The therapeutic effects of ADSCs on photoaging of skin induced by UVB irradiation.

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.

[Clinical characteristics and genetic analysis of a child with Char syndrome caused by TFAP2B gene variant].

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Char syndrome. METHODS: A child who was presented at the Department of Child Health, Henan Children's Hospital in February 2022 was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had mainly manifested facial dysmorphism, patent ductus arteriosus, growth retardation, curving of fifth fingers and middle toes. Whole exome sequencing revealed that she has harbored a heterozygous c.944A>C (p.Glu315Ala) variant of the TFAP2B gene, which was verified to be de novo by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated to be likely pathogenic (PM1+PM2_Supporting+PM6+PP3). CONCLUSION: The heterozygous c.944A>C (p.Glu315Ala) variant of the TFAP2B gene probably underlay the Char syndrome in this child. Above finding has expanded the mutational and phenotypic spectra of the TFAP2B gene, which has facilitated early identification and diagnosis of Char syndrome.

Studies of Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography in the Evaluation of Vascularization in Early Bone Regeneration.

OBJECTIVE: The aim of this study was to investigate value of superb microvascular imaging (SMI) and contrast-enhanced ultrasonography (CEUS) in evaluating the neovascularization of early bone regeneration. METHODS: Twenty-five Sprague-Dawley male rats were implanted with recombinant human bone morphogenetic protein-2/calcium phosphate cement (rhBMP-2/) in the muscle space of the left hind limb near the femoral head to establish the rat model of intramuscular ectopic osteogenesis. Ultrasonography and pathologic analysis were performed on the 3rd, 7th, 14th, 21st, and 28th days after modeling. Two-dimensional ultrasonography, SMI, and CEUS were used to assess neovascularization and bone formation. RESULTS: Pathologic examination showed that different levels of neovascularization were observed in the graft bone over time after modeling, which increased significantly from the 3rd to 14th day, and then gradually decreased. CEUS and SMI showed no obvious microvessels inside the graft bone on the 3rd day. On the 7th day after modeling, a small number of neovascular vessels were observed around the graft bone. On the 14th day, neovascularization was observed in both the peripheral and inner parts of the graft bone. The number of neovascular vessels inside the graft bone had decreased gradually by the 21st and 28th days. The results of SMI and CEUS indexes showed that the vascular index, peak intensity, enhancement intensity, and enhancement rate first increased and then decreased with time. Their peak points were found on the 14th day. Arrival time, time to peak, and enhancement time decreased gradually over time (P < .05). CONCLUSION: The combined application of SMI and CEUS may be useful in evaluating the neovascularization of early osteoanagenesis.

A single-dose, randomized, crossover bioequivalence study of levamlodipine besilate tablets in healthy subjects.

Levamlodipine, the levorotatory form of amlodipine racemate, has a blood pressure-lowering effect that is twice that of the racemate. The study aims to establish a foundation for the clinical application of the test drug by conducting a phase I clinical bioequivalence trial, comparing its bioequivalence and safety with the reference drug in healthy Chinese subjects. Recruiting 26 healthy subjects for separate bioequivalence trials in both fasting and fed conditions. The subjects will orally administer 2.5-mg test drug and 5-mg reference drug. A chiral method was used for bioanalytics and liquid chromatography-tandem mass spectrometry was employed to quantify the (S)-amlodipine concentrations at various time points after administration. In fasting condition, the geometric mean ratios (GMRs) for the primary pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ are 100.24%, 103.63%, and 103.24%, respectively. The 90% confidence intervals (CIs) fall within the range of 80-125%, satisfying the established bioequivalence criteria. Similarly, upon oral administration of the drugs in the fed condition, the GMRs for Cmax, AUC0-t, and AUC0-∞ are 96.48%, 99.90%, and 99.62%, respectively. The corresponding 90% CIs are within the limits of 80-125%, meeting the predefined bioequivalence standards. Furthermore, both drugs exhibited favorable safety profiles. The results show that the two drugs are bioequivalent in healthy Chinese subjects under both fasting and fed conditions. The two drugs both had similar PK parameters and good safety.

The SARS-CoV-2 spike protein contains a furin cleavage site located in a short loop between antiparallel ß-strands.

