Superb microvascular imaging for evaluating the activity of juvenile localised scleroderma: a preliminary study.

OBJECTIVES: To investigate microvascular changes in juvenile localised scleroderma (JLS) lesions using superb microvascular imaging (SMI) and assess SMI's utility in evaluating disease activity. METHODS: This prospective study enroled 16 children (7 males) with pathologically diagnosed JLS between January 2021 and June 2023. Lesions were assessed using Localised Scleroderma Cutaneous Assessment Tools, including the localised scleroderma skin activity index (LoSAI) and localised scleroderma skin damage index (LoSDI). Lesions with LoSAI scores > 0 were classified as active. The thickness and blood flow of the lesions and healthy skin layers of the contralateral site were evaluated using ultrasound. SMI was used to detect microvascular blood flow in the lesions and healthy skin, and the vascular index (VI) was calculated. The difference in VI between active lesions and healthy skin was correlated with LoSAI and total scores. RESULTS: Of 46 lesions, 23 were active and 23 inactive. The skin thickness of the lesion was 0.094 ± 0.024 cm, and that of the healthy site was 0.108 ± 0.026 cm (p < 0.001). The VI of the active lesions and healthy skin were 7.60 (3.60, 12.80)% and 1.10 (0.50, 2.10)%, respectively (p < 0.001). The VI of the inactive lesions and the healthy skin were 0.85 (0.00, 2.20)% and 1.60 (1.00, 3.10)%, respectively (p = 0.011). VI differences between active lesions and healthy skin positively correlated with the LoSAI clinical score (r = 0.625, p = 0.001) and total score (r = 0.842, p < 0.001). CONCLUSION: SMI can quantitatively detect microvascular blood flow changes in JLS skin, indicating lesion activity and severity. CLINICAL RELEVANCE STATEMENT: SMI is a convenient, non-invasive, technique for detecting active JLS lesions and can provide valuable information to guide treatment options. KEY POINTS: Current grading systems of juvenile localised scleroderma rely on subjective clinical information. Superb Microvascular Imaging identified that vascular indexes between active lesions and healthy skin positively correlated with clinical scores. Superb Microvascular Imaging effectively assesses microvascular blood flow, aiding juvenile localised scleroderma lesion activity evaluation.

Right ventricular function indices and platelet parameters for early prediction value of bronchopulmonary dysplasia: a retrospective study.

BACKGROUND: To examine the value of early echocardiographic indices for the right ventricular function combined with platelet(PLT) parameters for predicting bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: This retrospective study included infants with gestational age (GA) below 32 weeks, who were admitted to the neonatal intensive care unit(NICU). The detection rate of tricuspid regurgitation jet velocity (TRVJ), ventricular septal flattening, pulmonary artery widening, right ventricular dilation, and right atrial enlargement on the 7th day of life (DOL 7) were compared between BPD and non-BPD infants. Echocardiographic indices of the right ventricular function including tricuspid annular plane systolic excursion (TAPSE) and right ventricular index of myocardial performance (RIMP) were measured on 1 day of life (DOL 1)、on DOL 7 and on 14 day of life (DOL 14) respectively. The PLT parameters including the PLT count, mean platelet volume (MPV), platelet hematocrit (PCT) level, and platelet distribution width (PDW) were measured on the DOL 1,DOL 7, and DOL 14. Multivariate logistic regression was used to analyze the relationship between these parameters and BPD. Receiver operating characteristic curve analysis was performed to assess the predictive value of the right ventricular function indices and PLT parameters for BPD. RESULTS: A total of 220 preterm infants were included in this study, and of these, 85 infants developed BPD among them. The RIMP of the BPD group on DOL 14 was higher than that of the non-BPD group (P < 0.05). The TAPSE of the BPD group on DOL 14 was lower than that of the non-BPD group (P < 0.05). The PLT count of the BPD group on DOL 1 was lower than that of the non-BPD group (P < 0.05), and the MPV of the BPD group on DOL 1 was higher than that of the non-BPD group (P < 0.05). Using multivariate logistic regression, GA、invasive mechanical ventilation duration ≥ 7 days、 PLT、 MPV、 TAPSE and RIMP were found to be independent risk factors for BPD. The area under the receiver operating characteristic curve was 0.846 (95CI: 0.794∼0.899), which improved when using right ventricular function indices combined with platelet parameters. CONCLUSION: TAPSE and RIMP combined with PLT count and MPV can help identify preterm infants at an increased risk of developing BPD.

