A fast and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of prodrug of paclitaxel (Pro-PTX) and paclitaxel (PTX) in rat plasma was developed. The plasma samples were subjected to protein precipitation with acetonitrile (0.1% formic acid), and then separated by LC with an Ultimate AQ-C18 column (50 mm × 3.0 mm, 3 μm) and acetonitrile-1 mmol·L^-1 ammonium formate (containing 0.1% formic acid) as the mobile phase. Multiple reaction monitoring (MRM) scanning mode was used to detect the ion responses m/z 983.4→415.2 (Pro-PTX), m/z 854.4→286.1 (PTX) and m/z 808.3→527.2 (Docetaxel, internal standard) by using a triple quadrupole tandem mass spectrometer with electrospray ionization source and positive ion mode. The method validation results show that the linear ranges of Pro-PTX and PTX in plasma were 2.00-500 ng·mL^-1 (r > 0.99) and 4.00-1 000 ng·mL^-1 (r > 0.99), the lower limit of quantification was 2.00 ng·mL^-1 and 4.00 ng·mL^-1, respectively; the quality control samples with low, medium and high concentrations of Pro-PTX and PTX were within the batch, the relative standard deviation (RSD) between batches were all less than 9%; the relative deviation (RE) was within the range of ± 9%; In the stability test, both Pro-PTX and PTX in plasma were stable under various storage conditions. The method was sensitive, specific, and reproducible, and was suitable for the pharmacokinetic study of Pro-PTX in rats. Animal experiments were approved by the Ethics Committee of Laboratory Animal Management and Animal Welfare, Institute of Materia Medica, Chinese Academy of Medical Sciences (No.: 00003552).

OBJECTIVETo study the correlation between arachidonic acid (AA) and acute red blood cells damage in rats, and to build a model with hidden blood loss in vivo, and to explore the pathological mechenism of hidden blood loss.

METHODSA total of 50 male adult Sprague-Dawley rats weighing (200 ± 20) g were randomly divided into five groups (n = 10): control group and four experimental groups. The rats in the experimental groups were given 0.5 ml different concentrations of AA dilu- ents, 5, 10, 20, 40 mmol/L respectively. The blood samples were collected from orbital venous at the beginning and 24, 48, 72 hours after administration. Then the changes of hemoglobin (Hb) ,red blood cell count (RBC), glutathione peroxidase (GSH- PX) activity, total superoxide dismutase (T-SOD) activity and hydrogen peroxide (H202) in the blood samples were tested.

RESULTSSignificant hidden blood loss occurred when the concentration was 10 mmol/L in the experimental group, with the RBC and Hb sharply reduced in blood samples. The Hb and RBC were reduced in all the experimental groups and control group at 24 hours after administration, while in the experimental groups they changed more obviously. The GSH-PX activity, T-SOD activity and H₂O₂were also significantly reduced in all groups, and the changes showed significant differences. The Hb and RBC were relatively stable in the control group and the experimental groups at 48 hours after administration; while GSH-PX activity, T-SOD activity and H₂O₂were all significantly decreased, and the changes in the experimental groups were more notable.

CONCLUSIONElevated levels of AA in the blood causes oxidative stress in the red blood cells, leading to the damage of red blood cells and hemoglobin, which is responsible for hidden blood loss.

Animals ; Arachidonic Acid ; toxicity ; Erythrocytes ; drug effects ; metabolism ; Glutathione Peroxidase ; blood ; Hemoglobins ; analysis ; Male ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood

OBJECTIVETo observe the clinical characteristics of triceps brachii tendon rupture at olecranon ending.

METHODSFrom June 2005 to November 2011,19 patients with triceps brachii tendon rupture at olecranon ending were treated with surgical technique. Among the 19 patients, 7 patients were male, with an average age of 24.1 years old (ranged, 15 to 41 years old); 12 patients were female, with an average age of 51.4 years old (ranged, 16 to 73 years old). Eight patients had injuries in the left elbows, and 11 patients had injuries in right elbows. Seventeen patients had injuries induced by walking fall and 2 patients had injuries induced by falling down. Thirteen patients were simple triceps brachii tendon rupture at olecranon ending, 6 patients were associated with other elbow injuries. Five patients were associated with radial fracture; 1 patient with capitellum fracture; 1 patient with coronoid process fracture; 1 patient with epitrochlear. All the lateral radiographs of the injuried elbow demenstrated the flecks of avulsed osseous material from the olecranon (flake sign). The associated injuries had the homologus presence. All the patients were treated with surgical techniques:15 patients were treated with figure-of-eight tension-band wire; figure-of-eight tension band wire and Kirschner wire in 1 patient; wire cerclage in 1 patient; nonabsorbable suture in 2 patients. The associated injuries were treated simultaneously. Plaster was applied after operation in 2 patients with heavier elbow associated injuries, other patients without any external fixation. The Mayo elbow score were observed to determinate the function of the elbow.

