Application value of multi-gene mutation detection in the clinical management of pediatric papillary thyroid carcinoma: a preliminary exploration.

Objectives: Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as BRAF, RAS, and RET/PTC have been widely used in adult PTC. It is currently unclear whether these molecular markers have equivalent potential for application in pediatric patients. This study aims to explore the potential utility of a multi-gene conjoint analysis based on next-generation targeted sequencing for pediatric papillary thyroid carcinoma (PTC). Materials and methods: The patients diagnosed with PTC (aged 18 years or younger) in the pediatrics department of Lishui District Hospital of Traditional Chinese Medicine were retrospectively screened. A targeted enrichment and sequencing analysis of 116 genes associated with thyroid cancer was performed on paraffin-embedded tumor tissues and paired paracancerous tissue of fifteen children (average age 14.60) and nine adults (average age 49.33) PTC patients. Demographic information, clinical indicators, ultrasonic imaging information and pathological data were collected. The Kendall correlation test was used to establish a correlation between molecular variations and clinical characteristics in pediatric patients. Results: A sample of 15 pediatric PTCs revealed a detection rate of 73.33% (11/15) for driver gene mutations BRAF V600E and RET fusion. Compared to adult PTCs, the genetic mutation landscape of pediatric PTCs was more complex. Six mutant genes overlap between the two groups, and an additional seventeen unique mutant genes were identified only in pediatric PTCs. There was only one unique mutant gene in adult PTCs. The tumor diameter of pediatric PTCs tended to be less than 4cm (p<0.001), and the number of lymph node metastases was more than five (p<0.001). Mutations in specific genes unique to pediatric PTCs may contribute to the onset and progression of the disease by adversely affecting hormone synthesis, secretion, and action mechanisms, as well as the functioning of thyroid hormone signaling pathways. But, additional experiments are required to validate this hypothesis. Conclusion: BRAF V600E mutation and RET fusion are involved in the occurrence and development of adolescent PTC. For pediatric thyroid nodules that cannot be determined as benign or malignant by fine needle aspiration biopsy, multiple gene combination testing can provide a reference for personalized diagnosis and treatment by clinical physicians.

Spin-Phonon Coupling in Iron-Doped Ultrathin Bismuth Halide Perovskite Derivatives.

Spin in semiconductors facilitates magnetically controlled optoelectronic and spintronic devices. In metal halide perovskites (MHPs), doping magnetic ions is proven to be a simple and efficient approach to introducing a spin magnetic momentum. In this work, we present a facile metal ion doping protocol through the vapor-phase metal halide insertion reaction to the chemical vapor deposition (CVD)-grown ultrathin Cs3BiBr6 perovskites. The Fe-doped bismuth halide (Fe:CBBr) perovskites demonstrate that the iron spins are successfully incorporated into the lattice, as revealed by the spin-phonon coupling below the critical temperature Tc around 50 K observed through temperature-dependent Raman spectroscopy. Furthermore, the phonons exhibit significant softening under an applied magnetic field, possibly originating from magnetostriction and spin exchange interaction. The spin-phonon coupling in Fe:CBBr potentially provides an efficient way to tune the spin and lattice parameters for halide perovskite-based spintronics.

Identification of a novel genomic variance of BRAF1 in papillary thyroid carcinoma: A case report.

