Self-evolving persistent luminescence nanoprobes for autofluorescence-free ratiometric imaging and on-demand enhanced chemodynamic therapy of pulmonary metastatic tumors.

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.

The rapid change of shear rate gradient is beneficial to platelet activation.

Fluid shear plays a key role in hemostasis and thrombosis, and the purpose of this study was to investigate the effect of shear gradient change rate (SGCR) on platelet reactivity and von Willebrand factor (vWF) activity and its mechanism. In this study, we developed a set of microfluidic chips capable of generating different shear gradients and simulated the shear rate distribution in the flow field by COMSOL Multiphysics software. Molecular markers of platelet activation (P-selectin, activated GPIIb/IIIa, phosphatidylserine exposure, and monocyte-platelet aggregate formation) were analyzed by flow cytometry. Platelet aggregation induced by shear gradient was studied by a microfluidic experimental platform, and plasma vWF ristocetin cofactor (vWF: RCO) activity was investigated by flow cytometry. The expression of p-Akt was studied by Western blotting. The results showed that the faster the SGCR, the higher the expression of platelet p-Akt, and the stronger the platelet reactivity and vWF activity. This indicates that fluid shear stress can activate platelets and vWF in a shear gradient-dependent manner through the PI3K/AKT signal pathway, and the faster the SGCR, the more significant the activation effect.

What is the context? Recent studies have shown that fluid shear stress plays a key role in platelet activation and thrombosis. However, its mechanism and effect have not been fully elucidated.The development of microfluidic chip technology enables people to study platelet function in a precisely controlled flow field environment.Previous studies have shown that the PI3K-AKT signal pathway may be a mechanically sensitive signal transduction pathway.What is new?In this study, we designed a microfluidic model with different narrow geometry, and controlled the injection pump to perfuse fluid at the same flow rate, so that the platelets flowing through the model experienced the flow field environment of different shear gradients.We studied the activities of platelets and von Willebrand factor in different flow fields and explored their signal transduction pathways.What is the impact? Our results suggest that vascular stenosis does increase platelet activity and the risk of thrombosis. However, its ability to activate platelets is not only related to the peak shear rate and shear time, but also closely related to the decreasing rate of shear gradient. Even if the peak shear rate at the stenosis is the same, the faster the shear rate decreases, the higher the reactivity of platelets and von Willebrand factor, which may be mediated by the PI3K-AKT signal pathway. This study not only helps clinicians to judge the risk of thrombosis in patients with atherosclerosis or percutaneous coronary intervention, but also helps us to better understand the mechanism of shear-induced platelet activation.

Orthodontic appliances for the treatment of pediatric obstructive sleep apnea: A systematic review and network meta-analysis.

This systematic review and network meta-analysis aims to preliminarily investigate the efficacy of different orthodontic appliances for the treatment of pediatric obstructive sleep apnea (OSA). Electronic databases were systematically searched. Randomized and non-randomized controlled trials with patients <18 y treated with either mandibular advancement appliance (MAA), rapid maxillary expansion (RME), or myofunctional therapy (MFT) were included. A network meta-analysis using multivariate random effects was conducted to estimate pooled differences using the apnea-hypopnea index (AHI) as the main outcome. Eleven studies (595 patients) were included in the analysis. Compared with control, MAA was associated with significant reductions in AHI of -2.18/h (95%CI -3.48 to -0.89, p = 0.001). Combined treatment of RME + adenotonsillectomy (AT) and RME + MAA showed a significant decrease in AHI, with -5.13/h (95%CI -7.50 to -2.76, p < 0.0001) and -3.79 (95%CI -5.21 to -2.37, p < 0.0001), respectively. MFT was associated with a -2.45/h (95%CI -4.76 to -0.14, p = 0.038) decrease in AHI. However, RME alone was not associated with significant AHI reduction (0.02, 95%CI -1.72 to 1.75, p = 0.985). The heterogeneity of the network meta-analysis was I2 = 32.6%. Limited evidence indicated that MAA (alone or combined with RME) and RME + AT were associated with benefits for pediatric patients with OSA. This study could not find convincing evidence of a significant benefit of other orthodontic appliances over control.

Magnetic resonance imaging features of bile duct adenoma.

