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

Objective To investigate the effects of intraperitoneal injection of valproic acid (VPA) combined with transplantation of bone marrow mesenchymal stem cells (BMSCs) on neurological function recovery after spinal cord injury (SCI) in rats.Methods BMSCs from 3-4 weeks old healthy male Sprague-Dawley (SD) rats were cultured in vitro.The third generation BMSCs were detected by flow cytometry.Spinal cord injury model was made by modified Allen's technique.Sixty adult male SD rats were randomly divided into five groups(n =12 in each group):Sham operation group and model group(received the same dose of normal saline at the same time point),VPA group(VPA,one time per q12 h with 300 mg· kg-1 · d-1).BMSCs group (1 × 106 cell· mL-1BMSCs 1 mL injected into the spinal cord of injured segment)and combined group(VPA + BMSCs).The BBB scale at the 14 d after injury was evaluated.The expression of Caspase-3 protein was detected by immunohistochemistry.Then the neuronal apoptosis rate was observed by TdT-mediated dUTP nick-end labeling(TUNEL) staining.Results BBB Rating:On the 14 d after SCI,the rate in sham operation group,model group,VPA group,BMSCs group and combined group were 21,(4.51 ± 0.41),(7.25 ± 0.95),(7.32 ± 0.55),(9.76 ± 0.95)point.The BBB score of the three treatment groups was significantly higher than that of model group with significantly (P ＜ 0.05).On the 14 d after SCI,the caspase-3 expression in sham operation group,model group,VPA group and BMSCs group and combined group were (1.64 ± 0.41) ％,(26.22 ± 4.81) ％,(21.21 ± 4.04) ％,(21.47 ± 3.32) ％,(16.15 ± 3.09) ％.The expression of Caspase-3 in three treatment groups was significantly lower than that model group with significantly(P ＜0.05).While the expression of caspase-3 in combined group was significantly lower than that in VPA group and BMSCs group with significantly(P ＜0.05).On the 14 d after SCI,the apoptosis rate in sham operation group,model group,VPA group and BMSCs group and combined group were (4.18 ± 0.39)％,(40.51 ± 3.81)％,(19.95 ± 2.04)％,(20.87 ±2.32)％,(12.83 ± 1.09)％.Compared with model group,the apoptosis rate of the three treatment groups was lower with significantly(P ＜ 0.05).The apoptosis rate of combined group was significantly lower than that of VPA group and BMSCs group with significantly (P ＜ 0.05).Conclusion It is very significant effects of intraperitoneal injection of VPA combined with BMSCs on neurological function recovery after spinal cord injury in rats.The mechanism may be related to down-regulation of Caspase-3 expression,leading to inhibition of apoptosis.

Objective:To assess the usage of the robot-assisted core-needle biopsy for the bone tumors, moreover to compare its outcomes with the manual technique.Methods:A retrospective study was conducted from February 2019 to February 2021, the medical records of the patients with bone lesions that had received core-needle biopsy were collected. There were 57 males and 45 females, the age was 45.9 (10~79) years. Eight patients received robot-assisted biopsy, whereas 94 patients underwent C-arm/ CT guided biopsy, the recorded data included operational duration, aspirational direction adjustment, etc. The pathological diagnosis reports of the biopsy specimens and the operational specimens were compared.Results:The diagnosis outcomes included metastases (33 cases), osteosarcoma (12 cases), chondrosarcoma (12 cases), giant cell tumor of bone (12 cases), fibrous dysplasia (7 cases), chronic osteomyelitis (7 cases), lymphoma (4 cases), multiple myeloma (4 cases), chronic fracture (3 cases), chondroblastoma (2 cases), pleomorphic undifferentiated sarcoma (2 cases), leiomyosarcoma (1 case), and Langerhans cell histiocytosis (1 case). Eighty-seven cases (85.29 %) lesions were found in the limbs, whereas 15 cases (14.71%) were in the axial locations. Compared with the manual group, the robot-assisted group had more axial locations: 7/8 vs. 11.70%(11/94), P<0.01; fewer aspirational direction adjustment: (0.4 ± 0.1) times vs. (3.1 ± 1.5) times, P<0.01 ; longer operational duration: (48.8 ± 8.8) min vs. (29.6 ± 6.0) min, P<0.01. There were no statistical differences between the two groups regarding the sex, age, pathological fracture, diagnostic accuracy, open biopsy rate and complications ( P>0.05). Conclusions:The robot-assisted core-needle biopsy is a reliable technique, it helps decrease the operational difficulty. The usage of this technique is recommendable for the bone lesions with great difficulty for biopsy, such as the minimal bone tumors and the lesions in the spine and the pelvis.

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 review and investigate the optimal preoperative diagnostic means and treatment principles of hepatic angiomyolipoma (HAML).

METHODSThe clinical features, treatment, prognostic and follow-up data of 169 HAML patients treated between January 1992 and May 2010 were retrospectively analyzed. The median age of the patients, including 46 male and 123 female (male/female, 1/2.7), was 45 years (range, 17 - 73 years). The mean case history was 0.54 year with a range of 2 d to 16 years.

RESULTSAmong the 169 patients, 149 patients (88.2%) had a solitary tumor and 96 patients (56.8%) were detected in the right lobe. The overall preoperative diagnostic rate was 13.6% and 119 patients (70.4%) were misdiagnosed as hepatocellular carcinoma or hepatic cavernous hemangioma. The diagnostic accuracy of MRI is higher than CT in distinguishing the nature of the tumor (χ² = 5.508, P = 0.019). One hundred and sixty-eight patients received surgical resection and one received percutaneous microwave coagulation therapy. One patient occurred postoperative hemorrhage and 3 patients developed hydrothorax. The postoperative mortality and recurrence for all the patients were 0. Postoperative pathology confirmed the diagnosis of hepatic angiomyolipoma. Follow-up study showed a benign course and no signs of recurrence.

CONCLUSIONSMRI is the main diagnostic means of HAML. Treatment strategies of HAML depends largely on tumor size, location and growth rate. Surgical management is suggested to patients with the following criteria: (1) tumor size greater than 5 cm; (2) with clinical symptoms; (3) faster tumor growth; (4) the tumor located at 1, 4, 5, 8 segments of liver.

Adolescent ; Adult ; Aged ; Angiomyolipoma ; diagnosis ; surgery ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; surgery ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; 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