RATIONALE: Papillary thyroid carcinoma (PTC), the predominant subtypes accounting for approximately 85% of thyroid carcinomas, has a rapidly increasing global incidence rate. Statistically, approximately 74.6% PTC patients had the genomic variants of BRAF, especially BRAFV600E mutation, which has been reported to stratify patients and guide clinic-therapies. However, some PTC patients may carry other nonclassical mutation patterns of BRAF, due to the complex of genomic instability. And the spectrum of BRAF mutation was not fully characterized. We reported a novel BRAF mutation pattern of PTC. PATIENT CONCERNS: A 59-year-old woman was admitted to our hospital because of the slight enlargement of bilateral cervical lymph nodes in July 2023. DIAGNOSIS: Ultrasonography revealed that the bilateral thyroid nodules of the patients both presented 1 hypoechoic nodule, which was graded as 3 of the elastic score, and the small calcification in the right lobe (Chinese-Thyroid Imaging Reporting and Data System 4c). Pathological diagnosis showed the interstitial collagen change and focal follicular epithelial papillary hyperplasia with atypical hyperplasia of the bilateral thyroid. Further puncture pathology showed that the patient had a malignant thyroid lesion with the phenotypes of papillary carcinoma and diagnosed with malignancy subsequently. Additionally, the patient harbored a novel insert on BRAF exon 15, a 6-base fragment AGACAG inserting between c.1798 and c.1799. INTERVENTIONS: The patient was undergone on microwave ablation of thyroid carcinoma on July 28, 2023. After the surgery, the patient was treated on anti-infection, cold saline external application of bilateral thyroid swelling supportive treatment. OUTCOMES: No postoperative complications or recurrence and metastasis were found. LESSONS: This is the first case of the novel nonclassical genomic variant of BRAF. Our study extends the spectrum of BRAF mutations. The patient had a favorable response to microwave ablation, indicating that in spite of the association between this mutation and high-grade malignant phenotype, this genomic variant of BRAF did not have a detrimental effect on the response of clinical treatment.

Zuo Gui Wan Promotes Osteogenesis via PI3K/AKT Signaling Pathway: Network Pharmacology Analysis and Experimental Validation.

OBJECTIVE: Osteogenesis is vitally important for bone defect repair, and Zuo Gui Wan (ZGW) is a classic prescription in traditional Chinese medicine (TCM) for strengthening bones. However, the specific mechanism by which ZGW regulates osteogenesis is still unclear. The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis. METHODS: A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs). RESULTS: In total, 487 no-repeat targets corresponding to the bioactive components of ZGW were screened, and 175 target genes in the intersection of ZGW and osteogenesis were obtained. And 28 core target genes were then obtained from a PPI network analysis. A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress, metal ions, and lipopolysaccharide. Additionally, KEGG pathway enrichment analysis revealed that multiple signaling pathways, including the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were associated with ZGW-promoted osteogensis. Further experimental validation showed that ZGW could increase alkaline phosphatase (ALP) activity as well as the mRNA and protein levels of ALP, osteocalcin (OCN), and runt related transcription factor 2 (Runx 2). What's more, Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT, and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002. Finally, the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002. CONCLUSION: ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.

Therapeutic mechanism of Liangxue-Guyuan-Yishen decoction on intestinal stem cells and tight junction proteins in gastrointestinal acute radiation syndrome rats.

On the basis of the previous research, the Traditional Chinese Medicine theory was used to improve the drug composition for gastrointestinal acute radiation syndrome (GI-ARS). The purpose of this study was to study the therapeutic mechanism of Liangxue-Guyuan-Yishen decoction (LGYD) on GI-ARS and to provide a new scheme for the treatment of radiation injury. Here, we investigated the effects of LGYD on intestinal stem cells (ISCs) in a GI-ARS rat model. Rat health and survival and the protective efficacy of LGYD on the intestines were analyzed. The active principles in LGYD were detected using liquid chromatography-mass spectrometry (LC-MS). ISC proliferation, intestinal epithelial tight junction (TJ) protein expression and regulatory pathways were explored using immunohistochemistry, western blotting (WB) and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. Involvement of the WNT and MEK/ERK pathways in intestinal recovery was screened using network pharmacology analysis and validated by WB and RT-qPCR. LGYD administration significantly improved health and survival in GI-ARS rats. Pathological analysis showed that LGYD ameliorated radiation-induced intestinal injury and significantly promoted LGR5+ stem cell regeneration in the intestinal crypts, upregulated TJ protein, and accelerated crypt reconstruction in the irradiated rats. LC-MS revealed ≥13 constituents that might contribute to LGYD's protective effects. Collectively, LGYD can promote crypt cell proliferation and ISCs after radiation damage, the above effect may be related to WNT and MEK/ERK pathway.

Predicting BRAFV600E mutations in papillary thyroid carcinoma using six machine learning algorithms based on ultrasound elastography.

