ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol^-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

Colorectal cancer is one of the common malignant tumors of the digestive tract.With the popularization of screening methods and advancement of endoscopic technology,an increasing number of T1 stage colorectal cancers can be discovered.Accurately predicting lymph node metastasis risk is significantly important for guiding clinical treatment decisions,reducing complications and mortality.Current research on risk factors for lymph node metastasis in T1 stage colorectal cancer covers multiple aspects including clinical pathological features,molecular phenotypes and genetic characteristics.Some studies have built prediction models by integrating these factors,which show higher sensitivity,specificity and accuracy compared to current clinical guidelines.These models provide valuable experience for clinical practice.

OBJECTIVE To study the intervention effect and metabolic mechanism of Mongolian medicine Echinops sphaerocephalus extract on D-galactose-induced osteoporosis. METHODS Thirty-six 12-week-old male Wistar rats were selected and randomly divided into blank group， model group， Gushukang group， E. sphaerocephalus high-dose， medium-dose and low- dose groups， with 6 rats in each group. Except for blank group， other groups were intraperitoneally injected with D-galactose at 120 mg/kg per day. After 8 weeks of continuous injection， E. sphaerocephalus high-dose， medium-dose and low-dose groups were given drugs intragastrically at dose of 878， 439， 219.5 mg/kg， respectively. Gushukang group was given Gushukang 105.1 mg/kg intragastrically， once a day， for consecutive 8 weeks. After last administration， blood was collected from the abdominal aorta. Enzyme-linked immunosorbent assay was used to measure the contents of bone metabolism indexes [hydroxyproline （HYP）， alkaline phosphatase （ALP）] and oxidative stress indexes [total antioxidant capacity （TAOC）， superoxide dismutase （SOD）， malondialdehyde （MDA）] in serum of rats. Positron emission tomography/computedtomography （PET/CT） was used to analyze the changes of bone microstructure in right tibia bone. Meanwhile， metabolomic technology was used to study the regulation effect of E. sphaerocephalus on osteoporosis model rats. RESULTS Compared with blank group， HYP， ALP， MDA， ratio of bone surface to bone volume （BS/BV）， and trabecular separation （Tb·Sp） in model group were significantly increased （P＜0.05）， while TAOC， SOD， bone mineral density （BMD）， bone volume fraction （BVF）， trabecular E-mail：Xpfdc153@163.com thickness （Tb·Th） and trabecular number （Tb·N） were significantly decreased （P＜0.05）. Compared with model group， above indexes of administration groups were all reversed to different extents. The results of metabonomics study showed that after intervened with the extract of E. sphaerocephalus， 18 metabolites such as arachidonic acid， phenylalanine， tyrosine， tryptophan， isoleucine and uric acid in the serum of rats changed significantly， involving 15 metabolic pathways such as arachidonic acid， phenylalanine and tyrosine， of which arachidonic acid metabolism， phenylalanine metabolism and tyrosine metabolism were the main influencing pathways. CONCLUSIONS E. sphaerocephalus extract can effectively improve D-galactose-induced oxidative stress and the deterioration of bone microstructure， which interferes with metabolic pathways such as arachidonic acid metabolism and amino acid metabolism.