Objectives: To evaluate the magnetic resonance imaging (MRI) features of bile duct adenoma. Methods: The data of 28 patients [with 32 pathologically confirmed bile duct adenomas, including 15 with malignant change (malignant group) and 17 without malignant change (benign adenoma group)] were retrospectively reviewed. Abdominal MRI was performed for all patients; in addition, dynamic enhanced MRI was performed for 18 lesions. The MRI features, including lesion location, maximum size, morphology, signal characteristics, enhancement type, and appearance of the bile duct, were assessed by two abdominal radiologists. Apparent diffusion coefficient (ADC) values were measured and compared. Results: Of the 32 bile duct adenomas, 22 (68.75%) involved the common bile duct (CBD). While 14/32 (43.75%) lesions presented as focal eccentric-type masses, 9/32 (28.13%) presented as plaque-like masses, 4/32 (12.50%) as bile duct casting masses, and 5/32 (15.62%) as infiltrative masses. A frond-like superficial appearance was seen in 8/32 (25%) lesions. Infiltrative masses were significantly more common in the malignant group than in the benign adenoma group (P = 0.015). While 23/32 (71.88%) lesions were isointense on T1-weighted imaging (T1WI), 24/32 (75%) were hyperintense on T2-weighted imaging (T2WI). Bile duct dilatation was present upstream of the lesion in all cases. Bile duct dilatation at the lesion was seen in 24/32 (75%) cases and downstream of the lesion in 6/32 (18.75%) cases. Of the 18 lesions that underwent dynamic enhanced MRI, 14 (77.78%) showed moderate enhancement and 13 (72.22%) showed persistent enhancement. On diffusion-weighted imaging (DWI), 27/32 (84.37%) lesions showed hyperintensity. Mean ADC value was comparable between the malignant group and the benign adenoma group (P = 0.156). Conclusions: Bile duct adenoma primarily presents as intraductal growth in the CBD, usually with bile duct dilatation at the lesion site or upstream to it. Most lesions are isointense on T1WI, are hyperintense on T2WI and DWI, and show moderate enhancement. A superficial frond-like appearance of the lesion and bile duct dilatation at the lesion or downstream to it might be characteristics of bile duct adenoma. An infiltrative appearance might indicate malignant transformation.

Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family.

OBJECTIVE: Variants in wingless-type MMTV integration site family member 10A (WNT10A) have been proposed to be the most common cause of non-syndromic oligodontia (NSO). The goal of the present study was to identify the novel WNT10A variants in Chinese families with NSO. DESIGN: Clinical data were collected from 39 families with oligodontia admitted to the Hospital of Stomatology Hebei Medical University (China) from 2016 to 2022. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify WNT10A variants in three families with non-syndromic oligodontia. Amino acid conservation analysis and protein conformational analysis were conducted for the WNT10A variant. Genotype-phenotype analysis was performed on the previously reported WNT10A variants related to NSO. RESULTS: We found a novel heterozygous WNT10A variant c.1127 G>A (p.Cys376Tyr) and two reported heterozygous variants c.460 C>A (p.Leu154Met) and c.511 C>T (p.Arg171Cys). Structural modeling showed that the novel WNT10A variant was located in a highly conserved domain, which led to structural damage of WNT10A protein. In addition, we found that the phenotype of the WNT10A variants affected the maxillary second premolars, followed by the mandibular second premolars, and rarely affected the maxillary central incisor. Herein, it is the first time to report that NSO patients with WNT10A monoallele mutation carry taurodontism phenotype and 6.1% prevalence of taurodontism in WNT10A-related NSO patients. CONCLUSIONS: Our results demonstrated that the novel variant c.1127 G>A (p.Cys376Tyr) of WNT10A causes NSO. The present study expanded the known variation spectrum of WNT10A and provided valuable information for genetic counseling of families.

Age-related hypertrophy of adenoid and tonsil with its relationship with craniofacial morphology.