The most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). The BRAFV600E gene encodes a protein-dependent kinase (PDK), which is a key component of the mitogen-activated protein kinase pathway and essential for controlling cell proliferation, differentiation, and death. The BRAFV600E mutation causes PDK to be activated improperly and continuously, resulting in abnormal proliferation and differentiation in PTC. Based on elastography ultrasound (US) radiomic features, this study seeks to create and validate six distinct machine learning algorithms to predict BRAFV6OOE mutation in PTC patients prior to surgery. This study employed routine US strain elastography image data from 138 PTC patients. The patients were separated into two groups: those who did not have the BRAFV600E mutation (n = 75) and those who did have the mutation (n = 63). The patients were randomly assigned to one of two data sets: training (70%), or validation (30%). From strain elastography US images, a total of 479 radiomic features were retrieved. Pearson's Correlation Coefficient (PCC) and Recursive Feature Elimination (RFE) with stratified tenfold cross-validation were used to decrease the features. Based on selected radiomic features, six machine learning algorithms including support vector machine with the linear kernel (SVM_L), support vector machine with radial basis function kernel (SVM_RBF), logistic regression (LR), Naïve Bayes (NB), K-nearest neighbors (KNN), and linear discriminant analysis (LDA) were compared to predict the possibility of BRAFV600E. The accuracy (ACC), the area under the curve (AUC), sensitivity (SEN), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV), decision curve analysis (DCA), and calibration curves of the machine learning algorithms were used to evaluate their performance. ① The machine learning algorithms' diagnostic performance depended on 27 radiomic features. ② AUCs for NB, KNN, LDA, LR, SVM_L, and SVM_RBF were 0.80 (95% confidence interval [CI]: 0.65-0.91), 0.87 (95% CI 0.73-0.95), 0.91(95% CI 0.79-0.98), 0.92 (95% CI 0.80-0.98), 0.93 (95% CI 0.80-0.98), and 0.98 (95% CI 0.88-1.00), respectively. ③ There was a significant difference in echogenicity,vertical and horizontal diameter ratios, and elasticity between PTC patients with BRAFV600E and PTC patients without BRAFV600E. Machine learning algorithms based on US elastography radiomic features are capable of predicting the likelihood of BRAFV600E in PTC patients, which can assist physicians in identifying the risk of BRAFV600E in PTC patients. Among the six machine learning algorithms, the support vector machine with radial basis function (SVM_RBF) achieved the best ACC (0.93), AUC (0.98), SEN (0.95), SPEC (0.90), PPV (0.91), and NPV (0.95).

Evolutionary roles of polyploidization-derived structural variations in the phenotypic diversification of Panax species.

Genomic structural variations (SVs) are widespread in plant and animal genomes and play important roles in phenotypic novelty and species adaptation. Frequent whole genome duplications followed by (re)diploidizations have resulted in high diversity of genome architecture among extant species. In this study, we identified abundant genomic SVs in the Panax genus that are hypothesized to have occurred through during the repeated polyploidizations/(re)diploidizations. Our genome-wide comparisons demonstrated that although these polyploidization-derived SVs have evolved at distinct evolutionary stages, a large number of SV-intersecting genes showed enrichment in functionally important pathways related to secondary metabolites, photosynthesis and basic cellular activities. In line with these observations, our metabolic analyses of these Panax species revealed high diversity of primary and secondary metabolites both at the tissue and interspecific levels. In particular, genomic SVs identified at ginsenoside biosynthesis genes, including copy number variation and large fragment deletion, appear to have played important roles in the evolution and diversification of ginsenosides. A further herbivore deterrence experiment demonstrated that, as major triterpenoidal saponins found exclusively in Panax, ginsenosides provide protection against insect herbivores. Our study provides new insights on how polyploidization-derived SVs have contributed to phenotypic novelty and plant adaptation.

[Molecular mechanism of ginsenoside Rg_1 against radiation enteritis: based on network pharmacology and in vitro experiment].