CircRAD54L2 promotes triple-negative breast cancer progression by regulating the miR-888 family/PDK1 axis.

BACKGROUND: The long-term prognosis of breast cancer with metastasis remains extremely poor. Genetic alterations in tumor cells result in cellular heterogeneity, promoting cancer cells invasion and colonization in some organs during the metastatic process. CircRNAs are very promising as critical biological markers and precise diagnoses in identifying disease mechanisms and developing new methods for effective treatment. However, the role of aberrant expression of circRNAs in breast cancer progression remains largely unknown. METHODS: RNase R treatment and quantitative RT-PCR (qRT-PCR) were performed for circRNA detection. Transwell chamber assays were used to examine the chemotactic migration and invasion of breast cancer cells. RESULTS: This study identified and characterized the circRAD54L2 originating from exon 1, 2, 3, and 4 of the RAD54L2 gene. Importantly, we found that circRAD54L2, rather than RAD54L2 linear mRNA, was significantly upregulated in breast cancer cell lines. Furthermore, we found that inhibiting circRAD54L2 expression markedly reduced the invasion, metastasis, and proliferation of breast cancer cells via sponging of the miR-888 family, which downregulated the expression of pyruvate dehydrogenase kinase 1 (PDK1). CONCLUSION: Our results showed that circRAD54L2 could regulate PDK1 expression by sponging the miR-888 family competing for the ceRNA mechanism, indicating that circRAD54L2 may act as an essential upstream regulator and providing further mechanistic evidence to support the notion that circRAD54L2/miR-888s/PDK1 is a promising therapeutic target in the treatment of breast cancer.

Epidemiological investigation and ultrasonic diagnosis of developmental dysplasia of the hip in Chinese infants: A large multi-center cohort study.

ABSTRACT: Developmental dysplasia of the hip (DDH) is common among Chinese infants, but a lack of large-scale, multi-center epidemiological studies has made it difficult to characterize the risk factors associated with this disease.This multi-center cohort study included 19,833 Chinese infants aged 14 days to 6 months. A multi-center ultrasound protocol was used to diagnose hip abnormalities, and epidemiological data of the infants were collected through questionnaires. Categorical variables were expressed as percentages and compared using χ2 test. Multivariate analysis was performed through logistic regression.Of 19,833 infants, 345 had DDH (1.7%). DDH incidence was higher in female infants (n = 279) than in male infants (n = 66) (χ2 = 95.89, P < .05), and there were more left hip cases (n = 149) than right hip cases (n = 79) (χ2 = 12.49, P < .05). DDH incidence was statistically different amongst different age groups in months (χ2 = 451.71, P < .05), and it gradually decreased with age (P < .05). The prevalence of a positive DDH family history, breech presentation, oligohydramnios, swaddling style, and other musculoskeletal deformities was higher in the positive group than in the negative group (all P < .05). No significant differences were found in terms of delivery by cesarean section, multiple births, or premature birth between both groups.Family history, breech presentation, oligohydramnios, musculoskeletal deformities, and female sex are high-risk factors for DDH in Chinese infants. The incidence of DDH gradually decreases with age. The results of this study provide evidence for the epidemiology of infant DDH in China.

[Protein microarray analysis on changes in protein phosphorylation in recurrent nasopharyngeal carcinoma].

OBJECTIVE: To compare the differential phosphorylation level of proteins between relapsed nasopharyngeal carcinoma (rNPC) and primary nasopharyngeal carcinoma (pNPC). METHODS: Total protein was extracted from 4 pNPC tissue and 4 rNPC tissue samples from January 2003 to September 2005. Then it was analyzed by antibody microarray with 656 antibodies. The differential phosphorylation level of proteins was screened and clustering analysis conducted. The phosphorylation status of the protein sites and its functional pathways were analyzed via an online database of PhosphoSite Plus. The protein expressions were detected by immunohistochemistry. RESULTS: Relapsed and primary nasopharyngeal carcinomas had differential phosphorylation level of proteins. And 6 differentially expressed proteins were identified. The phosphorylation levels of KIT, ATP1A1, Synapsin, SEK1 and histone H2AX were up-regulated in rNPC (P = 0.007 - 0.048) while c-Jun was down-regulated (P = 0.030). The expression of P-H2AX in rNPC was significantly higher than that in pNPC [0.390 (0.175) vs 0.290 (0.155)], but p-c-Jun was significantly lower in rNPC than that in pNPC [0.625 (0.145) vs 0.725 (0.178)] (both P < 0.05). Among them, the changes in the phosphorylation levels of c-Jun, histone H2AX, SEK1 and KIT might play important roles in the relapse of NPC through improving DNA damage repair ability, inhibiting apoptosis and promoting tumorigenesis. CONCLUSION: The changes of protein phosphorylation may help to explain the recurrent mechanisms of NPC and provide new therapeutic anti-recurrence targets.

