ObjectiveTo evaluate the effect of Ningying Formula （宁瘿方） combined with low-dose antithyroid drugs （ATDs） on the relapse risk for patients with Graves' hyperthyroidism （GH） during the remission phase， and to analyze the related factors between GH relapse and thyrotropin receptor antibody （TRAb） negativity， so as to provide evidence for the standardized management of GH in remission stage. MethodsA single-center retrospective cohort study was conducted， including 269 GH patients in the remission stage. After propensity score matching （PSM）， 102 matched pairs （204 patients） were established. The control group received low-dose ATDs as maintenance therapy， while the exposure group received the core Ningying Formula in addition to low-dose ATDs. The primary outcome was the GH recurrence rate； the secondary outcome was the thyrotropin receptor antibody （TRAb） negativity rate （TRAb＜1.75 IU/L）. Safety outcomes included treatment-related adverse events. Differences between groups were assessed using Cox regression models and Kaplan-Meier curves， with sensitivity analysis performed using inverse probability of treatment weighting （IPTW）. ResultsThe median follow-up in the matched cohort was 28.07 months. Regarding the GH recurrence outcome， the recurrence rate in the exposure group （18/102， 17.6%） was significantly lower than that in the control group （31/102， 30.4%； χ²=4.539， P=0.033）； regarding the TRAb negativity outcome， the TRAb negativity rate in the exposure group （50/102， 49.0%） was significantly higher than that in the control group （23/102， 22.5%； χ²=15.551， P＜0.001）. Multivariate Cox regression analysis for recurrence showed that Ningying Formula treatment reduced the risk of recurrence ［HR=0.324， 95%CI（0.170， 0.617）， P＜0.001］. Male ［HR=2.209， 95%CI（1.079， 4.520）， P=0.030］， higher initial TRAb level ［per 1 IU/L increase： HR=1.033， 95%CI（1.003， 1.064）， P=0.032］， and larger thyroid volume ［per 1 ml increase： HR=1.045， 95%CI（1.003， 1.088）， P=0.035］ were identified as independent risk factors for recurrence； multivariate Cox regression analysis for TRAb negativity indicated that Ningying Formula treatment promoted TRAb negativity ［HR=1.826， 95%CI（1.091， 3.056）， P=0.022］， while a higher initial TRAb level was associated with a lower probability of negativity ［HR=0.974， 95%CI（0.950， 0.998）， P=0.032］. Survival analysis showed significant differences in relapse rate between groups （Log-Rank P=0.003） and in TRAb outcomes （Log-Rank P=0.034）. The incidence of treatment-related adverse events was similar between groups （P=0.757）. The IPTW sensitivity analysis was consistent with the primary analysis， indicating robust results. ConclusionThe Ningying Formula combined with low-dose ATDs can significantly reduce the risk of recurrence and can improve the TRAb negativity rate in GH patients during the remission stage， without increasing common adverse events， making it an optional strategy for reducing relapse risk during remission. Male gender， higher baseline TRAb level， and larger thyroid volume indicate a higher risk of recurrence， warranting focused follow-up and stratified management.

Objective To investigate the capacity of municipal and county-level Centers for Disease Control (CDC) in Shandong Province for γ radionuclides in food as well as gross α and gross β in drinking water, and to provide evidence for strengthening radiological laboratories. Method Data regarding radioactive detection capacity were collected from 16 prefecture-level cities and 136 county-level CDCs. Chi-square test and Fisher's exact tests were used to compare capacity differences across regions and between cities with and without nuclear power plants. Correlation analysis was used to evaluate the spatial equity of gross α and gross β detection capacity for drinking water. Result The detection capacity of gross α and gross β in drinking water varied significantly among counties (χ²=81.026, P<0.001），no significant difference was found between coastal and inland cities (χ²=2.021，P>0.155); Cities with nuclear power plants showed better detection capacity (χ²=20.253，P<0.01). The detection capacity for γ radionuclides in food was primarily concentrated in the prefecture-level cities that host nuclear power plants. Conclusion The overall detection capacity for radioactivity in drinking water was acceptable but spatially uneven. The capacity for monitoring radioactive contamination in food was generally weak. It is necessary to strengthen capacity building at the grassroots level.