Via network pharmacology, molecular docking, and cellular experiment, this study explored and validated the potential molecular mechanism of ginsenoside Rg_1(Rg_1) against radiation enteritis. Targets of Rg_1 and radiation enteritis were retrieved from BATMAN-TCM, SwissTargetPrediction, and GeneCards. Cytoscape 3.7.2 and STRING were employed for the construction of protein-protein interaction(PPI) network for the common targets, and screening of core targets. DAVID was used for Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict the possible mechanism, followed by molecular docking of Rg_1 with core targets and cellular experiment. For the cellular experiment, ~(60)Co-γ irradiation was performed for mo-deling of IEC-6 cells, which were then treated with Rg_1, protein kinase B(AKT) inhibitor LY294002, and other drugs to verify the effect and mechanism of Rg_1. The results showed that 29 potential targets of Rg_1, 4 941 disease targets, and 25 common targets were screened out. According to the PPI network, the core targets were AKT1, vascular endothelial growth factor A(VEGFA), heat shock protein 90 alpha family class A member 1(HSP90AA1), Bcl-2-like protein 1(BCL2L1), estrogen receptor 1(ESR1), etc. The common targets were mainly involved in the GO terms such as positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, positive regulation of cell proliferation, and other biological processes. The top 10 KEGG pathways included phosphoinositide 3-kinase(PI3K)/AKT pathway, RAS pathway, mitogen-activated protein kinase(MAPK) pathway, Ras-proximate-1(RAP1) pathway, and calcium pathway, etc. Molecular docking showed that Rg_1 had high binding affinity to AKT1, VEGFA, HSP90AA1, and other core targets. Cellular experiment indicated that Rg_1 can effectively improve cell viability and survival, decrease apoptosis after irradiation, promote the expression of AKT1 and B-cell lymphoma-extra large(BCL-XL), and inhibit the expression of the pro-apoptotic protein Bcl-2-associated X protein(BAX). In conclusion, through network pharmacology, molecular docking, and cellular experiment, this study verified the ability of Rg_1 to reduce radiation enteritis injury. The mechanism was that it regulated PI3K/AKT pathway, thereby suppressing apoptosis.

Evaluation of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma Using Clinical-Ultrasound Radiomic Machine Learning-Based Model.

We aim to develop a clinical-ultrasound radiomic (USR) model based on USR features and clinical factors for the evaluation of cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC). This retrospective study used routine clinical and US data from 205 PTC patients. According to the pathology results, the enrolled patients were divided into a non-CLNM group and a CLNM group. All patients were randomly divided into a training cohort (n = 143) and a validation cohort (n = 62). A total of 1046 USR features of lesion areas were extracted. The features were reduced using Pearson's Correlation Coefficient (PCC) and Recursive Feature Elimination (RFE) with stratified 15-fold cross-validation. Several machine learning classifiers were employed to build a Clinical model based on clinical variables, a USR model based solely on extracted USR features, and a Clinical-USR model based on the combination of clinical variables and USR features. The Clinical-USR model could discriminate between PTC patients with CLNM and PTC patients without CLNM in the training (AUC, 0.78) and validation cohorts (AUC, 0.71). When compared to the Clinical model, the USR model had higher AUCs in the validation (0.74 vs. 0.63) cohorts. The Clinical-USR model demonstrated higher AUC values in the validation cohort (0.71 vs. 0.63) compared to the Clinical model. The newly developed Clinical-USR model is feasible for predicting CLNM in patients with PTC.

A comparison of DP-TOF Mass Spectroscopy (MS) and Next Generation Sequencing (NGS) methods for detecting molecular mutations in thyroid nodules fine needle aspiration biopsies.

Mutations in the B-Raf proto-oncogene, serine/threonine kinase (BRAF), have been linked to a variety of solid tumors such as papillary thyroid carcinoma. The purpose of this study was to compare the DP-TOF, a DNA mass spectroscopy (MS) platform, and next-generation sequencing (NGS) methods for detecting multiple-gene mutations (including BRAFV600E) in thyroid nodule fine-needle aspiration fluid. In this study, we collected samples from 93 patients who had previously undergone NGS detection and had sufficient DNA samples remaining. The MS method was used to detect multiple-gene mutations (including BRAFV600E) in DNA remaining samples. NGS detection method was used as the standard. The MS method's overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.8%, 100%, 100%, and 88%, respectively in BRAFV600E gene mutation detection. With a kappa-value of 0.92 (95%CI 0.82-0.99), the level of agreement between these methods was incredibly high. Furthermore, when compared to NGS in multiple-gene detection, the MS method demonstrated higher sensitivity and specificity, 82.9% and 100%, respectively. In addition, we collected the postoperative pathological findings of 50 patients. When the postoperative pathological findings were used as the standard, the MS method demonstrated higher sensitivity and specificity, at 80% and 80%, respectively. Our findings show that the MS method can be used as an inexpensive, accurate, and dependable initial screening method to detect genes mutations and as an adjunct to clinical diagnosis.