BACKGROUND: When analyzing the relationship between adenotonsillar hypertrophy and craniofacial morphology, researchers generally regarded hypertrophied adenoids and tonsils as a whole. It remains unclear whether different enlarged sites of pharyngeal lymphoid tissue would correlate with multiple craniofacial subtypes. We hypothesized there would be craniofacial subtypes correlated with different locations of hypertrophied adenoid and tonsil. METHODS: Lateral cephalometric radiographs were obtained from 466 children (171 boys and 295 girls, aged 12.27 ± 2.69 years). They were divided into four groups according to different sites of enlarged pharyngeal lymphoid tissue: adenoid hypertrophy group (AG, n = 126), tonsillar hypertrophy group (TG, n = 59), adenotonsillar hypertrophy group (ATG, n = 69) and control group (CG, n = 212). Five commonly used angles for cephalometric measurements were investigated: SNA (Sella-Nasion-Point A), SNB (Sella-Nasion-Point B), ANB (Point A-Nasion-Point B), mandibular plane angle (MP/SN) and Y-axis angle (SGn/FH). RESULTS: Children with isolated tonsillar hypertrophy correlated with increased SNA (unstandardized regression coefficient B = 1.38, p = 0.009) and SNB (B = 1.99, p = 0.001) compared with controls. However, children with isolated adenoid hypertrophy correlated with decreased SNB (B=-0.94, p = 0.036), increased ANB (B = 0.74, p = 0.014) and increased MP/SN (B = 2.22, p < 0.001). Similarly, children with adenotonsillar hypertrophy correlated with decreased SNB (B=-1.36, p = 0.015), increased ANB (B = 1.35, p < 0.001) and increased MP/SN (B = 2.64, p = 0.001). CONCLUSIONS: Isolated adenoid hypertrophy correlated with a retrognathic mandible, an increased maxillo-mandibular sagittal discrepancy, and an increased mandibular plane angle. Isolated tonsillar hypertrophy correlated with maxillary and mandibular protrusion. Adenotonsillar hypertrophy did not show a superimposed craniofacial pattern of the above two but showed the same craniofacial pattern as isolated adenoid hypertrophy.

Readout-segmented diffusion weighted imaging of the testis at 3.0 T: comparison with single-shot echo-planar imaging.

OBJECTIVE: The current study aimed to explore the feasibility of readout-segmented echo-planar imaging (RS-EPI) of the testis at 3.0 T, by comparing with single-shot echo-planar imaging (SS-EPI) in qualitative image quality and quantitative apparent diffusion coefficient (ADC) values. METHODS: 66 patients undergoing scrotal MRI for various clinical indications were included retrospectively. RS-EPI image quality was rated from 1 (severe distortion or artifact, or nondiagnostic) to 4 (nearly no distortion or artifact, or outstanding). The comparative image quality (RS- vs. SS-EPI) was rated from - 2 (SS-EPI severe or greater conspicuity) to 2 (RS-EPI severe or greater conspicuity). The confidence interval of proportions (CIOP) of comparative image quality and Wilcoxon rank sum test were performed to assess the preferences between RS-EPI and SS-EPI. Paired samples t-test and Bland-Altman analysis were performed to compare the mean ADC values of RS-EPI and SS-EPI. The mean, maximum, and minimum ADC values measured by RS-EPI were compared in normal testicular parenchyma, benign and malignant intratesticular lesions. RESULTS: The evaluation of RS-EPI image quality showed RS-EPI with the characteristics of slight geometric distortion and susceptibility artifact, and good lesion conspicuity. The assessment of comparative image quality showed SS-EPI with obvious geometric distortion and susceptibility artifact, and RS-EPI preferred in lesion conspicuity. The CIOP ranged from 97 to 100% among three readers, with preferring to RS-EPI improving image quality (P < 0.001). There was a strong correlation and good agreement between mean ADC values measured by RS-EPI and SS-EPI. The mean, maximum and minimum ADC values by RS-EPI were significantly different in normal testicular parenchyma, benign and malignant intratesticular lesions. CONCLUSION: RS-EPI DWI of the testis improved image quality in geometric distortion, susceptibility artifacts, and lesion conspicuity, and provided highly correlated and consistent mean ADC values when compared to SS-EPI DWI, indicating the feasibility of RS-EPI DWI of testes.

Novel Antiplatelet Activity of Ginsenoside Re Through the Inhibition of High Shear Stress-Induced Platelet Aggregation.

