Objective To investigate the mechanism of Sini San Formula in the treatment of ulcerative colitis and depression through"homotherapy for heteropathy"based on network pharmacology and molecular docking.Methods The TCMSP database was used to obtain the potential active components and their related targets;GeneCards,CTD,and TTD databases were used to screen the disease-related targets of ulcerative colitis and depression;the intersection of the predicted targets of the active components and the disease-related targets was used to obtain the potential targets(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,and Cytoscape 3.7.2 software to construct a"Chinese medicinals-active components-diseases-common targets"network to analyze the core components;importing the common targets into the STRING database,constructing a common protein-protein interaction(PPI)network.The GO function and KEGG pathway enrichment of the shared targets were analyzed by DAVID database,and molecular docking between the core components and the key targets was verified.Results A total of 136 active components of Sini San Formula were obtained,and 220 potential targets of action(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,involving 657 biological processes,70 cellular components,147 molecular functions and 133 signaling pathways.The screening yielded core active compounds such as quercetin,kaempferol,lignans,naringenin,7-methoxy-2-methylisoflavone,key target proteins such as JUN,MAPK3,STAT3,AKT1,and MAPK1,as well as signaling pathways such as TNF,IL-17,Th17 cellular differentiation,HIF-1,and Toll-like receptor.Five potential key targets have strong binding activity to quercetin,kaempferol,lignans and naringenin.Conclusion Sini San Formula may act on key targets such as JUN,MAPK3,STAT3,AKT1,MAPK1,etc.through active components such as quercetin,kaempferol,lignocerotonin,naringenin,etc.,and play the role of"homotherapy for heteropathy"for ulcerative colitis and depression through the signaling pathways such as TNF,IL-17,HIF-1,Toll-like receptor and Th17 cell differentiation.

Objective: To excavate the mechanism of the combination of Radix Ophiopogonis and Schisandra chinensis to treatatherosclerosisbased on network pharmacology to discuss its mechnism. Methods: This paper excavated the associated proteins with Radix Ophiopogonis and Schisandra chinensis from the TCMGeneDIT database, and constructed the multicomponent protein network of Radix Ophiopogonis, Schisandra chinensis and proteins ApoE-/- mice were randomly divided into control group, model group, low, medium, high dose group and atorvastatin calcium group. Except the control group, other groups were fed with H10540 high fat diet for 12 weeks. From the 4th week, the atrovastatin calcium group was given atrovastatin calcium liquid 6 mg/kg by gavage. The low, medium and high dose groups were administed 4.68, 2.34 and 1.17 g/kg, respectively, once a day by gavage for 8 weeks. The oil red staining was applied to observe the pathological changes of atherosclerotic aortic wall. Western blot was subjected to detect the expression change of mitogen activated protein kinases p38 (p38), ATP binding cassette subfamily G member 1 (ABCG1), Toll like receptor 4 (TLR4), heat shock protein 90 alpha family class a member 1 (HSP90AA1), MMP-9 and arachidonate 5-lipoxygenase (ALOX5) in liver tissue, as well as nuclear factor related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in brain tissue. Results: It was found that eleven components were interacted with 37 proteins, forming a protein interaction network with 48 nodes and 190 boundaries without isolated nodes. Compared to the model group, the level of p-p38/p38 (2.12 ± 0.12, 1.76 ± 0.11, 1.69 ± 0.10 vs. 2.45 ± 0.16), TLR4 (1.98 ± 0.10, 1.64 ± 0.11, 1.55 ± 0.12 vs. 2.68 ± 0.06), HSP90AA1 (1.79 ± 0.10, 1.66 ± 0.09, 1.59 ± 0.11 vs. 2.06 ± 0.07), MMP9 (1.84 ± 0.11, 1.75 ± 0.12, 1.66 ± 0.08 vs. 2.68 ± 0.10) in liver tissue of low, medium and high dose groups significantly decreased, the level of ABCG1 (0.53 ± 0.08, 0.78 ± 0.09, 0.81 ± 0.10 vs. 0.45 ± 0.04), ALOX5 (0.59 ± 0.04, 0.67 ± 0.09, 0.88 ± 0.07 vs. 0.47 ± 0.02) in liver tissue of low, medium and high dose groups significantly increased (P<0.05). The expression of Nrf2 (1.62 ± 0.12, 1.32 ± 0.09, 1.14 ± 0.06 vs. 2.12 ± 0.08) in cytoplasm of brain tissue significantly decreased, and Nrf2 (1.12 ± 0.09, 1.61 ± 0.07, 1.68 ± 0.11 vs. 1.07 ± 0.08) in cell nucleus of brain tissue significantly increased. The expression of HO-1 (1.16 ± 0.09, 1.73 ± 0.11, 1.82 ± 0.08 vs. 1.05 ± 0.04) in brain tissue significantly increased. Conclusions Network pharmacology and molecular biology were used to elucidate the molecular mechanism of the combination of Schisandra chinensis and Ophiopogon japonicus in the prevention and treatment of atherosclerosis, also to validate the related mechanism via Nrf2 pathway, which provided a reference for the further study of the combined prescription.