ObjectiveTo explore the effects of compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata on the expression of type 2 innate lymphoid cells（ILC2s）-related factors in the lung of allergic rhinitis（AR）mice. MethodsAccording to the random number table method，fifty-four C57BL/6J mice were randomly divided into the following groups： Blank group，model group，Mahuang Fuzi Xixintang group，Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba and Asari Radix et Rhizoma group，Ephedrae Herba and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba group，Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group （6 mice in each group）. Except the blank group，the other groups were subjected to intraperitoneal injection of ovalbumin（OVA）and intranasal challenge to induce AR. After the AR model was established，the mice in the blank group and the model group were given 0.2 mL·d^-1 normal saline by gavage，while those in the Mahuang Fuzi Xixintang group（2.31 g·kg^-1），Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group（1.54 g·kg^-1）， Ephedrae Herba and Asari Radix et Rhizoma group（1.16 g·kg^-1）， Ephedrae Herba and Aconiti Lateralis Radix Praeparata group（1.93 g·kg^-1），Ephedrae Herba group（0.77 g·kg^-1），Aconiti Lateralis Radix Praeparata group（1.16 g·kg^-1），and Asari Radix et Rhizoma group（0.39 g·kg^-1）were given corresponding medicine by gavage，with the treatment lasting for 14 consecutive days. The survival state of mice in each group was observed， and the levels of serum immunoglobulins E（IgE）after intranasal challenge were measured by enzyme-linked immunosorbent assay（ELISA）. The pathological changes of nasal and lung tissues were observed by hematoxylin-eosin（HE）staining. The expression of ILC2s in lung tissue of mice was detected by immunofluorescence（IF）. The mRNA expression of GATA binding protein 3（GATA3），retinoic acid receptor-related orphan receptor-α（RORα）， and inhibitor of DNA binding 2（ID2）in the lung tissue of mice was detected by quantitative real-time polymerase chain reaction（real-time PCR）. The levels of IgE，interleukin（IL）-4，IL-5， and IL-13 in serum were detected by ELISA. ResultsCompared with the blank group，the model group had poor survival state of mice and significantly increased serum IgE level after intranasal challenge（p<0.01）. Additionally，the mice in the model group showed a large amount of neutrophil infiltration in the mucosa of the posterior turbinate， obvious nasal mucosal bleeding and purulent secretion，shed epithelium， thickened bronchial wall，obvious intravascular hyperemia and edema，diffusion and infiltration of a large number of inflammatory cells，seriously damaged alveolar structure，and local lung consolidation. The model group also exhibited significantly increased expression of ILC2s in the lung tissue（P<0.01），increased mRNA expression of GATA3 and RORα，decreased mRNA expression of ID2（P<0.05，P<0.01），and increased levels of serum IgE， IL-4，IL-5，and IL-13（P<0.05，P<0.01）. Compared with the model group，the Mahuang Fuzi Xixintang group and the other medicine treatment groups showed improved survival state of mice， significantly reduced inflammatory cell infiltration in the nasal and lung tissues，a small amount of nasal mucosal bleeding，trachea wall thinning，and no hyperemia，edema， and nasal secretions. Furthermore， the expression of ILC2s in lung tissue was significantly decreased（P<0.01）. The mRNA expression level of GATA3 was decreased（P<0.05），especially in the Aconiti Lateralis Radix Praeparata group（P<0.01）. The expression mRNA levels of RORα were decreased only in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group and the Ephedrae Herba group（P<0.05）. The levels of serum IgE were decreased（P<0.05）， and IL-5 levels were significantly decreased（P<0.01）. IL-4 levels were significantly decreased in the groups except the Aconiti Lateralis Radix Praeparata group（P<0.01），and the level of IL-13 in the Mahuang Fuzi Xixintang group was decreased（P<0.05）. The levels of IL-13 in were significantly decreased in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group， Ephedrae Herba group， Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group（P<0.01）. ConclusionDifferent compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata can reduce the inflammation of OVA-induced AR mice and has more advantages in reducing the secretion of IgE and IL-5. The compatibility of Ephedrae Herba and Aconiti Lateralis Radix Praeparata has the most advantage in reducing the mRNA expression of GATA3 and RORα to inhibit the expression of ILC2s and thus exert the anti-allergic effect，while the other compatibility has the extensive advantage in inhibiting the mRNA expression of GATA3.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.
Humans ; Sleep Apnea, Obstructive/pathology* ; Aging/physiology* ; Oxidative Stress/physiology* ; Animals

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals ; TOR Serine-Threonine Kinases/genetics* ; Male ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans

To determine the optimal cultivation duration and harvest period for cultivated Notopterygium incisum and promote its industrial development, this study established a characteristic chromatographic profile of cultivated N. incisum and employed chemometrics combined with entropy-weighted grey correlation analysis to assess differences in agronomic traits and quality indicators across different cultivation years and harvest periods. By comparing with reference substances, ten common peaks were identified, including chlorogenic acid, p-coumaric acid, ferulic acid, marmesinin, nodakenin, isochlorogenic acid B, notopterol, phenethyl ferulate, isoimperatorin, and falcarindiol. The similarity between the characteristic chromatographic profiles of N. incisum at different cultivation years and the reference profile was all above 0.932. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) revealed that the quality of 1-to 3-year-old cultivated N. incisum was highly dispersed and unstable, whereas the quality of 4-year-old cultivated N. incisum remained relatively stable across different harvest periods. This suggests that the accumulation of relevant compounds in the medicinal material had reached a plateau, confirming that the optimal cultivation period for N. incisum is four years. Entropy-weighted grey correlation analysis indicated that the quality of 4-year-old cultivated N. incisum across different harvest periods ranked from highest to lowest as follows: November, December, October, August, July, and September, demonstrating that November is the optimal harvest time. The findings of this study establish the suitable cultivation duration and optimal harvest period for N. incisum, providing a scientific basis for cultivation guidance and quality standardization.
Chromatography, High Pressure Liquid/methods* ; Apiaceae/chemistry* ; Entropy ; Chemometrics/methods* ; Drugs, Chinese Herbal/chemistry* ; Principal Component Analysis ; Quality Control

This study predicts the potential mechanism of Hippocampus in the treatment of knee osteoarthritis(KOA) through network pharmacology, with preliminary verification using molecular docking and animal experiments. The database was used to screen the active chemical components of Hippocampus and the targets of KOA, and Gene Ontology(GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and molecular docking were performed on the relevant core targets to preliminarily explore the potential targets and mechanisms of Hippocampus in the treatment of KOA. A rat KOA model was constructed by intra-articular injection of sodium iodoacetate, and the rats were intervened with different doses of Hippocampus decoction and celecoxib. The expression of relevant targets was detected through hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), RT-qPCR, and Western blot to further validate the network pharmacology results. A total of 23 drug-like components of the Hippocampus were screened, and 128 common targets with KOA were identified, involving interleukin-17(IL-17) signaling pathway, transcription factor(FoxO) signaling pathway, tumor necrosis factor(TNF) signaling pathway. Molecular docking results showed that the screened core chemical components exhibited good affinity with key targets. HE staining demonstrated that Hippocampus improved the morphology of the cartilage layer. ELISA confirmed that Hippocampus significantly reduced the levels of IL-6 and TNF-α in the serum of KOA rats. Western blot and RT-qPCR analysis showed that Hippocampus significantly reduced the expression of IL-6, TNF-α, matrix metalloproteinase(MMP) 13, IL-17A, nuclear factor κB activator 1(ACT1), tumor necrosis factor receptor-associated factor 6(TRAF6) and nuclear factor κB(NF-κB) in cartilage tissue. The results suggest that Hippocampus can alleviate the degree of joint damage in the KOA rat model induced by sodium iodoacetate. The mechanism of action is related to the inhibition of the IL-17 signaling pathway, reduction of inflammation, and inhibition of extracellular matrix(ECM) degradation.
Animals ; Molecular Docking Simulation ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Male ; Osteoarthritis, Knee/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Humans ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Hippocampus/chemistry*