HLA-A * 0201, HLA-A * 1101, and HLA-A * 2401 CTL restricted epitopes of platelet membrane glycoprotein II b/III a antibody of human and mice were predicted by use of SYFPEITHI, RANKPEP, BIMAS, SVMHC, PREDEP, MHCPRED, and PROPRED predictive programs. In the results, the peptides (found in HLAPRED) that can lead to autoimmune disease and have been published were removed; and the epitopes of HLA-A * 0201 must cover the epitopes of HLA-A * 1101 and HLA-A * 2401 being combined to predTAP and TAPPred for predicting the binding affinity of peptides toward the TAP transporter and NetChop, MAPPP, PAProc for predicting cleavages; HLA-DR Th restricted epitopes of GPII b/III a antibody were predicted by SYFPEITHI, RANKPEP, MHCPRED, and HLAPRED, after removal of the peptides (found in HLAPRED) that can lead to autoimmune disease and have been published, the Th epitopes must cover the CTL mixed epitopes as being stated above. The secondary structure, hydrophobic regions, flexibility, surface probability and the B cell epitope were predicted by using various methods. Ten mixed peptides of T cell epitopes were selected from more than 1 740 peptides. They were located at the aa9-115, aa24-38, aa50-64, aa65-81, aa109-121 of anti-GP II b/III a-Human and the aal-15, aa26-40, aa46-60, aa68-82, aa93-107 of anti-GP II b/III a-Mice. B cell epitopes of anti-GP II b/III a-Human might locate at aa5-9, aa22-30, aa40-46, aa55-71, aa80-90, aa100-105, aa110-115; and the epitopes of anti-GP II b/III a-Human might locate at aa5-10, aa38-43, aa58-70, aa77-84, and aa99-105.
Animals ; Antibodies ; immunology ; Epitopes, B-Lymphocyte ; immunology ; Epitopes, T-Lymphocyte ; immunology ; Humans ; Mice ; Platelet Glycoprotein GPIIb-IIIa Complex ; immunology ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Vaccines ; immunology

Objective: To study the inhibition effect of siRNA on the expression of Wisp-1 gene in Hca-F of mouse hepatocellular carcinoma cells strain and also its effect on the proliferation, migration and adhesion of hepatocellular carcinoma cells. Methods: Three expression vectors of siRNA were constructed. Lipo2000 was employed to transfect Hca-F cells and Western blot was used to detect the inhibition effect of siRNA on the expression of Wisp-1 gene. Afterward, CCK8 was adopted to detect the effect of Wisp-1 siRNA on the proliferation of Hca-F cells; Annexin V-FITC/PI double staining flow cytometry was used to detect the effect of Wisp-1 siRNA on the apoptosis of Hca-F cells; Transwell was used to detect the effect of Wisp-1 siRNA on the migration of Hca-F cells. The in vitro cell adhesion kit was used to detect of Wisp-1 siRNA on the change in the components of extracellular matrix to which Hca-F cells adhered. Western blot was used to detect the activation of protein kinase B (AKT)/glycogen synthase kinase-3β pathway and the expression of downstream target protein p53 and matrix metalloproteinases-2. Results: The siRNA showed interference effect on the expression of Wisp-1 gene. Compared with the control group, after being transfected to cells, Wisp-1 siRNA could significantly inhibit the proliferation, migration and adhesion of Hca-F cells and also promote the cell apoptosis, which was related to the down-regulated phosphorylation of AKT and glycogen synthase kinase-3β and the expression of p53 and matrix metalloproteinases-2 (P < 0.05). Conclusions: The inhibition of Wisp-1 expression can reduce the proliferation, migration and adhesion of mouse hepatocellular carcinoma cells, which is related to the AKT/glycogen synthase kinase-3β pathway. Wisp-1 gene may be the potential target to cure the hepatocellular carcinoma.