OBJECTIVE To study the absorption characteristics of phenylpropanoids of Mongolian medicine Tabson-2 decoction(TBD) in Caco-2 cells and to preliminarily clarify the oral absorption mechanism of TBD. METHODS Caco-2 cell monolayer model was used to analyze the uptake components of TBD in Caco-2 cells by UPLC-MS/MS, and UPLC-MS/MS analysis method was established to determine the nine best absorbed components of TBD, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptogenic acid, 1,5-dicaffeinate quinic acid, isochlorogenic acid C, caffeic acid, dihydrocaffeic acid, chlorogenic acid. The effects of time, concentration and P-glycoprotein inhibitor on the absorption of each component were investigated. RESULTS The overall intake of caffeic acid and dihydrocaffeic acid showed an upward trend in 0-180 min, and did not show saturation. The absorption of 3-hydroxycinnamic acid was constant at about 90 min and tended to saturation. The intakes of cryptochlorogenic acid, 1,5-dicaffeinate, quinic acid, isochlorogenic acid C, neochlorogenic acid, chlorogenic acid and protocatechuic acid first decreased and then increased with time from about 90 min. The addition of P-glycoprotein inhibitor verapamil and cyclosporin A had an effect on the absorption of dihydrocaffeic acid compared with the phenylpropanoid components, indicated that dihydrocaffeic acid was the substrate of P-glycoprotein. CONCLUSION The main phenylpropanoids of TBD enter Caco-2 mainly by passive diffusion, supplemented by active transport, and the absorption process of the other eight components is not affected by the efflux of P-glycoprotein except dihydrocaffeic acid.

Objective: To study the effects of Phellodendron amurense on herpes simplex virus 1 (HSV-1) and cytokines, and to explore the mechanism of Phellodendron amurense inhibiting HSV-1 virus through multiple channels. Methods: Viruses were inoculated into medicine treated HeLa cells. The proliferation of virus was observed by fluorescence microscopy. The transcriptional levels of glycoprotein gD and functional protein US1 on the surface of virus envelope were detected by quantitative (q) PCR. After incubating HeLa cells for 24 h, qPCR was used to detect the expression of intrinsic immune factors such as IP-10, IL-12, IFN-gamma and transcription factor NF-kappa B (P65). The expression and nuclear location of NF-kappa B (P65) protein were detected by immunofluorescence. Results: Fluorescence showed that the proliferation of virus decreased significantly at 8 and 40 ng/ml (P<0.01), and the transcription levels of viral protein gD and US1 decreased (P<0.05). After incubation for 24 hours, the transcription levels of IP-10, IL-12 and IFN-gamma in HeLa cells increased significantly (P<0.01). The transcription level of transcription factor NF-kappa B (P65) also increased (P<0.05), and immunofluorescence showed that the nuclear penetration rate of p65 subunit of NF-kappa B (P65) in each group increased (P<0.05). Conclusions Phellodendron amurense extract can inhibit HSV-1 by inhibiting the transcription of viral functional protein and promoting the expression of cellular immune factors.

Objective To investigate the efficacy of TACE combined with radiofrequency ablation (RFA) in treatment of advanced hepatocellular carcinoma.Methods A total of 72 patients with advanced hepatocellular carcinomas were analyzed retrospectively,including 35 patients underwent TACE combined with RFA (combined group),37 patients underwent single TACE (control group).After the operation,the short-term effect,the changes of liver function,serum alpha-fetoprotein (AFP) level,the complication and the long-term survival rates of the two groups were compared.Results The total effective rate of the combined group (29/35,82.86％) was significantly higher than that of control group (20/37,54.05％;P=0.009).In the combined group,the AFP reduced to (102.19±32.13)μg/L,and the control group reduced to (218.46±49.87)μg/L,which had statistical difference (P＜0.001).The survival rates of 1-year,2-year and 3-year in the combined group were 82.86 ％,54.29 ％,34.29 ％ with a median survival time of 25 months;while in the control group those were 54.05％,32.43％,13.51％ with a median survival time of 16 months;there were statistically significant differences in the survival rate between two groups (P=0.009).After treatment,the hepatic functions of both group had a transient change,and 2 weeks after the operation,there was no significant difference between the two groups (all P＞0.05).Conclusion The combination of TACE and RFA is an effective method for the treatment of advanced hepatocellular carcinoma.