RESULTSAll the patients were followed up, 1 patient died of other disease at one year after operation, the other 18 patients were followed up with an average of 47.9 months (ranged from 14 to 91 months). According to the Mayo elbow score, 16 patients got an excellent result and 2 good.

CONCLUSIONTraumatic rupture of triceps brachii tendon at olecranon ending is not a rare injury, which is common in female older than fifty and in male younger then thirty. Surgical results are generally excellent. But dysfunction frequently remains in patients with associated elbow injuries.

Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Olecranon Process ; injuries ; Rupture ; Tendon Injuries ; surgery

OBJECTIVETo investigate the value of the noninvasive examinations for localization of insulinoma.

METHODSThe clinical materials of 88 cases of insulinoma treated in Peking Union Medical College Hospital between January 2005 and November 2008 were analyzed retrospectively. There were 40 males and 48 females aged from 15 to 74 years old (averaged, 46.5 years old).

RESULTSThe positive rates for localization were 19.3% (17/88), 52.4% (11/21), 95.5% (64/67), 1/6, 30.0% (6/20), 83.9% (26/31), 8/8 and 5/5 respectively in transabdominal ultrasound, enhanced CT, multislice spiral CT pancreatic perfusion, MRI, somatostatin receptor scintigraphy, endoscopic ultrasound, laparoscopic ultrasound and intraoperative ultrasound. Thirty-one multiple tumors in 8 patients were resected. The positive rates of locating the multiple insulinomas of multislice spiral CT pancreatic perfusion and Intraoperative Ultrasound were 48.4% (15/31) and 100% (14/14) respectively.

CONCLUSIONSThe locating diagnosis of insulinoma has came to noninvasive examination era. Multislice spiral CT pancreatic perfusion is the first choice for localization. Intraoperative ultrasound might play an important role in locating tumors for patients with multiple insulinomas.

Adolescent ; Adult ; Aged ; Female ; Humans ; Insulinoma ; diagnosis ; Male ; Middle Aged ; Pancreatic Neoplasms ; diagnosis ; Retrospective Studies ; Young Adult

Paclitaxel( PTX) is used as a broad spectrum anti-tumor medicine. However,serious drawbacks restrict clinical application of PTX. In this study,we prepared tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel( BSALC/DOPE-PTX) to study the effective antitumor activity. The in vivo targeting ability of the nanocarrier in tumor bearing nude mice was evaluated by using a Kodak in vivo imaging system FX PRO. The in vivo anti-tumor activity was evaluated in MDA-MB-231 tumor bearing mice,and representative sections were stained with hematoxylin and eosin( H&E),and examined by light microscopy. The results showed that DiR-loaded FA-BSA-LC/DOPE selectively targeted tumor,and had a relatively long residence in the tumor tissue. According to the in vivo anti-tumor activity study,FA-BSA-LC/DOPE-PTX exhibited an outstanding tumor inhibition effect with a tumor growth inhibition rate of 79.3%,and tumor tissue sections stained by hematoxylin and eosin( HE) showed severe necrosis areas and many dead cells with condensed nuclei in the FA-BSA-LC/DOPE-PTX group. Therefore,FA-BSA-LC/DOPE-PTX is a biocompatible,tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier,with a very marked anti-tumor activity in tumor-bearing mice in vivo.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Drug Carriers ; Hydrogen-Ion Concentration ; Lipoproteins ; Mice ; Mice, Nude ; Nanoparticles ; Neoplasms, Experimental ; drug therapy ; Paclitaxel ; pharmacology

OBJECTIVETo approach the biopathological features of hilar cholangiocarcinoma and surgical pathological factors which influence the long-term survivals of patients with hilar cholangiocarcinoma.

METHODSA systemic and retrospective multi-parameter analysis was performed on 205 patients of hilar cholangiocarcinoma who received surgical treatments and had complete clinicopathological data as well as follow-up results during a ten-year-period from April 1998 to April 2008. The single factor analysis was performed on age, sex, content of pre-operative serum CA19-9, Child-pugh grading, TNM classification, operation pattern, resection margin status of bile duct, vascular invasion, adjacent liver involvement, grade differentiation, infiltration-depth of bile duct, lymph node metastasis and perineural infiltration. A multivariate analysis was performed through Cox proportional hazard model.

