We have developed an HPLC method for the determination of tirapazaming (3-Amino-1,2,4-Benzotriazine -1,4-dioxide, TPZ) in rabbits and have studied the related pharmacokinetics in rabbits. After protein was precipitated, TPZ in plasma was determinated on HPLC with UV detection at 266 nm, and the mobile phase consisted of methyl alcohol and phosphoric buffer (10: 90, adjusted to pH6.5 +/- 0.1 with NaOH). TPZ and endogenous substances could be separated. Its calibration curve was linear (r=0.9995) within the range of 0.150-59. 98 mg/L, the detection limits was 0.5 ng (S/N>3), the recovery was more than 95% (n=3), the intra-day and inter-day precision was less than 6.0% (n = 5). The concentration-time curve of TPZ in rabbit plasma could be fitted to two-compartment model. These data indicate the method is sensitive, simple and reliabe. It is suitable for the pharmacokinetic study of TPZ in rabbits.
Animals ; Chromatography, High Pressure Liquid ; Rabbits ; Radiation-Sensitizing Agents ; pharmacokinetics ; Sensitivity and Specificity ; Triazines ; blood ; pharmacokinetics

OBJECTIVETo investigate miR-20a expression in human glioma and normal brain tissues and its effect on the proliferation of glioma cells in vitro.

METHODSThe expression of miR-20a was detected in human normal brain tissues and glioma tissues by real-time RT-PCR. miR-20a mimics were synthesized and transfected into U251 cells via liposome, and the cell proliferation were detected using MTT assay and flow cytometry.

RESULTSThe glioma tissues showed significantly up-regulated expression of miR-20a compared with normal brain tissues (P=0.035). The expression level of miR-20a was higher in high-grade than in low-grade gliomas. miR-20a mimics significantly enhanced the proliferation of U251 cells and the percentage of S-phase cells.

CONCLUSIONmiR-20a shows potent effect in promoting the growth of glioma cells, suggesting its important role in the pathogenesis of human glioma.

Adult ; Brain Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Glioma ; genetics ; metabolism ; pathology ; Humans ; Male ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Young Adult

Objective:To summarize the experience of robotic and thoracoscopic segmentectomy in Daping Hospital, Army Medical University, and comparison analysis the clinical application value for early-stage lung cancer.Methods:A retrospective cohort study was conducted to continuously enroll 190 patients, 100 who received robotic(33 males and 67 females, median age of 51 years)and 90 who received VATS(34 males and 56 females, median age of 54 years), who underwent segmentectomy between June 2018 and October 2019. Perioperative outcomes(the operation time, intraoperative blood loss, postoperative thoracic drainage volume and time, pain score, complications, postoperative hospital stay and survival and mortality) were compared.Results:All the patients successfully completed the surgery and recovered from hospital, with no perioperative death.The baseline characteristics(sex, age, clinical symptoms, smoking status, underlying disease, tumor size, pathological type) and type of segmentectomy were comparable. There was significant difference in operative time[120(interquartile range, IQR 60-225)min vs. 155( IQR 75-330)min, P<0.001], blood loss[30( IQR 20-400) ml vs. 100( IQR 20-1 600) ml, P<0.001] between the robotic and VATS groups, respectively. But there was no significant difference in postoperative thoracic drainagevolume[4( IQR 1-15) days vs. 4( IQR 2-29) days, P=0.547], postoperative thoracic time[755( IQR 200-3 980)ml vs. 815( IQR 280-3 920)ml, P=0.902], pain score[2.33( IQR 0.88-4.75) points vs. 3.13( IQR 0.95-5.29)points, P=0.199], complications[7.4%(14/190) vs. 6.3%(12/190), P=0.303], postoperative hospital stay[7( IQR 3-19) days vs. 6( IQR 4-21) days, P=0.405] , number of lymph nodes[(4.83±3.18) vs.(6.15±4.1), P=0.255] between the robotic and VATS groups, respectively. The follow-up time was 6.5( IQR 1-26) months in the two groups, without recurrence, metastasis or death. Conclusion:Robotic lung segmentectomy is safe and feasible. This approach might lead to a better in operative time and blood loss. The short-term efficacy is similar with thoracoscopy, and the long-term efficacy needs further follow-up time.

Objective: To assess clinical effect and safety of botulinum toxin A injection in external urethral sphincter for male patient with neurogenic detrusor underactivity(DU). Methods: A prospective and self-controlled trail was conducted from August 2012 to October 2017. Male patients with nerve injury, dysuria more than 6 months, DU(bladder contractility index less than 100) were enrolled in this study. Exclusion criteria included patients with acute urinary tract infection, bladder stone, benign prostate hyperplasia, urethral stricture and urethral diverticulum.100 IU BTX-A was dissolved in 4ml normal saline, and the solution of BTX- A was injected into 4 different points(3-o’clock, 6-o’clock, 9-o’clock, and 12-o’clock) in external urinary sphincter with each point of 1ml solution. Patients were evaluated at baseline and 12 weeks after injection. The outcomes included post void residual (PVR), maximum flow rate (Q_max), maximum detrusor pressure during voiding phases (P_det.max), maximum urethral closure pressure (MUCP), the case number of intermittent catheterization (IC)and the score of quality of life (QOL score). Adverse events were also recorded. Results: A total of 58 male patients (all from Guangdong provincial work injury rehabilitation hospital)with mean age 28.6 years suffered from cerebral palsy (n=2), cerebrovascular accident(n=19)and spinal cord injury(n=37) were included into the study. Compared to baseline data, significant difference were observed at week 12 in PVR (56.68 ml vs. 280.11 ml, P<0.001), P_det.max(23.95 cmH₂O vs. 30.01 cmH₂O, P=0.019), Q_max(6.74 ml/s vs. 3.28 ml/s, P=0.042), MUCP(48.25 cmH₂O vs. 79.34 cmH₂O, P<0.001), the case number of IC(40 vs. 58, P<0.001) and QOL score(3.63 vs.5.22, P<0.001) respectively. 5 cases developed perineal pain and 16 cases developed mild transient haematuria. These adverse events were disappeared by medical symptomatic treatment during 3-5 days. Conclusions BTX-A externalurethral sphincter injections help reduce urethra resistance and also improve the quality of life for patients with neurogenic detrusor underactivity.