Objective To indentify the cognitive status of Chinese patients to acne and the influencing factors to theirs' cognitive status,so as to provide solid evidences for the prevention and treatment of acne.Methods A self-designed questionnaire was made to conduct this survey of 16,156 acne patients,who seeked to the treatment in the dermatological departments from 112 hospitals in China.The survey consisted of several parts,including the general status of patients,the patients' cognition of occurrence,development and risk factors of acne,whether the first choice was seeking treatment at the hospital when the patients had acne and the condition of selection of skin care products.The factors were analyzed,which could impact the cognition of the patients' behavior of treatment,how did the patients' cognition to influence their medical behavior and skin care as well as the consistency of assessment of the severity of acne by doctors and patients themselves.Results The acne patients studied had the best knowledge of "acne is a skin disease","it not only occurs in the period of adolescence" and "the disease can be prevented and cured",which accordingly accounted for 80.65％,69.16％ and 65.49％ of the total patients respectively.However,the awareness of acne patients to heredity,high sugar and dairy products as risk factors for acne was insufficient,which accounted for 48.72％,42.40％ and 18.25％ of the total patients,respectively.Gender,age,educational level,occupation and health knowledge were the main factors affecting the cognitive level of patients;the survey also found that men,patient with educational level of junior high or even lower educational condition,occupation of labor workers or farmers and patients were lack of health education with poor knowledge of the genetics and dietary were risk factors for acne;patients with age over 36 years or with mild illness had poor knowledge of dietary risk factors for acne;the difference was statistically significant (P＜0.05).The analysis of the influence of cognitive status on medical treatment behavior and skin care showed that the better the cognition,the higher the probability of patients would choose medical treatment as the first choice as well as choosing functional skin care products;the difference was statistically significant (P＜0.05).The consistency of assessment of the severity of acne by doctors and patients was poor (Kappa value ＜0.4),and the assessment of severity of acne by patients was more serious than doctors' assessment.Conclusions Patient's cognitive status will affect their medical behavior and skin care,and there is also a phenomenon that patients have a more serious assessment of their acne condition.It is suggested that health education for acne patients should be strengthened in clinical medicine so as to improve their knowledge of acne as well as preventing from acne effectively.

Objective To observe the effect of hydroxysafflor yellow A (HSYA) on the protection of blood brain barrier of cerebral ischemia mice, and explore the mechaniam. Methods Seventy-two C57/BL mice were divided into 6 groups: the sham operation group, the cerebral ischemia mice group, the TLR4 blocking group, the TLR4 blocking+cerebral ischemia mice group, the HSYA intervention+cerebral ischemia mice group, HSYA intervention+TLR4 blocking+cerebral ischemia mice group. Cerebral ischemia mice group were subjected to the middle cerebral artery occlusion (MCAO) model, TLR4 blocking was used, while TLR4 blocking was injected TLR4 antibody via right common carotid artery, and HSYA intervention group was injected 2 mg/kg HSYA by tail vein 0.5 h before cerebral ischemia. RT-PCR and western blot were applied to detect the mRNA and protein expression change of Wnt3a and β-catenin in each group. Results Compared with the cerebral ischemia mice group,the expression of TLR4 mRNA(1.63 ± 0.05,1.53 ± 0.04,1.84 ± 0.03 vs. 1.97 ± 0.05) significantly decreased (P<0.05 or P<0.01), the Wnt3a mRNA (0.56 ± 0.01, 0.58 ± 0.01, 0.50 ± 0.04 vs.0.42 ± 0.03),β-catenin mRNA(0.61 ± 0.03,0.74 ± 0.02,0.58 ± 0.04 vs.0.50 ± 0.03),Claudin-5 mRNA (0.54 ± 0.02, 0.58 ± 0.01, 0.47 ± 0.01 vs. 0.46 ± 0.02) mRNA significantly increased(P<0.05 or P<0.01), the protein expression of TLR4 (1.73 ± 0.05, 1.57 ± 0.03, 1.79 ± 0.08 vs. 1.89 ± 0.02) significantly decreased (P<0.05 or P<0.01), the protein expression of Wnt3a (0.67 ± 0.03, 0.74 ± 0.03, 0.57 ± 0.01 vs. 0.46 ± 0.01), Occludin(0.66 ± 0.02,0.73 ± 0.02,0.67 ± 0.01 vs.0.53 ± 0.01),Claudin-5(0.71 ± 0.01,0.73 ± 0.01,0.66 ± 0.01 vs. 0.64 ± 0.03) significantly increased (P<0.05 or P<0.01) in the TLR4 blocking+cerebral ischemia mice group, the HSYA intervention+cerebral ischemia mice group, HSYA intervention+TLR4 blocking+cerebral ischemia mice group. Conclusions TLR4 plays a critical regulatory role on the activation of Wnt3a and β-catenin in cerebral ischemic mice model. HSYA could intervene on the tight junction of cerebral ischemic brain through the intervention of Wnt3a and β-catenin, thus exerting the protection for cerebral ischemic brain.

Objective: To investigate the effect and significance of GSK-3β inhibitor(LiCl)and RANK-RANKL on the renal tissue of diabetic nephropathy(DN) rats. Methods: SD rats were divided into normal control group (NC), DN model group (DN) and GSK-3β inhibitor intervention group (LiCl). Twenty-four hour urine protein of rats were determined by Coomassie brilliant blue. Kidney tissue sections were stained by HE. The expression of GSK-3β, RANK and RANKL protein were determined by immunohistochemistry staining. The mRNA of GSK-3β, RANK, RANKL was detected by RT-qPCR. Results: Compared with NC group[(14.72±3.37)g], the level of 24-hour urinary protein[(154.17±20.65)g] increased significantly in DN group; compared with DN Group, the level of 24-hour urinary protein [(107.22±31.15)g]decreased in LiCl group(P<0.05). Compared with NC group(2.10±0.60, 1.10±0.20, 1.21±0.20; 19.52±3.20, 1.80±1.10, 1.81±0.50), the pathological changes of renal tissues of DN group aggravated, the mRNA and expression of protein of GSK-3β, RANK and RANKL increased(9.10±2.15, 8.95±2.40, 9.90±2.60; 32.70±7.20, 19.20±4.32, 20.92±5.90); compared with DN group, the pathological changes of renal tissues of LiCl group alleviated, mRNA and the expression of protein of factors above declined(2.70±0.80, 2.32±0.65, 3.58±1.10; 22.35±3.25, 4.20±2.42, 5.90±2.36; P<0.05). Conclusion RANK and RANKL play an important role in the development of DN, LiCl influence Wnt and NF-κB signal pathway down-regulating RANK and RANKL to suspend development of diabetic nephropathy.

