This paper investigated the inhibitory effect of carbonized Scutellariae Radix(Cb-SR) on pyroptosis in endometrial epithelial cells of mice with endometritis and its correlation with the IKBKE/NLRP3 signaling axis. Mice model of endometritis was established by using an intrauterine injection of 10 μL polysaccharides(LPS, 5 mg·mL~(-1)), and the mice were randomly divided into model group(LPS), low-dose group of Cb-SR(L-Cb-SR, 0.55 g·kg~(-1)), medium-dose group of Cb-SR(M-Cb-SR, 1.10 g·kg~(-1)), high-dose group of Cb-SR(H-Cb-SR, 2.20 g·kg~(-1)), crude Scutellariae Radix group(Cr-SR, 1.63 g·kg~(-1)), and Fuke Qianjin Capsule group(FQC, 0.30 g·kg~(-1)), with 10 mice in each group. Ten healthy female mice were selected and injected with PBS of equal volume into the bilateral uterus, and they were set as the sham group. The mice in the drug treatment groups were given the corresponding doses of Cb-SR, Cr-SR, FQC, or physiological saline of equal volume by gavage twice a day for seven days. Thirty minutes after the last administration, each mouse was euthanized by cervical dislocation. Hematoxylin-eosin(HE) staining and transmission electron microscopy were applied to observe the histopathological morphology of the uterine tissue. Immunohistochemistry was used to detect the expression of CD38 and CD138. Myeloperoxidase(MPO) values in neutrophils were measured by the kit; Enzyme-linked immunosorbent assay(ELISA) was used to measure the secretion of interleukin-18(IL-18), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Immunofluorescence and Western blot were used to analyze the expression of the proteins related to the IKBKE/NLRP3 signaling axis. Mouse endometrial epithelial cells(MEECs) were separated and purified from the uterine tissue of pregnant female mice through in vitro experiments and injured by LPS for 24 h, and then they were cultured with Cb-SR-containing serum. The anti-endometritis effect of Cb-SR was investigated by CCK-8 assay, scanning electron microscopy, and Western blot. The results showed that Cb-SR significantly reduced MPO values, attenuated uterine tissue damage, inhibited the expression of CD38 and CD138, decreased the levels of IL-1β, IL-18, and TNF-α, and inhibited the expression of proteins associated with IKBKE/NLRP3 signaling axis in mice with endometritis. In addition, Cb-SR-containing serum reduced swelling of MEECs organelles induced by LPS, decreased the expression of inflammatory factors, and suppressed the expression of IKBKE/NLRP3 signaling axis-related proteins. These results suggest that Cb-SR can inhibit endometrial epithelial cell pyroptosis in endometritis by suppressing the IKBKE/NLRP3 signaling axis.
Animals ; Female ; Mice ; Pyroptosis/drug effects* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/chemistry* ; Endometritis/chemically induced* ; Lipopolysaccharides/adverse effects* ; Scutellaria baicalensis/chemistry* ; Humans ; Epithelial Cells/drug effects*

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

Objective: To investigate the characteristics of the time-point distribution of the occurrence of laryngopharyngeal reflux (LPR) by 24-hour multichannel intraluminal impedance-pH monitoring (24 h MII-pH) and to provide guidance for the development of individualized anti-reflux strategies for LPR patients. Methods: We conducted a retrospective analysis of 24 h MII-pH data from 408 patients [339 males and 69 females, aged 23-84 (55.08±11.08) years] attending the Department of Otorhinolaryngology Head and Neck Surgery at the Sixth Medical Center of the PLA General Hospital from January 2013 to March 2020. The number of gas acid/weak-acid reflux, mixed gas-liquid acid/weak-acid reflux, liquid acid/weak-acid reflux and alkaline reflux events at different time points were recorded and statistically analyzed through SPSS 26.0 software. Results: A total of 408 patients were included. Based on the 24 h MII-pH, the total positive rate of LPR was 77.45% (316/408). The type of positive gaseous weak-acid reflux was significantly higher than the remaining types of LPR (χ²=297.12,P<0.001). Except the gaseous weak-acid reflux, the occurrence of the remaining types of LPR showed a tendency to increase after meals, especially after dinner. Liquid acid reflux events occurred mainly between after dinner and the following morning, and 47.11% (57/121) of them occurred within 3 h after dinner. There was a significant positive association between Reflux Symptom Index scores and gaseous weak-acid reflux(r=0.127,P<0.01), liquid acid reflux(r=0.205,P<0.01) and liquid weak-acid reflux(r=0.103,P<0.05)events. Conclusions: With the exception of gaseous weak-acid reflux events, the occurrence of the remaining types of LPR events has a tendency to increase after meals, especially after dinner. Gaseous weak-acid reflux events accounts for the largest proportion of all types of LPR events, but the pathogenic mechanisms of gaseous weak-acid reflux are needed to further investigate.
Male ; Female ; Humans ; Laryngopharyngeal Reflux/diagnosis* ; Retrospective Studies ; Esophageal pH Monitoring ; Otolaryngology ; Software ; Electric Impedance

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.
Medicine, Tibetan Traditional ; Reproducibility of Results

Humans ; Laryngopharyngeal Reflux ; Hypopharynx ; Respiratory System

Objective: To investigate the effect of gastroesophageal reflux disease (GERD) on the clinical characteristics of patients with laryngopharyngeal reflux disease(LPRD). Methods: The data of 141 patients with symptoms of LPRD, who were admitted to the Department of Pharyngology, Laryngology& Phonosurgery at the Sixth Medical Center of the PLA General Hospital from November 2020 to October 2021, were retrospectively analyzed.There were 118 males and 23 females, aged 28-75 (56.72±10.04) years old. The included patients underwent simultaneous 24-hour hypopharyngeal and esophageal multichannel intraluminal impedance pH monitoring (24h-HEMII-pH), salivary pepsin test at multiple times, Reflux Symptom Index (RSI), and Reflux Finding Score (RFS). One laryngopharyngeal reflux event on 24 h-HEMII-pH monitoring results was used as a diagnostic criterion for LPRD. And the duration of lower esophageal pH<4.0>4.0% at 24 h or DeMeester score>14.7 were used as diagnostic criteria for GERD. Among them, patients with both positive LPRD and GERD were classified as L&G group, patients with positive LPRD and negative GERD were classified as IL group, patients with negative LPRD and positive GERD were classified as IG group, and patients with both negative LPRD and GERD were classified as N group. The differences in the clinical characteristics of reflux and salivary pepsin assay in each group were statistically analyzed. SPSS 23.0 software was applied for statistical analysis. Results: According to the 24 h-HEMII-pH results, 116 (82.3%) patients were diagnosed with LPRD and 45 (31.9%) with GERD, including 82 (58.2%) in the IL group, 34 (24.1%) in the L&G group, 11 (7.8%) in the IG group, and 14 (9.9%) in the N group. Based on the salivary pepsin test, a total of 106 patients had positive results, and the L&G group had a significantly higher rate of positive total salivary pepsin test (94.1%) and positive morning test (70.6%) than the IL group (75.6%, 26.8%), IG group (63.6%, 27.3%) and N group (35.7%, 28.6%), with chi-square values of 19.01 and 20.81, both with P<0.001. The patients in the L&G group had a significantly higher RSI score (14.0) than the IL group (7.0), IG group (1.0) and N group (0), H=52.26,P<0.001. The difference in RFS between the L&G and IL groups was not statistically significant (Z=-0.92,P>0.05). Conclusion: Combined with GERD, LPRD patients have more obvious clinical symptoms and higher positive rate of pepsin test in saliva.
Aged ; Female ; Humans ; Male ; Middle Aged ; Esophageal pH Monitoring ; Hypopharynx ; Laryngopharyngeal Reflux ; Pepsin A ; Retrospective Studies ; Adult

