OBJECTIVE:To evaluate the efficacy and toxicity of paclitaxel combined with cisplatin in the treatment of advanced non-small cell lung cancer(NSCLC) by weekly-,biweekly- and three-weekly-regimens.METHODS:180 patients who had been confirmed by pathology and cytology as having NSCLC(Ⅲ～Ⅳstage) were enrolled into the study and divided to three groups:Biweekly - regimen(n= 60):paclitaxel 80 mg?m~(-2) plus cisplatin 40 mg?m~2 ivgtt on day 1 and day 8 in every 21 days;Weekly- regimen(n= 60):paclitaxel 55 mg?m~(-2) plus cisplatin 30 mg?m z ivgtt on day 1,8,and 15 in every 28 days;Three - weekly regimen(n = 60):paclitaxel 160 mg?m~(-2) plus cisplatin 80 mg?m~(-2) ivgtt on day 1 in every 21 days.Serum concentrations of paclitaxel at 3,12,24 h after administration were determined,and the efficacy and toxicity after two- cycle treatment were evaluated.RESULTS:The overall response rates of weekly-,biweekly -and three weekly regimens were 43.1%,35.8%and 34.0%respectively,showing no statistical differences among groups,but the incidence of main toxicities of biweekly-regimen was lower as compared with the other regimens.CONCLUSION:Biweekly -regimen is optimal for the treatment of advanced NSCLC with mild toxicity,which deserves to be applied in clinical practice.

Objective To investigate effects of new nursing experimental teaching mode on professional ability of nursing students. Methods Traditional experimental teaching mode was used in control group (402 nursing students of 2006 grade) and experimental teaching model was used in experimental group (564 nursing students of 2007 grade). Questionnaires survey was conducted among clinical teachers to evaluate 8 abilities (service consciousness, knowledge application, practical abil-ity, communication ability. etc) of nursing students after 3 months' clinical practice. Satisfaction de-gree of experimental teaching and the first time employment rate of nursing students were recorded. All data were sorted out and analyzed by Epidata 3.1 and SPSS 13.0. Total score of students' profes-sional capacity was compared by independent t test. Score of the scale item was compared by rank sum test. Satisfaction rating for experimental teaching, passing rate of nurse practicing qualification examination and the first time employment rate were compared by chi-square test. All statistical tests were two-sided and P<0.05 was considered statistically significant different. Results Students' scores of communication ability, innovation capacity, capability to identify problems, practical ability, knowl-edge application, ability of organization and independent learning ability were 2.86±0.23, 2.86±0.17, 2.85±0.19, 2.84±0.24, 2.79±0.20, 2.78±0.19, 2.65±0.19 in experimental group, higher than those in control group. Satisfaction degree of experimental teaching and the first employment rate of students in experimental group were 94.5%(536/567) and 84.5%(479/567), higher than those in con-trol group with statistically significant differences(P<0.05). Conclusion New teaching mode of nurs-ing experiment can improve the professional ability of nursing students.

