ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Aim To investigate the effect of dipeptidyl peptidase-4 inhibitor(DPP-4i)on serum creatinine(Cr)in patients with type 2 diabetes mellitus(T2DM).Methods A systematic search was performed across data-bases of PubMed,Embase,Cochrane Library and Web of Science,and randomized controlled trials(RCT)of DPP-4i therapy for regulating Cr in T2DM patients was included.A fixed-effect or random-effect model was used for data fitting,heterogeneity was quantitatively evaluated according to the index of I2,and sensitivity analysis and publication bias testing were performed by using the standard methods.Results After searching the database through the system,12 RCTs were included,with a total of 2 276 participants.Due to the potential heterogeneity,a random effect model was used for data fitting.DPP-4i treatment could mildly increase Cr levels in T2DM patients(WMD:0.15 mg/L,95％CI:0.03～0.27,I=1 8％,P=0.02),and the results showed statistical differences.According to sensitivity testing,the results of Meta-analysis were relatively reliable.No publication bias was observed according to Begg's and Egger's tests.Conclusions The use of DPP-4i for hypoglycemic treatment in T2DM patients may result in mild elevation of blood Cr lev-els.Further multicenter studies with larger samples are needed in the future to explore the clinical significance of DPP-4i treatment induced changes in Cr levels.

Objective To analyse the differential metabolites and related metabolic pathways in stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome by serum metabolomics.Methods This study observed 60 patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome and 60 healthy volunteers in the same period.Liquid chromatography-mass spectrometry(LC-MS)was performed on the serum metabonomics.The differential metabolites were identified by multivariate statistical analysis of the original spectrogram and original data,and enrichment analysis of KEGG metabolic pathway was analyzed.Results A total of 60 patients in the group of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome participated in the study,and a total of 60 healthy volunteers in the control group participated in the study.There was no statistical difference in general information and biochemical indicators between the two groups(P>0.05);Eighteen differential metabolites were found respectively,including phenylacetaldehyde,orthophosphate,guanosine,diethyl phosphate,2-dehydro-d-gluconate,guanine and 5-(2-hydroxyethyl)-4-methylthiazole down-regulated expression,taurocholate,2-propylglutaric acid,8-amino-7-oxononanoate,l-tyrosine,s-sulfo-l-cysteine,cyclohexanecarboxylic acid,porphobilinogen,(r)-acetoin,octanoylglucuronide,melatonin and solanine up-regulated expression,involving phenylalanine metabolism,thiamine metabolism,purine metabolism.Conclusion The differential metabolites reveal the metabolic essence of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome from the micro level,and can provide clues for clinical early warning of patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndromet.

Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in innate immunity, immune regulation, maintenance of tissue homeostasis, and tissue repair and remodeling. Besides the conventional innate lymphocytes including NK cells and lymphoid tissue-inducer cells, the ILC family can be categorized into three groups, ILC1s, ILC2s and ILC3s. These non-cytotoxic ILC subsets have been identified to confer a diverse array of functions in oncogenesis and metastasis, immune surveillance, and antitumor immunity. In this review, we summarized the emerging findings in recent years regarding the roles of ILCs in immuno-oncology, and highlighted their potentials in immunotherapeutic approaches to tumors.

Objective To evaluate the regulatory effects of Astragalus polysaccharide (APS) on macrophage polarization and NK cell-mediated anti-tumor responses in mice. Methods C57BL/ 6 mice were injected intraperitoneally with APS once a day for seven consecutive days. Activation of immune cells was then induced by intraperitoneal injection of polyinosinic-polycytidylic acid (Poly I : C) 24 h after the APS intervention. Peritoneal macrophages were collected 24 h after induction to analyze the status of polari-zation and the production of nitric oxide (NO). Cytotoxicity and exocytosis of activated NK cells were meas-ured to assess the effector functions of these cells. NK cell activities induced by NKG2D were studied in the absence of the whole JNK or JNK2 signaling pathway. Results Intraperitoneal injection of APS promoted the polarization of macrophages induced by tumor cells in mice, and enhanced the cytotoxicity of NK cells to tumor cells. However, APS was in need of the involvement of appropriate stimulatory factors to have regula-tory effects. Complete inhibition of JNK signaling pathway dramatically reduced the effector functions of NK cells, which could not be recovered by APS administration. Conclusions APS was involved in the regula-tion of anti-tumor innate immunity through enhancing the M1-polarization of macrophages and improving the effector functions of NK cells. This study might to some extent elucidate the mechanism of APS in immune regulation and anti-tumor immunity.