Objective To study the cardioprotective function of Zhurihen dripping pills in experimental animals.Methods By hypoxia tolerance model and isoproterenol hydrochloride induced acute hypoxia model, measuring the time of death in mice.For rat serum LDH, CK, SOD and MDA were measured to observe protective effect of Zhurihen dripping pills on vasopressin-induced acute myocardial ischemia model.The effect of Zhurihen dripping pills on latency and durations were observed in acute arrhythmia induced by inhaled chloroform – epinephrine rabbits model.Results The hypoxia tolerance in mice and myocardial hypoxia tolerance significantly improved by Zhurihen dripping pill, and prolonged the survival time in mice.The serum level of LDH, CK, SOD and MDA significantly improved, and protected the impaired myocardial cell in rats.The latent period of arrhythmia was significantly prolonged and duration of arrhythmia was shortened in rabbits.Conclusion Zhurihen dropping pills an improve myocardial oxygen deficiency, anti-arrhythmia effect and protect myocardial cells.

Inflammatory cytokines are closely related to the development of gastric cancer. Pro-inflammatory cytokines, anti-inflammatory cytokines and their associated signaling pathways play different roles on the stages of gastric cancer, such as occurrence, development and prognosis, through different channels. This article summarizes the expression and function of Helicobacter pylori, IL-1β, TNF-α, IL-8, TGF-β, IL-10, IL-18 and T lymphocytes in gastric tissue or blood. The inflammatory cytokines and their associated signaling pathways which working as therapeutic targets for gastric cancer are also concluded.

Objective To evaluate the safety and efficacy of percutaneous endobiliary radiofrequency ablation combined with biliary stenting in treating malignant obstructive jaundice. Methods Percutaneous endobiliary radiofrequency ablation combined with biliary stenting was carried out in 2 patients with malignant obstructive jaundice after they received percutaneous transhepatic biliary drainage. The curative effect, complications and stent patency at 50 days after the treatment were recorded. The results were analyzed. Results Successful endobiliary radiofrequency ablation and intraluminal stent implantation was accomplished in both patients, with a technical success rate of 100%. Segmental radiofrequency ablation procedure was employed. After the treatment the serum total bilirubin level was significantly decreased. No bile duct bleeding, perforation of bile duct, bile leakage or other serious complications occurred. The stent remained unobstructed during the follow - up period of 50 days. Conclusion As a new treatment for malignant obstructive jaundice, percutaneous endobiliary radiofrequency ablation combined with biliary stenting is clinically safe and effective, although its long - term efficacy needs to be further proved with randomized controlled trials.

Objective To retrospectively analyze the effect of interventional embolization for hepatocelluar carcinoma (HCC) associated with arteriovenous shunting (AVS), and to discuss the factors influencing the therapeutic results. Methods The clinical data of 62 cases with HCC associated with AVS , who were treated with interventional chemoembolization , were retrospectively analyzed. Based on the type and extent of AVS identified by angiographic manifestations, appropriate obstruction of the shunt and Lipiodol chemoembolization of HCC were conducted. The curative effect of the shunt embolization was assessed by DSA at one or two months after the treatment. The relevant factors influencing the prognosis of embolization were analyzed by using univariate and multivariate Cox regression analysis methods. Results Of the 62 patients, arterioportal shunting (APS) was detected in 44, hepatic arterio-venous shunting (HAVS) in 11, APS together with HAVS in 4, and hepatic artery-pulmonary artery shunting (HAPAS) in 3. Re-examination with DSA was carried out in 53 patients at 1 - 2 months after the treatment , which showed that the shunting disappeared in 18 cases, obvious reduction of the shunt flow was seen in 19 cases, the lesion remained stable in 9 cases and the disease became worse in 7 cases. Univariate analysis indicated that the kind of embolic material and the presence of tumor thrombus could affect the obstructive result of the shunt , while multivariate Cox regression analysis showed that portal tumoral thrombus was an independent risk factor. The embolization effect of polyvinyl alcohol (PVA) particles and Lipiodol-ethanol mixture, used as the embolic agents, was better than that of gelatin sponge particles. Conclusion To ensure a successful interventional chemoembolization for HCC combined with AVS the procedure should be individualized according to the type and extent of the arteriovenous shunting. The type of embolic materials used for embolization can affect the results to a certain degree.