Reversible severe fatty liver induced by capecitabine: A case report.

RATIONALE: Capecitabine (CAP) is a chemotherapeutic agent used to treat breast and gastrointestinal cancers. The most common adverse reactions of CAP primarily included gastrointestinal and dermatological effects. Whereas, the CAP-induced fatty liver had never been reported. PATIENT CONCERNS: In this study, a-69-year old female presented a history of hypertension with regulated blood pressure, whereas diabetes mellitus, hyperlipidemia, and hepatitis were excluded. No alcohol,tobacco, or other drugs use was declared. DIAGNOSES: She was diagnosed as infiltrating ductal carcinoma of left breast with the hepatic and pulmonary metastasis. The dihydropyrimidine dehydrogenase (DPD) deficiency is not involved. INTERVENTIONS: She received treatment with CAP that was administered orally at a dosage of 1500mg twice daily intermittently (2weeks on/1 week off). The treatment was well-tolerated any typical adverse reactions such as diarrhea, nausea, and hand-foot syndrome (HFS) were noted. The parameters of the functional liver, the total cholesterol, and triglyceride were in normal ranges before and after therapy. After 3 cycles of the treatment, computed tomography (CT) scan revealed signs of fatty liver. After a 10-cycle course, CAP was substituted with tamoxifen because of the further aggravation of fatty liver. OUTCOMES: Several months after withdrawal, the follow-up CT scans demonstrated significant improvement of fatty liver. LESSONS: We presented a case of breast cancer with severe fatty liver as a consequence of the administration of CAP that was not involved in DPD deficiency or CAP-associated hypertriglyceridemia; these potential adverse effects of therapy with CAP should be intensely investigated.

Expression of RSK4 in lung adenocarcinoma tissue and its clinicopathological value: a study based on RNA-seq data and immunohistochemistry.

The clinical significance of p90-kDa ribosomal S6 kinase (RSK) family members in lung adenocarcinoma (LUAD) is unknown. The aim of this study was to analyze genomic alterations in RSK family membersand investigate the expression and clinicopathological significance of RSK4 in LUAD tissues. Genomic calterations of RSK family, overall survival, andinteraction networks were analyzed in patients with LUAD (n=522), using data from The Cancer Genome Atlas (TCGA) database. The expression of RSK4 protein was investigated in an independent cohort of patients with LUAD (n=127) by immunohistochemistry, and relationships between RSK4 protein levels and clinicopathological parameters of LUAD were analyzed. Patients with LUAD with RSK genomic alterations had significantly better overall survival than patients without alterations (P=0.026). RSK4 mRNA was overexpressed in LUAD compared with noncancerous lung tissue (P=0.013), and the diagnostic value of RSK4 expression was moderate, as evaluated by a value of 0.603 for the area under the receiver operator characteristic curve (95% CI, 0.551-0.655; P=0.01). RSK4 protein levels were significantly higher in LUAD than in para-carcinoma tissue (P=0.002); moreover, RSK4 protein expression was closely associated with TNM stage (P<0.001), tumor diameter (P<0.001), lymphatic metastasis (P<0.001), and distant metastasis (P=0.003). In conclusion, alterations to RSK family members may affect tumor progression in LUAD. RSK4 is a potentially useful molecular biomarker for LAUD diagnosis and may predict disease progression in patients with this condition.

MiR-133a is downregulated in non-small cell lung cancer: a study of clinical significance.

