Depression is a common mental disorder that falls under the category of "stagnation syndrome" in traditional Chinese medicine （TCM）. Its complex pathogenesis poses challenges for the development of novel therapeutic agents. Currently， clinically used antidepressants are often accompanied by significant side effects， and statistics show that about one-third of patients do not respond to these medications. TCM demonstrates advantages in the treatment of depression through multi-target， multi-pathway and multi-mechanistic approaches. Pinelliae Rhizoma， a phlegm-resolving herb， exhibits effects such as drying dampness and resolving phlegm， as well as eliminating stuffiness and reducing masses. The characteristics of harmonizing Yin and Yang and resolving stagnation in the middle energizer align precisely with the pathogenesis of depression syndrome， demonstrating therapeutic efficacy in affected patients. Literature studies have found that the active ingredients of Pinelliae Rhizoma， such as cavidine， baicalein， β-sitosterol， as well as Pinelliae Rhizoma herb pairs， such as Pinelliae Rhizoma-Magnoliae Officinalis Cortex， Pinelliae Rhizoma-husked sorghum， Pinelliae Rhizoma-Prunellae Spica， exhibit significant antidepressant effects. Furthermore， TCM formulas containing Pinelliae Rhizoma as the principal therapeutic agent， such as Banxia Xiexin Tang， Banxia Houpo Tang， and Wendan Tang， as well as formulas incorporating Pinelliae Rhizoma like compound Xiaochaihu Tang， Chaihu Jia Longgu Muli Tang， and Erchen Tang， have also demonstrated favorable antidepressant efficacy. The antidepressant mechanism of these agents may involve modulation of 5-hydroxytryptamine （5-HT） and dopamine （DA） levels， up-regulation of brain-derived neurotrophic factor （BDNF） expression， regulation of the hypothalamus-pituitary-adrenal （HPA） axis， reduction of oxidative stress， modulation of nuclear transcription factor-κB （NF-κB） signaling pathway， and inhibition of microglia-mediated inflammatory responses. This review summarized the antidepressant mechanisms and clinical applications of the active components， herb pairs， and TCM formulas containing Pinelliae Rhizoma， aiming to provide a reference for modern research on the use of Pinelliae Rhizoma in antidepressant therapy.

ObjectiveIn order to provide a reference for the optimization of preparation process of stir-fried Glycyrrhizae Radix et Rhizoma（sf-GRR）， the quality changes during the processing was studied. MethodsGlycyrrhizae Radix et Rhizoma was processed by stir-frying for 17 min， and samples were collected every 1 min during the processing. The appearance color of the samples was determined by visual analysis technology， the moisture and extract of the process samples were detected by the drying method and the hot extraction method of alcohol-soluble extract in the general rules of the 2020 edition of Chinese Pharmacopoeia（part Ⅳ）， and the contents of liquiritin apioside， liquiritin， isoliquiritin apioside， isoliquiritin， licoricesaponin G₂ and glycyrrhizic acid in the process samples were determined by high performance liquid chromatography（HPLC）. Then principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and Spearman correlation analysis were used for clustering， discrimination and correlation analysis of the appearance color， moisture， extract and the contents of six internal components. Based on artificial neural network and random forest algorithm， the prediction model of processing degree of sf-GRR was established. On this basis， based on the five principles of quality marker（Q-Maker）， explore the monitoring Q-Maker of sf-GRR. ResultsThe color of Glycyrrhizae Radix et Rhizoma deepened after stir-frying， and the appearance color of the sample changed from light yellow to dark yellow during processing. During the stir-frying process， the moisture content showed a decreasing trend with the extension of processing time， while the extract content showed an increasing trend with the extension of processing time. After stir-frying， the contents of liquiritin apioside， liquiritin and licoricesaponin G₂ showed an overall decreasing trend， while the contents of isoliquiritin apioside and isoliquiritin increased， and the content of glycyrrhizic acid increased slightly. The correlation analysis showed that moisture was positively correlated with brightness（L^*） and red/green value（a^*）， and negatively correlated with yellow/blue value（b^*） and total color difference（E^*ab）. Isoliquiritin apioside and isoliquiritin had negative correlation with L^* and a^*， and positive correlation with b^* and E^*ab. The processing process of sf-GRR could be divided into two stages of the early stage（0-14 min） and the late stage（15-17 min）， and could be divided into three stages of the early stage（0-6 min）， the middle stage（7-14 min） and the late stage（15-17 min） by combining the moisture， extract， the contents of 6 components and color values. Based on artificial neural network analysis and random forest algorithm， isoliquiritin apioside， isoliquiritin， liquiritin and glycyrrhizic acid were selected as monitoring markers for sf-GRR. ConclusionBased on the analysis of the exterior-interior indicators of process samples of sf-GRR， this paper ultimately identifies four processing monitoring markers， which can provide a basis for optimizing the processing technology of sf-GRR.

BACKGROUND:Exosomes can be detected in synovial fluid and plasma at levels that vary with the progression of osteoarthritis in patients with osteoarthritis,and may play a relieving role in the local inflammation of osteoarthritis,cartilage calcification,and osteoarthritic joint degradation. OBJECTIVE:To comprehensively understand the function and mechanism of exosomes from different stem cells in the diagnosis and treatment of osteoarthritis,and to present the prospects and challenges of exosome therapy for osteoarthritis. METHODS:We searched the articles published from October 2003 to October 2023 included in PubMed and CNKI databases with the keywords of"exosomes,osteoarthritis,mesenchymal stem cells,stem cells"in Chinese and English,respectively.A total of 99 articles were finally included for review. RESULTS AND CONCLUSION:The appearance of exosomes brings hope to the diagnosis and treatment of osteoarthritis.The differences of RNA,protein,and lipid content in exosomes can be used as biomarkers for the diagnosis of osteoarthritis.At the same time,exosomes from various stem cells can effectively protect chondrocytes,relieve inflammation,maintain cartilage matrix metabolism,and regulate angiogenesis and subchondral bone remodeling,showing excellent potential in the treatment of osteoarthritis.The engineered exosomes break through the traditional limitations and enhance the specificity and efficiency of treatment by modulating the expression of specific non-coding RNA,providing a new strategy for the treatment of osteoarthritis.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

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In the past, aortic dissection, aortic aneurysm, and other aortic diseases, primarily rely on surgical intervention. In recent years, due to breakthroughs in materials science, endovascular therapy has become the first choice for the surgical treatment of most aortic diseases. However, traditional endovascular repair cannot fully meet the clinical needs for certain complex lesions involving the aortic arch and the originations of visceral arteries. The emergence of physician-modified stent technology has brought new hope for the treatment of complex aortic diseases. This article provides a detailed introduction to the concept, development, technical characteristics, and applications of physician-modified stents in the treatment of aortic diseases, analyzing their advantages and limitations. Physician-modified stents serve as a powerful complement to traditional endovascular interventions and commercial branched stents, yet further research and refinement are still required.

Traditional mass measurement methods are not applicable in microgravity environments,and the main challenge for in-orbit body mass measurement technology based on inertial principles is to address the random errors brought about by the weightless environment.These include additional torques due to shifts in the center of mass,nonlinear accelerations due to non-rigid human bodies,mechanical energy consumption due to organ vibrations,and random vibrations of the measurement device itself.To address the above difficulties,the project proposes a technical scheme based on the principle of linear acceleration,designs and constructs a ground-specific air-floating experimental and simulation platform,studies key data such as motion trajectory,acceleration change,and vibration frequency amplitude during the mass measurement process,and simulates the changes in the center of mass and random vibrations of the human body in a weightless environment.The project has designed an adjustable posture bracket to adapt to changes in the center of mass,enhance body restraint,and greatly reduce shaking;it has also developed an integrated four-bar linkage motion guidance mechanism,high-precision integrated photoelectric distance measurement,and modular motion constant force measurement device to ensure the accurate measurement of acceleration and constant force data.The product has undergone simulation calculations,ground human applicability tests,and in-orbit applicability verification in the space station.Ground test results show that the device achieves a body mass measurement accuracy better than 0.5%,and the dispersion is better than 0.38%;after flight mission verification and evaluation,the in-orbit body mass measurement dispersion is less than 0.4%,which is superior to the SLAMMD,a mass measurement device of the same principle on the International Space Station,and is at the forefront internationally,achieving accurate body mass measurement.