The furin cleavage site (FCS) of the SARS-CoV-2 spike protein, which connects the S1/S2 junction, is essential for facilitating fusion with host cells. The wild-type (Wt) SARS-CoV-2 spike protein, PDB ID: 6yvb, lacks a sequence of amino acid residues, including the FCS that links the S1/S2 junction. For the first time, we demonstrated that a stretch of 14 amino acid residues (677QTNSPRRARSVASQ689) forms an antiparallel ß-sheet and contains the PRRAR sequence in the FCS within a short loop. Upon comparing the loop content of the S1/S2 junction with that of Wt SARS-CoV-2 containing PRRAR in the FCS, we observed a decrease in antiparallel ß-sheet content and an increase in loop content in the B.1.1.7 variant with HRRAR in the FCS. This short loop within an antiparallel ß-sheet can serve as a docking site for various proteases, including TMPRSS2 and α1AT. We conducted a 300-ns simulation of the SARS-CoV-2 receptor binding domain (RBD) using several antibacterial and antiviral ligands commonly used to treat various infections. Our findings indicate that the receptor binding domain (RBD) comprising the receptor binding motif (RBM) utilizes ß6 and a significant portion of the loop to bind with ligands, suggesting its potential for treating SARS-CoV-2 infections.

[Evaluation on preparation process of brevisapin colon-specific tables and its in vitro release].

OBJECTIVE: To prepare the new traditional Chinese medicine preparation--pH-dependent brevisapin colon-specific tablets, and investigate its in vitro release, in order to discuss the feasibility of preparing colon-targeted traditional Chinese medicines. METHOD: With scutellarin, the active ingredient in brevisapin, as the evaluation index, coating prescriptions of the preparation was screened. The in vitro release determination method was adopted to detect the in vitro release performance of the preparation. RESULT: The in vitro release determination results showed no brevisapin in artificial pH 1. 2 dilute hydrochloric acid solution for 2 h, an accumulated dissolution rate of less than 5% in pH 6. 8 phosphate buffer solution for 4 h, but an accumulated dissolution rate exceeding 90% in pH 7. 6 phosphate buffer solution for 1 h. CONCLUSION: Brevisapin colon-specific tablets prepared can realize colon-specific release.

[Simultaneous determination of ephedrine hydrochloride, D-pseudoephedrine and amygdalin in xiao'er pingchuan qutan granule by HPLC].

OBJECTIVE: To establish an HPLC method for the determination of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule. METHOD: Pheny ether chromatographic column (4.6 mm x 250 mm, 5 microm) was adopted, with acetonitrile-0.1% phosphoric acid (containing 0.1% three ethylamine) (3:97) as the mobile phase. The UV detection wavelength was at 210 nm, with the flow rate of 1 mL x min(-1), and column temperature was at 35 degrees C. RESULT: The linearity of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin ranged between 0.078 60-3.144 microg (r = 1.000 0), 0.103 4-2.068 microg (r = 0.999 7) and 0.430 5-3.157 microg (r = 0.999 8), respectively. Their average recoveries were 98.46% (RSD 1.1%), 103.0% (RSD 1.5%) and 97.15% (RSD 2.1%), respectively. CONCLUSION: The method is simple, stable and reliable that it can be used to determine the content of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule.

Development of an interpretable machine learning model for Ki-67 prediction in breast cancer using intratumoral and peritumoral ultrasound radiomics features.

Background: Traditional immunohistochemistry assessment of Ki-67 in breast cancer (BC) via core needle biopsy is invasive, inaccurate, and nonrepeatable. While machine learning (ML) provides a promising alternative, its effectiveness depends on extensive data. Although the current mainstream MRI-centered radiomics offers sufficient data, its unsuitability for repeated examinations, along with limited accessibility and an intratumoral focus, constrain the application of predictive models in evaluating Ki-67 levels. Objective: This study aims to explore ultrasound (US) image-based radiomics, incorporating both intra- and peritumoral features, to develop an interpretable ML model for predicting Ki-67 expression in BC patients. Methods: A retrospective analysis was conducted on 263 BC patients, divided into training and external validation cohorts. From intratumoral and peritumoral regions of interest (ROIs) in US images, 849 distinctive radiomics features per ROI were derived. These features underwent systematic selection to analyze Ki-67 expression relationships. Four ML models-logistic regression, random forests, support vector machine (SVM), and extreme gradient boosting-were formulated and internally validated to identify the optimal predictive model. External validation was executed to ascertain the robustness of the optimal model, followed by employing Shapley Additive Explanations (SHAP) to reveal the significant features of the model. Results: Among 231 selected BC patients, 67.5% exhibited high Ki-67 expression, with consistency observed across both training and validation cohorts as well as other clinical characteristics. Of the 1698 radiomics features identified, 15 were significantly correlated with Ki-67 expression. The SVM model, utilizing combined ROI, demonstrated the highest accuracy [area under the receiver operating characteristic curve (AUROC): 0.88], making it the most suitable for predicting Ki-67 expression. External validation sustained an AUROC of 0.82, affirming the model's robustness above a 40% threshold. SHAP analysis identified five influential features from intra- and peritumoral ROIs, offering insight into individual prediction. Conclusion: This study emphasized the potential of SVM model using radiomics features from both intra- and peritumoral US images, for predicting elevated Ki-67 levels in BC patients. The model exhibited strong performance in validations, indicating its promise as a noninvasive tool to enable personalized decision-making in BC care.

Value of Ultrasound Combined with Immunohistochemistry Evaluation of Central Lymph Node Metastasis for the Prognosis of Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is often accompanied by cervical lymph node metastasis (LNM). The accuracy of the preoperative ultrasound diagnosis of central LNM (CLNM) is limited. LNM is a high-risk factor for local recurrence and may affect the prognosis. Factors not directly related to tumor proliferation are used for risk assessment in the tumor-node-metastasis (TNM) staging system for thyroid cancer. The present study aimed to investigate the value of ultrasound and immunohistochemistry in predicting the presence of CLNM and the prognosis of PTC. PATIENTS AND METHODS: The ultrasound and immunohistochemistry features of 303 patients with first-ever PTC and who underwent surgery between 01/2014 to 12/2016 were analyzed, as well as the prognosis of the patients. Univariable and multivariable analyses were carried out to determine the risk factors of CLNM and recurrence. RESULTS: Among 303 patients, 125 (41.3%) were pathologically confirmed with CLNM. Multivariable analysis showed that multifocality, taller-than-wide shape, grade III-IV blood flow, capsular invasion, Ki-67 >10%, p53 ≥5%, T2 or T3 stages were independent risk factors for CLNM. The median follow-up was 56 months. Cox regression analysis showed that age ≥55 years, maximum tumor diameter >20 mm, multifocality, capsular invasion, Ki-67 5-10%, Ki-67 >10%, p53 ≥5%, T3 stage and N1a stage were independent risk factors for PTC recurrence. The Kaplan-Meier showed that recurrence-free survival (RFS) was different according to age (P=0.017), tumor size multifocality, capsular invasion, Ki-67, p53, T stage and N stage (all P<0.001). CONCLUSION: For PTC with rich blood flow, taller-than-wide shape, multifocality, capsular invasion, p53 ≥5%, Ki-67 >10%, T2 or T3 stages prophylactic CLNM dissection might be indicated. Age≥55 years, maximum tumor diameter >20 mm, multifocality, capsular invasion, high Ki-67, p53 ≥5%, T3 and N1a stages affected the clinical outcome.

Evaluation of thyroid hemangioma by conventional ultrasound combined with contrast-enhanced ultrasound: a case report and review of the literature.

Primary thyroid hemangioma is an extremely rare clinical disease. Only 31 cases have been reported to date according to a PubMed search, and most were postoperatively diagnosed by pathologic examination. Ultrasonography is the first-line imaging modality for thyroid disease screening. However, preoperative ultrasonic diagnosis of thyroid hemangioma has been rarely reported. We herein describe a 24-year-old woman with a painless mass in the left thyroid lobe. Routine ultrasound (US) and contrast-enhanced US (CEUS) were performed. Routine US revealed an anechoic tumor with linear echogenic septal lines and compressibility. CEUS showed a characteristic "slow in and slow out" pattern of contrast filling and perfusion. Based on the combined findings of routine US and CEUS, the initial diagnosis was thyroid venous hemangioma. Postoperative pathological examination demonstrated multiple irregular dilated vessel lumens filled with red blood cells and multiple hemorrhagic zones. Immunohistochemical staining showed positivity for CD31 and smooth muscle actin.. Overall, this case showed US characteristics of a rare case of thyroid hemangioma, which is of importance for preoperative planning to avoid a large amount of blood loss during surgery. This case together with our literature review will help radiologists to bridge the knowledge gap of thyroid hemangioma, especially at the initial US screening.