Objective    To evaluate the feasibility and clinical value of robot-assisted lobectomy through anterior approach. Methods    We retrospectively analyzed the clinical data of 180 patients who underwent robot-assisted lobectomy through anterior approach in our hospital between April 2017 and February 2018. There were 97 males and 83 females, aged 59.5 (32.0-83.0) years. The clinical effects were analyzed. Results    One patient was transferred to thoracotomy due to tumor invasion of adjacent blood vessels and injury to the blood vessels, and there was no perioperative death. There were 8.5 (1.0-35.0) dissected lymph nodes for each patient. The median operation time was 120 (50-360) min, including robot Docking time 5 (1-23) min and robot operation time 65 (7-270) min. The median blood loss was 50 (5-1 500) mL, 132 (73.3%) patients had malignant tumors and median drainage time was 5 (2-30) d. The mean postoperative pain score was 3.4±0.7 points and the postoperative hospital time was 8 (2-32) d. At the median follow-up of 24 months, 11 patients developed recurrence and metastasis, and 3 died. Conclusion    Robot-assisted lobectomy through anterior approach is a safe and convenient operation method, which is worthy of clinical application.

Objective    To explore the clinical value of three-dimensional computed tomography bronchography and angiography (3D-CTBA) in robotic lung segmentectomy. Methods    A non-randomized control study was performed and continuously enrolled 122 patients who underwent robotic lung segmentectomy in our hospital from January 2019 to January 2020. 3D-CTBA was performed before operations in 53 patients [a 3D-CTBA group, including 18 males, 35 females, with a median age of 52 (26-69) years] and not performed in the other 69 patients [a traditional group, including 23 males, 46 females, with a median age of 48 (30-76) years]. The clinical data of the patients were compared between the two groups. Results    All the patients were successfully completed the surgery and recovered from hospital, with no perioperative death. The baseline characteristics of the patients were not significantly different between the two groups (P>0.05). No significant difference was found in the operative time [120 (70-185) min vs. 120 (45-225) min, P=0.801], blood loss [50 (20-300) mL vs. 30 (20-400) mL, P=0.778], complications rate (17.0% vs. 11.6%, P=0.162), postoperative hospital stay [7 (4-19) d vs. 7 (3-20) d, P=0.388] between the two groups. In the 3D-CTBA group, 5 (9.4%) patients did not find nodules after segmentectomy, and only 1 (1.9%) of them needed lobectomy, but in the traditional group, 8 (11.6%) patients did not find nodules and had to carry out lobectomy, the difference was statistically significant (P<0.05). The follow-up time was 10 (1-26) months, and during this period, there was no recurrence, metastasis or death in the two groups. Conclusion    3D-CTBA is helpful for accurate localization of nodules and reasonable surgical planning before operations, and reducing wrong resections in segmentectomy, without increasing the operation time, blood loss and complications. It is safe and effective in anatomical lung segmentectomy.

Objective    To evaluate the feasibility and clinical value of robot-assisted lung segmentectomy through anterior approach. Methods    We retrospectively analyzed the clinical data of 77 patients who underwent robotic lung segmentectomy through anterior approach in our hospital between June 2018 to October 2019. There were 22 males and 55 females, aged 53 (30-71) years. Patients' symptoms, general conditions, preoperative imaging data, distribution of resected lung segments, operation time, bleeding volume, number of lymph node dissected, postoperative duration of chest tube insertion, drainage volume, postoperative hospital stay, postoperative complications, perioperative death and other indicators were analyzed. Results    All operations were successfully completed. There was no conversion to thoracotomy, serious complications or perioperative death. The postoperative pathology revealed early lung cancer in 48 patients, and benign tumors in 29 patients. The mean clinical parameters were following: the robot Docking time 1-30 (M=4) min, the operation time 30-170 (M=76) min, the blood loss 20-400 (M=30) mL, the drainage tube time 2-15 (M=4) days, the drainage fluid volume 200-3 980 (M=780) mL and the postoperative hospital time 3-19 (M=7) days. Conclusion    Robotic lung segmentectomy through anterior approach is a safe and convenient operation method for pulmonary nodules.

Objective    To investigate the feasibility and safety of single utility port Da Vinci robot-assisted lung resection via anterior approach. Methods    The clinical data of 21 patients who underwent single utility port Da Vinci robot-assisted lung resection from February to March 2021 were retrospectively analyzed. There were 10 males and 11 females, with a median age of 50 (34-66) years. The operation time, blood loss, postoperative hospitalization time, postoperative complications and other indicators were analyzed. Results    All patients completed the operation successfully with no transition to thoracotomy or perioperative death. Overall surgery time was 103 (70-200) min, Docking time was 5 (3-10) min, operation time was 81 (65-190) min. The blood loss was 45 (20-300) mL. All patients had malignant tumors, the number of dissected lymph node station was 3 (1-6), and the number of lymph nodes was 5 (2-16). The postoperative indwelling time was 3 (2-5) d. The postoperative hospitalization time was 5 (3-7) d. The pain score for the first 3 days after surgery was 3±1 points. Conclusion    Single utility port robot-assisted lung resection via anterior approach is safe, less traumatic, more convenient and effective, which can be gradually promoted and applied to clinical trials.

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects