Sarcopenia is a systemic skeletal muscle disease characterized by the gradual decline of muscle mass，strength，and function，and its occurrence and development are related to multiple factors，involving several signaling pathways. Among them，the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway，as a key pathway regulating cellular growth，survival，and metabolism，plays an important role in the formation and development of sarcopenia. Its abnormal activation or deactivation may lead to an imbalance in muscle protein metabolism，resulting in muscle atrophy and reduction. Modern medicine is still in the exploratory stage of treatment for sarcopenia. Traditional Chinese medicine （TCM），with its multi-pathway and multi-target characteristics，has shown increasing advantages in the prevention and treatment of sarcopenia. In recent years，various monomers， extracts，and compound formulas of TCM have been proven to effectively prevent and treat sarcopenia by promoting muscle cell protein synthesis，reducing protein degradation，inhibiting cell apoptosis and inflammatory response，and improving mitochondrial function. This paper reviewed the improvement effects of TCM on sarcopenia based on the PI3K/Akt pathway and explored its specific action mechanisms， aiming to provide new insights for the treatment of sarcopenia with TCM.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Sarcopenia is a clinical syndrome characterized by a decrease in skeletal muscle strength and quality， often accompanied by adverse outcomes such as falls， loss of function and weakness. The pathogenesis of sarcopenia is complex， and studies have shown that dysfunction due to impaired mitochondrial quality control is an important pathological factor in the occurrence and development. Traditional Chinese medicine（TCM） has been widely favoured for regulating mitochondrial homeostasis and preventing sarcopenia by virtue of its multi-target and multi-pathway advantages. They can play a role in the prevention and treatment of sarcopenia by regulating the mitochondrial quality control system to inhibit the occurrence of mitochondrial oxidative stress， regulate the balance of mitochondrial dynamics， inhibit mitochondrial autophagy， promote mitochondrial biosynthesis， resist the occurrence of mitochondrial apoptosis， and maintain the mitochondrial calcium and protein homeostasis. Based on this， the paper reviewed the relationship between mitochondrial quality control and sarcopenia， as well as the mechanism of TCM in intervening the mitochondrial quality control system to treat sarcopenia， in order to provide a new idea for the prevention and treatment of sarcopenia by TCM and to a theoretical basis for the clinical research on TCM intervention in sarcopenia.

OBJECTIVE To systematically investigate the changes of volatile components in Euphorbia wallichii after milk and wine processing， and preliminarily elucidate the material basis for reducing toxicity. METHODS Using headspace gas chromatography-mass spectrometry technology， the volatile components in raw E. wallichii， milk-processed E. wallichii， and wine- processed E. wallichii were isolated and identified， and the relative percentage content of each component was calculated by the peak area normalization method. Combining chemometric methods such as principal component analysis and orthogonal partial least- squares discriminant analysis， changes in volatile components in samples after milk and wine processing were compared. Differential components were screened. RESULTS A total of 66 volatile components were identified from the three samples， with the types of compounds primarily comprising alkanes， olefins， heterocycles and esters， among others. A total of 39， 24 and 36 volatile components were identified from raw E. wallichii， milk-processed E. wallichii， and wine-processed E. wallichii， respectively， with 10 components common to all three preparations. Compared with raw E. wallichii， the relative percentage of other components in milk-processed E. wallichii decreased， except for alkanes and esters. The relative percentage of alkanes， olefins， aldehydes and esters in wine-processed E. wallichii increased， but the contents of heterocyclic compounds， ketones， ethers and alcohols decreased. The results of chemometric analysis showed that the volatile components of raw and processed products were significantly different. A total of 5 kinds of differential components in milk-processed products and 3 kinds of differential components in wine-processed products were screened out. Among them， the relative percentage of potential toxic components such as linalool， octanal and 3-pentanone decreased significantly after processing（P＜0.05）. CONCLUSIONS Milk and wine processing may exert a toxicity-reducing effect by reducing the contents of toxic components such as linalool， octanal and 3-pentanonein E. wallichii.

Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Cinnabar(HgS) was widely used in ancient times for medicinal purposes, religious rituals, and pigments. A group of bright red powdery clumps was excavated from Mawangdui Tomb No.3 of the Han Dynasty. Early studies considered the clumps as evidence of cinnabar's medicinal use during the Qin-Han period. This study employed a range of archaeometric techniques, including extended-depth-of-field stereo imaging, micro-CT, scanning electron microscopy-energy dispersive spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrometry FTIR, to systematically analyze the material composition and structural characteristics of these remains. The results revealed that the cinnabar particles were granular, finely ground, and tightly bound to silk matrix, with no detectable excipients typically associated with medicinal formulations. Micro-CT imaging indicated a well-preserved textile structure, with clear signs of sedimentary accumulation and mechanical damage. Based on historical and archaeological studies, this study suggested that these remains were more likely degraded accumulations of cinnabar-colored silk textiles rather than medicinal cinnabar. By clarifying the diversity of ancient cinnabar applications and preservation states, this study provides new insights for the archaeological identification of mineral medicinal materials and contributes to the standardized study of Chinese medicinal materials and understanding of the historical use of cinnabar.
History, Ancient ; China ; Humans ; Medicine, Chinese Traditional/history* ; Archaeology ; Drugs, Chinese Herbal/history* ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; Mercury Compounds

OBJECTIVE: To explore the construction method of a resistant multiple myeloma (MM) patient-derived xenotransplantation (PDX) model. METHODS: 1.0×10⁷ MM patient-derived mononuclear cells (MNCs), 2.0×10⁶ MM.1S cells and 2.0×10⁶ NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdc^scid Il2rg^tm1/Bcgen (B-NDG) mice with a volume of 100 μl per mouse to establish mouse model. The morphologic, phenotypic, proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining, immunohistochemical staining (IHC), cell cycle analysis, flow cytometry and fluorescence in situ hybridization (FISH). The sensitivity of PDX tumor to bortezomib and anlotinib monotherapy or in combination was investigated through cell proliferation, apoptosis and in vitro and in vivo experiments. The effects of anlotinib therapy on tumor blood vessel and cell apoptosis were analyzed by IHC, TUNEL staining and confocal fluorescence microscope. RESULTS: MM PDX model was successfully established by subcutaneously inoculating primary MNCs. The morphologic features of tumor cells from MM PDX model were similar to those of mature plasma cells. MM PDX tumor cells positively expressed CD138 and CD38, which presented 1q21 amplification, deletion of Rb1 and IgH rearrangement, and had a lower proliferative activity than MM cell lines. in vitro, PDX, MM.1S and NCI-H929 cells were treated by bortezomib and anlotinib for 24 hours, respectively. Cell viability assay showed that the IC₅₀ value of bortezomib were 5 716.486, 1.025 and 2.775 nmol/L, and IC₅₀ value of anlotinib were 5 5107.337, 0.706 and 5.13 μmol/L, respectively. Anlotinib treatment increased the apoptosis of MM.1S cells (P < 0.01), but did not affect PDX tumor cells (P >0.05). in vivo, there was no significant difference in PDX tumor growth between bortezomib monotherapy group and control group (P >0.05), while both anlotinib monotherapy and anlotinib combined with bortezomib effectively inhibited PDX tumor growth (both P < 0.05). The vascular perfusion and vascular density of PDX tumor were decreased in anlotinib treatment group (both P < 0.01). The apoptotic cells in anlotinib treatment group were increased compared with those in control group (P < 0.05). CONCLUSION Bortezomib-resistant MM PDX model can be successfully established by subcutaneous inoculation of MNCs from MM patients in B-NDG mice. This PDX model, which retains the basic biological characteristics of MM cells, can be used to study the novel therapies.
Animals ; Bortezomib ; Humans ; Multiple Myeloma/pathology* ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Mice, Inbred NOD ; Disease Models, Animal ; Cell Proliferation ; Transplantation, Heterologous

OBJECTIVE: To investigate the predictive value of morphology, immunology, and cytogenetics for isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation in newly diagnosed acute myeloid leukemia (AML) patients. METHODS: The clinical data of 186 newly diagnosed AML patients (except M3 subtype) in the First People's Hospital of Changzhou were retrospectively analyzed, and the variables associated with IDH1/2 mutation in patients were screened using LASSO regression to construct a multivariate logistic regression analysis model. The Bootstrap method was used for internal validation of the model and nomograms were used to visualize the model, and receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model. RESULTS: A total of 60 AML patients had IDH1/2 mutation at initial diagnosis. LASSO regression screened 9 predictive variables associated with IDH1/2 mutation, including CD7, CD56, CD11b, CD15, CD64, HLA-DR, platelet count≥50×10⁹/L, isolated +8 and normal karyotype. The nomogram and ROC curve were plotted based on the above 9 variables. The area under the ROC curve (AUC) of the training set and the validation set were 0.871 and 0.806, respectively. Internal validation showed that the nomogram had good predictive ability. CONCLUSION The prediction model based on MIC typing constructed in this study has a good predictive ability for the presence of IDH1/2 mutations in newly diagnosed AML patients and has important clinical application value when the gene mutation detection results are unavailable.
Humans ; Isocitrate Dehydrogenase/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Retrospective Studies ; Nomograms ; Female ; Male ; ROC Curve ; Middle Aged