Aim To explore the mechanism of action of the active ingredients of Callerya nitida var.hirsutissima corresponding to the target gene in the treatment of triple-negative breast cancer(TNBC), using network pharmacology, molecular docking technology and in vitro experimental verification.Methods Based on literature research and combined with database screening, the main active components of Callerya nitida var.hirsutissima and the related targets of TNBC were obtained.Intersection genes were found to construct a protein interaction(PPI)network diagram, and core targets were screened according to the size of the correlation.A core target interaction network model of "Traditional Chinese Medicine-Ingredients-Targets-Disease" was constructed.The intersection targets were analyzed for gene GO function and KEGG pathway enrichment analysis.Finally, molecular docking and in vitro experimental verification of the selected components and the target were carried out.Results A total of 38 active components of Callerya nitida var.hirsutissima were collected, as well as 388 related potential targets, 3 919 TNBC targets, and 277 Callerya nitida var.hirsutissima therapeutic targets for TNBC.It mainly acted on multiple targets such as PIK3R1, PIK3CA, MAPK1, AKT1, SRC, etc.In in vitro experiments, it could be seen that the chloroform fraction of Callerya nitida var.hirsutissima and the monomer compounds luteolin and betulin had certain inhibitory effects on cell proliferation.All groups could inhibit the expression of VEGFA, AKT, PIK3CA, CDK1, CDK4 within the range of administration concentration.Conclusions Based on network pharmacology and molecular docking methods, this study explores the possible targets and signaling pathways of Callerya nitida var.hirsutissima in the treatment of TNBC, and conducts in vitro verification experiments to further verify the prediction of network pharmacology.

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1β), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.
Databases, Factual ; Drugs, Chinese Herbal ; Humans ; Inflammation ; Molecular Docking Simulation ; Osteoarthritis, Knee

The natural forest and artificial shed are the main cropping modes of Coptis chinensis. This study is aimed to reveal the rhizosphere soil bacterial community structure difference between under tow C. chinensis cropping modes-natural forest and artificial shed, and to assist us to completely understand soil quality condition,and provide theoretical guidance for soil improvement and C. chinensis planting. The rhizosphere soil samples of 1-5-year-old C. chinensis under tow cropping modes-natural forest and artificial shed were collected. Illumina high-throughput sequencing technology was used to analyze the alpha diversity, community composition, community structure of soil bacteria under the tow cropping modes,and the effects of soil nutriment indices on soil bacterial community structure. Through the analysis of species number, Shannon, Chao1 index and ACE index of bacterial community, it was found that the bacterial diversity of 1-year-old C. chinensis soil under natural forest cropping mode was significantly lower than that under artificial shed cropping mode, and the diversity of bacterial communities in soil of 2-5-years old C. chinensis were not significant different between two cropping modes. A total of 53 phyla,60 classes,140 orders and 266 families were detected in the rhizosphere soil of C. chinensis under the cropping modes of natural forest, respectively. The rhizosphere soil of C. chinensis under the cropping modes of artificial shed included 54 phyla,65 classes,140 orders and 264 families, respectively. Under the two cropping modes, the top 10 dominant species of bacterial community abundance are the same, they are Proteobacteria, Acidobacteria, Actinobacteria,Bacteroidetes, Planctomycetes, Chloroflexi, Verrucomicrobia, Gemmatimonadetes, Firmicutes and Cyanobacteria, but there are differences in the abundance sequence. The top 10 dominant species of bacterial community abundance accounted for 74.36% to 74.30% of the total bacteria, and 3.15% to 3.92% of the bacteria are unclassified. The results of Metastat analysis showed that the abundance of Gemmatimonadetes in the rhizosphere soil of C. chinensis under the cropping modes the artificial shed was significantly higher than that under the natural forest cropping mode(P<0.05). MRPP analysis of community structure differences showed that under tow cropping modes, there were significant differences in the bacterial community structure of 1-4-year-old soil bacteria, among which the difference between 1-year-old soil samples was the largest. With the increase of cropping years, the difference gradually decreases, and there is no significant difference in the bacterial community structure between 5-year-old soil samples. RDA analysis and correlation analysis of bacterial community structure and soil physical and chemical properties showed that the order of environmental factors on the rhizosphere soil bacteria of Coptis chinensis was: pH>available P> total P> total K>bulk density>total N>available N>organic matter. The results are helpful to understand the soil health of C. chinensis and provide scientific basis and theoretical guidance for soil improvement and C. chinensis planting.
Child, Preschool ; Coptis ; Forests ; Humans ; Infant ; Rhizosphere ; Soil ; Soil Microbiology