BACKGROUND: Endothelin(ET) -1 is a peptide with potent actions on blood vessels and nerve system. Its expression increases in the central nervous system(CNS) in a variety of pathological conditions, inducing harmful effects on the nervous tissue. However it is not clearly elucidated whether the over-expressed ET-1 can directly induce neuronal apoptosis.OBJECTIVE: To investigate whether ET-1 can directly induce apoptosis in primarily cultured brain neurons of rat, and which ET receptor subtype(s) is involved in this action.DESIGN: Completely randomized and controlled experimental study based on cells.SETTING: Neurological department in a university hospital, pathological department of a university and laboratory center of tissue transplantation and immunology, life science and technology college.MATERIALS: This study was completed in the Pathology Department, the Institute of Tissue Transplantation and Immunology, the Life Science and Technology College of Jinan University. The subjects were primarily-cultured neurons obtained from cerebral cortex of newborn rats that were provided by the Experimental Animal Center of the Medical College, Sun Yat-sen University.INTERVENTIONS: After culturing for five days, the neurons were treated with ET-1 (0. 2 nmol/L and 20 nmol/L) for 24 hours. Apoptotic neurons were semi-quantitatively measured with Annexin V and Hoechst 33258 staining respectively. ET-1(20 nmol/L), with BQ123(a selective antagonist for ET receptor A, 1 mmol/L) or with BQ788(a selective antagonist for ET receptor B, 1 mmol/L), was added respectively into the cultures simultaneously. And the apoptotic neurons were quantitatively measured with flow cytometry 24 hours later. Equal amount of PBS, instead of ET-1, waw added into the control subjects.MAIN OUTCOME MEASURES: The effect of ET-1 on apoptosis rate of cultured rat cortical neurons, and the ET receptor subtypes involved in this action.RESULTS: Twenty-four hours after treated with 0.2 nmol/L ET-1, the Annexin-V, and Hoechest 33258 positive stained cell rates[ (23.00 ± 9.96)%,(9.82 ±0.95)% ] were of no difference as compared with those of the controls[ (13.50 ± 3.35)%, (8.21 ± 2. 17)% ]. By contrast, after incubation with the higher dose of ET-1 (20 nmol/L), significant higher rate of apoptosis was measured in Annexin V staining[(50.50 ± 10.78)%, P=0.01, n=4] and Hoechest 33258 staining[(13.78±1.52)%, P= 0. 000, n = 8] . Analyzed with flow cytometry, the apoptosis rate was (0.20±0. 15)% in the control group, (26. 11 ±3.28)% in 20 nmol/LET-1 group, and(13.58 ±4. 92)% in BQ123 +ET-1 and(9.99 ±3.30)% in BQ788 +ET-1 respectively, indicating that BQ123 and BQ788 partially-blocked the apoptosis effect of ET-1 on. cultured neurons(BQ123 + ET-1 vs ET-1, P = 0. 005; BQ788 + ET-1 vs ET-1, P = 0. 001, n = 4, respectively).CONCLUSION: The higher dose of ET-1 (20 nmol/L) can directly induce apoptosis of primarily-cultured cerebral neurons of rats. The effect of ET-1 inducing neuronal apoptosis may be mediated via both ET receptors A and B.

OBJECTIVE: To explore the effect of isoflurane preconditioning on the plasma concentration of matrix metalloproteinase (MMP)-9 and myocardial ultramicrostructure in patients undergoing cardiac valve replacement. METHODS: Thirty patients undergoing elective cardiac valve replacement with cardiopulmonary bypass (CPB) were randomly assigned to a control group (ný15) and an isoflurane group (ný15). In the isoflurane group, isoflurane of 1.0 minimum alveolar concentration end-tidal( 1.1% approximately 1.2%) was administered for 30 min followed by a 15 min washout period before the CPB. The control group did not inhale isofurane, and there was no difference in the other drugs in the 2 groups. Blood samples for MMP-9 were obtained before incision(T(0)) and at 30 min (T(1)),6 h (T(2)),12 h (T(3)), and 24 h (T(4)) after the reperfusion. Right atrial biopsies were collected before and after the CPB to observe the myocardial ultramicrostructure. RESULTS: Compared with T(0), the mean MMP-9 level significantly increased at T(1), T(2) and T(3) in the control group(P<0.01), while the MMP-9 level only at T(1) significantly increased in the isoflurane group (P<0.01). The mean MMP-9 level was significantly reduced in the isoflurane group at T(2) compared with each time point in the control group. The difference in MMP-9 levels between T(1), T(2), T(3) and T(0) was significantly lower in the isoflurane group than that in the control group (P<0.01). The ultramicrostructure injury of myocardium under electron microscope in the control group was worse than that in the isoflurane group. CONCLUSION The plasma concentration of MMP-9 is inhibited by isoflurane preconditioning in patients undergoing cardiac valve replacement after CPB, which might be part of its protective mechanism against myocardium injury after CPB.
Adolescent ; Adult ; Cardiopulmonary Bypass ; Cardiotonic Agents ; therapeutic use ; Female ; Heart Valve Prosthesis Implantation ; methods ; Humans ; Ischemic Preconditioning, Myocardial ; methods ; Isoflurane ; therapeutic use ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Myocardium ; ultrastructure ; Young Adult