【Objective】 To explore the effect of nifedipine controlled-release tablets on left wrist pulse wave transit time (PWTT) in hypertensive patients. 【Methods】 We selected 262 essential hypertensive patients hospitalized at Chinese PLA General Hospital Hainan Branch from August 2021 to December 2022. The patients were divided into observation group (n=140) and control group (n=122) according to whether or not taking nifedipine controlled release tables. The left wrist PWTT at 0.5 h, 2.5 h, 4.5 h, 6.5 h and 8.5 h after administration of the medicine was collected with a smart watch for statistical analysis. 【Results】 ①The PWTT in the observation group (93±15, 93±13, 87±15, 85±15, 84±10) and the control group (98±18, 92±16, 90±10, 89±8, 89±9) decreased gradually with the extension of time (F=11.448, P<0.001). ②The PWTT decreased by the same amplitude (F=2.206, P>0.05). ③There was no significant difference in PWTT between the observation group and the control group at five time points (F=1.164, P>0.05). 【Conclusion】 Administration of nifedipine controlled-release tablets does not affect PWTT of primary hypertensive patients’ left wrist.

ObjectiveIn this study， based on ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS） and high-throughput transcriptome sequencing technology（RNA-seq）， we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid（mRNA） expression to improve diabetic kidney disease（DKD）. MethodSD rats were randomly divided into normal group ， model group and Yishen Huashi granules group， with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg^-1·d^-1 of Yishen Huashi granules by gavage， and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment， the body weight and blood glucose of rats were monitored， and the rats were anesthetized 24 hours after the last administration， blood was collected from the inferior vena cava， serum was separated， and renal function， blood lipid， and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde， and stained with hematoxylin-eosin（HE）， Masson and periodic acid-Schiff（PAS） to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression， and real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group， rats in the model group showed a decrease in body weight， a significant increase in blood glucose， urinary microalbumin to urinary creatinine ratio（UACR）， blood urea nitrogen（BUN）， cystatin-C（Cys-C）， β₂-microglobulin（β₂-MG）， interleukin-6（IL-6）， triglyceride（TG） and total cholesterol（TC）， and a significant decrease in total superoxide dismutase（T-SOD）（P<0.01）. After the intervention of Yishen Huashi granules， all the indexes were improved to different degrees in rats（P<0.05， P<0.01）. Compared with the normal group， the model group showed renal mesangial stromal hyperplasia， fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group， the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified， the target metabolites were mainly enriched in 20 metabolic pathways， including sphingolipid metabolism， glycerophospholipid metabolism， and the biosynthesis of phenylalanine， tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways， glycerophospholipid metabolism， arachidonic acid metabolism， purine metabolism， primary bile acid biosynthesis， ascorbic acid and uronic acid metabolism， and galactose metabolism， were enriched by serum differential metabolites and renal differential mRNAs， among them， there were 7 differential metabolites such as phosphatidylethanolamine（PE） and 7 differential mRNAs such as recombinant adenylate cyclase 3（ADCY3）. Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic（ROC） curve， and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR， BUN and other biochemical indexes， correct the disorder of glucose and lipid metabolism， and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites， and expression of Phospho1 and other mRNAs in the kidney， of which six pathways， including glycerophospholipid metabolism， may play an important role.

Background:Portal-vein stent combined with one iodine-125 (I) seed strand has become a new treatment for portal vein tumor thrombosis. However, dosimetric aspects of this irradiation stent have not been reported. Therefore, we aimed to undertake dosimetric analyses comparing portal-vein stents combined with different numbers ofI seed strands.

Methods:A water cylinder was created by a treatment-planning system to simulate a portal-vein stent. The stent was combined with one, two, or threeI seed strands (Groups I, II, and III, respectively). At different prescribed doses (PDs),I seeds of identical activities were loaded on Groups I-III. Conformation number (CN), external volume index, and homogeneity index were calculated. Linear regression analyses were used to evaluate the obtained data.