Aim To investigate the change of miR-124 expression in methamphetamine-induced addiction in PC12 cells and the possible regulatory mechanism that it involves.Methods PC12 cells were randomly divided into 6 groups as follows: control group, methamphetamine group, agomir Negative Control group, miR-124 agomir group, agomir Negative Control+methamphetamine group and miR-124 agomir+methamphetamine group.After the treatment, the total RNA and protein were extracted in PC12 cells.The expression of miR-124 was measured by Real-time PCR and the expression of GluR2 was determined by Western blot in PC12 cells.Results Compared with those in the control group, the expression of miR-124 was remarkably decreased and the expression of GluR2 was significantly increased in the methamphetamine group in PC12 cells.Compared with those in the agomir Negative Control+methamphetamine group, the expression of miR-124 was remarkably increased and the expression of GluR2 was significantly decreased in the miR-124 agomir+methamphetamine group in PC12 cells.Conclusion MiR-124 might involve in methamphetamine-induced addiction in PC12 cells by inhibiting GluR2.

Objective To compare the therapeutical effect of puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A on cerebral ischemia reperfusion mice. Methods The mice were randomly assigned for sham group, model group, puerarin group, ligustrazine group, ginsenoside Rb1 group, and Hydroxysafflor yellow A group, 24 mice for each group. All the groups were subjected to middle cerebral artery occlusion (MCAO) by 1 h ischemia and 24 h of reperfusion except the sham group. The puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A were administrated by tail vein injection with 3μmol/kg at the onset of 1 h of ischemia. The neurologic deficit score, infarct area calculated by TTC staining, cerebral cortex blood flow monitored by laser doppler flowmetry, NO content measured by chemical colorimetry and western blot were applied to determine the expression for cleaved-caspase-3 and nuclear transcription factor NF-κB for each group. Results Compared with the model group, the infarct area (15.83%± 1.83%, 22.00%± 2.53%, 22.83%± 1.83%, 17.83%± 1.72%vs. 34.67%± 2.66%) in the puerarin group, ligustrazine group, ginsenoside Rb1 group, Hydroxysafflor yellow A group was significantly decreased (P<0.01 or P<0.05);the cerebral cortex blood flow (598.81 ± 9.90 μl/kg?min-1, 614.78 ± 9.20 μl/kg?min-1, 577.83 ± 5.55 μl/kg?min-1, 583.54 ± 7.98 μl/kg?min-1 vs. 548.43 ± 1.97 μl/kg?min-1) significantly increased (P<0.01 or P<0.05);the NO content (17.09 ± 1.18μmol/L, 18.54 ± 0.54μmol/L, 18.17 ± 0.49μmol/L, 15.10 ± 0.73μmol/L vs. 20.63 ± 0.73μmol/L) ignificantly decreased (P<0.01 or P<0.05);the expression of cleaved-caspase-3 (1.02 ± 0.08, 1.12 ± 0.04, 0.87 ± 0.08, 1.07 ± 0.08 vs. 1.30 ± 0.06) and NF-κB p-p65/NF-κB p65 (1.03 ± 0.19, 1.15 ± 0.05, 1.12 ± 0.08, 0.72 ± 0.08 vs. 1.45 ± 0.08) ignificantly decreased (P<0.01 or P<0.05) Conclusions Four Chinese herbal monomers could improve nerve and cerebral dysfunctions and ameliorate ischemia symptoms with varying degrees. The mechanisms were involved with the enhancement of cerebral cortex blood flow and inhibition of cell apoptosis and the activation of inflammatory signaling pathways.

