Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Compressed Sensing Image Reconstruction of Ultrasound Image for Treatment of Early Traumatic Myositis Ossificans of Elbow Joint by Electroacupuncture.

This article conducts a retrospective analysis of 500 patients with posttraumatic elbow dysfunction admitted to our department from March 2019 to September 2020. The average time from injury to operation is 11 months (2-20 months). We adopt a personalized treatment method to completely remove the hyperplastic adhesion tissue and heterotopic ossification around the joint, remove part of the joint capsule and ligament, and release it to achieve maximum function. After the operation, an external fixator was used to stabilize the loosened elbow joint, and the patient was guided to perform rehabilitation exercises with the aid of a hinged external fixator, and celecoxib was used to prevent heterotopic ossification. Mayo functional scoring system was used to evaluate the curative effect before and after surgery. The rapid realization of ultrasound imaging under the framework of compressed sensing is studied. Under the premise of ensuring the quality of ultrasound imaging reconstruction, the theory of ultrasound imaging is improved, and a plane wave acoustic scattering ultrasound echo model is established. On this basis, the theory of compressed sensing is introduced, the mathematical model of compressed sensing reconstruction is established, and the fast iterative shrinkage thresholding algorithm (FISTA) of compressed sensing reconstruction is improved to reduce the computational complexity and the number of iterations. This article uses FISTA directly to reconstruct medical ultrasound images, and the reconstruction results are not ideal. Therefore, a simulation model of FISTA training and testing was established using the standard image library. By adding different intensities of noise to all images in the image library, the influence of noise intensity on the quality of FISTA reconstructed images is analyzed, and it is found that the FISTA model has requirements for the quality of the images to be reconstructed and the training set images. In this paper, Rob's blind deconvolution restoration algorithm is used to preprocess the original ultrasound image. The clarity of the texture details of the restored ultrasound image is significantly improved, and the image quality is improved, which meets the above requirements. This paper finally formed a reconstruction model suitable for ultrasound images. The reconstruction strategy verified by the ultrasound images provided by the Institute of Ultrasound Imaging of a medical university has achieved a significant improvement in the quality of ultrasound images.

Development of gestation-specific reference intervals for thyroid hormones in normal pregnant Northeast Chinese women: What is the rational division of gestation stages for establishing reference intervals for pregnancy women?

BACKGROUND: A laboratory- and region-specific trimester-related reference interval for thyroid hormone assessment of pregnant women was recommended. Whether the division by trimester is suitable requires verification. Here, we tried to establish appropriate reference intervals of thyroid-related hormones and antibodies for normal pregnant women in Northeast China. METHODS: A total of 947 pregnant women who underwent routine prenatal care were grouped via two methods. The first method entailed division by trimester: stages T1, T2, and T3. The second method entailed dividing T1, T2, and T3 stages into two stages each: T1-1, T1-2, T2-1, T2-2, T3-1, and T3-2. Serum levels of TSH, FT3, FT4, Anti-TPO, and Anti-TG were measured by three detection systems. RESULTS: No significant differences were found in TSH values between T1-1 group and the non-pregnant women group. However, the TSH value of the T1-1 group was significantly higher than that of T1-2 group (P<0.05). The TSH values in stage T3-2 increased significantly compared to those in stage T3-1 measured by three different assays (P<0.05). FT4 and FT3 values decreased significantly in the T2-1 and T2-2 stages compared to the previous stage (P<0.05). The serum levels of Anti-TPO and Anti-TG were not having significant differences between the six stages. CONCLUSION: The diagnosis and treatment of thyroid dysfunction during pregnancy should base on pregnancy- and method-specific reference intervals. More detailed staging is required to assess the thyroid function of pregnant women before 20 gestational weeks.