ABSTRACT: Bleeding is one of the most serious side effects of antiplatelet drugs. Efforts have been made to find new antiplatelet agents without bleeding complications. Shear-induced platelet aggregation (SIPA) occurs only under pathological conditions and is a promising target for overcoming bleeding problems. This work demonstrates that the ginsenoside Re selectively inhibits platelet aggregation induced by high shear stress. Human platelets were exposed to high shear stress using microfluidic chip technology, and aggregation, activation, and phosphatidylserine (PS) exposure were measured. The Von Willebrand Ristocetin Cofactor (vWF:RCo) assay and western blot were used to evaluate the effect of the vWF-GPⅠb/PI3K/Akt signal pathway. The coagulation and bleeding risk were evaluated by measuring the coagulation parameters PT, APTT, TT, and thromboelastography. The 3-dimensional morphology of platelet aggregates was observed by a microscopic 3-dimensional imaging. Re was a potent inhibitor of SIPA, with an IC 50 of 0.071 mg/mL. It effectively blocked shear stress-induced platelet activation without any significant toxicity. It was highly selective against SIPA, effectively inhibiting vWF-GPIb and the downstream PI3K/Akt signaling pathway. Most importantly, Re did not affect normal blood coagulation and did not increase the risk of bleeding. In conclusion, Re inhibits platelet activation through the inhibition of the vWF-GPIb/PI3K/Akt pathway. Thus, it might be considered as a new antiplatelet drug in the prevention of thrombosis without increasing the risk of bleeding.

Netrin-1 promotes the vasculogenic capacity of human adipose-derived stem cells.

Adipose derived stem cells (ADSCs) have been increasingly explored for use in cell-based therapy against ischemic diseases. However, unsatisfactory angiogenesis limits the therapeutic efficacy. Netrin-1, a known axon guidance molecule, improves neovascularization in the ischemic region. Thus, our study was performed to evaluate the potential effect of Netrin-1 on the angiogenic behaviors of human ADSCs (hADSCs). hADSCs acquired from human abdominal adipose tissue were modified by liposome transfection of Netrin-1 plasmid, and the proliferation of hADSCs was determined by Cell Counting Kit-8 (CCK-8) assay. The transcript levels of pro-invasive proteins such as matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP-9), were measured to test migratory and invasive capabilities, and the levels of vascular endothelial growth factors were assayed to monitor angiogenic activity. Our results showed that Netrin-1 overexpression enhanced the proliferation of hADSCs, and promoted the migration and invasion of hADSCs, as indicated by increased levels of MMP-2 and MMP-9. Furthermore, Netrin-1 overexpression increased the expression of vascular endothelial growth factor and placental growth factor in hADSCs. Our results highlighted the possibility that genetic modification of hADSCs by Netrin-1 overexpression might be beneficial for cell transplantation therapy against ischemic diseases.

Diagnostic value of dual-energy CT and clinicopathological and imaging feature analysis of mixed endometrial stromal and smooth muscle tumors with intracardiac extension.

Objective: To describe the clinicopathological and imaging features of mixed endometrial stromal and smooth muscle tumors with intracardiac extension and to explore the diagnostic value of dual-energy computed tomography (DECT) for this rare entity. Materials and methods: This retrospective study analyzed the clinicopathological data and images of a 41-year-old female patient with pathologically documented mixed endometrial stromal and smooth muscle tumors with intracardiac extension who had undergone DECT examination. Seven virtual monoenergetic images (VMIs) in 10-kiloelectron volt (keV) intervals (range = 40-100 keV), iodine density (ID) maps, and Z effective (Zeff) maps were reconstructed, and lesion conspicuity was assessed. Tumor homology was analyzed using quantitative DECT parameters and energy spectrum attenuation curve. Results: The patient complained of a 10-day history of bilateral lower extremity edema. Computed tomography showed a hypoattenuating filling defect located within the paracervical vein that extended into the right atrium to the ventricle through the right iliac veins and inferior vena cava (IVC). Intracardiac and intravenous lesions mainly demonstrated moderate progressive enhancement, with localized non-enhancing necrotic areas on contrast-enhanced CT. Multiple nodules showing progressive enhancement (long-T1 signal, long-T2 signal) were observed at the fundus of the uterus on dynamic contrast-enhanced magnetic resonance imaging (MRI), which were deemed the primary lesions of the tumor. Overall, the tumor was characterized by a small primary lesion with extensive vascular extension. In addition, the 40 keV VMIs reconstructions were found to provide best visualization for the early detection of tumors. Conclusion: Although a definitive diagnosis of MESSMT with intracardiac extension requires confirmation by histopathological examination, imaging examination can be used to characterize the extent of the lesion. The dual-energy dataset facilitates tumor visualization and homology evaluation.

