OBJECTIVE:To observe clinical efficacy and safety of Tianqi jiangtang capsules combined with metformin in the treatment of elderly patients with type 2 diabetes mellitus complicated with cerebral microvascular lesions. METHODS:A total of 96 elderly patients with type 2 diabetes mellitus complicated with cerebral microvascular lesions were randomly divided into control group(48 cases)and observation group(48 cases). Control group was given Metformin hydrochloride tablets 0.5 g orally,3 times a day. Observation group was additionally given Tianqi jiangtang capsules 1.6 g orally,3 times a day,on the basis of control group. Both groups received treatment for 4 weeks. Clinical efficacies of 2 groups were observed as well as total score of TCM symptoms,the levels of blood glucose(FPG,2 hPG,HbA1c),blood lipid(TC,TG,HDL-C,LDL-C),hs-CRP,ET-1,blood rheology and oxidative stress indexes(MDA,SOD),the occurrence of ADR. RESULTS:The total response rate of observation group was significantly higher than that of control group(89.58% vs. 70.83%),with statistical significance(P<0.05). After treat-ment,total score of TCM symptoms,the levels of blood glucose,hs-CRP,ET-1,TC,TG,LDL-C,blood rheology indexes and MDA in 2 groups were significantly lower than before;total score of TCM symptoms,the levels of FPG,2 hPG,hs-CRP,ET-1, TC,TG,LDL-C,blood rheology indexes and MDA in observation group were significantly lower than control group;the level of SOD in 2 groups were significantly higher than before,and the observation group was significantly higher than control group,and the level of HDL-C in observation group was significantly higher than before treatment and control group,with statistical signifi-cance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Tianqi jiangtang capsules combined with metformin show significant therapeutic efficacy in the treatment of elderly patients with type 2 diabetes mellitus,and can re-duce the levels of blood glucose and lipid,improve blood rheology and oxidative stress reaction,with goud safety.

Objective: To investigate the changes of brain gray matter volume in patients with occupational noise-induced hearing loss by voxel based morphometry (VBM) . Methods: 16 age-and education-matched healthy controls and 42 patients with occupational noise induced hearing loss, including 27 in mild group and 15 in severe group, received MRI 3D-FSPGR sequence T1WI sagittal scan, and then underwent VBM of brain gray matter volume data analysis. Results: The brain gray matter volume of the left occipitotemporal lateral gyrus, the anterior cingulate gyrus, the bilateral angular gyrus, the precuneus and the near midline area of cerebellum differed between experimental group and control group (P<0.01) . Conclusion The volume of gray matter in specific brain areas of patients with occupational noise-induced hearing loss was changed, and the effect of noise on brain structure was revealed from the perspective of imaging.

PURPOSE: Staphylococcal enterotoxin B (SEB) has been well-documented to induce liver injury. miRNA-222-3p (miR-222-3p) was implicated in SEB-induced lung injury and several liver injuries. This study aimed to explore the role of miR-222-3p in SEB-induced liver injury. MATERIALS AND METHODS: Expression of miR-222-3p and suppressors of cytokine signaling 1 (SOCS1) was detected using real-time quantitative PCR and western blot. Liver injury was determined by levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory cytokines, numbers of infiltrating mononuclear cells using AST/ALT assay kit, enzyme-linked immunosorbent assay (ELISA), and hematoxylin-eosin staining, respectively. Target binding between miR-222-3p and SOCS1 was predicted on targetScan software, and confirmed by luciferase reporter assay. RESULTS: SEB induced liver injury in D-galactosamine (D-gal)-sensitized mice, as demonstrated by increased serum levels of AST and ALT, elevated release of interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-2, and promoted infiltrating immune cells into liver. Expression of miR-222-3p was dramatically upregulated, and SOCS1 was downregulated in SEB-induced liver injury both in mice and splenocytes. Moreover, miR-222-3p knockout (KO) mice exhibited alleviated liver injury accompanied with SOCS1 upregulation. Besides, splenocytes under SEB challenge released less INF-γ, TNF-α, IL-6, and IL-2 during miR-222-3p knockdown. Mechanically, SOCS1 was targeted and downregulated by miR-222-3p. Upregulation of SOCS1 attenuated INF-γ, TNF-α, IL-6, and IL-2 release in SEB-induced splenocytes; downregulation of SOCS1 could block the suppressive role of miR-222-3p knockdown in SEB-induced splenocytes. CONCLUSION: Inhibition of miR-222-3p relieves SEB-induced liver inflammatory injury by upregulating SOCS1, thereby providing the first evidence of miR-222-3p in SEB-induced liver injury.
Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Blotting, Western ; Cytokines ; Down-Regulation ; Enterotoxins ; Enzyme-Linked Immunosorbent Assay ; Interferon-gamma ; Interleukin-2 ; Interleukin-6 ; Liver ; Luciferases ; Lung Injury ; Mice ; Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; Up-Regulation

