AIM:To investigate the effect of hypericin(Hyp)on the heart of rats with myocardial ischemia-re-perfusion injury(MIRI),and to explore its mechanism.METHODS:Thirty SPF male SD rats were divided into 5 groups:sham group,MIRI group,low-dose Hyp(L-Hyp)group(MIRI+L-Hyp group),high-dose Hyp(H-Hyp)group(MIRI+H-Hyp group),and positive control trimetazidine(TMZ)group(MIRI+TMZ group),with 6 rats in each group.Apart from the sham group,the MIRI model was established by ligating the anterior descending branch of the left coronary artery and then recanalizing it in the remaining four groups of rats.The success of the modeling was determined by monitor-ing the electrocardiogram.We assessed the cardiac function in rats using echocardiography.TTC staining was employed to measure the area of myocardial infarction in rats,and HE staining was utilized to observe the morphological traits of rat myocardium.We assayed the activities of lactate dehydrogenase(LDH)and superoxide dismutase(SOD)and the levels of malondialdehyde(MDA)in rat serum using biochemical kits.ELISA kits were applied to assess the contents of cardiac troponin I(cTnI)and reactive oxygen species(ROS)in rat serum.Western blot analysis was perfomed to measure the pro-tein expression levels of AMPK,p-AMPK,Nrf2,and HO-1 in rat myocardial tissues.RESULTS:The rats in MIRI group exhibited increased myocardial tissue injury,larger myocardial infarction areas,decreased left ventricular ejection fraction(LVEF),and reduced left ventricular fractional shortening(LVFS)compared with sham group,as shown by echo-cardiography.Additionally,there were increases in LDH activity,cTnI,MDA and ROS levels,along with significant de-creases in SOD activity,and p-AMPK,Nrf2 and HO-1 protein levels(P<0.05).Compared with MIRI group,the rats in MIRI+L-Hyp,MIRI+H-Hyp and MIRI+TMZ groups showed decreased myocardial histopathological damage and reduced myocardial tissue infarction area,increased LVEF and LVFS,and lowered serum levels of LDH activity,cTnI,MDA and ROS,while SOD activity,p-AMPK,Nrf2 and HO-1 protein levels were elevated(P<0.05).CONCLUSION:Hypericin attenuates myocardial ischemia-reperfusion injury in rats,possibly by modulating the AMPK/Nrf2/HO-1 signaling path-way.

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

Child ; Family ; Humans ; Neuroectodermal Tumors, Primitive/pathology* ; Neuroectodermal Tumors, Primitive, Peripheral/pathology* ; Oropharynx

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.
Acute-On-Chronic Liver Failure ; Humans ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.
Animals ; Diabetes Mellitus ; Diabetic Nephropathies/drug therapy* ; Drugs, Chinese Herbal ; Insulin Resistance ; Podocytes ; Pyroptosis ; Rats

Objective To explore the dosimetric differences of radiotherapy plan for cervical cancer with 4 different fluence smoothing (FS) parameters using Monaco treatment planning system (Monaco TPS). Methods Fifteen patients with ⅠB2 stage cervical cancer in our hospital were enrolled in this study. And a 2 Volumetric Modulated Arc Therapy (VMAT) plan for each patient were completed by Monaco 5.11 TPS according to the X-Ray Voxel Monte Carlo (XVMC) method. For each plan was optimized by FS function, with the level of Off, Low, Medium and High. To compare the difference of plan optimization time, conformity index (CI), Homogeneity index (HI), D_mean, D_min, D_2% of PTV，dose to the organ at risk (OAR)，the number of Segments# and MU#，estimated total delivery time (ETDT), quantum Efficiency (QE) of the plans, the formation of Segments# with the same angle and verification of inserting 729 two-dimensional matrix into PTW octavius 4D module of different FS function levels, with the precondition of the Prescription isodose curve covering 95% of the target area. The data was analysed by multivariate factor analysis with the application of SPSS, and P < 0.05 was considered as statistically significant. And the Planned revenue score of different FS levels was also calculated. Results Except for the D_min of PTV (the lowest value is (32.09 ± 0.26) Gy for the Off group, and the highest value is (35.98 ± 0.42) Gy for the High group), V₄₀ of the rectum (the lowest value in the Medium group is 55.88% ± 2.02%, and the highest value in the High group was 61.90% ± 2.98%) and bladder (the lowest value was 45.01% ± 2.08% in the Medium group, and the highest value is 50.45% ± 1.98% in the High group), the V₂₀ (the lowest value High group was 49.05% ± 1.98%, the highest value Off group was 56.52% ± 1.75%) of femoral head (P < 0.05), there was no significant difference of the dose assessment results for PTV and OARs in 4 different FS function levels. In the High level, the ETDT, QE and MU# were showed better than other groups evidently, however, the number of Segments# showed no significant difference. The plan validation results was increased with the improvement of FS function level, and the level of High was considered to be the optimal. To compare the score of overall benefits of the plan, the level of Medium (−17.18 ± 0.05) got the highest score, and the Low group (−17.58 ± 0.05) and the High group (−17.42 ± 0.06) have similar scores, and Off group (−18.81 ± 0.08) has the lowest score. Conclusion Different FS levels of the Monaco 5.11 TPS can optimize the radiotherapy plan for cervical cancer, but the level of Medium is considered to be the most applicable.

Objective:To investigate the pharmacodynamics effects of antiobesity, lipid-lowering and the regulations of serum bile acid profiles of Lidan Ruanjian prescription (LDRJ) in obesity rats induced by high-fat diet. Method:The 42 rats were fed high-fat diet for 9 weeks to establish model of obese rats，24 rats were randomly divided into model group, high and low-dose LDRJ group (30,15 g·kg^-1). Another 8 normal rats were selected as the normal group.The model group and normal group were given normal saline, and drug group was given the corresponding dose of drug for 4 weeks. Body weight, liver weight, white adipose tissue (WAT) weight were determined after administration medicine for 4 weeks. The bile flow of the rats was measured by bile duct intubation and fasting serum lipid levels of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were detected by automatic biochemical analyzer. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was used to test serum bile acid profile of each group rats. Result:Compared with the control group, the average body weight, liver weight, WAT weight of the model group were significantly increased (P<0.01), while the fasting serum TC, TG and LDL-C levels were elevated (P<0.05，P<0.01). The total bile secretion and bile flow at each test point within 2 h were decreased and the proportion of primary bile acids was decreased (P<0.05).The serum total bile acid content decreased significantly（P<0.01），levels of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), taurohyodeoxycholic acid (THDCA) and glycodeoxycholic acid (GDCA) were significantly reduced (P<0.05，P<0.01). Compare with model group, body weight, liver weight in high and low-dose LDRJ groups reduced significantly(P<0.05，P<0.01). Fasting serum TC, TG and LDL-C levels were decreased in high-dose group(P<0.05，P<0.01), so did as TG levels in low-dose group(P<0.05). The bile flow rate increased significantly in high-dose group 1~1.5 h after administration (P<0.05). All dose treatment groups increased the proportion of primary bile acids (P<0.05) and changed the bile acid profile, especially elevated the bile acid levels of TCA, DCA, glycocholic acid (GCA), GDCA in high-dose LDRJ group (P<0.05，P<0.01), while TCA and TCDCA in low-dose group (P<0.05). Conclusion:LDRJ has significant lipid-lowering and antiobesity effects and the mechanism might involve the increase of bile secretion, the stimulation of primary bile acid synthesis and the regulation of bile acid profile.