Characteristics of salivary microbiota in children with obstructive sleep apnea: A prospective study with polysomnography.

Objectives: The present study aimed to investigate the characteristics of salivary microbiota of children with obstructive sleep apnea (OSA) and to assess longitudinal alterations in salivary microbiota before and after adenotonsillectomy. Methods: A set of cross-sectional samples consisted of 36 OSA children (17 boys and 19 girls, 7.47 ± 2.24 years old) and 22 controls (9 boys and 13 girls, 7.55 ± 2.48 years old) were included in the study, among which eight OSA children (five boys and three girls, 8.8 ± 2.0 years old) who underwent treatment of adenotonsillectomy were followed up after 1 year. Saliva samples were collected, and microbial profiles were analyzed by bioinformatics analysis based on 16S rRNA sequencing. Results: In cross-sectional samples, the OSA group had higher α-diversity as estimated by Chao1, Shannon, Simpson, Pielou_e, and observed species as compared with the control group (p < 0.05). ß-Diversity based on the Bray-Curtis dissimilarities (p = 0.004) and Jaccard distances (p = 0.001) revealed a significant separation between the OSA group and control group. Nested cross-validated random forest classifier identified the 10 most important genera (Lactobacillus, Escherichia, Bifidobacterium, Capnocytophaga, Bacteroidetes_[G-7], Parvimonas, Bacteroides, Klebsiella, Lautropia, and Prevotella) that could differentiate OSA children from controls with an area under the curve (AUC) of 0.94. Linear discriminant analysis effect size (LEfSe) analysis revealed a significantly higher abundance of genera such as Prevotella (p = 0.027), Actinomyces (p = 0.015), Bifidobacterium (p < 0.001), Escherichia (p < 0.001), and Lactobacillus (p < 0.001) in the OSA group, among which Prevotella was further corroborated in longitudinal samples. Prevotella sp_HMT_396 was found to be significantly enriched in the OSA group (p = 0.02) with significantly higher levels as OSA severity increased (p = 0.014), and it had a lower abundance in the post-treatment group (p = 0.003) with a decline in each OSA child 1 year after adenotonsillectomy. Conclusions: A significantly higher microbial diversity and a significant difference in microbial composition and abundance were identified in salivary microbiota of OSA children compared with controls. Meanwhile, some characteristic genera (Prevotella, Actinomyces, Lactobacillus, Escherichia, and Bifidobacterium) were found in OSA children, among which the relationship between Prevotella spp. and OSA is worth further studies.

Native T1 mapping for differentiating the histopathologic type, grade, and stage of rectal adenocarcinoma: a pilot study.

BACKGROUND: Previous studies have indicated that T1 relaxation time could be utilized for the analysis of tissue characteristics. T1 mapping technology has been gradually used on research of body tumor. In this study, the application of native T1 relaxation time for differentiating the histopathologic type, grade, and stage of rectal adenocarcinoma was investigated. METHODS: One hundred and twenty patients with pathologically confirmed rectal adenocarcinoma were retrospectively evaluated. All patients underwent high-resolution anatomical magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and T1 mapping sequences. Parameters of T1 relaxation time and apparent diffusion coefficient (ADC) were measured between the different groups. The diagnostic power was evaluated though the receiver operating characteristic (ROC) curve. RESULTS: The T1 and ADC values varied significantly between rectal mucinous adenocarcinoma (MC) and non-mucinous rectal adenocarcinoma (AC) ([1986.1 ± 163.3 ms] vs. [1562.3 ± 244.2 ms] and [1.38 ± 0.23 × 10-3mm2/s] vs. [1.03 ± 0.15 × 10-3mm2/s], respectively; P < 0.001). In the AC group, T1 relaxation time were significantly different between the low- and high-grade adenocarcinoma cases ([1508.7 ± 188.6 ms] vs. [1806.5 ± 317.5 ms], P < 0.001), while no differences were apparent in the ADC values ([1.03 ± 0.14 × 10-3mm2/s] vs. [1.04 ± 0.18 × 10-3mm2/s], P > 0.05). No significant differences in T1 and ADC values were identified between the different T and N stage groups for both MC and AC (all P > 0.05). CONCLUSIONS: Native T1 relaxation time can be used to discriminate MC from AC. The T1 relaxation time was helpful for differentiating the low- and high-grade of AC.