OBJECTIVE：To e stablish UPLC characteristics fingerprints of Lysimachia christinae ，and to simultaneously determine 3 effective components and to comprehensively evaluate the quality of L. christinae from different production areas. METHODS：UPLC method was adopted to establish characteristics fingerprint of the whole plant ，stem and leaves of 10 batches of L. christinae ，and determine the contents of kaemperfol- 3-O-rutinoside，quercetin，kaemperfol. The determination was performed on Waters CORTECS UPLC T 3 column with mobile phase consisted of acetonitrile- 0.2％ phosphoric acid aqueous solution （gradient elution ）at the flow rate of 0.2 mL/min. The detection wavelength was set at 364 nm，and column temperature was 30 ℃. The sample size was 1 µL. Similarity Evaluation System for TCM Chromatographic Fingerprint （2012 edition）was adopted to evaluate its similarity ， and common peaks were confirmed. Using the contents of kaemperfol- 3-O-rutinoside， quercetin， kaemperfol，total ash ，acid-insoluble ash and sulfur dioxide residue ，the ethanol-soluble extract as index ，entropy weight TOPSIS was used to evaluate the overall quality of L. christinae comprehensively. RESULTS ：There were 7 common peaks in the whole plant，stem and leaves of 10 batches of L. christinae ，among which 3 peaks were identified as kaemperfol- 3-O-rutinoside， quercetin and kaemperfol. The similarity of same part in the whole plant of L. christinae from different batches were not lower than 0.830. The similarity between stem and leaves of L. christinae in same batch was 0.504-0.859； the similarity between whole plant and stem was 0.593-0.904；the similarity between whole plant and leaves was 0.885-0.995. The linear ranges were 0.392 0-39.197 0 μg/mL for kaempferol-3-O-rutinoside， 0.397 0- 39.703 4 μg/mL for quercetin，0.380 9-38.093 0 μg/mL for kaempferol（r＞0.999 0）. RSDs of precision ，stability and repeatability tests were all lower than 2％. The recoveries were 96.43％（RSD＝0.63％，n＝9），100.32％（RSD＝0.46％，n＝9）， 101.80％（RSD＝0.32％，n＝9），respectively. The content range of above components in L. christinae were 0.006 3％-0.041 1％， 0.002 9％-0.008 6％，0.004 4％-0.017 5％（stem）；0.024 8％-0.290 5％，0.000 9％-0.009 0％，0.001 3％-0.012 4％（leaves）； 0.007 9％-0.118 0％，0.001 5％-0.008 8％，0.002 8％-0.012 5％（whole plant ）. There was no significant difference in the contents of 3 components in L. christinae among different producing areas （P＞0.05）. The order of the contents of kaempferol- 3-O- rutinoside in different parts of L. christinae was leaves ＞whole plant ＞stem. The contents of quercetin and kaempferol were high relatively in the stem. Results of entropy weight TOPSIS method showed that mean values of Ci for L. christinae from Zhongjiang county and Shuangliu county of Sichuan province ，Shizhu county of Chongqing city were 0.446，0.512，0.287. CONCLUSIONS ： Established fingerprint and content determination method are stable and feasible ，and multi-index evaluation model constructed by characteristic chromatogram combined with entropy weight TOPSIS analysis method can be used for comprehensive quality evaluation of L. christinae . The quality of L. christinae from Sichuan province is better.

Objective To comprehensively characterize the diterpene alkaloids in Radix Aconiti Kusnezoffii.Methods The diterpene alkaloids were isolated and purified by strong acid cation exchange resin solid phase extraction column(SCX-SPE),and identified by ultra high performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS).Results A total of 99 diterpene alkaloids were identified from Radix Aconiti Kusnezoffii,including 27 diester diterpene alkaloids(DDA),29 monoester diterpene alkaloids(MDA),40 amide diterpene alkaloids(ADA),2 polyester diterpene alkaloids(PDA)and 1 long-chain ester diterpene alkaloid(LDA).Conclusion The SCX-SPE combined with UHPLC-Q-Exactive Orbitrap MS method,established in this paper,can rapidly identify a large number of diterpene alkaloids in Radix Aconiti Kusnezoffii,which provides scientific proof for the study of pharmacodynamic substance basis and quality control of Radix Aconiti Kusnezoffii.

Purpose/Significance To deeply analyze the research progress on the application of medical knowledge graph in the field of stroke,to discuss the problems of the development of stroke knowledge graph in China,and to put forward suggestions for the construc-tion of stroke knowledge graph.Method/Process By reviewing and analyzing the relevant literature,the application of medical knowledge graph in the field of stroke is sorted out and summarized.Result/Conclusion There are still many deficiencies in the development of stroke knowledge graph in China,and in the future,in-depth research can be carried out from four aspects,namely,expanding the ap-plication scope of knowledge graph,promoting the fusion of knowledge graph,developing more efficient algorithms,and upgrading to cog-nitive graph by joint artificial intelligence(AI).

OBJECTIVE To analyze and identify the metabolites of isoimperatorin in normal rats in vivo. METHODS After the rats were intragastrically administered, the plasma, urine and feces samples of rats in normal and dosed groups were collected, and the samples were processed by solid phase extraction. Then, UHPLC-HRMS(Q-Exactive Orbitrap MS) high- resolution mass spectrometry was used to analyze biological samples, and the metabolites were screened and identified. RESULTS In both positive and negative ion modes, a total of 32 metabolites were accurately analyzed and identified based on the precise molecular masses obtained, chromatographic retention behavior, control mass spectral cleavage patterns, characteristic fragment ions, and relevant literature reports. The main metabolic pathways were furan ring opening, lactone hydrolysis, oxidation, methylation, glucuronidation, sulfation and their complex reactions. Among them, the glucuronidation product was discovered for the first time. CONCLUSION This study comprehensively clarifies the transformation pathways of isoimperatorin in rats, which can provide a basis for its pharmacodynamic study and metabolism study analysis of the other furocoumarins.

Objective:To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19).Methods:Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV.Results:Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs.Conclusions:The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.