ethnic groups. However, the molecular mechanism underlying the association is not fully understood. The aim of this study is to discover the underlying mechanism of the association between keloid and AD by integrating comprehensive bioinformatics techniques and machine learning methods. The gene expression profiles of keloid and AD were downloaded from the Gene Expression Omnibus (GEO) database. A total of 449 differentially expressed genes (DEGs) were found to be shared in keloid and AD using the training datasets of GEO (GSE158395 and GSE121212). The hub genes were identified using the protein-protein interaction network and Cytoscape software. 20 of the most significant hub genes were selected, which were mainly involved in the regulation of the inflammatory and immune response. Through two machine learning algorithms of LASSO and SVM-RFE, CCR5 was identified as the most important key gene. Subsequently, upregulated CCR5 gene expression was confirmed in validation GEO datasets (GSE188952 and GSE32924) and clinical samples of keloid and AD. Immune infiltration analysis showed that T helper (Th) 1, 2 and 17 cells were significantly enriched in the microenvironment of both keloid and AD. Positive correlations were found between CCR5 and Th1, Th2 and Th17 cells. Finally, two TFs of CCR5, NR3C2 and YY1, were identified, both of which were downregulated in keloid and AD tissues. Our study firstly reveals that keloid and AD shared common inflammatory and immune pathways. Moreover, CCR5 plays a key role in the pathogenesis association between keloid and AD. The common pathways and key genes may shed light on further mechanism research and targeted therapy, and may provide therapeutic interventions of keloid with AD.

Possible Mechanism and Treatment Results of Combined Pediatric Fractures of the Humeral Lateral Condyle and Ipsilateral Ulnar Olecranon.

OBJECTIVE: Combined fractures of the lateral condyle of the humerus and the ipsilateral ulnar olecranon are rarely seen in children. Therefore, the mechanism and suitable treatments remain debatable. This study describes the possible mechanism of combined humeral lateral condyle and ipsilateral ulnar olecranon fractures and presents the treatment results. METHODS: Children diagnosed with combined fractures of the humeral lateral condyle and ipsilateralulnar olecranon from July 2010 to July 2020 were retrospectively analyzed. Humeral lateral condyle fractures were treated with open reduction and internal fixation with bioabsorbable pins. Ulnar olecranon fractures were treated with closed reduction and percutaneous pinning with K-wires for Mayo type IA fractures and with tension-band wiring or a locking plate for Mayo type IIA fractures. The postoperative function and appearance of the elbow were evaluated using the Flynn criteria and Mayo Elbow Performance Score (MEPS) at follow-up. RESULTS: The cohort comprised 19 patients aged from 4 to 11 years. Bony compression and avulsion by attached muscles and ligaments may be the leading factors causing the combined injuries, as the children fell with an outstretched and supinated elbow. The average follow-up time was 33 months. High MEPS of >90 indicated that good to excellent results were obtained without complications. CONCLUSIONS: This study proposed a reasonable hypothesis for the mechanism of combined humeral lateral condyle and ipsilateral ulnar olecranon fractures in children. Satisfactory outcomes were achieved with bioabsorbable pins for lateral condyle fractures and closed reduction and percutaneous pinning with K-wires, tension-band wiring, or locking plate for olecranon fractures.

Risk factors for osteonecrosis of the humeral head after internal fixation of proximal humeral fractures: a systematic review and meta-analysis.

BACKGROUND: Osteonecrosis of the humeral head (ONHH) is a severe complication after the internal fixation of proximal humeral fractures (IFPHF). The risk factors remain controversial though many studies have reported. In this research, meta-analysis was used to evaluate which surgeon-level factors can be modified to lower the risk and we hope to provide evidence-based support for preventing ONHH. METHODS: Literature was retrieved from PubMed, Cochrane Library, Embase, Web of Science, and Scopus for eligible studies published up to January 2023. The pooled odds ratios (ORs) were calculated with their corresponding 95% confidence intervals (CIs) to evaluate. STATA 15.1 software was applied for data synthesis, sensitivity synthesis, and publication bias. RESULTS: 45 articles were published between 2000 and 2022, and 2482 patients were finally included. All articles were observational research, with 7 case-control studies and 38 cohort studies, and the Newcastle Ottawa Scale (NOS) score ranged from 7 to 9. The pooled results suggested that age (OR 0.32, 95% CI 0.14-0.74, P = 0.01), reduction quality (OR 0.08, 95% CI 0.01-0.44, P = 0.00), fracture type (OR 0.44, 95% CI 0.25-0.78, P = 0.01), surgical approach (OR: 4.06, 95% CI 1.21-13.61, P = 0.02) and fixation implant (OR = 0.68, 95% CI = 0.34-1.33, P = 0.02) were risk factors for ONHH after IFPHF. According to sensitivity analysis, Begg (P = 0.42) and Egger (P = 0.68) tests, the results were stable and exhibited no publication bias. CONCLUSIONS: The study showed that age, reduction quality, fracture type, surgical approach and fixation implant were risk factors for ONHH after IFPHF, while gender, varus or valgus, timely operation, injured side, and the existence of medial support have little influence on ONHH, as they could not be considered risk factors and still need further investigations.

