Mechanism of Cervi Cornu Pantotrichum in Treatment of Osteoarthritis Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology. MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man （OMIM）. The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets， and STRING was adopted to build a protein-protein interaction （PPI） network. DAVID was used for gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin， and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor （TNF）-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin. ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained， of which ceramide， 6'-O-β-D-glucosylgentiopicroside， cerebroside， oleuropein， sphingomyelin， and cholesterol ferulate did not meet the screening conditions. Therefore， a total of 14 active ingredients were finally screened out， and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect， which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process， positive regulation of RNA polymerase Ⅱ promoter transcription， inflammatory response， protein synthesis， osteoclast differentiation， TNF signaling pathway， signaling pathways in cancer， mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and cyclic adenosine monophosphate （cAMP） signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H2O2-induced oxidative damage （P<0.05， P<0.01） and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide （LPS）-induced inflammation （P<0.05）. ConclusionBased on the network pharmacology method， the mechanism of the multi-component， multi-target and multi-pathway treatment of OA by antler antler was explained， and the anti-inflammatory and antioxidant activities of antler antler were confirmed， which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.

Study on antidepressant effect of total alkaloids of Fibraurea recisa / 中国中药杂志

This study aimed to investigate the antidepressant effects of total alkaloids of Fibraurea recisa in HT22 cells damaged by corticosterone (CORT) in vitro and in a mouse model of chronic unpredictable mild stress (CUMS) as well as the underlying mechanisms.In cellular experiments,the viability of CORT-damaged HT22 cells was detected using cell counting kit-8 (CCK-8),and the cell apoptosis was detected by Hoechst 33258 staining.In animal experiments,C57BL/6N mice were randomly divided into the control group,model group,low (100 mg·kg~(-1)),medium (200 mg·kg~(-1)) and high (400 mg·kg~(-1))-dose of total alkaloids of F.recisa groups,and positive control group.After 21 days of CUMS exposure,their depressive behaviors were observed in behavioral and Morris water maze tests.The serum levels of 5-hydroxytryptamine (5-HT),dopamine (DA),and norepinephrine (NE) were assessed by ELISA.The expression levels of apoptosis-related proteins Bcl-2,Bax and cleaved caspase-3 in HT22 cells and mouse hippocampus were detected by Western blot.The results suggested that total alkaloids of F.recisa alleviated the damage of HT22 cells induced by CORT in a dose-dependent manner.The Hoechst 33258 staining uncovered that total alkaloids of F.recisa better reduced the blue spots and inhibited cell apoptosis.The results of animal experiments showed that total alkaloids of F.recisa significantly improved the depression-like behaviors of mice and increased the serum levels of 5-HT,DA and NE as compared with those in the model group.The Western blot assays revealed a significant up-regulation of Bcl-2 protein expression,but an obvious reduction in Bax and cleaved caspase-3protein expression in the total alkaloids of F.recisa group.In conclusion,total alkaloids of F.recisa inhibited depression possibly by regulating the apoptosis-related protein expression or elevating the monoamine neurotransmitter levels in the brain.

Effects of goal-directed fluid therapy on inflammatory cytokines under combined anesthesia / 实用医学杂志

Objective To investigate effects of goal-directed fluid therapy on inflammatory cytokines under combined anesthesia.Methods 60 patients undergoing colorectal cancer surgery,aged 60 to 85 years old,which were classified as American Society of Anesthesiology(ASA)classⅡ~Ⅲ,were randomly assigned to Goal-directed fluid therapy group(group G,n = 30)and central venous pressure liquid management group(group C,n = 30). Life sign and BIS indexes were collected at the time points,before surgery(T1),after the start of the operation (T2),one hour after surgery(T3),after the operation(T4).Hemodynamic indexes were recorded.Two milliliter blood sample were phlebotomized for evaluation of TNF-α and IL-6 from each patient at T1,T3,T4.The infusion volume, the amount of bleeding,the operation time,anal exhaust time,and length of postoperative hospital stay were recorded. Results Comparing information between the two groups,infusion volume and colloid had an obvious decrease than that of group C(P<0.05).SVV and CVP of group G were much stable than group C.The levels of TNF-α and IL-6 of group G were lower than those of group C(P<0.01).The length of anal exhaust time and post-operative hospital stay group G were faster than that of group C(P<0.01).Conclusions Goal-directed fluid ther-apy is superior on fluid administration. It can reduce the release of IL-6 and TNF-α. It is beneficial to elderly colorectal cancer patients with hypertension.

Anti-platelet/anti-coagulation and their prognosis in advanced aged patients with ACS complicated atri-al fibrillation after PCI / 心血管康复医学杂志

Objective:To explore anti-platelet/anti-coagulation treatment and their influence on prognosis in advanced aged patients with acute coronary syndrome (ACS)complicated atrial fibrillation (AF)after percutaneous coronary intervention (PCI).Methods:A total of 204 advanced aged ACS + AF patients treated in our heart center were se-lected.All patients received CHA2 DS2 Vasc score assessment,male had score ≥2 scores and female had score ≥3 scores.A total of 160 cases received dual anti-platelet therapy combined anticoagulant treatment of warfarin,and they were randomly divided into low intensity group [n=80,international normalized ratio (INR)remained 1.8~2.3]and high intensity group (n=80,INR remained 2.3~2.8),both groups were followed up for 18 months.Inci-dence rates of major adverse cardiovascular and cerebrovascular events (MACCE),ischemic and hemorrhage events were observed.Results:Both groups were followed up for a mean 18 months,and there were no significant differ-ence in all-cause mortality,incidence rates of MACCE and fatal hemorrhage between two groups,P > 0.05 all.Compared with low intensity group,there were significant rise in incidence rates of severe hemorrhage (3.8% vs. 12.5%),P <0.05.Conclusion:Low intensity warfarin anticoagulant therapy can effectively reduce incidence rates of MACCE and ischemic events,and incidence rate of hemorrhage events is low in advanced aged ACS + AF pa-tients after PCI.

Anti-platelet/anti-coagulation and their prognosis in advanced aged patients with ACS complicated atri-al fibrillation after PCI / 心血管康复医学杂志

Objective:To explore anti-platelet/anti-coagulation treatment and their influence on prognosis in advanced aged patients with acute coronary syndrome (ACS)complicated atrial fibrillation (AF)after percutaneous coronary intervention (PCI).Methods:A total of 204 advanced aged ACS + AF patients treated in our heart center were se-lected.All patients received CHA2 DS2 Vasc score assessment,male had score ≥2 scores and female had score ≥3 scores.A total of 160 cases received dual anti-platelet therapy combined anticoagulant treatment of warfarin,and they were randomly divided into low intensity group [n=80,international normalized ratio (INR)remained 1.8~2.3]and high intensity group (n=80,INR remained 2.3~2.8),both groups were followed up for 18 months.Inci-dence rates of major adverse cardiovascular and cerebrovascular events (MACCE),ischemic and hemorrhage events were observed.Results:Both groups were followed up for a mean 18 months,and there were no significant differ-ence in all-cause mortality,incidence rates of MACCE and fatal hemorrhage between two groups,P > 0.05 all.Compared with low intensity group,there were significant rise in incidence rates of severe hemorrhage (3.8% vs. 12.5%),P <0.05.Conclusion:Low intensity warfarin anticoagulant therapy can effectively reduce incidence rates of MACCE and ischemic events,and incidence rate of hemorrhage events is low in advanced aged ACS + AF pa-tients after PCI.

Influence of FasL gene expression on hepatic metastasis of colorectal carcinoma.

BACKGROUND: FasL expression was reported to be associated with hepatic metastasis of colorectal cancer. The aim of this study was to study FasL gene expression in colorectal carcinoma and its influences on biological behavior and hepatic metastasis of colorectal carcinoma. METHODS: FasL gene expressions were examined with reverse transcriptase-polymerase chain reaction (RT-PCR) in the primary focus of colorectal carcinoma, adjacent cancerous mucosae, and metastasized liver focus from colorectal cancer. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rate and response to 5-FU and carboplatin were observed and analyzed with the MTT method. RESULTS: FasL gene expression was detected in the primary focus of colorectal cancer (n=58), adjacent cancerous mucosae (n=58), and metastasized hepatic tumor tissues (n=28). The positive rate of FasL expression was 24% (14/58), 8% (5/58), and 100% (58/58) in the primary focus, adjacent cancerous mucosae and metastasized hepatic tumor tissues respectively. FasL expression rate in the metastasized hepatic tumor tissues was higher than that in the primary focus (X(2)=43.49, P<0.01) and adjacent cancerous mucosae (X(2)=57.66, P<0.01). In a group of patients with hepatic metastasis, the FasL expression rate in primary focus was higher than that in patients without hepatic metastasis (X(2)=3.96, P<0.05). In vitro study positive expression of FasL was shown in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and controlled cancer cells (t=9.02, t=11.93, P<0.01). Under the same concentration of chemotherapeutic agents, the survival rate of FasL positive HR-8348 cells was higher than that of controlled cells. CONCLUSIONS: FasL positive cancer cells are powerfully resistant to chemotherapeutic agents. The expression of the FasL gene in colorectal cancer cells is related to immune evasion to escape from being killed by immune cells, showing stronger drug-resistance, and it facilitates hepatic metastasis.

[The influence of FasL gene expression upon hepatic metastasis of colorectal carcinoma].

OBJECTIVE: To study FasL gene expression in colorectal carcinoma and its influences on biological behaviour of colorectal cancer and hepatic metastasis. METHODS: FasL gene expressions were examined with RT-PCR technique in the primary locus of colorectal cancer, mucosa adjacent to cancer, and hepatic metastasis. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rates and cell response to 5-FU and carboplatin were observed and analysed with MTT method. RESULTS: FasL gene expressions were detected in the primary site of colorectal cancer (n = 58), cancer adjacent mucosa (n = 58), and hepatic metastasis (n = 28). The positive rate of FasL expression was 24% (14/58), 14% (8/58), 100% (28/28), respectively, in primary site, tumor adjacent mucoca and hepatic metastasis. FasL expression rate in hepatic metastasis was higher than that in the primary site (chi2 = 43.49, P < 0.01) and tumor adjacent mucosa (chi2 = 57.66, P < 0.01). In a group of patients with hepatic metastasis, FasL expression rate in primary site was higher than that in patients without hepatic metastasis (chi2 = 3.96, P < 0.05). In vitro experiment, positive expression of FasL was found in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and control cancer cells (t = 9.02, t = 11.93, P < 0.01). Under same concentration of chemotheraputic agent, survival rate of FasL positive HR-8348 cells was higher than that of control cells. CONCLUSIONS: FasL positive cancer cells have more powerful resistance to chemotheraputic drugs. Expression of FasL gene in colorectal cancer cells is related with immune evasion to escape killing by immune cells, showing stronger drug-resistance, and it facilitates hepatic metastasis.