Application of multiplex competitive PCR combined with capillary electrophoresis in carrier screening of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive, fatal neurological disorder in children. The pathogenic gene of SMA is survival motor neuron1 (SMN1). There are many methods to detect SMN1 gene copy number, but few techniques are suitable for large-scale population screening. In order to find a rapid and accurate experimental technique for mass screening of SMA carriers in the population, the SMN1 gene copy number of 12 SMA patients and their parents was analyzed by multiplex competitive PCR combined with capillary electrophoresis. Meanwhile, the copy number of SMN1 gene in 151 healthy pregnant women in Jiangsu was screened with the MLPA technology to confirm their copy number of the SMN genes. The results showed that the 12 SMA patients had 0 copy of SMN1 gene, and all their parents had 1 copy of SMN1 gene only. Among 151 healthy subjects, 3 cases (2.0%) had 1 copy of SMN1 gene, and hence designated as SMA carriers. One hundred and thirty-four cases (88.7%) had 2 copies of the SMN1 gene. There were 14 cases (9.3%) with more than 2 copies of the SMN1 gene. Therefore, multiplex competitive PCR combined with capillary electrophoresis is a rapid, simple and accurate method for the detection of SMA carriers; and potentially applicable to mass screening of SMA carriers in the population.

Radiomic Model for Determining the Value of Elasticity and Grayscale Ultrasound Diagnoses for Predicting BRAFV600E Mutations in Papillary Thyroid Carcinoma.

BRAFV600E is the most common mutated gene in thyroid cancer and is most closely related to papillary thyroid carcinoma(PTC). We investigated the value of elasticity and grayscale ultrasonography for predicting BRAFV600E mutations in PTC. Methods: 138 patients with PTC who underwent preoperative ultrasound between January 2014 and 2021 were retrospectively examined. Patients were divided into BRAFV600E mutation-free group (n=75) and BRAFV600E mutation group (n=63). Patients were randomly divided into training (n=96) and test (n=42) groups. A total of 479 radiomic features were extracted from the grayscale and elasticity ultra-sonograms. Regression analysis was done to select the features that provided the most information. Then, 10-fold cross-validation was used to compare the performance of different classification algorithms. Logistic regression was used to predict BRAFV600E mutations. Results: Eight radiomics features were extracted from the grayscale ultrasonogram, and five radiomics features were extracted from the elasticity ultrasonogram. Three models were developed using these radiomic features. The models were derived from elasticity ultrasound, grayscale ultrasound, and a combination of grayscale and elasticity ultrasound, with areas under the curve (AUC) 0.952 [95% confidence interval (CI), 0.914-0.990], AUC 0.792 [95% CI, 0.703-0.882], and AUC 0.985 [95% CI, 0.965-1.000] in the training dataset, AUC 0.931 [95% CI, 0.841-1.000], AUC 0. 725 [95% CI, 0.569-0.880], and AUC 0.938 [95% CI, 0.851-1.000] in the test dataset, respectively. Conclusion: The radiomic model based on grayscale and elasticity ultrasound had a good predictive value for BRAFV600E gene mutations in patients with PTC.

Fabrication of SEBS Block Copolymer-Based Ultrasound Phantom Containing Mimic Tumors for Ultrasound-Guided Needle Biopsy Training.

The creation of various phantoms is important in medical education, especially for intern physicians who need to practice their skills. Ultrasound phantoms are particularly useful for training in ultrasound-guided needle biopsy. SEBS, or poly(styrene-ethylene-butylene-styrene), is a thermoplastic elastomer that can be used with mineral oil to make ultrasound phantoms and a tumor-like structure. SEBS block copolymer-based phantoms are inexpensive, non-toxic and shelf-stable, and are easy to modulate. Most importantly, such ultrasound phantoms have acoustic and mechanical properties similar to those of human soft tissues. The quality of ultrasound images of phantoms and mimic tumors is excellent and can be maintained even after several biopsy needle punctures, making them excellent ultrasound phantoms for physician practice as needed.