A Rare Combined Injury in Children during Side Impact: The Possible Mechanism and Treatment Results.

OBJECTIVE: Proximal humeral fracture combined with contralateral midshaft clavicle fracture is an extremely rare injury in children. Few studies focus on the injury mechanism and treatment scheme. The aim of this study is to propose the possible mechanism of this injury and present the treatment results. METHODS: This retrospective study included children diagnosed with proximal humeral fractures combined with contralateral midshaft clavicle fractures from August 2016 to March 2019 in the corresponding author's institution. The patients received elastic stable intramedullary nails and external fixation as treatment. The radiological and clinical outcomes of treatments were evaluated using the imaging and the Constant-Murley score (CMS) in follow up. RESULTS: Twelve patients (eight males and four females) with an average age of 7.83 years old (age 5-12) were included in this research. All the patients had suffered a side impact in a road traffic accident or outdoor environment. Hypothesis about the mechanism was the proximal humerus was directly impacted at first and caused the surgical neck fracture, then the contralateral shoulder hits the solid object and the contralateral midshaft clavicle was fractured. During the average 45.2 months (range 36-57) follow-up, all the patient's fractures achieved clinical and radiological union before 14 weeks without complications. Every patient had a satisfactory score (range from 92 to 100) on the CMS criteria for both shoulders. CONCLUSION: The hypothesis about the mechanism of this combined injury in this study sounds reasonable. It highlights the need for safety-related education about using a safety seat or wearing a seat belt to parents and caregivers, so as to avoid such injury even if the treatment with external fixation (EF) and proximal humeral and elastic stable intramedullary nailing (ESIN) showed good results.

Cadmium exposure and the risk of GDM: evidence emerging from the systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) has become a global concern for its severe adverse effects on both mother and fetus. Recent epidemiological studies reported inconsistent results of the association between cadmium (Cd) exposure and GDM. Therefore, a systematic review and meta- analysis were performed. PubMed, Web of Science, Scopus, Embase, and SpringerLink were searched up to July 2021. Observational studies containing the adjusted relative risks between Cd exposure and GDM were included in the quantitative synthesis. The retrieval comprised 218 articles out of which 11 met our criteria and 9 were included in the meta-analysis, representing a total of 32,392 subjects (2881 GDM). In total, Cd exposure might increase the risk of GDM in some extent (OR = 1.21, 95% CI [0.89, 1.64]), even without statistical significance in high heterogeneity (Q = 28.45, p < 0.05, I2 = 71.9%). Filtering two outliers indicated by Galbraith plot yielded a similar risk (OR = 1.19, 95% CI [1.02, 1.39]) with statistical significance. However, the heterogeneity among studies was obviously reduced (Q = 11.75, p = 0.068, I2 = 48.9%). Additionally, biological specimen, study design, and diagnostic criteria contributed to the high heterogeneity according to the subgroup analysis. Since some important results do not deny that Cd exposure increases the risk of GDM, high-quality multi-centered large cohort studies are required in the future.

[Association of phthalate and polycyclic aromatic hydrocarbon exposure during early pregnancy with premature delivery: A cohort study].

OBJECTIVE: To explore the relationship of the exposure to phthalate esters (PAE) and polycyclic aromatic hydrocarbons (PAH) with clinical premature delivery during early pregnancy. METHODS: We conducted a baseline questionnaire survey among 821 pregnant women undergoing prenatal examination in Hubei Provincial Maternal and Child Health Care Hospital, collected their morning urine samples and followed them up to the outcomes of pregnancy. We quantitatively analyzed 10 PAE and 10 PAH metabolites in the urine samples, followed by Mann-Whitney U test, chi-square test, and logistic regression analysis. RESULTS: The detection rate of the 5 factors exposed to was >80% while that of phthalic acid monobenzyl ester (MBzP) was <50% in PAEs; that of the 5 factors exposed to was >80%, that of 3-hydroxyphene (3-OHPHE) was 86.91% while that of 4-hydroxyphene (4-OHPHE) was <50% in PAHs. Logistic regression analysis showed that the risk of premature delivery was higher in the high MBzP- than in the low MBzP-exposure group (aOR = 2.26, 95% CI: 1.17－4.39). CONCLUSION: High MBzP-exposure may be a risk factor for premature delivery.