Objective To investigate the mechanism of Ganmao Qingre Pills(GQP)against lung injury based on network pharmacology,molecular docking and in vivo experiments.Methods The potential targets of GQP in the treatment of lung injury were screened through traditional Chinese medicine systems pharmacology database and analysis platform(TCM-SP)and Genecards.A"Chinese medicine-active ingredients-targets"network was constructed using Cytoscape 3.9.0 software,then gene ontology(GO)function and Kyoto encyclopaedia of genes and genomes(KEGG)pathway enrichment analysis for potential targets were conducted using a bioinformatics cloud platform.We established a protein-protein interaction(PPI)network,which was intersected with"Chinese medicine-active ingredients-targets"network to obtain core targets.The molecular docking between key target proteins and active ingredients was performed.The effect of GQP on these key target proteins was verified by using a mouse model of lung injury.Results A total of 707 targets for the treatment of lung injury by GQP were identified,corresponding to 107 active ingredients in 11 Chinese medicines.It was found that GQP might regulate targets such as PTGS1,AR,and ACHE through active ingredients including stigmasterol,luteolin,and acacetin using the"Chinese medicine-active ingredients-targets"network analysis.Core targets such as SRC,EGFR,and STAT3 were discovered by using the PPI network.Key target proteins,including CDK1,CDK2,EGFR,ESR1 and SRC,were screened through the intersection analysis of the PPI network and"Chinese medicine-active ingredients-targets"network.Molecular docking study showed that stigmasterol,luteolin and acacetin had good binding effects with CDK1,CDK2,EGFR,ESR1,and SRC,respectively.In vivo experiments revealed that GQP dose-dependently attenuated lung injury and inflammatory infiltration,reduced the release of pro-inflammatory factors TNF-α,IL-1β and IL-6,increased the expression of CDK1 and CDK2,and decreased the expression of EGFR,ESR1 and SRC in lung injury mice.Conclusion The therapeutic effect of GQP against lung injury may be achieved through interaction of key active ingredients(stigmasterol,luteolin,and acacetin)and key target proteins(CDK1,CDK2,EGFR,ESR1,SRC),and regulation of key signaling pathways such as neuroactive ligand-receptor interactions,cancer pathways,and calcium signaling pathways.

Objective:To investigate the distribution characteristics of skeletal muscle mass and strength in the older adults over 65 years old in 18 longevity areas in China.Methods:The subjects were selected from the Healthy Aging and Biomarkers Cohort Study conducted in 18 longevity areas of China. A total of 4 662 older adults over 65 years old from a cross- sectional survey in 2021 were included in the study. The information about their sociodemographic characteristics, lifestyle, nutrient intake and other factors were collected through questionnaire surveys and physical examinations. Grip strength was measured by using professional electronic grip dynamometer. Total skeletal muscle mass (TSM) was measured using bioelectrical impedance analysis, and TSM was adjusted by height squared and BMI to obtain TSM Ht2 and TSM BMI. The proportion of individuals with low muscle mass and strength was determined according to the recommended method by the Asian Working Group for Sarcopenia (AWGS). Descriptive analysis was conducted on the population and regional distribution characteristics of people with different muscle mass and grip strength. A generalized additive model was used to analyze the age-related trends of muscle mass and grip strength. Results:The age of 4 662 study subjects was (82.69±10.54) years, men accounted for 46.85% (2 184 cases) and Han Chinese accounted for 96.27% (4 488 cases). The M( Q1, Q3) of TSM, TSM Ht2 and TSM BMI in men were 23.30 (20.50, 26.20) kg, 9.02 (8.13, 9.89) kg/m 2, and 1.01 (0.90, 1.13) kg·(kg/m 2) -1, respectively, which were all higher than those in women [TSM: 18.20 (15.70, 20.70) kg, TSM Ht2: 8.18 (7.42, 9.07) kg/m 2 and TSM BMI: 0.79 (0.69, 0.90) kg·(kg/m 2) -1], the differences were significant (all P<0.001). The grip strength of men [ M( Q1, Q3): 24.50 (17.80, 30.80) kg] was higher than that of women [ M( Q1, Q3): 15.60 (11.10, 19.90) kg], the difference was significant ( P<0.001). Southern elderly men had lower TSM and TSM Ht2 compared with northern elderly men (all P<0.001), while there was no significant regional difference in TSM BMI ( P>0.05). Southern elderly women had higher TSM Ht2 and TSM BMI compared with northern elderly women (all P<0.001), while there was no significant regional difference in TSM ( P>0.05). Furthermore, according to the method recommended by AWGS, the elderly with low muscle mass and grip strength were characterized by older age, illiteracy, being unmarried/divorced/widowed, poor chewing ability, impaired activity of daily living and living in southern region. Conclusion:There were population and regional differences in muscle mass and grip strength in the older adults over 65 years in 18 longevity areas of China, and these differences showed decreasing trends with age.

