Objective To observe effects of ganoderma lucidum triterpenoids(GLT) on learning and memory function and anti-oxidative ability of aging model mice induced by D-galactose. Methods Senile model mice were established by D-galactose hypodermic injection for 8 weeks.GLT had been administered to two therapy groups.All the mice of different groups were tested with Morris water maze.Then the mice were killed and biochemically assayed of total anti-oxidative capacity(T-AOC),superoxide dismutase(SOD) and malondialdehyde(MDA) in the brain. Results The model mice showed worse ability in learning and memory in comparison with control mice.The T-AOC activity and SOD activity in the brain decreased and the MDA content increased in model rats in comparison with control.GLT significantly improved the changes mentioned above. Conclusion GLT improved the learning and memory dysfunction in aging model mice by modulation of the anti-oxidative ability.

Tangcao pill is commonly applied in adjuvant and even alternative therapy for patients with AIDS. However, the herb contains complex ingredients, but with unknown effect against anti-HIV drug and unknown function. Because CYP450 emzyme is the main metabolic enzymes of the drug, it is of important significance to study the regulation of CYP450 enzymes before and after the combined administration of Tangcao pill and EFV. Proteomics, due to its high throughout and high sensitivity, has been widely applied in CYP450 enzyme study. In this paper, liver microsomes were separated through differential centrifugation. Their proteins were separated through SDS-PAGE. The three protein bands that CYP450 enzymes were located were cut and identified by liquid chromatography tandem mass spectrometry. Totally 16 CYP450 isoenzymes were identified. Furthermore, in order to make a quantitative analysis on the effect of tang herb on CYP450 emzyme, the multiple reaction monitoring (MRM) technology based on MS was adopted. The CYP2C11 was selected based on the results of the mass spectrum identification of proteins. The characteristic polypeptides were obtained through searching Expasy blast database. The m/z of the fragment ions was less than 800. In the paper, the m/z of ion pairs of CYP2C11 were 711.5/232.1, 711.5/319.2, 711.5/466.2 and 711.5/595.3, and the m/z of ESAT-6 (internal standard, IS) were 735.5/215.3, 735.5/389.3, 735.5/460.3 and 735.5/524.3. The relative peak (analyte/IS) area was adopted for the relative quantitative analysis. Compared with the EFV single administration group, the EFV and Tangcao pill combined administration group showed a 1.6-fold increase in CYP2C11. The results of the paper indicated that Tangcao pill may affect drug metabolism by regulating metabolic enzymes such as CYP2C11, but the specific mechanism still unknown.
Animals ; Cytochrome P-450 Enzyme System ; chemistry ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Electrophoresis, Polyacrylamide Gel ; Male ; Microsomes, Liver ; chemistry ; drug effects ; enzymology ; Proteomics ; Rats ; Rats, Sprague-Dawley

Abstract: Objective To investigate the influence of the variation of SARS-CoV-2 on the clinical feature, and to provide early warning signs for the variation of SARS-CoV-2 in clinical work. Methods From Jan 2, 2021 to Jun 30, 2021, a total of 105 COVID-19 patients were included in the study using a case-control method. Nasal swab samples were collected from the study subjects, the viral genes were sequenced, and patients were divided into Delta variant group and non-Delta variant group according to their gene sequences. Clinically relevant data were collected from the two groups, and indicators such as days of hospitalization, age distribution, lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, and IL-10 were compared; subgroup analysis was performed based on the number of days of viral negativity in the study subjects as the basis for grouping, and differences in immunological characteristics were compared, including lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, IL-10, etc. Results The theoretical hospitalization days of Delta variant group were (22.2±8.33) d, which were significantly longer than (17.6±10.50) d of non-Delta variant group (t=2.396, P<0.05). The total lymphocyte count and IL-4 of Delta variant group were (1.22±0.86) ×109/L and (0.80±0.23) ng/mL, which were significantly lower than corresponding (1.91±0.70) ×109/L and (1.59±0.59) ng/mL of non-Delta variant group (t=4.329, 9.072, P<0.05), while IL-10 was (7.16±7.77) ng/mL, which was significantly higher than (4.26±3.91) ng/mL of non-Delta mutation group (t=1.980, P<0.05). Subgroup analysis showed that the total lymphocyte count and IL-4 concentration in Delta variant group were (1.04±0.60) ×109/L and (0.74±0.25) ng/ml, which were significantly lower than corresponding (1.62±0.56) ×109/L and (1.56±0.52) ng/mL in non-Delta variant group, in patients with delayed discharge (P<0.05). Conclutions SARS-CoV-2 variant has an impact on clinical manifestations. The patient's B cell count and IL-10 concentration increased or IL-2 and IL-4 concentration decreased within 12 hours of admission indicated variant virus infection. The decrease of total lymphocyte count, especially T lymphocyte reduction, strongly suggests discharge delay due to viral clearance disorder.

Objective To know the microcystins pollution caused by cyanobactcria bloom in two drinking water sources in Ningbo city.Methods Water samples were collected at four sampling sites in Yaojiang River and three sampling sites in Miehu reservoir from 20 July,2007 to 31 August,2007.The algae in these water samples were classified and counted,and Microcystin-LR (MC-LR),MC-RR were determined by UPLC-MS-MS.Results The Cyanobacteria cell concentration in Yaojiang River and Meihu reservoir ranged from 0.8?10~6 to 6.7?10~7,and from 1.21?10~7 to 9.928?10~8 cells/L respectively.The MC-LR and MC-RR in Yaojiang River weren't detected,and neither was the MC-RR in MeiHu reservoir.However,the MC-LR was detected at sometimes,and the maximum concentration of MC-LR was 0.84?g/L.Conclusion There is no microcystins pollution in Yaojiang River,but there existed MC-LR pollution in MeiHu Reservoir,and the MC-LR concentration in it was below national standard limit of 1.0?g/L after the treatment of controlling alage and microsystins.

This study is to prepare the W/O microemulsion containing NaCl and fluorouracil (5-Fu) as a model drug to investigate the transdermal characteristics and skin irritation of the microemulsion in vitro. Isopropylmyristate (IPM) acting as oil phase, Aerosol-OT (AOT) as surfactant, Tween 85 as cosurfactant, NaCl solution was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, and then 5-Fu powder was added. According to the area of microemulsion based on the pseudo-tertiary phase diagrams, the optimum formulation was screened initially. And the permeation flux of fluorouracil across excised mice skin was determined in vitro using Franz diffusion cells to study the influence of the amount of water and the drug loading capacity and optimize the formulation further. Refer to 5-Fu cream, the irritation of microemulsion on the rat skin was studied. The optimum formulation was composed of 0.7% (w/v) 5-Fu, 50% NaCl solution (0.05 mol x L(-1)), 20% mix-surfactant (AOT/Tween 85, K(m) = 2) and 29.3% oil (IPM). The cumulative amount of fluorouracil permeated in 12 h was (2 013.4 +/- 41.6) microg x cm(-2), 20.23 folds and 10.38 folds more than 0.7% fluorouracil aqueous solution and 2.5% (w/w) fluorouracil cream, respectively. Microemulsion exhibited some irritation, but could be reversed after drug withdrawal. The addition of NaCl significantly increased the content of water and the drug loading in microemulsion systems. The NaCl/AOT-Tween 85/IPM microemulsion system promoted the permeation of fluorouracil greatly, which may be a promising vehicle for the transdermal delivery of fluorouracil and other hydrophilic drug.
Administration, Cutaneous ; Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; pharmacokinetics ; Dioctyl Sulfosuccinic Acid ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Emulsions ; Exanthema ; chemically induced ; Fluorouracil ; administration & dosage ; adverse effects ; pharmacokinetics ; In Vitro Techniques ; Male ; Mice ; Myristates ; chemistry ; Oils ; chemistry ; Polysorbates ; chemistry ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; Sodium Chloride ; chemistry ; Surface-Active Agents ; chemistry ; Water

This study is to prepare the microemulsion-based gel based on the W/O microemulsion and fluorouracil (5-Fu) as a model drug to study the transdermal characterization and observe its skin irritation of the microemulsion-based gel in vitro. IPM acted as oil phase, AOT as surfactant, Tween 85 as cosurfactant, water was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, then 5-Fu powder was added. The gelatin was used as substrate to prepare 5-Fu microemulsion-based gel. The permeation flux of 5-Fu from 5-Fu microemulsion-based gel across excised mice skin was determined in vitro using Franz diffusion cell to study the influence of the amount of gelatin and the drug loading capacity. Refer to 5-Fu cream, the irritation of microemulsion and microemulsion-based gel on the rat skin was studied. Based on the water/AOT/Tween 85/IPM microemulsion, only the gelatin can form the microemulsion-based gel. At 25 degrees C, 32 degrees C and 40 degrees C, the amount of gelatin required for the formation of microemulsion-based gel were 7%, 14% and more than 17%, respectively. The 12 h transdermal cumulated permeation amount of 5-Fu from microemulsion-based gel containing 14% gelatin and 0.5% drug loading were (876.5 +/- 29.1) microg x cm(-2), 12.3 folds and 4.5 folds more than 0.5% 5-Fu aqueous solution and 2.5% (w/w) 5-Fu cream, respectively. Microemulsion-based gel exhibited some irritation, but could be subsided after drug withdrawal. Microemulsion-based gel may be a promising vehicle for transdermal delivery of 5-Fu and other hydrophilic drug.
Administration, Cutaneous ; Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; pharmacokinetics ; Dioctyl Sulfosuccinic Acid ; Drug Carriers ; Drug Delivery Systems ; Emulsions ; Exanthema ; chemically induced ; Fluorouracil ; administration & dosage ; adverse effects ; pharmacokinetics ; Gelatin ; chemistry ; Male ; Mice ; Myristates ; chemistry ; Polysorbates ; chemistry ; Skin ; pathology ; Skin Absorption ; Succinates ; chemistry ; Surface-Active Agents ; Viscosity

AIMTo prepare silybin-phospholipid complex and study its physicochemical properties. To compare the pharmacokinetic characteristics and bioavailability after oral administration of silybinphospholipid complex and silybin material in rats.