Ultrasound-Guided Thermal Ablation of Thyroid Nodules: Technicalities Progress and Clinical Applications, Especially in Malignant Thyroid Nodules.

Thyroid nodules are commonly encountered in health care practice. They are usually benign in nature, with few cases being malignant, and their detection has increased in the adult population with the help of ultrasonography. Thyroidectomy or surgery is the first-line treatment and traditional method for thyroid nodules; however, thyroidectomy leaves permanent scars and requires long-term use of levothyroxine after surgery, which makes patients more reticent to accept this treatment. Thermal ablation is a minimally-invasive technique that have been employed in the treatment of benign and malignant thyroid nodules nodules, and have been shown to be effective and safe. Several studies, including long-term, retrospective, and prospective studies, have investigated the use of ablation to treat benign thyroid nodules and malignant thyroid nodules, including papillary thyroid carcinoma. Here, we review the recent progress in thermal ablation techniques for treating benign and malignant nodules, including their technicalities, clinical applications, pitfalls and limitations, and factors that could affect treatment outcomes. Special in-depth elaboration on the recent progress of the application of thermal ablation therapy in malignant thyroid nodules.

Synergistic Effects of Graphene and Ammonium Polyphosphate Modified with Vinyltrimethoxysilane on the Properties of High-Impact Polystyrene Composites.

Ammonium polyphosphate (APP) was modified with a silane coupling agent (vinyltrimethoxysilane, Si-171), and then the synergistic flame retarding effect of graphene and surface-modified APP (APP@Si-171) on high-impact polystyrene (HIPS) was investigated. Surface modification and thermal stability characterization of APP were analyzed by Fourier transform infrared spectroscopy (FTIR), energy dispersive spectrometer (EDS), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The results showed that surface-modified APP (APP@Si-171) exhibited significantly better dispersion and less agglomeration tendencies compared with pure APP. A series of target HIPS composites containing different mass fractions of the two flame retardants were prepared by melt blending. TGA and cone calorimeter tests (CCT) were conducted to quantitatively investigate the thermal and flammability properties of the composites, respectively. Results from TGA and CCT demonstrated that the addition of the flame retardants delayed the onset and peak temperatures in differential thermogravimetry (DTG) curves and weakened the peak heat release rate (PHRR) and total heat release (THR). Moreover, the synergistic effect index (SE) was employed to quantify the synergistic behavior between the two fillers, and the results showed that APP@Si-171 and graphene had a synergistic effect on improving the thermal stability and flame retardancy of HIPS.

Efficacy of Liangxue Guyuan decoction on radiation-induced intestinal injury in rats via the toll-like receptor 4/myeloid differentiation primary response 88/ nuclear factor-kappa B pathway.

OBJECTIVE: To evaluate the efficacy of Liangxue Guyuan decoction ( LGD) on radiation-induced intestinal injury in rats, and the possible underlying mechanism of action. METHODS: A total of 255 male Sprague-Dawley rats were used. 15 rats were assigned to the control group and the remaining 240 rats were exposed to a 60Co source at a dose of 11 Gy. Irradiated rats were randomly divided into model, dexamethasone (DXM), low-dose LGD (LGDl), and high-dose LGD (LGDh) groups and treated for 11 d. The survival rate, weight of body, intestinal pathology and the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB) were recorded. RESULTS: Radiation reduced the survival rate and weight of rats, destroyed the intestinal structure, induced an inflammatory reaction, and increased both protein and mRNA expression of TLR4, MyD88, and NF-κB in ileum. However, LGDh increased the survival rate, inhibited weight loss, alleviated inflammation and improve the expression of TLR4 pathway. CONCLUSION: LGD increased the survival rate and inhibit weight loss of irradiated rats, and reduced inflammation and intestinal injury. The underlying mechanism may involve regulation of the TLR4/MyD88/NF-κB pathway.

Effect of Modified Xijiao Dihuang Decoction () on Intestinal Flora and Th17/Treg in Rats with Radiation Enteritis.

OBJECTIVE: To observe the effect of Modified Xijiao Dihuang Decoction (, MXDD) on rats with radiation enteritis, and explore its action mechanism. METHODS: Thirty female Sprague Dawley rats were divided into the control, model, dexamethasone (DXM), golden bifid (GB) and MXDD groups using random number table, 6 rats in each group. Except the control group, the other rats were developed into radiation enteritis model by exposing to a single 60Co-γ ray at a dose of 11 Gy. The rats in the DXM, GB and MXDD groups were treated with DXM (1.425 mg/kg), GB (0.8 g/kg) and MXDD (36.0 g/kg) for 3 days, respectively. Body weight and diarrhea condition of rats were evaluated daily. On day 3, the feces of rats were collected for intestinal flora detection and the small intestinal tissues were also collected. Bacterial species annotation, alpha and beta diversities as well as composition of intestinal flora were detected and compared. The protein and mRNA expressions of interleukin 17 (IL-17), retinoid-related orphan nuclear receptor gamma t (ROR-γt) and forkhead/ winged helix transcription factor p3 (FoxP3) were determined by Western blot and polymerase chain reaction, respectively. The abundance and diversity of intestinal flora as well as the proportion at the phylum and genus levels were assayed by 16S rRNA metagenome sequencing. Correlation between intestinal flora and Th17/Treg was analyzed by heatmap method. RESULTS: On day 1 to 3 after radiation, compared with the control group, the body weight in model group was decreased (P<0.05 or P<0.01). Compared with the model group, MXDD could alleviate weight loss and diarrhea caused by irradiation. At the phylum level, MXDD cause a significant increase in Firmicutes, and a decrease in Proteobacteria (P<0.05 or P<0.01). At the genus level, MXDD reduced the proportion of Escherichia Shigella (P<0.01). In addition, IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment (P<0.05). Besides, Firmicutes and Lactobacillus were positively correlated with FoxP3 (r=0.73, 0.79, respectively; P<0.01), negatively correlated with IL-17 (r=0.66, 0.64, respectively; P<0.01 or P<0.05) and ROR-γt (r0.73, 0.81, respectively; P<0.01). Proteobacteria and Escherichia Shigella both had positive correlation with IL-17 (r 0.77, 0.57, respectively; P<0.01 or P<0.05 ) and ROR-γt (r=0.94, 0.79, respectively; P<0.01) and negative correlation with FoxP3 (r0.74, 0.65; P<0.01). CONCLUSION: MXDD could improve the survival status of irradiated rats by regulating the richness, diversity and composition of intestinal flora, and restoring the balance of Th17/Treg.

Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in 13,069 Chinese Pregnant Women.

Spinal muscular atrophy (SMA) is a relatively common, life-shortening, autosomal recessive neuromuscular disease. The carrier frequency of SMA ranges from approximately 0.98% to 2.02%, depending on ethnicity. The American College of Medical Genetics has therefore recommended population screening for SMA carrier status, regardless of race or ethnicity. We performed the largest-scale carrier screening for SMA carriers in mainland China. Carrier screening was offered to 36,470 pregnant women between July 2017 and June 2019, of whom 13,069 women accepted the screening program [35.83%; 95% credibility interval (CI), 35.34%-36.33%]. Copy numbers of exons 7 and 8 in the SMN1 gene were detected by real-time quantitative PCR, and the results were confirmed by multiplex ligation-dependent probe amplification. A total of 231 women were identified as carriers (1.77%; 95% CI, 1.56%-2.01%), indicating a carrier prevalence of approximately 1:56 in the population. After detailed genetic counseling, 207 paternal partners were recalled and tested. Both partners were carriers in 10 couples, of whom prenatal diagnosis was implemented in seven, and one fetus was diagnosed with SMA. Carrier screening could provide couples with informed reproductive choices. Our workflow and experience of carrier screening may facilitate the popularization of SMA carrier screening in mainland China.

Diagnostic performance of combination of ultrasound elastography and BRAF gene detection in malignant thyroid nodule: a retrospective study.

