China is currently in an accelerated stage of population aging, and brain diseases pose a significant threat to the health of the elderly. " Preventing brain aging and maintaining brain health" has become a high-level goal of healthy aging. During the process of aging, the physiological and psychological states of elderly people change, making them prone to nervousness and exhaustion, which can disturb the brain spirit, damage the brain collaterals, and severely endanger brain health. Starting from the holistic view of cultivating both body and spirit in traditional Chinese medicine, based on the physical and mental characteristics of the elderly, this paper applies the concept and method of " relaxation and tranquility" in the protection of elderly brain health, focusing on maintaining relaxation and tranquility in both physical and mental aspects. Specific measures include emphasizing subjective consciousness, relaxing the heart and calming down; utilizing the daoyin method, relaxing the body and calming down, combining relaxation and tranquility, cultivating both body and spirit to prevent diseases and protect the brain, which enables the elderly to have a healthy mind and body, a sense of happiness and fulfillment, and to age gracefully. Simultaneously, advocating for tranquility is also called " respect" for relaxation, following nature to understand constant changes, and improving one′s ability to think positively in old age, in order to expand ideas for the protection of elderly brain health.

Myocardial fibrosis （MF）， characterized by decreased cardiac function and myocardial compliance， is a pathological process and a progression factor in various cardiovascular diseases. The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome is closely related to the development of MF. Recent studies have shown that traditional Chinese medicine （TCM） can regulate the NLRP3 inflammasome to alleviate MF. Based on this， this article systematically summarizes the research progress on the mechanisms by which TCM regulates the NLRP3 inflammasome to improve MF. It is found that active ingredients of TCM， such as alkaloids （lycorine，vincristine，bufalin）， saponins （astragaloside Ⅳ， diosgenin，ginsenoside Rg3）， terpenoids （celastrol，oridonin）， and phenols （polydatin，curcumin，phloridzin） as well as TCM formulas （Zhachong shisanwei pills，Zhilong huoxue tongyu capsules， Luqi formula） can inhibit the activation of the NLRP3 inflammasome， thereby suppressing the release of inflammatory factors such as interleukin-1β and IL-18， reducing inflammatory damage to myocardial tissue， alleviating excessive deposition of the extracellular matrix， and thus exerting the effect of improving MF.

OBJECTIVE To explore the clinical efficacy and safety of Huangkui capsule combined with cyclophosphamide and prednisone in the treatment of immunoglobulin A （IgA） nephropathy with renal insufficiency. METHODS A total of 117 patients with IgA nephropathy and renal insufficiency who were hospitalized in the department of nephrology of the Second Affiliated Hospital of Dalian Medical University from February 2021 to March 2024 were divided into prednisone group （n＝38）， cyclophosphamide group （n＝39） and Huangkui group （n＝40） according to the random number table method. On the basis of standardized basic treatment， the three groups were treated with prednisone， prednisone + cyclophosphamide， and prednisone + cyclophosphamide + Huangkui capsule， respectively， with a course of 6 months. The clinical efficacy， renal function indexes， immunoglobulin levels， inflammatory factor levels before and after treatment， and the incidence of adverse reactions during treatment were compared among the three groups. RESULTS Finally， 107 patients completed the study （35 in prednisone group， 37 in cyclophosphamide group， and 35 in Huangkui group）. After 6 months of treatment， there was a statistically significant difference in the total effective rate among the three groups （P＝0.028）， and the total effective rate of the Huangkui group was significantly higher than that of the prednisone group （P＝0.023）. In terms of renal function， the levels of blood urea nitrogen （BUN）， serum creatinine （Scr）， and urinary microalbumin （Umalb） in the three groups after treatment were significantly lower than those before treatment， while the estimated glomerular filtration rate （eGFR） was significantly higher than that before treatment （P＜0.05）. Among them， the Huangkui group was superior to the other two groups in reducing BUN level （P＜0.05）， and both the Huangkui group and cyclophosphamide group were superior to the prednisone group in improving Scr， Umalb and eGFR （P＜0.05）. In terms of immunology， both the Huangkui group and cyclophosphamide group were superior to the prednisone group in increasing IgG level and decreasing IgA and IgM levels （P＜0.05）. In terms of inflammatory factors， E-mail：amychina0411@163.com the Huangkui group was superior to the prednisone group and cyclophosphamide group in reducing tumor necrosis factor-α level （P＜0.05）， and superior to the prednisone group in reducing interleukin-6 level （P＜0.05）. There was no statistically significant difference in the total incidence of adverse reactions among the three groups （P＞0.05）. CONCLUSIONS Huangkui capsule combined with cyclophosphamide and prednisone has a good therapeutic effect on IgA nephropathy with renal insufficiency. It can further improve patients’ renal function and immune function， regulate inflammatory status， and has good safety.

ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group， a model group， and a Danshen Tongluo formula （28 mg·kg^-1·d^-1） group. The efficacy was evaluated by examining the cardiac ultrasound， determination of the plasma level of N-terminal pro-brain natriuretic peptide， and pathological staining. After single-cell sequencing， SingleR package， public datasets， and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis， and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide （ NT-proBNP ） level （P<0.05）， ameliorated myocardial cell damage and fibrosis， and increase left ventricular ejection fractions （LVEF） in the rat model of heart failure after myocardial infarction（P<0.05）. Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells， venous endothelial cells， and capillary-arterial endothelial cells， while reducing the proportion of capillary-venous endothelial cells. In addition， this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells， while downregulating Mif-（CD74⁺CXCR44） signaling in endothelium-M1 macrophages and Mif-（CD74⁺CD44） signaling in endothelium-M2 macrophages. It reduced the citric acid cycle， oxidative phosphorylation， and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells， venous endothelial cells， and venous capillary endothelial cells can all regulate oxidative phosphorylation， cell adhesion molecules， and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Objective:To investigate the importance of cell block and immunohistochemistry in the accurate diagnosis of serous effusion.Methods:A retrospective study was conducted on 3 124 cases of serous effusion from the Department of Pathology, Beijing Hospital from 2018 to 2022, include 2 213 cases of pleural effusion, 768 cases of peritoneal effusion, 143 cases of pericardial effusion. There were 1 699 males (54.4%) and 1 425 females (45.6%), average age 69 years old. Of which 1 292 cases were prepared with cell blocks and examined with immunohistochemical stain.Results:The percentage of malignant diagnosis increased from 64.9% (839/1 292) to 84.0% (1 086/1 292) after cell block preparation, and 1 086 cases were accurately diagnosed with histological type and/or origin of primary tumor. The undetermined diagnosis of suspected malignancy decreased from 13.3% (172/1 292) to 0.1% (1/1 292) and that of atypical hyperplasia from 18.8% (243/1 292) to 0.4% (5/1 292). The negative result for malignancy rate increased from 3.0% (38/1 292) to 15.5% (200/1 292). The differences highlighted above were statistically significant (Pearson′s chi-squared test=12.739, P<0.01). Conclusion:Application of immunohistochemistry based on cell block can significantly improve malignant diagnosis in serous effusion, identify tumor origin and histological type as well as decrease the uncertain diagnosis.

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

Coronary microvascular dysfunction （CMD） is one of the important causes of myocardial ischemia and non-obstructive coronary artery ischemic symptoms. However， effective diagnostic methods and targeted treatment strategies for CMD are currently lacking. According to traditional Chinese medicine （TCM）， the comorbidity theory of "blood-vessel-cardiac collaterals" plays a central role throughout the entire development process of CMD. It suggests that in the clinical diagnosis and treatment of CMD， the treatment of blood， vessels， and cardiac collaterals should not be neglected. In light of this， insect medicines， known for their efficacy in promoting blood circulation， resolving stasis， and alleviating spasms， hold promise as a potential treatment for CMD. However， there is currently no research or summary on the use of insect medicines for the treatment of CMD. Therefore， this article took the comorbidity theory of "blood-vessel-cardiac collaterals" as the starting point and divided the pathogenesis of CMD into five evolution stages： Beginning in the blood （changes in blood components and hemorheology）， progressing in the vessels （atheromatous plaque formation and unstable plaques）， occurring in the cardiac collaterals （microvascular endothelial damage and microvascular constriction and spasms）， ending in the cardiac collaterals （microvascular remodeling）， and resulting in energy metabolism disorders throughout the process， so as to explore the pathogenesis and evolution of CMD. In addition， based on the modern pharmacological research on insect medicines， this article discussed the clinical application of insect medicines in the treatment of CMD from four aspects： Promoting blood circulation and removing blood stasis to relieve vessels' obstruction， relieving spasms to alleviate pain， combating poison with poison to disperse stagnation， and tonifying cardiac collaterals to nourish the heart， which aims to provide a theoretical basis for the use of TCM in treating CMD， broaden the scope of medication， and improve clinical efficacy.

ObjectiveThe biosynthetic pathways of benzylisoquinoline alkaloids（BIAs） in Nelumbo nucifera are of great theoretical and economic value. In this paper， N. nucifera O-methyltransferase（NnOMT） and N. nucifera N-methyltransferase（NnNMT） gene families were identified and analyzed by bioinformatics in order to facilitate the biosynthetic pathway of BIAs in N. nucifera. MethodBased on the whole genome of N. nucifera， UniPort and National Center for Biotechnology Information（NCBI） databases were used to identify the NnOMT and NnNMT gene families of N. nucifera， and analyze their physicochemical properties and subcellular localization， then TBtools， MEME， MEGA 11.0， FigTree 1.4.4 and other tools were used to analyze the phylogeny， sequence characteristics， gene structure， functional annotation and cis-acting elements of NnOMT and NnNMT genes identified in the previous stage. ResultA total of 61 NnOMT and NnNMT genes were identified in this paper， the number of amino acids encoded by these genes ranged from 168 aa to 580 aa， the isoelectric point ranged from 4.76 to 9.16， and the relative molecular weight ranged from 18 699.52 Da to 64 934.53 Da， most of which showed acidic and mostly hydrophilic proteins. There were 10 conserved motifs， Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis enriched a total of 12 pathways， including metabolism， biosynthesis of phenylpropane and isoquinoline alkaloids， etc. And Visualization of Gene Ontology（GO） enrichment results showed that 61 NnOMT and NnNMT genes were annotated to 32 items， which included 16 molecular functions［such as reduced nicotinamide adenine dinucleotide（NADH） activity and exopeptidase activity］ and 16 biological processes（such as metabolic process of carbon tetrachloride， anaerobic carbon tetrachloride metabolic process and responses to exogenous biological stimuli）. There were a variety of cis-acting elements in the promoter regions of NnOMT and NnNMT genes， mainly promoter and enhancer regions element， light responsive element and methyl jasmonate responsive element. ConclusionIn this study， a comprehensive bioinformatics analysis of 61 NnOMT and NnNMT genes is carried out based on the genome data of N. nucifera， which lays a foundation for research on the gene structure and function of NnOMT and NnNMT gene families， and provides a reference for biosynthetic pathway elucidation of BIAs in N. nucifera.