RESULTSThe single factor analysis showed that except age, sex and content of pre-operative serum CA19-9, the mainly significant factors influencing the survivals were Child-Pugh grading, TNM classification, operation pattern, bile duct margin, vascular invasion, adjacent liver involvement, grade differentiation, infiltrating-depth of bile duct, lymph node metastasis and perineural infiltration (P < 0.05). Lymph node metastasis and infiltration-depth of bile duct wall were found to be the two independent factors influencing overall survival by multivariate analysis through the Cox model.

CONCLUSIONSThe most important prognostic factors influencing the long-term survivals of patients with hilar cholangiocarcinoma after operation are lymph node metastasis and depth of tumor-infiltrating of involved bile duct. During the operation, standardized evaluation through frozen section should be carried out for detection of lymph node metastasis and depth of tumor-infiltrating of involved bile ducts, which can be used as the histological indicator for surgical expansion, and could be helpful to maximize avoiding the tumor cell residues and therefore, to improve the long-term effects of surgical resection.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms ; pathology ; surgery ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; pathology ; surgery ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; Young Adult

OBJECTIVETo observe the effect of postoperative transcatheter hepatic arterial chemoembolization (TACE) and thymosin alpha(1) (T(alpha1)) treatment on recurrence of hepatocellular carcinoma (HCC).

METHODSFrom Jan 2000 to Dec 2002, 57 patients with HCC were randomly divided into three groups: group A (n = 18) received hepatectomy plus postoperative TACE and T(alpha1), group B (n = 23) received hepatectomy plus postoperative TACE and group C (n = 16) received hepatectomy only. The recurrence rate, the time to tumor recurrence and the median survival for the three groups were investigated.

RESULTSFor group A, B and C, the 1 year recurrence rate was 83.3%, 87.0% and 87.5% (P = 0.926), respectively. The time to tumor recurrence was 7.0, 5.0 and 4.0 months (P = 0.039), respectively. The median survival was 10.0, 7.0 and 8.0 months (P = 0.002), respectively.

CONCLUSIONPostoperative TACE plus Talpha(1) treatment for HCC patients does not decrease the recurrence rate but may delay its occurrence and prolong surviving time.

Adjuvants, Immunologic ; administration & dosage ; Adult ; Aged ; Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Agents ; administration & dosage ; Carboplatin ; administration & dosage ; Carcinoma, Hepatocellular ; surgery ; therapy ; Chemoembolization, Therapeutic ; Doxorubicin ; administration & dosage ; Female ; Hepatectomy ; Humans ; Iodized Oil ; administration & dosage ; Liver Neoplasms ; surgery ; therapy ; Male ; Middle Aged ; Mitomycin ; administration & dosage ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Survival Rate ; Thymosin ; administration & dosage ; analogs & derivatives

BACKGROUNDGastric cancer is one of the most common types of malignant tumors in China and East Asia and has the highest mortality rate of the malignant gastrointestinal tumors. Neoadjuvant chemotherapy is a systemic or local chemotherapy that is given prior to the local treatment of malignant tumors. Neoadjuvant therapy is currently showing some positive prospects; however, its clinical effects remain controversial. In this study, we used the modified FOLFOX7 (mFOLFOX7) regimen as a neoadjuvant chemotherapy regimen. Perioperative clinical and pathological efficacy, toxicity, effects of surgery, postoperative observation, and prognosis were studied to investigate its clinical efficacy and safety.

METHODSEighty patients with advanced gastric cancer were treated in our surgery department from 2005 to 2009; 38 of these patients received mFOLFOX7 neoadjuvant chemotherapy, the other 42 patients assigned to the control group. The perioperative effects of mFOLFOX7 chemotherapy, including clinical effects and toxicity, were observed in each patient.

RESULTSAfter mFOLFOX7 chemotherapy, clinical and pathologic stages decreased in 21.1% and 36.8% of the patients, respectively, but the results were not statistically significant (P = 0.129). The clinical response rate was 50% (19/38). Toxicity was mild; most adverse events were grade I or II and involved no severe infections or deaths. Compared with the control group, the radical resection rate increased (92.1% vs. 85.7%; P = 0.437); surgical effects were completed without an increased incidence of perioperative complications. The 1-, 2-, and 3-year survival rates were 78.70%, 57.40%, and 51.66%, respectively, in the neoadjuvant chemotherapy group and 78.57%, 56.87%, and 43.16%, respectively, in the control group.