METHODSUsing acetone as a reaction medium, silybin and phospholipid were resolved into the medium, when the organic solvent was clear, then removed under vacuum evaporation, silybin-phospholipid complex was obtained. The new complex' s physicochemical properties including DSC, UV, IR were determined. The concentrations of non-conjugated and total silybin after oral administration of silybin-phospholipid complex and silybin material at different time in rats were determined by RP-HPLC. The pharmacokinetic parameters were computed by software program 3P97.

RESULTSExperiment results showed that silybin and phospholipid in the silybin-phospholipid complex were combined by non-covalent-bond, not forming a new compound and the solubility of silybin-phospholipid complex in water and n-octanol was effectively enhanced. It was found that mean plasma concentration-time curve of silybin after oral administration of silybin-phospholipid complex in rats was in accordance with one-compartment model with first-order absorption. Pharmacokinetic parameters of non-conjugated and total silybin in rats were respectively T(max) 10 min and 2 h; C(max) 0.11 and 1.08 microg x mL(-1); T1/2 2.18 and 3.84 h; AUC(0-infinity) 1.71 and 12.94 microg x mL(-1) x h. However, after oral administration of silybin material, plasma levels of both non-conjugated and total silybin were within the analytical detection limit.

CONCLUSIONIt was concluded that after oral administration of silybin-phospholipid complex in rats the bioavailability of silybin increased greatly. This was mainly due to an obvious improvement of the lipophilic property of silybin-phospholipid complex compared with silybin material and an increase in gastrointestinal absorption.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Drug Compounding ; Male ; Phospholipids ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Silymarin ; administration & dosage ; blood ; pharmacokinetics ; Solubility

To explore the mechanism of the absorption enhancement of borneol, the effect of borneol on the intestinal absorption and the pharmacokinetics of tetramethylpyrazine phosphate after oral administration were investigated. In situ intestinal recirculation was performed to study the effect of various concentrations of borneol on the absorption of tetramethylpyrazine phosphate at duodenum, jejunum, ileum and colon. After oral administration of tetramethylpyrazine phosphate, the mixture of tetramethylpyrazine phosphate and borneol and the mixture of tetramethylpyrazine phosphate and verapamil in rats, the concentrations of tetramethylpyrazine phosphate in plasma were determined by RP-HPLC at predesigned time. The pharmacokinetic parameters were compared based on the results of the three animal experiments, and analyzed with software program 3p97. The result showed that tetramethylpyrazine phosphate could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: colon > duodenum > jejunum > ileum, but without saturation, which demonstrated that tetramethylpyrazine phosphate was absorbed via simple diffusion. Borneol could enhance the intestinal absorption of tetramethylpyrazine phosphate, however, not in proportion. There was no obvious difference between the test group and the control group when 10 microg x mL(-1) borneol was added (P > 0.05), while when the concentration comes to 25 microg x mL(-1) and 50 microg x mL(-1), significant differences were observed (P < 0.05). Borneol and verapamil did enhance the bioavailability of tetramethylpyrazine phosphate after oral administration in rats. The enhancing effect of borneol showed only when the concentration came to a certain level but with no specific sites existed in the intestine. One of the mechanisms of borneol on the enhancing effect on absorption of tetramethylpyrazine phosphate might be the inhibition of the metabolism of CYP 3A and exocytosis of P-gp.
Animals ; Biological Availability ; Bornanes ; pharmacokinetics ; Herb-Drug Interactions ; Intestinal Absorption ; drug effects ; Male ; Pyrazines ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo summarize the surgical outcome of patients with small cell esophageal carcinoma(SCEC).

METHODSClinical data of patients with esophageal carcinoma were retrospectively collected from March 2000 to March 2011 at the Thoracic Surgery Department of the Peking University Cancer Hospital. Data included tumor characteristics, staging, treatment, response, short-term outcome, and long-term survival.

RESULTSA total of 546 patients with esophageal carcinoma were identified, among whom there were 15 patients with SCEC(2.7%). Fourteen cases received multimodality treatment based on operation and one underwent operation alone. Four patients had preoperative chemotherapy and 10 had postoperative chemotherapy. Four patients had postoperative radiation. After excluding one case of postoperative death within 3 months, the median overall survival was 14.3 months(range, 4 to 99 months), significantly worse than those with non-SCEC(42.2 months, P<0.05).

CONCLUSIONSCEC is rare and the outcomes are poor. It should be considered as a systematic disease.

Adult ; Aged ; Carcinoma, Small Cell ; surgery ; therapy ; Combined Modality Therapy ; Esophageal Neoplasms ; surgery ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome