This study predicts the potential mechanism of Hippocampus in the treatment of knee osteoarthritis(KOA) through network pharmacology, with preliminary verification using molecular docking and animal experiments. The database was used to screen the active chemical components of Hippocampus and the targets of KOA, and Gene Ontology(GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and molecular docking were performed on the relevant core targets to preliminarily explore the potential targets and mechanisms of Hippocampus in the treatment of KOA. A rat KOA model was constructed by intra-articular injection of sodium iodoacetate, and the rats were intervened with different doses of Hippocampus decoction and celecoxib. The expression of relevant targets was detected through hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), RT-qPCR, and Western blot to further validate the network pharmacology results. A total of 23 drug-like components of the Hippocampus were screened, and 128 common targets with KOA were identified, involving interleukin-17(IL-17) signaling pathway, transcription factor(FoxO) signaling pathway, tumor necrosis factor(TNF) signaling pathway. Molecular docking results showed that the screened core chemical components exhibited good affinity with key targets. HE staining demonstrated that Hippocampus improved the morphology of the cartilage layer. ELISA confirmed that Hippocampus significantly reduced the levels of IL-6 and TNF-α in the serum of KOA rats. Western blot and RT-qPCR analysis showed that Hippocampus significantly reduced the expression of IL-6, TNF-α, matrix metalloproteinase(MMP) 13, IL-17A, nuclear factor κB activator 1(ACT1), tumor necrosis factor receptor-associated factor 6(TRAF6) and nuclear factor κB(NF-κB) in cartilage tissue. The results suggest that Hippocampus can alleviate the degree of joint damage in the KOA rat model induced by sodium iodoacetate. The mechanism of action is related to the inhibition of the IL-17 signaling pathway, reduction of inflammation, and inhibition of extracellular matrix(ECM) degradation.
Animals ; Molecular Docking Simulation ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Male ; Osteoarthritis, Knee/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Humans ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Hippocampus/chemistry*

To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals ; TOR Serine-Threonine Kinases/genetics* ; Male ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans

Background A simple measurement of central venous pressure (CVP)-mean by the digital monitor display has become increasingly popular. However, the agreement between CVP-mean and CVP-end (a standard method of CVP measurement by analyzing the waveform at end-expiration) is not well determined. This study was designed to identify the relationship between CVP-mean and CVP-end in critically ill patients and to introduce a new parameter of CVP amplitude (ΔCVP= CVPmax - CVPmin) during the respiratory period to identify the agreement/disagreement between CVP-mean and CVP-end.Methods In total, 291 patients were included in the study. CVP-mean and CVP-end were obtained simultaneously from each patient. CVP measurement difference (|CVP-mean - CVP-end|) was defined as the difference between CVP-mean and CVP-end. The ΔCVP was calculated as the difference between the peak (CVPmax) and the nadir value (CVPmin) during the respiratory cycle, which was automatically recorded on the monitor screen. Subjects with |CVP-mean - CVP-end|≥ 2 mmHg were divided into the inconsistent group, while subjects with |CVP-mean - CVP-end| < 2 mmHg were divided into the consistent group.Results ΔCVP was significantly higher in the inconsistent group [7.17(2.77) vs.5.24(2.18), P<0.001] than that in the consistent group. There was a significantly positive relationship between ΔCVP and |CVP-mean - CVP-end| (r=0.283, P <0.0001). Bland-Altman plot showed the bias was -0.61 mmHg with a wide 95% limit of agreement (-3.34, 2.10) of CVP-end and CVP-mean. The area under the receiver operating characteristic curves (AUC) of ΔCVP for predicting |CVP-mean - CVP-end| ≥ 2 mmHg was 0.709. With a high diagnostic specificity, using ΔCVP<3 to detect |CVP-mean - CVP-end| lower than 2mmHg (consistent measurement) resulted in a sensitivity of 22.37% and a specificity of 93.06%. Using ΔCVP>8 to detect |CVP-mean - CVP-end| >8 mmHg (inconsistent measurement) resulted in a sensitivity of 31.94% and a specificity of 91.32%.Conclusions CVP-end and CVP-mean have statistical discrepancies in specific clinical scenarios. ΔCVP during the respiratory period is related to the variation of the two CVP methods. A high ΔCVP indicates a poor agreement between these two methods, whereas a low ΔCVP indicates a good agreement between these two methods.
Humans ; Central Venous Pressure ; Respiration ; ROC Curve

Objective To compare the efficacy of thrombus aspiration catheter combined with intracoronary tirofiban and nitroglycerol injection through the aspiration catheter versus the guiding catheter during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods Thirty-four patients with STEMI undergoing primary PCI and receiving thrombus aspiration catheter combined with intracoronary tirofiban and nitroglyeerol injection through the aspiration catheter were enrolled as the aspiration group (n =34),and those who had similar coronary angiography results and basic characteristics but receiving thrombus aspiration catheter combined with intracoronary tirofiban and nitroglycerol injection through the guiding catheter were served as the guiding group ( n =33 ).The outcomes of the two groups were observed and compared.Results There was no significant change of blood pressure between before and after injection in the aspiration group ( P ＞ 0.05 ),but the change of blood pressure was significant after injection compared with before injection in the guiding group ( P ＜ 0.01 ).The cTn-I,BNP,peak-value of CK-MB,peak-time of CK-MB,TIMI grade 3 flow,slow-reflow in IRA after PCI in the aspiration group were superior to those in the guiding group ( t =3.92,P ＜ 0.01 ;t =4.70,P ＜ 0.01 ; t =3.39,P ＜ 0.01 ; t =7.17,P ＜0.01 ; x2 =3.877,P ＜ 0.05 ; x2 =3.876,P ＜ 0.05 ).LVEF,LVEDd and LVESd after 1 month in the aspiration group were superior to those in the guiding group (t =5.99,P ＜ 0.01 ;t =4.53,P ＜ 0.01 ;t =8.12,P ＜ 0.01 ),but no significant differences of LVEF,LVEDd,LVESd were found after 1 week resolution of sum of ST-segment elevation and the MACE rates after PCI were found between the two group ( P ＞ 0.05 ).Conclusion Application of thrombus aspiration catheter combined with intracoronary tirofiban injection through the aspiration catheter is more effective than through the guiding catheter in patients with Acute ST-segment elevation myocardial infarction,which could decrease slow-reflow phenomenon and improve re-perfusion and left ventricular function with better clinical outcomes.

Objective To observe the safety and efficiency of DIVER thrombus aspiration catheter application during percutaneous coronary intervention(PCI) in patients with acute myocardial infarction(AMI)and to evaluate its impacts on the myocardial reperfusion,cardiac function and in-stent restenosis after 9months.Methods A total of 86 cases of ST-segment elevation patients of AMI treated with PCI and confirmed complete occlusion lesion by angiography from November 2008 to December 2010 were randomly divided into two groups:aspiration group(n =43)with DIVER thrombus aspiration cathetcrs were used,and non-aspiration group (n =43).ST-segment recovery within two hours,TIMI grade,the in-hospital adverse major cardiac events,the levels of Pro-BNP,coronary function determined by ultrasound heartbeat graph and the results of coronary angiography after PCI for 9 months were compared between two groups.Results There was significant difference on ST-segment recovery within two hours between these two groups[95.35％(41/43)vs 79.02％(34/43),x2 =11.862,P =0.0006].The incidence of TIMI 3 grade flow was significantly higher,the incidence of TIMI 2(slow flow)and TIMI 0-1(no-reflow)grade flow were much lower in aspiration group than those in non-aspiration group immediately after PCI[TIMI 3:93.02％(40/43) vs 81.40％(35/43),x2 =6.06,P =0.0335 ; TIMI 2:6.98％(3/43) vs 13.95 ％(6/43),x2 =3.12,P =0.0495 ; TIMI 0-1:0 vs 6.98 ％(3/43),x2 =5.29,P =0.0352].There was no difference on LVEF[(0.420±0.054) ％ vs(0.408±0.052)％,t =1.0496,P =0.766and LVEDD(56.5±4.5)mm vs(57.6±4.4)mm,t =1.0419,P =0.7832]between these two groups one day after PCL LVEF was significandy higher in aspiration group than that in non-aspiration group one and nine months after PCI[(0.452±0.050) ％ vs(0.432±0.049) ％,t =3.3957,P =0.0482 ;(0.469±0.053) ％ vs (0.413±0.052)％,t =4.9457,P =0.0336].LVEDD was significantly smaller in aspiration group than that in non-aspiration group one and nine months after PCI[(49.6±5.1) mm vs(53.4±4.6) mm,t =3.4548,P =0.0473 ;(46.5±4.4) mm vs(50.2±4.8) mm,t =3.7260,P =0.0421].There were no cardiovascular events (angina,myocardial infarction,heart failure,cardiac death)in both groups during 9 months follow-up.The coronary angiography results showed that the occurrence rate of in-stent restenosis in aspiration group was significantly lower than that in non-aspiration group(2.33％ vs 6.98％,x2 =4.4351,P =0.0463).Conclusion The application of DIVER thrombus aspiration catheters during PCI in all patients with AMI was safe and effective,it can improve the myocardial tissue perfusion and the post-operative cardiac function and can lower the occurrence rate of in-stent restenosis.

Objective To refrain the medical costs from out-of-control increase, and identify a per-disease payment mode suitable for New-CMS.Methods Case studies were conducted on all the data of five diseases in the course of three years, in a field study of the pilot counties for NRCMS in Anhui Province.Results This system of per-disease "pay by segmentation and quota" is composed of five parts: choice of diseases, measurement of payment criteria, method of settlement, method of compensation, and methods of supervision.Conclusion This system is an effective way to keep the medical costs in the NRCMS under control, given an effective play of the five supportive measures including the clinical pathways for individual diseases.

Objective To study CT manifestations of the malignant pleural mesothelioma(MPM) in rat.Methods 100 Wistar rats in the test group were injected with asbestos fibrous mixed fluid into closed right chest cavity 20 mg/ml one per month,the overall volume of asbestos was 40 mg,19 rats in the control group were injected with sterilized saline water of 1 ml per time,totally 2 ml as the same way.Dying or died rats were undergone CT scanning and pathologic examination,the experiment lasted for 2 years.Results In experimental group,there were 66 rats of MPM,14 cases of pleural hyperplasia and 12 cases without pleural change.There were 4 cases of pleural hyperplasia,10 cases without pleural change and no one of MPM in the control group.According to pathologic changes,they were divide into 66 cases of MPM,26 cases of non-MPM in the experimental rats and 14 cases of non-MPM in the control group.The occurrence rate,morphology and thickness of pleural thickening were significant among MPM group,non-MPM group and the control group.The specificity of nodular pleural thickening was 100%.The mean CT number of pleural thickening had no significance.The occurrence rate of masses of MPM in the chest cavity was 94.5%.The masses included tumors,abcesses or encapsulated effusion,the masses of MPM accounted for 62.5%.The mediastinal changes included irregular widening mediastinum,mediastinal pleural changes and masses and so on.But irregular widening mediastinum and adjacent invasion were more common and specified signs.Enlarge lymph nodes were not seen.Conclusion There were some specific CT signs in induced MPM.