Objective To investigate the clinical efficacy of peripheral blood stem cell transplantation from haploidentical and matched sibling donors for treatment of high-risk and refractory/relapsed acute myeloid leukemia (AML). Methods Data on the efficacy of haploidentical peripheral blood stem cell transplantation (Haplo-HSCT) with myeloablative conditioning regimen were retrospectively analyzed and compared with that of matched sibling donors' peripheral blood stem cell transplantation (MSD-HSCT) for treatment of high-risk refractory/relapsed AML in our center from January 1st, 2010 to June 30th, 2020. Results A total of 98 patients were enrolled, including 62 patients in the Haplo-HSCT group and 36 patients in MSD-HSCT group. The median age, conditioning regimen, and infusion doses of MNC and CD34+ cells were significantly different between the two groups, but no significant differences in other baseline parameters were found. Transplantation-related infectious complications and the incidence of acute and chronic graft-versus-host disease (GVHD) were also not significantly different between the two groups. The 3-year cumulative relapse in the Haplo-HSCT group was significantly lower than that in the MSD-HSCT group (16.2% vs. 41.1%, P=0.036). The 3-year DFS of the Haplo-HSCT and MSD-HSCT groups were 66.98% and 41.8%, respectively (P=0.140), and their OS were 73.37% and 51.41%, respectively (P=0.105). Conclusion The clinical efficacy of Haplo-HSCT for the treatment of high-risk and refractory/relapsed AML is similar to that of MSD-HSCT, and Haplo-HSCT may have better GVL effect.

Objective:To evaluate the value of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation detection in the differentiating malignant from benign with Bethesda system for reporting thyroid cytopathology (BSRTC) categories Ⅰ and Ⅲ nodules. Methods:From January 2019 to December 2020, a total of 264 nodules from 263 patients (79 males, 184 females; median age 46 years) were retrospectively enrolled and all patients underwent BRAF V600E mutation detection, fine-needle aspiration cytology (FNAC) and thyroid nodulectomy in the Affiliated Drum Tower Hospital of Nanjing University Medical School. Thirteen nodules of 12 patients had repeat aspirate samples and 51 nodules were examined with multiple genes assay in formalin fixed paraffin embedded tissues. Taken the postoperative histopathological results as the gold standard, the diagnostic efficiency of BRAF V600E mutation was analyzed by comparing the results of multiple genes assay and BRAF V600E mutation detection of repeated puncture samples. Results:Of 264 nodules, 230 were malignant (papillary thyroid cancer (PTC)) and 34 were benign, with BSRTC categories Ⅰ (nondiagnostic) and Ⅲ (follicular lesion) nodules of 58 and 206. The sensitivities of BRAF V600E mutation detection in BSRTC categories Ⅰ and Ⅲ nodules were 77.1%(37/48) and 78.0%(142/182), the specificities were 9/10 and 91.7%(22/24), the positive predictive values were 97.4%(37/38) and 98.6%(142/144), the negative predictive values were 45.0%(9/20) and 35.5%(22/62), and the accuracy rates were 79.3%(46/58) and 79.6%(164/206). The diagnostic concordance of BRAF V600E mutation detection was 90.2%(46/51) in the preoperative and postoperative samples of 51 nodules with preoperative BRAF V600E wild type but postoperative pathology confirmed as PTC and was 11/13 in repeat puncture samples. Conclusion:BRAF V600E mutation detection is an effective diagnostic method for BSRTC categories Ⅰ and Ⅲ nodules.

Objective:To investigate the clinical efficacy of high-dose non-T-cell depleted peripheral blood stem cells (PBSC) used as grafts in haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning (RIC-haplo-HSCT) in the treatment of elderly patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).Methods:The clinical data of AML or MDS 28 patients aged ≥50 years who underwent RIC-haplo-HSCT in the First Affiliated Hospital of Xinjiang Medical University from January 2014 to June 2022 were retrospectively analyzed. All patients received high-dose non-T-cell depleted PBSC as grafts. Anti-CD25 monoclonal antibody and glucocorticoid were added as intensive graft-versus-host disease (GVHD) prophylaxis.Results:All patients achieved hematopoietic reconstruction. The accumulative incidence of grade Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD within 100 d was 22.5% (95% CI 5.1%-39.9%) and 8.2% (95% CI 0-19.2%), respectively. The 3-year cumulative incidence of chronic GVHD was 26.8% (95% CI 7.8%-45.8%), and the incidence of extensive chronic GVHD was 5.9% (95% CI 0-17.1%). The median follow-up time was 35.5 (2-83) months. The 3-year cumulative incidence of relapse and non-relapse mortality was 16.7% (95% CI 2.0%-31.9%) and 12.2% (95% CI 0-25.2%), respectively. The 3-year disease-free survival and overall survival rates were 73.3% (95% CI 56.2%-90.4%) and 79.1% (95% CI 62.2%-96.0%), respectively. Conclusions:High-dose non-T-cell depleted PBSC used as grafts for RIC-haplo-HSCT can achieve good clinical efficacy in elderly patients with AML/MDS.

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor