Platelet Internalization Mediates Ferroptosis in Myocardial Infarction.

BACKGROUND: Myocardial cell death is the hallmark of myocardial infarction. In the process of myocardial injury, platelets contribute to the pathogenesis by triggering intense inflammatory responses. Yet, it is still unclear if platelets regulate cardiomyocyte death directly, thereby exacerbating myocardial injury in myocardial infarction. METHODS: We describe a mechanism underlying the correlative association between platelets accumulation and myocardial cell death by using myocardial infarction mouse model and patient specimens. RESULTS: Myocardial infarction induces platelets internalization, resulting in the release of miR-223-3p, a platelet-enriched miRNA. By targeting the ACSL3, miR-223-3p delivered by internalized platelets cause the reduction of stearic acid-phosphatidylcholine in cardiomyocytes. The presence of stearic acid-phosphatidylcholine protects cardiomyocytes against ferroptosis. CONCLUSIONS: Our work reveals a novel mechanism of platelet-mediated myocardial injury, highlighting antiplatelet therapies could potentially represent a multimechanism treatment of myocardial infarction, and implying ferroptosis being considered as novel target for therapeutics.

Hodge Decomposition of Single-Cell RNA Velocity.

RNA velocity has the ability to capture the cell dynamic information in the biological processes; yet, a comprehensive analysis of the cell state transitions and their associated chemical and biological processes remains a gap. In this work, we provide the Hodge decomposition, coupled with discrete exterior calculus (DEC), to unveil cell dynamics by examining the decomposed curl-free, divergence-free, and harmonic components of the RNA velocity field in a low dimensional representation, such as a UMAP or a t-SNE representation. Decomposition results show that the decomposed components distinctly reveal key cell dynamic features such as cell cycle, bifurcation, and cell lineage differentiation, regardless of the choice of the low-dimensional representations. The consistency across different representations demonstrates that the Hodge decomposition is a reliable and robust way to extract these cell dynamic features, offering unique analysis and insightful visualization of single-cell RNA velocity fields.

Assessment of aortic dilatation in Chinese children and adolescents with Turner syndrome: a single center experience.

BACKGROUND: Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. METHODS: This study included TS patients admitted to Shenzhen Children's Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada's method). RESULTS: A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those < 10 years old (16.6% vs. 1.8%, P = 0.009), and the proportion of patients with CoA or BAV who additionally exhibited AD was higher than those without these conditions (31.6% vs. 5.2%, P < 0.001). The ASI, A/D ratio, TSZ-score, and CHTSZ-score of the 11 patients with AD were 2.27 ± 0.40 cm/m2, 1.90 ± 0.37, 1.28 ± 1.08, and 3.07 ± 2.20, respectively. Among the AD patients, only 3 cases had a TSZ-score ≥ 2, and 2 cases had a TSZ-score ≥ 1. However, based on the assessment using the CHTSZ-score, 6 patients scored ≥ 2, and 5 patients scored ≥ 1. In contrast, the TSZ-score generally underestimated the aortic Z-scores in Chinese children with TS compared to the CHTSZ-score. CONCLUSIONS: The applicability of ASI and A/D ratio to children with TS is questionable, and racial differences can affect the assessment of TSZ-score in the Chinese population. Therefore, establishing the CHTSZ-score specifically tailored for Chinese children and adolescents is of paramount importance.

Sandwich Structured Metal oxide/Reduced Graphene Oxide/Metal Oxide-Based Polymer Electrolyte Enables Continuous Inorganic-Organic Interphase for Fast Lithium-Ion Transportation.

Introducing inorganic fillers into organic poly(ethylene oxide)(PEO)-based electrolyte has attracted substantial attention to enhance its ionic conductivity and mechanical strength, but limited inorganic-organic interphases are always caused by isolated particles agglomeration. Herein, a variety of sandwich structured metal oxide/reduced graphene oxide(rGO)/metal oxide nanocomposites to optimize lithium-ion conduction by interconnected amorphous organic-inorganic interphases in lithium metal batteries, are proposed. With the support of high surface area rGO, the agglomeration of metal oxide particles is precluded, forming continuous amorphous organic-inorganic interphases with stacked layer-by-layer structure, thus creating 3D interconnected lithium-ion transportation channels vertically and laterally. Besides, metal oxide nanoparticles with hydroxyls possess high affinity toward bis(tri-fluoromethanesulfonyl)imide anions by hydrogen bindings between hydroxyls and fluorine and metal-oxygen bonds, releasing more free lithium ions. Consequently, PEO-ZnO/rGO/ZnO electrolyte delivers superior ionic conductivity of 1.02 × 10-4 S cm-1 at 25 °C and lithium-ion transference number of 0.38 at 60 °C. Furthermore, ZnO/rGO/ZnO insertion promotes the formation of LiF-rich stable solid electrolyte interface, endowing Li symmetric cells with long-term cycling stability over 900 hours. The corresponding LiFePO4 cathode possesses a high reversible specific capacity of 130 mAh g-1 at 0.5C after cycling 300 cycles with a poor capacity fading of 0.05% per cycle.

mi-IsoNet: systems-scale microRNA landscape reveals rampant isoform-mediated gain of target interaction diversity and signaling specificity.

MicroRNA (miRNA) is not a single sequence, but a series of multiple variants (also termed isomiRs) with sequence and expression heterogeneity. Whether and how these isoforms contribute to functional variation and complexity at the systems and network levels remain largely unknown. To explore this question systematically, we comprehensively analyzed the expression of small RNAs and their target sites to interrogate functional variations between novel isomiRs and their canonical miRNA sequences. Our analyses of the pan-cancer landscape of miRNA expression indicate that multiple isomiRs generated from the same miRNA locus often exhibit remarkable variation in their sequence, expression and function. We interrogated abundant and differentially expressed 5' isomiRs with novel seed sequences via seed shifting and identified many potential novel targets of these 5' isomiRs that would expand interaction capabilities between small RNAs and mRNAs, rewiring regulatory networks and increasing signaling circuit complexity. Further analyses revealed that some miRNA loci might generate diverse dominant isomiRs that often involved isomiRs with varied seeds and arm-switching, suggesting a selective advantage of multiple isomiRs in regulating gene expression. Finally, experimental validation indicated that isomiRs with shifted seed sequences could regulate novel target mRNAs and therefore contribute to regulatory network rewiring. Our analysis uncovers a widespread expansion of isomiR and mRNA interaction networks compared with those seen in canonical small RNA analysis; this expansion suggests global gene regulation network perturbations by alternative small RNA variants or isoforms. Taken together, the variations in isomiRs that occur during miRNA processing and maturation are likely to play a far more complex and plastic role in gene regulation than previously anticipated.

Impact of COVID-19 pandemic on influenza virus prevalence in children in Sichuan, China.

We performed a retrospective analysis of influenza A and B virus antigen detection data in children in Sichuan Province from January 2019 to December 2021, with the goal of studying the impact of the COVID-19 pandemic on influenza circulation in children in Sichuan, China. During the pandemic, both the number of specimens and the positive rates of the influenza virus fell dramatically. The positivity for influenza A virus decreased from 22.5% in 2019 to 9.9% in 2020 to 0.2% in 2021 (p < 0.001). The lowest and highest positive rates for the influenza B virus occurred in 2020 and 2021, respectively, with a statistically significant 3-year comparison (p < 0.001). During the pandemic, the annual positivity remained higher in school-age than in preschoolers, while there was no difference in the annual positivity between the two gender groups, both consistent with the prepandemic results. During the pandemic, the seasonality of influenza A and B was different from that before the pandemic. In 2019, the epidemic season for influenza A was autumn and winter, while the epidemic season for influenza B was winter and spring. Seasonal changes in influenza A were insignificant after the pandemic, and influenza B became predominant in 2021, with a high prevalence in the autumn. Although influenza activity decreased during the COVID-19 pandemic, one should be on the lookout for a possible rebound in influenza circulation in the future.

e-MutPath: computational modeling reveals the functional landscape of genetic mutations rewiring interactome networks.

Understanding the functional impact of cancer somatic mutations represents a critical knowledge gap for implementing precision oncology. It has been increasingly appreciated that the interaction profile mediated by a genomic mutation provides a fundamental link between genotype and phenotype. However, specific effects on biological signaling networks for the majority of mutations are largely unknown by experimental approaches. To resolve this challenge, we developed e-MutPath (edgetic Mutation-mediated Pathway perturbations), a network-based computational method to identify candidate 'edgetic' mutations that perturb functional pathways. e-MutPath identifies informative paths that could be used to distinguish disease risk factors from neutral elements and to stratify disease subtypes with clinical relevance. The predicted targets are enriched in cancer vulnerability genes, known drug targets but depleted for proteins associated with side effects, demonstrating the power of network-based strategies to investigate the functional impact and perturbation profiles of genomic mutations. Together, e-MutPath represents a robust computational tool to systematically assign functions to genetic mutations, especially in the context of their specific pathway perturbation effect.

Combined assisted bone age assessment and adult height prediction methods in Chinese girls with early puberty: analysis of three artificial intelligence systems.

BACKGROUND: The applicability and accuracy of artificial intelligence (AI)-assisted bone age assessment and adult height prediction methods in girls with early puberty are unknown. OBJECTIVE: To analyze the performance of AI-assisted bone age assessment methods by comparing the corresponding methods for predicted adult height with actual adult height. MATERIALS AND METHODS: This retrospective review included 726 girls with early puberty, 87 of whom had reached adult height at last follow-up. Bone age was evaluated using the Greulich-Pyle (GP), Tanner-Whitehouse (TW3-RUS) and China 05 RUS-CHN (RUS-CHN) methods. Predicted adult height was calculated using the China 05 (CH05), TW3 and Bayley-Pinneau (BP) methods. RESULTS: We analyzed 1,663 left-hand radiographs, including 155 from girls who had reached adult height. In the 6-8- and 9-11-years age groups, bone age differences were smaller than those in the 12-14-years group; however, the differences between predicted adult height and actual adult height were larger than those in the 12-14-years group. TW3 overestimated adult height by 0.4±2.8 cm, while CH05 and BP significantly underestimated adult height by 2.9±3.6 cm and 1.3±3.8 cm, respectively. TW3 yielded the highest proportion of predicted adult height within ±5 cm of actual adult height (92.9%), with the highest correlation between predicted and actual adult heights. CONCLUSION: The differences in measured bone ages increased with increasing bone age. However, the corresponding method for predicting adult height was more accurate when the bone age was older. TW3 might be more suitable than CH05 and BP for predicting adult height in girls with early puberty. Methods for predicting adult height should be optimized for populations of the same ethnicity and disease.

Identification and Immune Characteristics Study of Pyroptosis­Related Genes in Endometriosis.

Endometriosis (EMT) is a prevalent gynecological disorder characterized by pain and infertility associated with the menstrual cycle. Pyroptosis, an emerging cell death mechanism, has been implicated in the pathogenesis of diverse diseases, highlighting its pivotal role in disease progression. Therefore, our study aimed to investigate the impact of pyroptosis in EMT using a comprehensive bioinformatics approach. We initially obtained two datasets from the Gene Expression Omnibus database and performed differential expression analysis to identify pyroptosis-related genes (PRGs) that were differentially expressed between EMT and non-EMT samples. Subsequently, several machine learning algorithms, namely least absolute shrinkage selection operator regression, support vector machine-recursive feature elimination, and random forest algorithms were used to identify a hub gene to construct an effective diagnostic model for EMT. Receiver operating characteristic curve analysis, nomogram, calibration curve, and decision curve analysis were applied to validate the performance of the model. Based on the selected hub gene, differential expression analysis between high- and low-expression groups was conducted to explore the functions and signaling pathways related to it. Additionally, the correlation between the hub gene and immune cells was investigated to gain insights into the immune microenvironment of EMT. Finally, a pyroptosis-related competing endogenous RNA network was constructed to elucidate the regulatory interactions of the hub gene. Our study revealed the potential contribution of a specific PRG to the pathogenesis of EMT, providing a novel perspective for clinical diagnosis and treatment of EMT.

A Novel Paclitaxel Derivative for Triple-Negative Breast Cancer Chemotherapy.

Paclitaxel-triethylenetetramine hexaacetic acid conjugate (PTX-TTHA), a novel semi-synthetic taxane, is designed to improve the water solubility and cosolvent toxicity of paclitaxel in several aminopolycarboxylic acid groups. In this study, the in vitro and in vivo antitumor effects and mechanisms of PTX-TTHA against triple-negative breast cancer (TNBC) and its intravenous toxicity were evaluated. Results showed the water solubility of PTX-TTHA was greater than 5 mg/mL, which was about 7140-fold higher than that of paclitaxel (<0.7 µg/mL). PTX-TTHA (10-105 nmol/L) could significantly inhibit breast cancer proliferation and induce apoptosis by stabilizing microtubules and arresting the cell cycle in the G2/M phase in vitro, with its therapeutic effect and mechanism similar to paclitaxel. However, when the MDA-MB-231 cell-derived xenograft (CDX) tumor model received PTX-TTHA (13.73 mg/kg) treatment once every 3 days for 21 days, the tumor inhibition rate was up to 77.32%. Furthermore, PTX-TTHA could inhibit tumor proliferation by downregulating Ki-67, and induce apoptosis by increasing pro-apoptotic proteins (Bax, cleaved caspase-3) and TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and reducing anti-apoptotic protein (Bcl-2). Moreover, PTX-TTHA demonstrated no sign of acute toxicity on vital organs, hematological, and biochemical parameters at the limit dose (138.6 mg/kg, i.v.). Our study indicated that PTX-TTHA showed better water solubility than paclitaxel, as well as comparable in vitro and in vivo antitumor activity in TNBC models. In addition, the antitumor mechanism of PTX-TTHA was related to microtubule regulation and apoptosis signaling pathway activation.

[Helsmoortel-Van der Aa syndrome due to hotspot mutation of ADNP gene and a literature review].

OBJECTIVE: To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis. METHODS: Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed. RESULTS: The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c.2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents. CONCLUSION: Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.

[Comparison of detection rates of chromosome G-banding karyotype analysis and fluorescence in situ hybridization among children with sex chromosome mosaicisms].

OBJECTIVE: To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. METHODS: A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. RESULTS: The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05). CONCLUSION: No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.

High PPT1 expression predicts poor clinical outcome and PPT1 inhibitor DC661 enhances sorafenib sensitivity in hepatocellular carcinoma.

BACKGROUND: Adaptive resistance and side effects of sorafenib treatment result in unsatisfied survival of patients with hepatocellular carcinoma (HCC). Palmitoyl-protein thioesterase 1 (PPT1) plays a critical role in progression of various cancers. However, its role on prognosis and immune infiltrates in HCC remains unclarified. METHODS: By data mining in the Cancer Genome Atlas databases, the role of PPT1 in HCC were initially investigated. Furthermore, HCC cell lines Hep 3B and Hep 1-6 were treated with DC661 or siRNA against PPT1. The biological function of PPT1 was determined by CCK-8 test, colony formation assay, TUNEL staining, immunofluorescence staining, Western blot test, and PI-Annexin V apoptosis assays in vitro. Animal models of subcutaneous injection were applied to investigate the therapeutic role of targeting PPT1. RESULTS: We found that PPT1 levels were significantly upregulated in HCC tissues compared with normal tissues and were significantly associated with a poor prognosis. Multivariate analysis further confirmed that high expression of PPT1 was an independent risk factor for poor overall survival of HCC patients. We initially found that PPT1 was significantly upregulated in sorafenib-resistant cell lines established in this study. Upon sorafenib treatment, HCC cells acquired adaptive resistance by inducing autophagy. We found that DC661, a selective and potent small-molecule PPT1-inhibitor, induced lysosomal membrane permeability, caused lysosomal deacidification, inhibited autophagy and enhanced sorafenib sensitivity in HCC cells. Interestingly, this sensitization effect was also mediated by the induction mitochondrial pathway apoptosis. In addition, the expression level of PPT1 was associated with the immune infiltration in the HCC tumor microenvironment, and PPT1 inhibitor DC661 significantly enhanced the anti-tumor immune response by promoting dendritic cell maturation and further promoting CD8+ T cell activation. Moreover, DC661 combined with sorafenib was also very effective at treating tumor models in immunized mice. CONCLUSIONS: Our findings suggest that targeting PPT1 with DC661 in combination with sorafenib might be a novel and effective alternative therapeutic strategy for HCC.

TPX2 Serves as a Cancer Susceptibility Gene and Is Closely Associated with the Poor Prognosis of Endometrial Cancer.

Background: Endometrial cancer (EC) is a common tumor of the genital tract that affects the female reproductive system but with only limited treatment options. We aimed to discover new prognostic biomarkers for EC. Methods: We used mRNA-seq data to detect differentially expressed genes (DEGs) between EC and control tissues. Detailed clinicopathological information was collected, and changes in the mRNA and protein levels of hub DEGs were analyzed in EC. Copy number variation (CNV) was also evaluated for its association with the pathogenesis of EC. Gene set enrichment analysis (GSEA) was conducted to enrich significant pathways driven by the hub genes. Cox regression analysis was used to select variables to create a nomogram. The nomogram was calibrated by applying the concordance index (C-index), and net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). Results: Differential expression analysis identified 24 DEGs as potential risk factors for EC. Survival analysis revealed that TPX2 expression was related to worsening overall survival in patients with advanced EC. A high CNV was associated with the overexpression of TPX2; this suggested that modifications in the cell-cycle pathway might be crucial in the advancement of EC. Moreover, an individualized nomogram was developed for TPX2 incorporating clinical factors; this was also evaluated for its ability to predict EC. Calibration and DCA analyses confirmed the robustness and clinical usefulness of the nomogram. Conclusion: We offer novel insights into the pathogenesis and molecular mechanisms of EC. The overexpression of TPX2 was related to a poorer prognosis and could serve as a biomarker for predicting prognostic outcomes in EC patients.

Polyethylene glycol recombinant human growth hormone in Chinese prepubertal slow-growing short children: doses reported in a multicenter real-world study.

BACKGROUND: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. METHODS: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). RESULTS: Five hundred and ten patients were included and grouped based on dosage as A (0.10-0.14 mg/kg/week), B (0.15-0.16 mg/kg/week), C (0.17-0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). CONCLUSIONS: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15-0.20 mg/kg/week might be preferred. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03249480 , retrospectively registered.

Construction of a new complete growth reference for urban Chinese children.

BACKGROUND: Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. METHODS: Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017-2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. RESULTS: Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. CONCLUSIONS: Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

Two cases of infantile-onset primary generalized glucocorticoid hypersensitivity and the effect of mifepristone.

BACKGROUND: Primary generalized glucocorticoid hypersensitivity (PGGH) is a very rare disease caused by terminal organ hypersensitivity to glucocorticoids for which the aetiology is unknown. The incidence of PGGH is extremely rare, especially in children. To date, the literatures about the etiology, prognosis and treatment of PGGH are scarce. Aim of the study is describing the cases of two Chinese children with infantile-onset PGGH in one family, one of whom died and one who was treated with mifepristone. They are the two youngest children with PGGH reported in the literature. CASE PRESENTATION: Two siblings with infantile-onset PGGH were affected in this family. The main manifestations of patient 1 were typical Cushing's syndrome-like manifestations, significantly aggravated symptoms after physiological doses of glucocorticoids and very low levels of serum cortisol and adrenocorticotropin hormone (ACTH) during attacks. After being diagnosed with PGGH, he was given guidance to avoid glucocorticoids and took mifepristone therapy for 5 months, and his symptoms improved. Patient 2 was the younger brother of patient 1, with similar manifestations to his brother at the age of 4 months. Patient 2 ultimately died at the age of 9 months. CONCLUSION: PGGH is a very rare disease that can lead to death if not diagnosed and treated in a timely manner. This article describes the cases of the two youngest children with PGGH reported in the literature, one of whom improved after mifepristone treatment, and increases the knowledge of the clinical manifestations of and the treatment experience in PGGH.