Results:For identicalI seed activity, when theI seed strand increased from one chain to two, D(dose delivered to 90% of the target volume) increased by ≥184%; when it increased from two chains to three, Dincreased by ≥63%. When the PD was 105 Gy andI seed strands increased from one chain to two, V(percentage of the target volume receiving ≥90% of the PD) increased by 158-249%; when it increased from two chains to three, Vincreased by 7-175%. CN was correlated positively withI seed activity (B = 0.479, P < 0.001) and number ofI seed strands (B = 0.201, P < 0.001) and was independent of PD (B = -0.002, P = 0.078).

Conclusions:A portal-vein stent combined with a singleI seed strand could not meet dosimetry requirements. For a stent combined with twoI seed strands, when the PD was 105 Gy and seed activity was 0.7 mCi, the dose distribution could satisfy dosimetry requirements. For a stent combined with threeI seed strands, if the PD was 105, 125, or 145 Gy, the recommended seed activities were 0.5, 0.5, and 0.6 mCi, respectively.

Renal fibrosis， the final pathological outcome of end-stage chronic kidney diseases， is associated with inflammation， oxidative stress， epithelial-mesenchymal transdifferentiation （EMT）， and extracellular matrix deposition. It belongs to the categories of edema， ischuria， anuria and vomiting， and consumptive disease in traditional Chinese medicine （TCM）， with the key pathogenesis of Qi deficiency and blood stasis and the primary treatment principle of replenishing Qi and activating blood. Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma mainly contains astragalosides， polysaccharides， calycosin， salvianolic acid， and tanshinone， with the effect of tonifying Qi and activating blood. Studies have shown that this herb pair and its active components can delay the progress of renal fibrosis by regulating multiple signaling pathways. With consideration to the pathogenesis of Qi deficiency and blood stasis， this article reviews the research progress in the mitigation of renal fibrosis by Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma from the aspects of protecting glomerular filtration barrier， inhibiting EMT and mesangial cell proliferation， improving renal hemodynamics， and protecting renal function. Furthermore， the mechanisms were summarized. Specifically， Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and its effective components can improve mitochondrial function and fatty acid metabolism， alleviate endoplasmic reticulum stress and autophagy disorders， and inhibit immune inflammation and oxidative stress by regulating nuclear factor E₂-related factor 2 （Nrf2）/PTEN-induced kinase 1 （Pink1）， Nrf2/antioxidant response element （ARE）， tumor necrosis factor-α （TNF-α）/nuclear transcription factor-κB （NF-κB）， miR-21/Smad7/transforming growth factor beta （TGF-β）， Wnt/β-catenin， long non-coding RNA-taurine up-regulated gene 1 （lncRNA-TUG1）/tumor necrosis factor receptor-associated factor 5 （TRAF5）， Ras-related C3 botulinum toxin substrate 1 （Rac1）/cell division cycle protein 42 （CDC42）， Ras homolog （Rho）/Rho-associated coiled-coil containing protein kinase （ROCK）， phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， peroxisome proliferator-activated receptor α （PPARα）/peroxisome proliferator-activated receptor γ coactivator l alpha （PGC-1α）， and p38 mitogen-activated protein kinase （p38 MAPK）. This review aims to provide references for the relevant research， give play to the role of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma， and provide guidance for the clinical treatment of renal fibrosis.

AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis (TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion (SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds (jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids (borneol or camphor) was higher than by the monocyclic monoterpenes (menthol or menthone), and promotion by compounds with a hydroxyl group (borneol or menthol) was higher than those with a carbonyl group (camphor or menthone). The apparent permeability coefficient (Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant (Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein (P-gp) and organic cation transporters (OCT), rather than multidrug resistance protein (MRP) and breast cancer resistance protein (BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.
Alkaloids ; chemistry ; pharmacokinetics ; Animals ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Intestinal Absorption ; Intestinal Mucosa ; metabolism ; Intestines ; chemistry ; Kinetics ; Mahonia ; metabolism ; Male ; Permeability ; Rats ; Rats, Sprague-Dawley

Amputation ; Animals ; Atrial Appendage/surgery* ; Atrial Fibrillation ; Dogs ; Echocardiography, Transesophageal ; Stroke ; Surgical Instruments