CONCLUSIONSThe mFOLFOX7 regimen was very effective and well-tolerated as a neoadjuvant chemotherapy for advanced gastric cancer. However, the 1-, 2-, and 3-year survival rates in the mFOLFOX7 group were not significantly different from the control group.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Leucovorin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; adverse effects ; methods ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Stomach Neoplasms ; drug therapy ; surgery

OBJECTIVETo analyze the factors associated with anastomotic leakage after anterior resection in rectal cancer with the technique of total mesorectal excision (TME).

METHODSFrom January 2005 and December 2007, 738 consecutive patients with rectal cancer underwent anterior resection. The data of those patients was collected and reviewed retrospectively. The associations between anastomotic leakage and 9 patient-related variables as well as 7 surgical-related variables were examined.

RESULTSLow rectal cancer (located 7 cm or less above the anal edge), non-specialized surgeon and transanal tube use were the risk factors associated with anastomotic leakage on univariate analysis. The anastomotic leakage rate of low-rectal cancer was significantly higher than that of high-rectal cancer (5.9% vs. 0.9%, P = 0.003). The anastomotic leakage rate of the cases operated by colorectal surgeon was significantly lower than that of the cases operated by non-specialized surgeon (3.9% vs. 11.3%, P = 0.031). There was a tendency for colorectal surgeons to operate on a greater proportion of low rectal cancer than non-specialized surgeons (72.1% vs. 52.8%, P = 0.003). The leakage rate of transanal tube group was unexpectedly higher than that in patients without transanal tube (14.5% vs. 3.6%, P < 0.001). On multivariate logistic regression analysis, diabetes mellitus (P = 0.027), distance less than 1 cm from tumor to distal resection margin (P = 0.009) and defunctioning stoma (P = 0.031) were also associated with anastomotic leakage rate besides low rectal cancer, non-specialized surgeon and transanal tube use. In a further analysis of 522 patients with low rectal cancer, the leakage rate of defunctioning stoma group was significantly lower than that of non-stoma group (2.9% vs. 8.5%, P = 0.007). By contract, the leakage rate of transanal tube group was still higher than that in patients without transanal tube (15.1% vs. 4.9%, P = 0.008) because of its poor protective effect as well as the selection bias.

CONCLUSIONSLow-rectal cancer, non-specialized surgeons and diabetes mellitus are risk factors of anastomotic leakage after rectal surgery. A defunctioning stoma was effective in preventing leakage after low-rectal cancer surgery.

Adult ; Aged ; Aged, 80 and over ; Anastomosis, Surgical ; adverse effects ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Postoperative Complications ; etiology ; prevention & control ; Rectal Fistula ; etiology ; Rectal Neoplasms ; surgery ; Rectum ; surgery ; Retrospective Studies ; Risk Factors ; Surgical Stomas

OBJECTIVETo identify the candidate auto-antigen of rheumatic heart disease as a molecular marker for this disease.

METHODSThe total RNA of the heart tissue of patients with rheumatic heart disease was extracted and reverse-transcribed into long cDNA to construct the phage expression library. The library was screened using the serum from patients with active rheumatic fever, and the positive clone was identified and analyzed by bioinformatics and expressed in vitro. The expressed products were evaluated with Western blotting and its cross-reactivity was assessed.

RESULTSThe phage expression library of the heart tissue of patients with rheumatic heart disease was constructed, with the titer of the primary library of 3.3×10(6) pfu/ml, recombinant rate of 99%, and 81% of the inserted segments were larger than 1 kb. An auto-antigen RHDAG1 was identified by screening, which was homologous to keratin 18. RHDAG1 was detected in the serum of patients with active rheumatic fever and of those with rheumatic heart disease, but not in the serum of healthy subjects.

CONCLUSIONPhage display library can be an effective strategy to screen the auto-antigens of rheumatic heart disease. The auto-antigen RHDAG1 can be a candidate molecular biomarker of rheumatic heart disease and/or rheumatic fever.

Autoantibodies ; blood ; immunology ; Autoantigens ; immunology ; isolation & purification ; Autoimmune Diseases ; blood ; immunology ; Humans ; Peptide Library ; Rheumatic Heart Disease ; immunology