Analysis of risk factors for complications of perforator propeller flaps used for soft tissue reconstruction after malignant tumor resection: A systematic review and meta-analysis.

BACKGROUND: Perforator propeller flaps (PPFs) have been widely used due to their numerous advantages; however, they were also associated with various complications. Herein, we analyzed the risk factors for complications of PPFs used for soft tissue reconstruction after malignant tumor resection. METHODS: We searched databases for articles on soft tissue reconstruction using PPFs after malignant tumor resection published between January 1991 and April 2021. Studies were selected according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Fixed effects models and relative risks were used for data analysis. Funnel plots and Begg's test were used to evaluate publication bias. RESULTS: Twenty-six articles met the inclusion criteria. Complications were found in 24.7% of all patients. The four significant risk factors were age equal or older than 60 years (pooled relative risk, 1.83; p = .04), smoking (pooled relative risk, 2.32; p = .03), diabetes (pooled relative risk, 2.59; p = .01) and radiotherapy (pooled relative risk, 2.09; p = .01). Hypertension, defects located in the extremities, flap size equal or greater than 100 cm2 , and pedicle rotation equal or greater than 120 degrees were not significant risk factors for complications. No publication bias was found in the included articles. CONCLUSION: Age equal or older than 60 years, smoking, diabetes and radiotherapy are four risk factors for complications when PPFs are used to reconstruct soft tissue defects resulting from malignant tumor resection.

A Systematic Review And Meta-Analysis: Botulinum Toxin A Effect on Postoperative Facial Scar Prevention.

BACKGROUND: Postoperative facial scarring can be a significant psychological burden for patients to carry after surgery, often resulting in prolonged mental health dysfunction. Currently, there is no established method to prevent facial scar formation; however, there are several methods to prevent facial scar hyperplasia and improve scar quality. Botulinum toxin A (BTA) has been widely used due to its properties of muscle paralysis and known success in plastic surgery and cosmetology. This meta-analysis aimed to evaluate the efficacy of BTA in preventing postoperative facial scar hyperplasia and improving scar quality. METHODS: PubMed, MEDLINE, EMBASE, web of science, and Cochrane libraries were searched for randomized controlled trials (RCTs) (published before May 2021) wherein BTA was used for the treatment of facial scars. The efficacy and safety of BTA were evaluated by the following scales: the Vancouver Scar Scale (VSS), Visual Analog Scale (VAS), Observer Scar Assessment Scale (OSAS), Patient Scar Assessment Scale (PSAS), and Stony Brook Scar Evaluation Scale (SBSES); the BTA effect on scar width and complications was also assessed. RESULTS: Ten RCTs involving 114 cases were included. Through quantitative analysis, the BTA injection group had a higher VAS score, lower VSS score, lower OSAS score, and smaller scar width. However, no significant difference was noted in the incidence of postoperative complications between the two groups. CONCLUSIONS: This meta-analysis demonstrated that BTA can safely improve the appearance of postoperative facial scars by significantly inhibiting scar hyperplasia and improving scar quality. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Clinical phenotype and genetic analysis of a Chinese pedigree affected with familial progressive hyperpigmentation and hypopigmentation].

OBJECTIVE: To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with familial progressive hyperpigmentation and hypopigmentation (FPHH). METHODS: Clinical data and family history for a child with FPHH were collected. Peripheral blood samples were collected from the child, his parents and two sisters. Following the extraction of DNA, high-throughput sequencing was carried out to screen for genetic variant associated with the disease. Candidate variant was verified by Sanger sequencing of his family members. RESULTS: The main clinical features of the proband have included progressive hyperpigmentation and hypopigmentation. High-throughput sequencing revealed that he has harbored a heterozygous c.105T>A (p.Asn35Lys) variant of the KITLG gene, which was unreported previously. Sanger sequencing confirmed that the variant has co-segregated with the disease phenotype in his pedigree. CONCLUSION: For infants with progressive skin pigmentation and hypopigmentation spots, FPHH should be suspected. The heterozygous c.105T>A (p.Asn35Lys) variant of the KITLG gene probably underlay the FPHH in this pedigree.