BACKGROUND: Despite present studies which suggested miR-133a as a promising biomarker for several cancers, there still exist no articles concerning the validated clinical significance of miR-133a in non-small cell lung cancer (NSCLC). Therefore, in this study, we targeted the correlation between miR-133a expression and clinicopathological significance in NSCLC patients. METHODS: The expression of miR-133a in 125 cases of NSCLC and their paired adjacent non-cancerous tissues was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Meanwhile, the relationship between miR-133a expression and several clinicopathological parameters and patient survival was analyzed. RESULTS: The relative level of miR-133a was 2.0108 ± 1.3334 in NSCLC tissues, significantly lower than that of the adjacent non-cancerous lung tissues (3.6430 ± 2.2625, P = 0.019). The area under curve (AUC) of low expression of miR-133a to diagnose NSCLC was 0.760 (95% CI: 0.702 ~ 0.819, P < 0.001). MiR-133a expression was negatively correlated to lymphatic metastasis (r = -0.182, P = 0.042), tumor size (r = -0.253, P = 0.04), clinical TNM stages (r = -0.154, P = 0.087), and EGFR protein expression (r = -0.612, P < 0.001). CONCLUSIONS: MiR-133a serves as a tumor-suppressive miRNA in human NSCLC, and its downregulation suggests deterioration in NSCLC patients.

Altered localization of p120 catenin in the cytoplasm rather than the membrane correlates with poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: P120 catenin (p120ctn), a regulator of cell adhesion, has previously been found in many malignancies, and suggested a role in invasion, metastasis and survival. The aim of this study was to investigate correlations between altered localization of p120ctn and clinical-pathological characteristics in esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical staining for p120ctn was performed on tissue samples from 118 patients with ESCC. The expression of p120ctn was scored for intensity and cellular localization by Image-pro Plus 6.0. Correlations between immunohistochemical staining of p120ctn and pathological characteristics and clinical prognosis were determined using SPSS 18.0 software. RESULTS: Membrane expression of p120ctn in ESCCs was lower than that in adjacentnormal esophageal epithelial tissues (P = 0.041), while overall cellular expression of p120ctn was not different between the two tissue types (P = 0.787). Furthermore, neither overall cellular expression nor localized membrane expression was associated with histological and clinical variables. The high ratio of membrane expression to overall cellular expression (M/C) of p120ctn was inversely associated with lymph node invasion (P = 0.001), tumor differentiation (P = 0.012) and advanced tumor stage (P = 0.005); however, it was poorly associated with T stage (P = 0.274). The high M/C ratio of p120ctn was inversely correlated with poor survival; the 5-year OS (overall survival) and the 5-year DFS (disease free survival) for the high M/C ratio group were significantly higher than those of the low M/C ratio group (41.0% vs. 6.7%, P = 0.000; 44.1% vs. 24.9%, P = 0.007). Both the M/C ratio of p120ctn and N status were independent variables for the prediction of overall survival (P = 0.007 and P = 0.027). The M/C of p120ctn predicted a 0.49-fold risk of ESCC death (p = 0.007, 95% CI 0.29-0.83). CONCLUSIONS: The reduced M/C ratio of p120ctn acted as an independent prognostic factor for ESCC patient survival and for the migration and invasive behavior of the disease.

Prognostic Nomogram for Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy.

This study was aimed to define possible predictors of overall survival in nasopharyngeal carcinoma (NPC). Patients were treated with intensity-modulated radiation therapy (IMRT), to establish an effective prognostic nomogram that could provide individualized predictions of treatment outcome in this setting. We reviewed the records of 533 patients with non-metastatic NPC who underwent IMRT with or without concurrent chemotherapy at the Department of Radiation Oncology of Sun Yat-Sen University from 2002 to 2009; none of these patients received induction or adjuvant chemotherapy. These data sets were used to construct a nomogram based on Cox regression. Nomogram performance was determined via a concordance index (C-index) and a calibration curve which was compared with the TNM staging system for NPC. The results were validated in an external cohort of 442 patients from the Department of Radiation Oncology of Wenzhou Medical College who were treated during the same period. Results showed that the greatest influence on survival were primary gross tumor volume, age, tumor stage and nodal stage (2002 Union for International Cancer Control [UICC] staging system), which were selected into the nomogram. The C-index of the nomogram for predicting survival was 0.748 (95%CI, 0.704-0.785), which was statistically higher than that of TNM staging system (0.684, P<0.001). The calibration curve exhibited agreement between nomogram-predicted and the actual observed probabilities for overall survival. In the validation cohort, the nomogram discrimination was superior to the TNM staging system (C-index: 0.768 vs 0.721; P = 0.026). In conclusion, the nomogram proposed in this study resulted in more-accurate prognostic prediction for patients with NPC after IMRT and compared favorably to the TNM staging system; this individualized information will aid in patient counseling and may be used for de-escalation trials in the future.