Objective To investigate the effects and probable mechanism ofShenfu injection on the oxidaitve damage of H2O2-induced PC12 cells.Methods PC12 cells were cultured and exposed to 100μmol/L H2O2 for 1 h to establish the oxidative damage model. The protective effect ofShenfu injection was observed by the cell survival rate measured by colorimetric MTT assay, and the leakage rate of lactic dehydrogense (LDH). Western blot methods were used to detect the expression of NF-κB signaling pathway.Results Compared with the model group,Shenfu injection at 5, 10, 20 ml/L could improve the PC12 cells survival rate (83.11% ± 2.59 %, 87.99% ± 0.59%, 85.26% ± 1.07%vs. 73.82% ± 1.82%;P<0.01 orP<0.05), decrease the LDH leakage rate (32.75% ± 4.10%, 28.52% ± 1.14%, 35.79% ± 1.62%vs. 64.34% ± 3.18%;P<0.01 or P<0.05). Western blot results showed thatShenfu injection could protect the PC12 cells from oxidaitve damage by suppressing the p-p65/p65 (1.30 ± 0.10, 1.17 ± 0.06, 1.37 ± 0.15 vs. 1.70 ± 0.10;P<0.01 orP<0.05), p-IκBα/IκBα (1.07 ± 0.12, 1.00 ± 0.10, 1.03 ± 0.06 vs. 1.17 ± 0.06; P<0.01 orP<0.05).ConclusionShenfu injection has a obvious antioxidant effect on PC12 cells in vitro.

Objective To evaluate the effect of dexmedetomidine on lipid peroxidation during lung ischemia-reperfusion (I/R) in rats.Methods Fifty-four pathogen-free healthy male Wistar rats,weighing 250-350 g,were randomly divided into 3 groups (n=18 each) using a random number table:sham operation group (S group),I/R group,and dexmedetomidine group (Dex group).In group Dex,dexmedetomidine 5 μg/kg was injected via the caudal vein once a day for 2 consecutive days.The equal volume of normal saline was given in S and I/R groups.At 30 min after administration on 2nd day,lung I/R was produced by clamping the left hilum of lung for 45 min followed by 120 min of reperfusion in I/R and Dex groups.At 45 min of ischemia,and 60 and 120 min of reperfusion,6 rats selected from each group were sacrificed,and the left lungs were removed for examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio),malondialdehyde (MDA) content and superoxide dismutase (SOD) activity.Results Compared with S group,the SOD activity was significantly decreased,and the MDA content and W/D ratio were significantly increased at 60 and 120 min of reperfusion in I/R and Dex groups (P＜0.05).Compared with I/R group,the SOD activity was significantly increased,and the MDA content and W/D ratio were significantly decreased at 60 and 120 min of reperfusion in Dex group (P＜0.05).The pathological changes of lungs were significantly attenuated in Dex group as compared with I/R group.Conclusion Dexmedetomidine mitigates lung I/R injury through inhibiting lipid peroxidation in rats.

Objective To evaluate the effect of lappaconitine on renal ischemia-reperfusion (I/R) injury in mice.Methods Thirty-six male Wistar rats,weighing 180-220 g,were randomly divided into 3 groups (n=12 each) using a random number table:sham operation group (group S),group I/R and lappaconitine group (group LA).Renal I/R was induced by occlusion of the left renal pedicle for 45 min with atraumatic microclips followed by reperfusion,and the right kidney was removed after atraumatic microclips were released.At 30 min before reperfusion,lappaconitine 4 mg/kg was injected intraperitoneally in group LA,and normal saline 2 ml was given in S and I/R groups.In group S,the left renal pedicle was only isolated.At 5 and 24 h of reperfusion,blood samples were taken from the inferior vena cava for determination of serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations,and kidney specimens were obtained for histopathologic examination (with light microscope) and for determination of the expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) in renal tissues (by immunohistochemistry).Results Compared with group S,the serum Cr and BUN concentrations were significantly increased,and the expression of COX-2 and MMP-2 in renal tissues was up-regulated at 5 and 24 h of reperfusion in I/R and LA groups.Compared with group I/R,the serum Cr and BUN concentrations were significantly decreased,the expression of COX-2 and MMP-2 in renal tissues was down-regulated at 5 and 24 h of reperfusion and histopathologic changes were reduced in group LA.Conclusion Lappaconitine can attenuate renal I/R injury through inhibiting the expression of COX-2 and MMP-2 in rats.