OBJECTIVETo develop a new method for the determination of cholesteryl palmitate in Oviductus Ranae.

METHODA HPLC method was set up, using Zorbax Silica column and cyclohexane-diethyl ether (40:1) as mobile phase with a flow rate of 1.0 mL x min(-1), and the UV detection wavelength was 203 nm.

RESULTThe calibration curve was linear over the range of 0.60-8.92 microg (r = 0.9997), the average recovery of the method was 98.4%. RSD 1.8% (n = 6).

CONCLUSIONThe results showed that method was reliable and accurate.

Animals ; Cholesterol Esters ; analysis ; Chromatography, High Pressure Liquid ; methods ; Female ; Materia Medica ; analysis ; chemistry ; Oviducts ; chemistry ; Quality Control ; Rana temporaria

AIMTo investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam.

METHODSCYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately.

RESULTSAfter a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001).

CONCLUSIONCYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.

Adult ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C9 ; Genotype ; Glyburide ; pharmacokinetics ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Male ; Piroxicam ; analogs & derivatives ; pharmacokinetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo study the cytotoxic T lymphocyte (CTL) response induced by dendritic cells (DC) transduced with recombinant adenovirus vector bearing hepatitis B virus surface antigen (HBsAg) gene in hepatocellular carcinoma HepG2. 2. 15 cells in vitro.

METHODSFull length HBsAg cDNAs were subcloned into pIND vector, followed by being cloned into pShuttle vector. The HBsAg gene fragments resulted from the pShuttle-S digested with PI-Sce and I-Ceu were linked to the linear adeno-X virus DNA. After packaged with HEK293 cells, the adenovirus expression vector was obtained. Then the recombinant adenovirus expression plasmid AdVHBsAg was transfected into human monocyte-derived dendritic cells, to construct AdVHBsAg hepatocarcinoma tumor vaccine. The effectiveness of transfection was detected by Western blot. Surface molecules of AdVHBsAg-DC were detected by FACS. Autologous T cell proliferation stimulated by AdVHBsAg-DC was detected by 3H-TdR assay. Cytotoxic CTL activity induced by AdVHBsAg-DC in vitro was detected by LDH assay.

RESULTSHBsAg gene in the inserted DNA of AdVHBsAg was confirmed by PCR, and predictive fragments proved by restriction enzyme digestion analysis were exhibited. Cell pathological changes appear after 10 days HEK293 cells transfected AdVHBsAg. Western blot analysis showed that HBV surface antigen gene was expressed in transfected DC, indicating that the transfection was effective. AdVHBsAg-DC was able to upregulate CD1a, CD11c, CD80, CD86 and HLA-DR. Autologus T cell proliferation induced by AdVHBsAg-DCs was significantly higher than that in DC control group and LacZ-DC group (P < 0.05). AdVHBsAg-DC activated CTL presented the specific killer ability to the hepatocellular carcinoma cells expressing HBsAg.

CONCLUSIONDC transduced with recombinant adenovirus HBsAg can express HBV-related hepatocellular carcinoma antigen (HBsAg), and AdVHBsAg-DC can induce potent immune response against HBsAg-positive hepatocellular carcinoma cells in vitro.

Adenoviridae ; genetics ; Antigens, CD1 ; metabolism ; CD11c Antigen ; metabolism ; Cancer Vaccines ; immunology ; Carcinoma, Hepatocellular ; immunology ; pathology ; virology ; Cell Line, Tumor ; Cell Proliferation ; Cytotoxicity, Immunologic ; immunology ; Dendritic Cells ; cytology ; immunology ; metabolism ; Genetic Vectors ; Hepatitis B Surface Antigens ; genetics ; metabolism ; Humans ; Liver Neoplasms ; immunology ; pathology ; virology ; Plasmids ; Recombinant Proteins ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Transfection

OBJECTIVETo perform a Meta-analysis on peginterferon with interferon in treatment of HIV patients coinfected with refractory genotype HCV.

METHODSA literature search of Medline was conducted to identify eligible randomized controlled trials. Meta analysis was conducted to evaluate peginterferon and interferon in treatment of coinfected HCV genotype 1 or 4 in HIV patients.

RESULTSix trials of 88 matched the selection criteria. Total 1,131 patients with coinfection of HCV genotype 1 or 4 and HIV were included. Sustain viral response was higher in patients treated with peginterferon plus ribavirin compared with that of interferon plus ribavirin (26 % compared with 8 %) or peginterferon alone (26 % compared with 13 %). Severe adverse effects and withdrawal rates were similar for patients treated with peginterferon and patients treated with interferon.

CONCLUSIONPeginterferon plus ribavirin in treatment of patients with coinfection of genotype 1 or 4 HCV and HIV can achieve higher sustain viral response and the likelihoods of serious adverse effects and withdrawal rates are similar to other therapies.

Adult ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Female ; Genotype ; HIV Infections ; complications ; drug therapy ; immunology ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; complications ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Polyethylene Glycols ; administration & dosage ; Randomized Controlled Trials as Topic ; Recombinant Proteins ; Ribavirin ; administration & dosage

OBJECTIVETo explore the association between high-sensitivity C-reactive protein (hs-CRP) and contrast-induced nephropathy (CIN) in patients with ST-segment elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) .

METHODSA total of 220 STEMI patients undergoing primary PCI from Guangdong general hospital were recruited. Patients were divided into four groups according to the quartile of hs-CRP (Q1 group:hs-CRP < 6.26 mg/L,Q2 group:6.26-14.44 mg/L, Q3 group:14.45-33.08 mg/L, Q4 group:hs-CRP > 33.08 mg/L) . Baseline data, CIN incidence and other in-hospital outcomes were compared among groups. CIN was defined as an increase in serum creatinine of more than 5 mg/L from baseline within 48-72 hours after contrast media exposure. Receiver operator characteristics (ROC) curves and multivariate logistic regression were used to assessed the correlation between hs-CRP and CIN.

RESULTSCIN occurred in 21 (9.8%) patients. CIN incidence of hs-CRP quartitles were 1.8%(1/55), 1.8% (1/55), 14.5% (8/55) and 20.0% (11/55) (P-trend < 0.01), respectively. In-hospital death (P-trend > 0.05) , required renal replace therapy (P-trend > 0.05) were similar among groups. ROC analysis revealed that the optimal cutoff value of hs-CRP to predict the onset of CIN was 16.85 mg/L (sensitivity: 81.0%, specificity: 61.8%, AUC: 0.748). Univariate logistic analysis showed that hs-CRP was strongly related with CIN incidence (OR = 6.88,95%CI:2.23-21.21, P < 0.01). Multivariate logistic regression analysis showed that after adjusting other traditional risk factors including female gender, anemia, ACEI/ARB use, IABP support, LVEF < 40%, age > 75 years, baseline eGFR and diabetes, hs-CRP > 16.85 mg/L was still a significant independent predictor of CIN in patients with STEMI undergoing primary PCI. Additionally, age > 75 years (OR = 7.27,95%CI:1.85-28.63, P < 0.01), eGFR (OR = 6.38,95% CI:1.48-27.41, P < 0.05) were also independent risk factors of CIN.

CONCLUSIONShs-CRP is positively correlated with CIN incidence. STEMI patients with higher hs-CRP level post PCI is at higher risk of developing CIN.

Aged ; C-Reactive Protein ; metabolism ; Contrast Media ; adverse effects ; Female ; Humans ; Kidney Diseases ; chemically induced ; Logistic Models ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; ROC Curve

OBJECTIVEQuantitative study of the effect of anti-human VEGF mAb E11 to VEGF level in serum of nude mice transplanted buccal carcinoma.

METHODSE11 was administered into BALB/c nu/nu mice which were transplanted human buccal carcinoma. The saline was administrated as negative control. Mice were killed at 18 days. The VEGF level in serum of mice was determined by improved indirect ELISA.

RESULTSCompared with the VEGF level in serum of mice in saline group, it was dramatically decreased in E11 group. The VEGF level in serum of mice treated E11 by subcutaneous was lowest and only reached (1.17 +/- 0.13) microg/L.

CONCLUSIONIt demonstrated that the anti-human VEGF mAb could reduce the VEGF level in serum by binding VEGF, and block its biological activity. It indicates that VEGF in serum of malignant tumor patient is a new tumor marker.

Animals ; Antibodies, Monoclonal ; pharmacology ; Biomarkers, Tumor ; blood ; Carcinoma ; blood ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; Mouth Mucosa ; pathology ; Neoplasm Transplantation ; Neoplasms ; blood ; Vascular Endothelial Growth Factor A ; blood

BACKGROUND: Beijing 2022 Olympic Winter Games was the second Games held amid the COVID-19 pandemic. To a certain extent, it has altered the way sporting activities operate. There is a lack of knowledge on injury risk and illness occurrence in elite winter sport athletes amid the COVID-19 pandemic. This study aimed to describe the incidence of injuries and illnesses sustained during the XXIV Olympic Winter Games in Beijing from February 4 to 20, 2022. METHODS: We recorded the daily number of injuries and illnesses among athletes reported by Beijing 2022 medical staff in the polyclinic, medical venues, and ambulance. We calculated injury and illness incidence as the number of injuries or illnesses occurring during competition or training, respectively, with incidence presented as injuries/illnesses per 100 athlete-days. RESULTS: In total, 2,897 athletes from 91 nations experienced injury or illness. Beijing 2022 medical staff reported 326 injuries and 80 illnesses, equaling 11.3 injuries and 2.8 illnesses per 100 athletes over the 17-day period. Altogether, 11％ of the athletes incurred at least one injury and nearly 3％ incurred at least one illness. The number of injured athletes was highest in the skating sports (n=104), followed by alpine skiing (n=53), ice track (n=37), freestyle skiing (n=36), and ice hockey (n=35), and was the lowest in the Nordic skiing disciplines (n=20). Of the 326 injuries, 14 (4.3％) led to an estimated absence from training or competition of more than 1 week. A total of 52 injured athletes were transferred to hospitals for further care. The number of athletes with illness (n=80) was the highest for skating (n=33) and Nordic skiing (n=22). A total of 50 illnesses (62.5％) were admitted to the department of dentistry/ophthalmology/otolaryngology, and the most common cause of illness was other causes, including preexisting illness and medicine (n=52, 65％). CONCLUSION: Overall, 11％ of athletes incurred at least one injury during the Games, which is similar to the findings during the Olympic Winter Games in 2014 and 2018. Regarding illness, 2％ of athletes were affected, which is approximately one-third of the number affected in the 2018 Olympic Winter Games.

Purpose: Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. Materials and Methods: Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. Results: We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Purpose: Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. Materials and Methods: Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. Results: We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Objective: To investigate the effects of a recombinant endoglin-macrophage inflammatory protein 3α Fc-fusion protein (EM) vaccine on tumor angiogenesis and growth in mice with H22 hepatocellular carcinoma. Methods: An in vivo hepatoma mouse model was established. Seven days after subcutaneous inoculation of H22 tumor cells, mice were randomly divided into four groups: EM, endoglin Fc-fusion protein, macrophage inflammatory protein 3α Fc-fusion protein, and normal saline groups. Tumor volume and survival rate of mice were studied at 3-day intervals. Microvessel density of the tumors and tumor cell proliferation were detected by immunohistochemistry, and tumor cell apoptosis was detected by TdT-mediated biotinylated-dUTP nick-end label staining. The number of CD11c and CD86 positive dendritic cells were detected by flow cytometry. Results: Compared with the other groups, the tumor volume became smaller, and the survival time was longer in the EM-treated group. Besides, microvessel density and cell proliferation index were significantly lower, while the tumor cell apoptosis index was significantly higher in the EM-treated group. Besides the number of CD11c and CD86 positive dendritic cells in EM-treated mice was larger than that in other groups. Conclusions: EM Fc-fusion protein could effectively inhibit tumor growth through inhibiting endoglin-related tumor angiogenesis and cell proliferation, promoting tumor cell apoptosis, and could induce a certain degree of antitumor immune responses.