Quantitative changes of upper airway in class III patients undergoing bimaxillary surgery after one-year follow-up: a retrospective study.

BACKGROUND: Bimaxillary surgery is often performed for class III malocclusion, and its complex influence on the upper airway has been well considered. The aim of this research was to provide a scaled formula between upper airway volume changes and bone movements in Class III patients after orthognathic surgery. MATERIALS AND METHODS: Using a retrospective study design, the investigators enrolled a total of 30 class III malocclusion patients who were undergoing bimaxillary surgery as the study subjects. The subjects included 15 males and 15 females, and their average age was 23.3 ± 3.4 years. CBCT (cone beam tomography) was performed both before and one year after the surgery for each patient. The changes in the soft palate, tongue and upper airway were measured by using CBCT data that was collected before and after surgery. 3D superimposition of CBCT was performed to calculate three-dimensional jaw movements. A multiple regression analysis was used to calculate the quantitative relationship between airway volume changes and jaw movements. RESULTS: The nasopharynx airway volume was observed to be increased by 1064.0 ± 1336.2 mm3, whereas the retropalatal and retroglossal airway volumes were observed to be decreased by 1399.0 ± 2881.6 mm3 and 1433.8 ± 3043.4 mm3, respectively, after the surgery. One millimetre forward and downward movements of the PNS resulted in increases of 626.90 mm3 and 392.18 mm3 in nasopharynx airway volume, respectively. Moreover, one millimetre retrogression of the B point caused decreases of 314.6 mm3 and 656.6 mm3 in the retropalatal and retroglossal airway volume, respectively. The changes in the soft palate contributed to the decrease in the retropalatal airway volume, whereas the tongue compensated for the decrease in the retroglossal airway volume. CONCLUSION: The movements of the PNS and B points could be used to predict upper airway volumetric changes in Class III patients after maxillary advancement and mandibular setback.

Inhibition of tumor necrosis factor improves conventional steroid therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis in a cohort of patients.

BACKGROUND: Systemic steroid therapies for Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been challenged because of their limited benefits. Whether additional tumor necrosis factor (TNF) α inhibition provides an optimized approach remains unexplored. OBJECTIVE: To investigate the efficacy of TNF-α inhibition combined with a steroid to treat SJS/TEN and to identify potential biomarkers. METHODS: Twenty-five patients with SJS/TEN were recruited and divided into 2 groups: 10 patients received methylprednisolone and 15 patients received etanercept plus methylprednisolone. Serum levels of granzyme B, perforin, interferon-γ, interleukin (IL) 6, IL-15, IL-18, macrophage inflammatory protein 1α, macrophage inflammatory protein 1ß, and TNF-α were measured by multiplex cytokine analysis kits during the acute and resolution phases. RESULTS: Compared with the steroid monotherapy, the combination therapy significantly shortened the course of the initial steroid treatment and the duration of the acute stage, hospitalization stay, and skin re-epithelialization. Although both therapies significantly reduced IL-15 levels; the combination therapy also decreased IL-6 and IL-18 levels. While the level of IL-15 was positively correlated with skin re-epithelialization time in both groups, the level of IL-6 served as an additional marker for the course of the disease in the combination therapy group. LIMITATIONS: The cohort size is relatively small. CONCLUSION: Additional TNF-α inhibition to steroid treatment appeared to improve outcomes for SJS/TEN.

Risk factors for additional postoperative adjuvant therapy in patients with locally advanced cervical cancer and construction of a risk model.

OBJECTIVE: To investigate the influencing factors of postoperative adjuvant therapy for stage IB1-IIA2 cervical cancer, and establish a nomogram model to predict the risk of postoperative adjuvant therapy for locally advanced cervical cancer (LACC). METHODS: A retrospective analysis was conducted on 144 patients with stage IB1-IIA2 cervical squamous cell carcinoma treated in Wuhan No.1 Hospital from June 2015 to January 2017, and their clinical data were analyzed. The clinical application value of the nomogram risk model was evaluated by receiver operating characteristic curve (ROC). RESULTS: Through logistic regression analysis, we found that squamous cell carcinoma antigen (SCC-Ag), International Federation of Gynecology and Obstetrics (FIGO) stage ≥ IIA1, and laparoscopic surgery were independent influencing factors for additional adjuvant therapy after laparoscopic surgery. The nomogram model for predicting the risk of postoperative adjuvant therapy for cervical cancer constructed according to the selected variables had good predictive performance (with C-index of 0.798) and conformity. The area under the curve of established model in predicting 1-, 3- and 5-year survival time was 0.730, 0.810 and 0.830, respectively, indicating that the model has good performance. CONCLUSION: History of diabetes, tumor size, FIGO stage ≥ IIA1, and SCC-Ag >1.5 are independent influencing factors for additional adjuvant therapy after laparoscopic surgery of LACC patients. In addition, the constructed risk model is effective in predicting the postoperative risk of additional adjuvant therapy, which is expected to provide a reference for clinical treatment selection.