OBJECTIVES: The aims of our study were to explore the preoperative diagnostic value of ultrasound elastography combined with BRAF gene detection in malignant thyroid nodule, and find whether shear wave elastography (SWE) combined with BRAF gene detection can improve the diagnostic sensitivity and specificity. METHODS: From 1480 patients with thyroid nodule examined between January 2015 and December 2017, a retrospective analysis was performed on 161 patients who underwent thyroidectomy. Diagnosis was confirmed by postoperative pathology, including 139 malignant thyroid nodules and 22 benign thyroid nodules. All the patients underwent SWE, BRAF gene detection, and the combination for their preoperative evaluation. The sensitivities, specificities, and accuracies of SWE, BRAF gene detection, and the combination for detection of malignant thyroid nodules were calculated and then compared using Fisher's exact probability test, based on the original preoperative reports and postoperative pathology. A receiver-operating characteristic curve analysis was performed to compare the diagnostic performance of SWE, BRAF gene detection, and combination for detecting malignant thyroid nodules. RESULTS: Based on the original preoperative reports and postoperative pathology, SWE, BRAF gene detection, and the combination showed sensitivities of 88.67%, 78.41%, 92.8%, and specificities of 72.77%, 77.27%, 95.45%. A correct diagnosis was obtained in 85.82%, 78.26%, 93.16% and missed diagnosis rates were 12.23%, 21.58%, and 7.19%. The sensitivities, specificities, and correct diagnosis rate in the combination group were significantly higher than any single detection method (P<0.05). The missed diagnosis rate in the combination group was significantly lower than any single detection method (P<0.05). The receptor operating characteristics curve analysis showed a significantly higher diagnostic performance for the combination than for SWE and BRAF gene detection (P<0.05). The interobserver agreement for detecting malignant thyroid nodule was better for the combination than for SWE or BRAF gene detection alone. CONCLUSION: For the detection of a malignant thyroid nodule, SWE combined with BRAF gene detection was more sensitive and showed a higher diagnostic performance than SWE or BRAF gene detection alone.

Extracts from Huangqi (Radix Astragali Mongoliciplus) and Ezhu (Rhizoma Curcumae Phaeocaulis) inhibit Lewis lung carcinoma cell growth in a xenograft mouse model by impairing mitogen-activated protein kinase signaling, vascular endothelial growth factor production, and angiogenesis.

OBJECTIVE: To study the anti-tumor effects of the extracts from Huangqi (Radix Astragali Mongolici) and Ezhu (Rhizoma Curcumae Phaeocaulis) on the growth of Lewis lung carcinoma (LLC) in a xenograft mouse model and to investigate the possible underlying mechanism. METHODS: LLC tumor-bearing C57BL/6 mice were treated with normal saline, cisplatin (2 mg/kg intraperitoneally every other day), or Huangqi (Radix Astragali Mongolici) and Ezhu (Rhizoma Curcumae Phaeocaulis) (1∶1, 2∶1, or 3∶1 ratio; 5 , 8 , or 11 g/kg crude drug intragastrically every day) for 15 d. Body weights and tumor volumes were measured every other day. Tumors were excised on day 15 and analyzed. Tumor microvessel density (MVD) was assessed by immunohistochemical staining of CD34; and expression of vascular endothelial cell growth factor (VEGF), the mitogen-activated protein kinases p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and Jun N-terminal kinase (JNK) and their phosphorylated forms were assessed by Western blotting. RESULTS: Treatment with cisplatin caused a significant loss of body weight compared with controls, whereas Huangqi (Radix Astragali Mongolici) and Ezhu (Rhizoma Curcumae Phaeocaulis) extract combinations had no effect. Extracts from Huangqi (Radix Astragali Mongolici) and Ezhu (Rhizoma Curcumae Phaeocaulis) significantly decreased tumor weight and tumor MVD compared with controls, and at the 3∶1 treatment group had similar efficacy to cisplatin in reducing MVD. Tumors from Huangqi (Radix Astragali Mongolici) and Ezhu (Rhizoma Curcumae Phaeocaulis) treatments also showed decreased p38 MAPK, p-p38 MAPK, ERK1/2, p-ERK1/2, JNK, and p-JNK expression compared with the control group (all P < 0.01). VEGF protein expression was significantly reduced in the 2∶1 and 3∶1 treatment groups compared with the control group (P < 0.01). CONCLUSION: Extracts from Huangqi (Radix Astragali Mongolici) and Ezhu (Rhizoma Curcumae Phaeocaulis) hindered LLC growth in the xenograft mouse model, possibly via inhibition of the MAPK signaling pathway, VEGF production, and tumor angiogenesis.