Role of shear wave elastography in the evaluation of the treatment and prognosis of supraspinatus tendinitis.

BACKGROUND: Supraspinatus tendinitis recurs easily after treatment. One of the main reasons is the lack of objective tools for the efficacy evaluation. Shear wave elastography (SWE) can quantitatively analyze the tissue elasticity of region of interest by measuring the Young's modulus (YM) value. AIM: To explore the role of SWE in the efficacy and prognostic evaluation of supraspinatus tendinitis. METHODS: Eighty-seven patients with supraspinatus tendinitis treated in Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences were recruited. Another 30 healthy volunteers were enrolled as the control group. The visual analogue scale (VAS) and Constant-Murley Score (CMS) were recorded before treatment. All participants were scanned by SWE scan, and the YM value of the region of interest were recorded. Spearman correlation analysis was performed on YM values with VAS and CMS. Univariate repeated measures analysis of variance was used to calculate the changing trend of VAS, CMS and SWE under different treatment courses. After treatment, the patients were further grouped based on who achieved significantly effective and curative treatment. The patients in the continued treatment group continued to receive treatment according to the YM value, and the remaining patients who stopped receiving treatment were included in the stopped treatment group. All patients were followed up for 1 year, and the difference in recurrence rates between the continued treatment group and the stopped treatment group were compared. RESULTS: The SWE images of supraspinatus muscle in healthy volunteers were mainly blue, while those of patients with supraspinatus tendinitis showed regional red and green areas. The average YM value of the supraspinatus muscle in healthy volunteers was 26.12 ± 4.03 kPa. The average YM value of patients with supraspinatus muscle was greater than that of healthy volunteers (average YM = 60.61 ± 11.53 kPa, t = 26.344, P < 0.001). The YM value was positively correlated with VAS (r = 0.564, P < 0.001) and negatively correlated with CMS (r = -0.411, P < 0.001). The changes of VAS and CMS were the most obvious in course 1 and then decreased gradually. The degree of change in YM values was similar in different courses. After a 1-year follow-up, the cumulative relapse-free rate in the continued treatment group was 91.43%, which was significantly higher than that in the stopped treatment group (64.71%, X 2 = 7.379, P = 0.007). CONCLUSION: SWE can objectively indicate the severity of supraspinatus tendinitis. Using the YM value as a criterion for curative effect may reduce the recurrence rate.

Correlations of PCNA expression with thyroid cancer ultrasound and histopathologic features.

OBJECTIVE: To investigate the correlations of proliferating cell nuclear antigen (PCNA) gene expression with thyroid cancer (TC) ultrasound (US) features, histopathology and clinical stage. METHODS: A total of 66 TC patients admitted and treated in the Department of Oncology of our hospital from April 2014 to April 2018 were enrolled randomly. The conventional US imaging data of the patients were collected. Paired carcinoma and para-carcinoma tissues were obtained after operation to detect the expression of PCNA protein by immunohistochemistry (IHC). The correlations of PCNA expression with the patients' US manifestations and clinical stages were analyzed. RESULTS: The positive rate of PCNA was 72.73% (48/66) in TC tissues and 13.64% (9/66) in paired para-carcinoma tissues, displaying a statistically significant difference between the two groups (P<0.05). The PCNA and US features suggested that there was no significant difference in tumor boundary between the PCNA positive group and PCNA negative group (P>0.05). However, significant differences in tumor diameter, echo, calcification and blood flow were found between the two groups (P<0.05). The pathologic data of preoperative US diagnosis and PCNA expression in postoperative TC specimens were analyzed, and the results indicated that PCNA expression was prominently associated with T stage and N stage in US diagnosis (P<0.05). The total correct rate of US in assessing the T stage was 75.8% (50/66), and the over-staging rate and under-staging rate in evaluating the T stage were 13.6% (9/66) and 10.6% (7/66), respectively. CONCLUSION: The expression of PCNA protein in TC tissues is significantly correlated with the diameter, echo, calcification and blood flow of US features as well as clinical stage detected by US. PCNA level and US examination can provide certain clinical values for TC treatment.

Value of superb micro-vascular imaging in predicting ischemic stroke in patients with carotid atherosclerotic plaques.

BACKGROUND: Unstable carotid atherosclerotic plaques are prone to cause ischemic stroke. Contrast-enhanced ultrasound (CEUS) is the primary method of assessing plaque stability, but CEUS cannot be a method for screening for unstable plaque. The emergence of superb micro-vascular imaging (SMI) offers the possibility of clinically screening for unstable plaque. AIM: To investigate the value of SMI in predicting ischemic stroke in patients with carotid atherosclerotic plaques. METHODS: Patients with carotid atherosclerotic plaques (luminal stenosis of 50%-70%) were enrolled into the present study. All patients received conservative medication. The patient's clinical baseline data, serological data, CEUS and SMI data were analyzed. All patients underwent a 3-year follow-up. The follow-up endpoint was the occurrence of ischemic stroke and patients were divided into stroke group and non-stroke group according to whether the prognosis occurred or not. Subsequently, the difference in clinical data was compared, the correlation of SMI and CEUS was analyzed, and multiple Cox regression and receiver operating characteristic curve were applied to investigate the value of SMI and CEUS in predicting cerebral arterial thrombosis in three years. RESULTS: In this study, 43 patients were enrolled in the stroke group and 82 patients were enrolled in the non-stroke group. Cox regression revealed that SMI level (P = 0.013) and enhancement intensity (P = 0.032) were the independent factors influencing ischemic stroke. There was a positive correlation between SMI level and enhancement intensity (r = 0.737, P = 0.000). The area under curve of SMI level predicting ischemic stroke was 0.878. The best diagnostic point was ≥ level II, and its sensitivity and specificity was 86.05% and 79.27%. The area under curve of enhancement intensity predicting ischemic stroke was 0.890. The best diagnostic point was 9.92 db, and its sensitivity and specificity was 88.37% and 89.02%. As the SMI level gradually increased, the incidence of ischemic stroke increased gradually (X 2 = 108.931, P = 0.000). CONCLUSION: SMI can be used as a non-invasive method of screening for unstable plaques and may help prevent ischemic stroke.

Reversing Cancer Multidrug Resistance in Xenograft Models via Orchestrating Multiple Actions of Functional Mesoporous Silica Nanoparticles.

A multistimuli responsive drug delivery system (DDS) based on sulfhydryl and amino-cofunctionalized mesoporous silica nanoparticles (SH/NH2-MSNs) has been developed, in which the multifunctional hyaluronic acid (HA) derivatives were grafted onto the SH/NH2-MSNs by disulfide bonds for targeting delivery, controlling drug release and reversing multidrug resistance (MDR). The doxorubicin (Dox) loaded multifunctional HA derivatives modified mesoporous silica nanoparticles (Dox/HHS-MSNs) were enzyme and redox sensitive, which could respond to the intracellular stimuli of hyaluronidase (HAase) and glutathione (GSH) successively and prevent drug leakage before reaching the tumor tissues. The cellular uptake experiments showed that Dox/HHS-MSNs were vulnerable to be endocytosed into the Dox-resistant human breast adenocarcinoma (MCF-7/ADR) cells, efficiently realized the endolysosomal escape and remained in the cytoplasm. Because of orchestrating multiple actions above including active targeting, endolysosomal escape and efficient multilevel drug release, Dox/HHS-MSNs could induce the strongest apoptosis and cytotoxicity of MCF-7/ADR cells. Furthermore, a series of in vivo studies on MCF-7/ADR tumor-bearing xenograft mouse models demonstrated that Dox/HHS-MSNs possessed the enhanced tumor-targeting capacity and the best therapeutic efficacy to reverse cancer MDR.