AIM:Observation of neuroprotective effects of Toddalia asiatica(TA)on cerebral ischemia-reper-fusion injury(CIRI)in rats by investigating the effects and mechanisms of drugs on the polarization of microglia M1/M2 subtype and the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)path-way.METHODS:The modified thread occlusion method was used to establish a rat model of CIRI,and the rats were ran-domly divided into the model group,Toddalia asiatica(1.08 g/kg)group,donepezil hydrochloride(0.45 mg/kg)group,and sham group,with 16 rats in each group.Based on the assessment of neurofunctional changes in each group of rats,HE and Nissl staining were used to observe the pathological changes in brain tissue.TUNEL staining was performed to de-tect neuronal apoptosis,immunohistochemistry was used to detect the expression of M1 microglia marker ionized calcium-binding adapter molecule 1(Iba1),M2 microglia marker arginase 1(Arg1),and TLR4 localization.Western blot was used to detect the expression of microglia polarization proteins and proteins related to TLR4/MyD88/NF-κB pathway in the hippocampus region.RESULTS:Compared with sham group,the model group rats had higher neurological function scores(P＜0.01),and neuronal arrangement in the hippocampus and cortex was loose and disordered,Nissl bodies de-creased,and neuronal apoptosis increased.The numbers of M1 microglia marker Iba1-,M2 microglia marker Arg1-,and TLR4-positive cells were significantly increased.In addition,the protein levels of TLR4,MyD88,p-NF-κB p65,NF-κB p65,p-NF-κB inhibitory factor(p-IκB),Iba1,interleukin-6(IL-6),and Arg1 in the hippocampus were elevated(P＜0.05),while IL-4 and IL-10 expression were decreased(P＜0.01).Compared with model group,the Toddalia asiatica group and Donepezil hydrochloride group showed increased protein expression of Arg1,IL-4 and IL-10(P＜0.05),while the other indicators were decreased(P＜0.05,P＜0.01).CONCLUSION:Toddalia asiatica possesses neuroprotective effects on CIRI rats,which may be attributed to its ability to regulate M1/M2 polarization and inhibit the TLR4/MyD88/NF-κB-mediated inflammatory pathway.

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Mice ; Animals ; Humans ; Glioblastoma/pathology* ; Endothelial Cells/pathology* ; DNA Copy Number Variations ; Brain/metabolism* ; Brain Neoplasms/pathology*

Tongxie Yaofang， also known as Baizhu Shaoyaosan， was first recorded in Danxi's Experiential Therapy （《丹溪心法》） by ZHU Danxi in the Yuan dynasty. It is composed of Atractylodis Macrocephalae Rhizoma， Paeoniae Radix Alba， Citri Reticulatae Pericarpium， and Saposhnikoviae Radix， and serves as the representative prescription for the treatment of painful diarrhea. It has the functions of tonifying the spleen， emolliating the liver， relieving pain， and checking diarrhea， and is mainly used in the treatment of gastrointestinal diseases such as irritable bowel syndrome （IBS） and ulcerative colitis （UC）. In addition， it is effective in treating gastrointestinal disorders with mental and psychological abnormalities， as well as obstinate anorexia in children， depression syndrome， and respiratory diseases. Experimental research and clinical practice have shown that Tongxie Yaofang has multi-component， multi-pathway， and multi-target characteristics in the treatment of diseases. The mechanism of Tongxie Yaofang in treating diseases is mainly attributed to anti-inflammation， immune function regulation， intestinal hypersensitivity improvement， emotion regulation， etc. Monoterpene glycosides， flavonoids， chromones， lactones， and other components contained play an important therapeutic role. The research on the systems biology of Tongxie Yaofang， such as metabolomics， proteomics， and network pharmacology， provides a scientific basis for clarifying its mechanism of action and expanding its clinical application. However， there are still some problems to be solved， such as difficulty in combining diseases and syndromes and lack of in-depth systematic research. Through the retrieval and collation of relevant literature， this paper systematically reviewed the material basis， pharmacological effects， and systems biology research of Tongxie Yaofang， aiming to lay a foundation for in-depth research on its mechanism in treating diseases and rational application in clinical practice.

Non-coding RNAs(ncRNAs) are special RNAs that they don't have protein coding function, but they can affect chromosome structure, gene transcription and participate in the processes of epigenetic modifications. ncRNAs include long non-coding RNAs, microRNA, etc. In recent years, it has been found that these ncRNAs can maintain bone remodeling by adjusting bone resorption and formation in osteoporosis(OP). In the future, it may be a key target of the drug action screening which is clarifying the regulatory mechanism of ncRNAs in the occurrence and development of OP. OP belongs to bone rheumatism category in traditional Chinese medicine, according to the theory of “the kidney generating marrow and dominating bone” in traditional Chinese medicine, kidney tonifying and bone strengthening formulas are used to treat the OP in clinic, and the curative effect is remarkable. It has been found that kidney tonifying and bone strengthening prescriptions can enhance the proliferation of osteoblasts or inhibit the differentiation of osteoclasts by up-regulating or down-regulating the expression of ncRNA, and finally maintain OP bone homeostasis, thus exerting therapeutic effect. However, the specific molecular mechanism is still in its exploratory stage. Therefore, this paper summarized the molecular mechanism of kidney tonifying and bone strengthening prescriptions regulating ncRNAs in the treatment of OP in recent years, in order to provide the new ideas for the screening of the key therapeutic targets of OP drugs and the prevention and treatment of OP with traditional Chinese medicine.

Objective:To investigate the effects of mitochondrial arginyl-tRNA synthase (RARS2) on cell proliferation, invasion, migration and chemotherapy resistance of pancreatic cancer.Methods:Human pancreatic cancer cell lines AsPC-1 and PANC-1 were divided into negative control group, RARS2 interference group-1, RARS2 interference group-2, RARS2 overexpression control group and RARS2 overexpression group. Cell proliferation and sensitivity to gemcitabine were detected by CCK-8 assay, and cell invasion and migration were detected by Transwell assay. Western blot was used to detect the expression of RARS2 under different concentrations and different times of gemcitabine treatment. Western blot and PCR were used to detect the expression of RARS2 in gemcitabine-resistant AsPC cell.Results:Inhibition of RARS2 expression in AsPC-1 and PANC-1 cells significantly inhibited cell proliferation and enhanced sensitivity of gemcitabine to chemotherapy. Overexpression of RARS2 enhanced cell proliferation and decreased sensitivity to gemcitabine. In AsPC-1 cells, the number of migrated cells (100×) in negative control group, RARS2 interference group-1, RARS2 interference group-2, RARS2 overexpression control group and RARS2 overexpression group were (586.7±37.4) cells/field, (195.7±18.6) cells/field, (237.0±17.1) cells/field, (157.7±19.1) cells/field, (456.0±23.1) cells/field, the number of invasive cells were (87.7±13.2) cells/field, (24.7±6.5) cells/field, (31.7±6.1) cells/field, (29.3±4.5) cells/field, (94.3±9.3) cells/field, respectively. The migration and invasion ability of cells were decreased after the expression of RARS2 was decreased, and the migration and invasion ability of cells were enhanced after the expression of RARS2 was increased. PCR and Western blot assay showed that RARS2 expression in the gemcitabine-resistant AsPC-1 was higher than that in the common cell line. In AsPC-1 cells, the expression of RARS2 increased with increasing gemcitabine concentration and treatment time.Conclusion:RARS2 promotes cell proliferation, invasion, migration and chemoresistance of pancreatic cancer, and expression of RARS2 is positively correlated with gemcitabine concentration and treatment time.

Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.

OBJECTIVE：To study the effects of gin seng root extract on autophagy ，proliferation and cytokine of splenic lymphocyte of mice ，and to study its mechanism. METHODS ：The splenic lymphocyte of mice were divided into blank control group，positive control group （concanavalin A ，5 μg/mL），different concentration of ginseng root extract groups （32，125，500 μg/mL，by lyophilized powder ）. After 48 h of culture with the corresponding medicine ，acridine orange staining method was used to detect autophagy of splenic lymphocyte ；CCK-8 assay was used to detect the cell proliferation ；ELISA assay was used to determine the levels of IL- 4，IL-6 and TNF-α in cell culture；Western blotting method was used to detect the expression of LC 3B and Beclin- 1，as well as the phosphorylation of AMPK ，AKT and mTOR. RESULTS ：Compared with blank control group ，32， 125，500 μg/mL ginseng root extract could increase the number of acidic autophagosomes in splenic lymphocytes of mice（P＜0.05 or P＜0.01）；125，500 μg/mL Ginseng root extract could significantly enhance the survival rate of splenic lymphocytes，the levels of IL- 4，IL-6 and TNF-α and the transformation of LC3BⅠ to LC 3BⅡ，significantly increased the protein expression of Beclin- 1， quinacrine cationic liposomes for treating non-small cell @163.com lung cancer[J]. J Drug Target ，2015，23（3）：232-243. the phosphorylation of AMPK protein ，and significantly reduced the phosphorylation level of AKT and mTOR proteins ，with statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS ：Ginseng root extract can induce autophagy of mice splenic lymphocytes，activate the activity of splenic lymphocytes ，regulate the secretion of cytokine by activating AMPK and inhibiting the activation of AKT which can inhibit the activity of mTOR ，so as to exert immune enhancement effect.

Objective To analyze the clinical features and clinical significance of patients with inflammatory bowel disease (IBD) complicated by thrombosis.Methods From March 14th,2001 to February sixth 2017,at Nanjing General Hospital of Nanjing Military Command,27 IBD patients with thrombosis diagnosed by clinical symptoms,endoscopy,imaging and pathology were enrolled.During the same period,81 gender and age matched IBD patients without thrombosis were included in the control group.The basic data,information of IBD diagnosis and treatment and thrombotic events of patients were collected and analyzed.T-test and Chi-square test were performed for statistical analysis.Binary logistics regression was used for risk factors analysis.Results The mean age of diagnosis of IBD patients with thrombosis was (44.8 ± 15.8) years,which was higher than that of the IBD patients of control group ((36.0 ± 14.4) years),and the difference was statistically significant (t =2.69,P =0.008).Among 27 IBD patients with thrombosis,arterial thrombosis was 51.9％ (14/27),deep venous thrombosis of the lower extremity veins was 29.6％ (8/27),portal venous system involved was 11.1％ (3/27),pulmonary embolism was 3.7％ (1/27) and disseminated intravascular coagulation accounted for 7.4％ (2/27).Nine patients (33.3％,9/27) underwent surgery six months before the diagnosis of thrombosis.The results of binary logistic regression indicated that the age of diagnosis and vascular catheterization were independent risk factors for thrombosis in IBD patients (odds ratio (OR) =1.04,95％ confidence interval (CI) 1.01 to 1.07,P=0.01;0R=5.64,95％ CI 1.39 to 22.96,P=0.02).After medicine treatment or surgery,81.5％ (22/27) of the patients improved,9.1％ (2/22) were worse and 13.6％ (3/22) died.Conclusion Screening and prevention of thrombosis should be paid attention in IBD patients with a history of vascular catheterization,at active phase and older age when diagnosed.