Objective To observe in vitro the effect of mechanical stress at different intensities on the pro-liferation, apoptosis and extracellular matrix of degenerative human nucleus pulposus cells. Methods The cells were isolated and cultured in vitro, and divided into a control group, a low-intensity group, a medium-intensity group and a high-intensity group. The low-, medium- and high-intensity groups were stretched mechanically by 1000 μ, 2000μor 4000μrespectively for 6 hours using a four-point bending system, while the control group was not stressed. Flow cytometry was used to explore any changes in the cell cycle and the proliferation index ( PI) . The expression of proliferating cell nuclear antigen ( PCNA) , B-cell lymphoma-2 ( BCL-2)/Bax, collagen II and aggrecan were meas-ured using real-time quantitative polymerase chain reactions. Results The mechanical stretching significantly influ-enced proliferation, apoptosis and the extracellular matrices compared with the control group. The PI and PCNA ex-pression increased at first and then decreased gradually with the exercise intensity. Compared with the control group, the mRNA expression level of Bcl-2/Bax increased significantly to 1.53 times that of the control group after 1000 μstretching, but to only 0.71 times that of the control group at 2000μand 0.43 times at 4000μ. The gene expression of collagen II increased significantly by 1. 1 times and that of aggrecan by 1. 3 times after 1000 μ stress stimulation compared with the control group ( P≤0.05) . However, the expression of collagen II and aggrecan was inhibited sig-nificantly at 2000 and 4000 μ , with the lowest levels at 4000 μ (P≤0.05). Conclusion Stretching at different intensities has different effects on the proliferation, apoptosis and extracellular matrix of human pulposus cells with degenerate nuclei.

The measurement of intramedullary pressure is particularly important in the research of spinal cord injury. This article ana-lyzed the influence factors and the measurement methods of intramedullary pressure. The influence factors included edema, vascular regula-tion and bleeding, spinal dural, pia mater spinalis, cerebrospinal fluid, canalis vertebralis and body position, etc. The measurement methods included direct measurement methods, as the sensor placed in the parenchyma of spinal cord, intradural extramedullary or lumbar catheter, and measuring in vitro, and indirect measurement methods, as computer modeling and intraocular pressure measuring.

With the development of science and technology, and the emergence of artificial intelligence, wearable technology is becom-ing a hot topic in the field of rehabilitation medicine. Wearable technology is characterized by miniaturization, intelligency and convenience, and has been widely researched and applied in many fields, such as neurological rehabilitation, orthopaedic rehabilitation, spinal cord injury rehabilitation and rehabilitation for senile degenerative diseases. The further research may focus on the reliability of signals under dynamic monitoring, the comfortable feeling during long-term use of wearable devices, the data security based on personal privacy, and so on.

Two­photon microscopy is a new technique which combines laser scanning con-focal microscopy and two-photon excitation technique. Two-photon fluorescence microscopy has the advantages of little light damage, small bleaching area, strong penetrability, high resolution, high fluorescence collection efficiency, and high image contrast. It is suitable for dark field imaging and multi-labeled compound measurement, and has been widely used in small animals in vivo optical imaging, such as research for tumour, gene therapy, stem cells, drug development, spinal cord injury, etc.

MicroRNAs are short non-coding RNAs that regulate and control the translation of target genes, and play an important role in gene expression involved in the development of spinal cord and spinal cord injury, which constitute novel targets for therapeutic intervention to promote repair and regeneration of the spinal cord, also they are the potential biomarkers of spinal cord injury. This article reviewed the mechanism of microRNAs and listed several microRNAs in spinal cord injury area.