To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.

Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Diseases ; drug therapy

Objective Study the diagnostic value of CT to assess the transfer of right recurrent nerve nodes(RRNN) on the thoracic esophageal squamous carcinoma,so as to provide reference for thoracic segment esophageal surgery way.Methods A retrospective analysis from January 2011 to February 2014 in the first affiliated hospital of zhengzhou university at the records of 132 cases of thoracic segment esophageal thoracic surgery with preoperative CT image data,recorded each patient's right recurrent nerve nodes in the largest length to diameter and the average CT number,and compared with postoperative pathologic results.Results With the ROC curve analysis,considering transfer when the length of RRNN' s diameter 8.5 mm or more in CT,the area under the curve is 0.911,the sensitivity is 85.7％,specificity is 78.8％.Considering transfer when the RRNN average CT number acuity 32.50 HU,the area under the curve is 0.815,the sensitivity is 85.7％,specificity is 76.9％.Whether RRNN transfer has significant correlation(P ＜ 0.05) with the length of tumor,tumor location and whether lymph node of other station transfer,doesn' t have significant correlation (P ＞ 0.05)with patients'age,sex,tumor differentiation degree and the T stage.Conclusion When the RRNN length to diameter 8.5 mm or RRNN average CT numberr acuity 32.50 HU,right recurrent nerve nodes should be considered lymph node metastasis,and choose chest conclusion laparoscopic radical prostatectomy.The upper thoracic portion esophageal tumor's length is 5 cm or more,or clinical suspected lymph node metastasis of other station is the risk factor for metastasis of RRNN.

OBJECTIVETo study the correlation between TCM syndrome type and liver tissue pathological changes in patients with chronic hepatitis B (CHB) in order to provide evidence for syndrome differentiation.

METHODSSyndrome typing as well as liver pathological grading and staging of liver biopsy were performed on 260 patients with CHB, then the relationship between them was analyzed.

RESULTS(1) The grade of liver inflammation was mainly G1 and G2 in patients of Gan-qi stagnation and Pi-deficiency type (type 1); G2 in patients of inner damp-heat retention type (type II); G3 in patients of Gan-Shen yin-deficiency type (type lII) and Pi-Shen yang-deficiency type (type IV); while G4 occurred mainly in patients of blood stasis blocking collateral type (type V), showing significant difference as compared with other syndrome types. (2) The liver pathological stage in patients of type I and II was mainly S1 and S2, while S3 and S4 occurred mainly in patients of type III and type IV. (3) The pathological change was mainly G3-G4 and S3-S4 in blood stasis syndrome, while it was mainly G1-G2 and S1-S2 in non-blood stasis syndrome.

CONCLUSIONThe TCM syndrome type is correlated with liver tissue pathological change to certain extent, among them, syndrome with or without blood stasis showed the closest correlation. The syndrome type of CHB patients developed, along with the aggravating of liver pathological injury, from sthenia to asthenia, from qi to blood, and finally to the blood stasis blocking collateral. So the treatment should be lay stress on activating blood circulation to remove stasis, and be implemented by 3 stages.

Adult ; Diagnosis, Differential ; Female ; Hepatitis B, Chronic ; diagnosis ; pathology ; Humans ; Liver ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Syndrome ; Yang Deficiency ; pathology ; Yin Deficiency ; pathology ; Young Adult