Perfluoropentane-filled chitosan poly-acrylic acid nanobubbles with high stability for long-term ultrasound imaging in vivo.

Reducing the size of ultrasound contrast agents (UCAs) will decrease the intensity of the ultrasound echogenic signals and reduce the stability of the bubbles. Therefore, it is a challenge to design nanobubbles that are less than 200 nm in size and that have both good imaging abilities and high stability for long-term imaging in vivo. In this work, we successfully prepared perfluoropentane-filled chitosan poly-acrylic acid (PFP-CS-PAA) nanobubbles with a size of about 100 nm via a direct simple core-template-free strategy. In vitro tests demonstrated that the nanobubbles showed satisfactory imaging capabilities in non-linear harmonic imaging mode and had significantly better stability than commercial Sonovue® lipid microbubbles. It was valuable to discover that the prepared PFP-CS-PAA nanobubbles could exhibit good imaging quality in rat livers for 10 min after intravenous injection. Also, the PFP-CS-PAA nanobubbles could maintain imaging capabilities in nude mouse tumors for 7 days after intratumoral injection, which indicated that these nanobubbles could keep their stability for a long time in vivo. To the best of our knowledge, the ultrasound imaging persistence time in vivo was the longest of currently reported polymer nanobubbles that are smaller than 200 nm. This new nanosized UCA with high stability has great potential for long-term ultrasound imaging in vivo. Tumor cellular uptake and histological analysis revealed that PFP-CS-PAA nanobubbles could be taken up into tumor cells, but no intracellular uptake was observed in the case of Sonovue®. Animal fluorescence imaging in vivo demonstrated that PFP-CS-PAA nanobubbles could be effectively cleared after intravenous injection within 168 h. MTT assays indicated that PFP-CS-PAA nanobubbles had appropriate biocompatibility. Abnormal levels of blood urea nitrogen were detected after the intravenous administration of PFP-CS-PAA nanobubbles to rats, and body-weight gain was inhibited for up to 6 d, but, after that, body weights recovered their tendency to increase.

Differences of Craniofacial Characteristics in Oral Breathing and Pediatric Obstructive Sleep Apnea.

BACKGROUND: Oral breathing (OB) was considered associated with specific craniofacial structures and same for pediatric obstructive sleep apnea (OSA). This study aimed to investigate the differences of craniofacial structures between OB and OSA. METHODS: In this retrospective study, 317 children under age 18 years were recruited and divided into OB group, OSA group, and control group. OSA group (15 boys, 4 girls) were referred from qualified sleep center and diagnosed as pediatric OSA with full-night polysomnography. OB group (10 boys, 10 girls) were mostly referral from pediatric or ENT department, some of whom undertook polysomnography and were not OSA. Control group consisted of orthodontic patients within the same period. Lateral cephalograms were obtained in all groups and their parameters were compared with Chinese normal values and each other. RESULTS: R-PNS of OB group (18.04 ±â€Š2.49 mm) was greater than OSA group (14.27 ±â€Š4.36 mm) and even control group (16.22 ±â€Š3.91 mm) (P < 0.01). U1-NA was also the greatest in OB group (7.15 ±â€Š2.92 mm), followed by OSA group (4.88 ±â€Š2.66 mm), while control group was the smallest (5.71 ±â€Š2.94 mm) (P < 0.05). In addition, OB group presented the smallest adenoids and tonsils among three groups. Bony nasopharynx development, mandibular length and growth direction of mandible of OB group were all better than OSA group. CONCLUSION: Despite of oral breathing, anatomical morphology (well-developed dentoalveolar structures; mild adenotonsillar hypertrophy) might protect children from developing OSA.