Objective To investigate the sensitizing effects and the mechanisms of selective cyclooxygenase-2(COX-2)inhibitor celecoxib on radiotherapy of pancreatic cancer.Methods Radiosen- sitization of celecoxib in pancreatic cancer cell SW1990 in vivo and in vitro were investigated by colony forming assay and xenograft tumor model.Expressions of proliferating cell nuclear antigen(PCNA)and Cyelin D1 were assessed by Western Blot.Effect on apoptosis was studied by TUNEL.Expression of bcl-2 and bax was assayed by RT-PCR.Expression and secretion of matrix metalloproteinases(MMPs) and tissue inhibitors of metalloproteinases(TIMPs)were assessed by RT-PCR and zymography.Results Celecoxib enhanced the effect of radiotherapy on pancreatic cancer in vitro and in vivo.TUNEL demonstrated a significant increase of apoptotic cells in vitro after treatment with celecoxib alone or com bined with radiation,but no change after radiation.Expression of bcl-2 was decreased by celecoxib;radi- ation induced the expression of bcl-2;combination of celecoxib and radiation significantly suppressed the expression of bcl-2.In vitro,angiogenesis and cell invasion potential of pancreatic cancer cells were in- hibited by celecoxib,and celecoxib combined with radiation,but without significant change in radiation group compared with the control group.Expression and secretion of MMP-2 and MMP-9 were closely related to the changes in angiogenesis and cell invasion potential,while the expressions of TIMP-1 and TIMP-2 did not alter significantly in all groups.Conclusions The selective eyclooxygenase 2 inhibitor celecoxib potently enhances the effect of radiation on the treatment of pancreatic cancer. Induction of apoptosis,inhibition of angiogenesis and invasion are involved in the mechanism of cele- coxib treatment.

Objective To summarize the placement, maintenance, and safety of a high-pressure resistant peripherally inserted central catheter. Methods Ten patients were peripherally placed with this catheter (included 4Fr-single lumen, 5Fr-dual lumen, and 6Fr-three lumen) using ultrasound-guided Seldinger technique in Peking Union Medical College Hospital in August 2010. The therapeutic effectiveness and safety were evaluated. Result Ten catheters were inserted successfully into the upper arms, with few complications noted during routine maintenance. Conclusions This peripherally inserted central catheter can be used for high-pressure injection, central venous pressure monitoring, and fast flow-speed transfusion. Therefore, it can be successfully applied for contrast-enhanced CT angiography and massive fluid infusion.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.
Administration, Intranasal ; Animals ; Area Under Curve ; Chromatography, Liquid ; Drug Carriers ; Drug Compounding ; Liposomes ; Male ; Neuroprotective Agents ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Particle Size ; Phenylcarbamates ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Rivastigmine ; Tandem Mass Spectrometry

Objective To evaluate the accuracy and clinical application of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) in diagnosis of occupying lesions in upper digestive tract and its pe-ripheral areas. Methods The data of 64 patients who underwent EUS-FNA for occupying lesions in upper di-gestive tract, between July 2006 and December 2007, were retrospectively analyzed. Results EUS-FNA was successfully performed on 62 patients, with a success rate of 96.88%. The overall diagnostic accuracy, sensi-tivity, specificity, positive predictive value and negative predictive value of EUS-FNA for occupying lesions in upper digestive tract and its peripheral areas were 88.71%, 86.54%, 100.00%, 100.00%, and 58.82%, respectively. There was no significant difference between the foei larger and smaller than 3cm (P > 0.05), re-garding the diagnostic accuracy and average puncture numbers. Diagnostic accuracy of those with real-time cy-tolngical evaluation was significantly higher than those without (P=0.029), and the puncture numbers were less (P=0.001). Among the total 99 punctures, the positive diagnostic accuracy of those with 5ml negative pressure suction was significantly higher than those of 10 ml (P = 0.044). Conclusion EUS-FNA is a safe and applicable approach to diagnosis of occupying lesions in upper digestive tract and its peripheral areas with higher diagnostic accuracy, sensitivity, specificity and positive predictive value. Moreover, the real-time cyto-logical evaluation and adequate negative pressure might facilitate the diagnosis accuracy.

Objective To construct a technical platform for scarless gene modification of Yersinia pestis and to study the functions of its specific genes.Methods The resistance fragment, including upstream and downstream homologous arms of targeted regions, was reamplified by asymmetric PCR.The amplicons were introduced into Y.pestis harboring plasmid pKD46.With the induction of L-arabinose,the recombinant related enzymes: Exo, Beta and Gam, were expressed to guide the homologous recombination.A donor plasmid, pKSI-1, which carried the desired modification fragment flanking by I-SceⅠ recognition sites, was introduced into Y.pestis as the second step of λ-Red recombination with the help of pREDTKI.Results and Conclusion Two mutant strains:△waaA and waaA(△9nt), were successfully constructed for Y.pestis strain 201.Scarless modification introduces no extra modification to the genome, and it is ideal for comprehensive functional genomic studies.