The Aurora kinase inhibitor AT9283 inhibits Burkitt lymphoma growth by regulating Warburg effect.

Objective: To investigate the effect of the kinase inhibitor AT9283 on Burkitt lymphoma (BL) cells and elucidate the underlying mechanisms. Methods: The effect of AT9283 on the proliferation of BL cell lines was tested using the MTT assay. Apoptosis and cell cycle were measured by flow cytometry. The proteins associated with the cell cycle, apoptosis, and the Warburg effect were detected using Western blotting. Alterations in glycolytic metabolism in terms of glucose intake and lactate concentrations were determined by glucose and lactate assays. Results: The current study utilized the GEPIA, the Human Protein Atlas (HAP) database and immunohistochemistry to conduct analyses, which revealed a high expression of Aurora kinases and Warburg effect-related proteins in malignant B-cell lymphoma tissues. AT9283 significantly inhibited the cell proliferation of BL cells and induced G2/M arrest. Additionally, AT9283 induced apoptosis in BL cells and reversed the Warburg effect by increasing glucose uptake and reducing lactate production. Moreover, the protein expression of hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A was significantly suppressed by AT9283, possibly through the inhibition of c-Myc and HIF-1α protein expression. Conclusion: The reversal of the Warburg effect in BL cells and the subsequent inhibition of cell proliferation and induction of apoptosis were observed by targeting Aurora A and Aurora B with AT9283. This finding may present new therapeutic options and targets for BL.

[Dorsal plate assisted fixation of dorsal lunate fossa fracture of distal radius].

OBJECTIVE: To explore clinical efficacy of dorsal plate assisted fixation of dorsal lunate fossa fracture block of distal radius. METHODS: From January 2019 to January 2022, 30 patients were treated with dorsal plate assisted fixation of dorsal lunate fossa fracture of distal radius, including 13 males and 17 females, aged from 42 to 68 years old with an average of (48.7±5.6) years old;According to Doi fracture classification, 24 patients were type 3 blocks and 6 patients were type 4 blocks. The degree of palmar angle of anterior and posterior distal radius was fixed by dorsal steel plate during operation. Fracture healing and functional recovery of wrist were observed after operation. Functional evaluation was performed by Gartland and Werley scoring system at 12 months after operation. RESULTS: All patients were followed up from 12 to 13 months with an average of (11.3±0.9) months. All fractures healed for 4 to 5 months with an average of(4.7±0.8) months. Median palpal inclination of anterior and posterior distal radius fixed by dorsal plate was 5.30°(4.85°, 6.03°), 12.45°(11.98°, 13.43°) respectively, and had statistical difference( P<0.01). Gartland and Werley scores was (1.1±0.4) at 12 months afteropertaion, and 27 patients got excellent result and 3 good. CONCLUSION: Dorsal plate assisted fixation of dorsal lunate fossa fractures is beneficial to reduction and stabilization of displaced dorsal fractures and restoration of palmar inclination.

Adjuvant Chemotherapy for Patients with Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.

LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials.

Objective: To compare the inhibition of LAG3-PD1 versus the inhibition of CTLA-4-PD1 in patients with previously untreated advanced melanoma. Methods: The individual participant data (IPD) were extracted from the KM plots using a graphical reconstructive algorithm. Log-rank, Cox proportional hazard model, Bayesian hierarchical model with time-varying hazard ratio (HR) effect, and restricted mean survival time (RMST) were performed to estimate survival benefits. Results: The CheckMate-067 (n = 630) and RELATIVITY-047 (n = 714) trials were included for analysis. The graphical reconstructive algorithm showed that IPD had similar HRs and log-rank values as the original plots. The HR of nivolumab plus relatlimab (LAG3 inhibitor) versus nivolumab plus ipilimumab (CTLA4 inhibitor) was 1.19 (95% confidence interval [CI] 0.96 to1.48). The 24-months RMST of nivolumab plus relatlimab versus nivolumab was 2.35 (95% CI 0.77-3.94) months, compared with 1.87 (95% CI, 0.25-3.49) months for nivolumab plus ipilimumab versus nivolumab. The Bayesian hierarchical model showed that patients treated with nivolumab plus relatlimab had earlier PFS benefits than those with nivolumab plus ipilimumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients using nivolumab plus relatlimab and 55.0% of patients using nivolumab plus ipilimumab. Conclusions: These findings suggest that the PFS of LAG3-PD1 and CTLA4-PD1 inhibition were similar and LAG3-PD1 inhibition exhibited earlier survival benefit and lesser TRAEs.

Development and validation of metabolism-related gene signature in prognostic prediction of gastric cancer.

Gastric cancer is one of the most common malignant tumours in the world. As one of the crucial hallmarks of cancer reprogramming of metabolism and the relevant researches have a promising application in the diagnosis treatment and prognostic prediction of malignant tumours. This study aims to identify a group of metabolism-related genes to construct a prediction model for the prognosis of gastric cancer. A large cohort of gastric cancer cases (1121 cases) from public database was included in our analysis and classified patients into training and testing cohorts at a ratio of 7: 3. After identifying a list of metabolism-related genes having prognostic value, we constructed a risk score based on metabolism-related genes using LASSO-COX method. According to the risk score, patients were divided into high- and low-risk groups. Our results revealed that high-risk patients had a significantly worse prognosis than low-risk patients in both the training (high-risk vs low-risk patients; five years overall survival: 37.2% vs 72.2%; p < 0.001) and testing cohorts (high-risk vs low-risk patients; five years overall survival: 42.9% vs 62.9%; p < 0.001). This observation was validated in the external validation cohort (high-risk vs. low-risk patients; five years overall survival: 30.2% vs 40.4%; p = 0.007). To reinforce the predictive ability of the model, we integrated risk score, age, adjuvant chemotherapy, and TNM stage into a nomogram. According to the result of receiver operating characteristic curves and decision curves analysis, we found that the nomogram score had a superior predictive ability than conventional factors, indicating that the risk score combined with clinicopathological features can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified a list of metabolic genes related to survival and developed a metabolism-based predictive model for gastric cancer. Through a series of bioinformatics and statistical analyses, the predictive ability of the model was confirmed.

Development and Validation of a Scoring System Based on 9 Glycolysis-Related Genes for Prognosis Prediction in Gastric Cancer.

Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients' sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis (p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival (p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient.In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. Based on the 9 genes, gastric cancer patients were separated into different risk groups related to survival.

Hexagonal and Monoclinic Phases of La2O2CO3 Nanoparticles and Their Phase-Related CO2 Behavior.

In this study, we prepared hexagonal and monoclinic phases of La2O2CO3 nanoparticles by different wet preparation methods and investigated their phase-related CO2 behavior through field-emission scanning microscopy, high-resolution transmission electron microscopy, Fourier transform infrared, thermogravimetric analysis, CO2-temperature programmed desorption, and linear sweeping voltammetry of CO2 electrochemical reduction. The monoclinic La2O2CO3 phase was synthesized by a conventional precipitation method via La(OH)CO3 when the precipitation time was longer than 12 h. In contrast, the hydrothermal method produced only the hexagonal La2O2CO3 phase, irrespective of the hydrothermal reaction time. The La(OH)3 phase was determined to be the initial phase in both preparation methods. During the precipitation, the La(OH)3 phase was transformed into La(OH)CO3 owing to the continuous supply of CO2 from air whereas the hydrothermal method of a closed system crystallized only the La(OH)3 phase. Based on the CO2-temperature programmed desorption and thermogravimetric analysis, the hexagonal La2O2CO3 nanoparticles (HL-12h) showed a higher surface CO2 adsorption and thermal stability than those of the monoclinic La2O2CO3 (PL-12h). The crystalline structures of both La2O2CO3 phases predicted by the density functional theory calculation explained the difference in the CO2 behavior on each phase. Consequently, HL-12h showed a higher current density and a more positive onset potential than PL-12h in CO2 electrochemical reduction.

Surgical Outcome and Long-Term Survival of Conversion Surgery for Advanced Gastric Cancer.

BACKGROUND: The present study aims to report the surgical outcome and long-term survival of conversion surgery and clarify its role in advanced gastric cancer. PATIENTS AND METHODS: A total of 95 primary advanced gastric adenocarcinoma patients who underwent systemic chemotherapy and conversion surgery were reviewed retrospectively. The survival of conversion surgery was analyzed by Cox regression and the Kaplan-Meier method. Surgical outcomes were analyzed according to the Clavien-Dindo classification. RESULTS: The median survival time (MST) of the 95 patients was 26.8 months, and the postoperative MST was 19.3 months. The MSTs of the patients in categories 1, 2, 3, and 4 were 28.8, 25.5, 43.6, and 11.3 months, respectively. The MSTs of the patients who underwent R0 resection (47 cases) and R1/2 resection (48 cases) were 49.3 months and 21.9 months, respectively. The MST of patients treated with total gastrectomy was shorter (21.9 months) than that of patients who underwent proximal (55.0 months) or distal (46.3 months) gastrectomy. Patients who received more than 6 cycles of induction chemotherapy had a longer MST than patients who received 3-5 cycles or 1-2 cycles (MST: 55.0 months versus 21.1 months versus 21.7 months). The incident postoperative complications and postoperative mortality rates were 10.5% and 1.1%, respectively. CONCLUSIONS: Advanced gastric cancer patients may obtain a survival benefit from conversion surgery, except category 4. Performing a sufficient number of cycles of induction chemotherapy (usually ≥ 6 cycles) is recommended. Surgical oncologists should perform R0 resection and avoid total gastrectomy.

(-)-Epigallocatechin-3-gallate induces cell apoptosis in chronic myeloid leukaemia by regulating Bcr/Abl-mediated p38-MAPK/JNK and JAK2/STAT3/AKT signalling pathways.

Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, possesses remarkable chemopreventive and therapeutic potential against various types of cancer, including leukaemia. However, the molecular mechanism involved in chronic myeloid leukaemia (CML), especially imatinib-resistant CML cells, is not completely understood. In the present study, we investigated the effect of EGCG on the growth of Bcr/Abl+ CML cell lines, including imatinib-resistant cell lines and primary CML cells. The results revealed that EGCG could inhibit cell growth and induce apoptosis in CML cells. The mechanisms involved inhibition of the Bcr/Abl oncoprotein and regulation of its downstream p38-MAPK/JNK and JAK2/STAT3/AKT pathways. In conclusion, we documented the anti-CML effects of EGCG in imatinib-sensitive and imatinib-resistant Bcr/Abl+ cells, especially T315I-mutated cells.

[Case-control study on calcaneal locking plates and tension band with Kirschner's nail for the treatment of patellar fracture].

OBJECTIVE: To compare clinical effect between calcaneal locking plates and tension band with Kirschner's nail for the treatment of patellar fracture. METHODS: From December 2009 to December 2017, 58 patients with patellar fracture were divided into plate group(calcaneal locking plate) and tension band(tension band with Kirschner's nail) by surgical method. There were 29 patients in plate group, including 14 males and 15 females, aged from 18 to 72 years old with an average of (36.9±11.5) years old; while there were 29 patients in tension band group, including 17 males and 12 females, aged from 20 to 70 years old with an average of (37.7±14.4) years old. Operative time, blood loss, fracture healing time, follow-up time and postoperative complications were compared between two groups. Böstman score was applied to compared therapeutic effects at 12 months after operation. RESULTS: There was no significant differences in following-up time between plate group(18.4±2.6) months and tension band group(17.8±3.6) months. According to Böstman score at 12 months after operation, plate group was (28.5±4.6) and (25.7±4.3) in tension band group, and had statistical difference between two group(t=2.395, P=0.020). Twenty-six patients got excellent results, 3 moderate in plate group; while 14 patients got excellent results, 11 moderate and 4 poor in tension band group, and had obviously meaning between two groups(χ²=12.17 P=0.02). There were no significant differences in operative time(t=1.978, P=0.53), blood loss(t=1.740, P=0.87), fracture healing time(t=0.65, P=0.517) and postoperative complications(χ²=0.268, P=0.604) between two groups. CONCLUSIONS: Calcaneal locking plates for patellar fracture has advantages of more wide range of clinical application, more reliable fixation, and more satisfactory surgical curative method, its clinical effects is better than that of tension band with kirschner nail.

[Surgical treatment of ulnar lateral mass fractures of distal radius].

OBJECTIVE: To investigate the type and corresponding operation methods of ulnar lateral mass in distal radial fractures. METHODS: From January 2004 to September 2010,32 cases of distal radial fractures with ulnar lateral mass were treated by surgical incision and relocate ulnar lateral mass,including 23 males and 9 females with an average age of (34 +/- 9) years old ranging from 28 to 65 years old. According to the classification of Melone-Doi, 2 cases with type I, 24 cases of type II, 6 cases with type III. The operative appoach involved palm-radial, palm-ulnar, radial-dorsal. Among them, 28 patients with closed fractures were fixed with plate, 4 cases (including 2 cases of open fractures) were fixed by Kirschner pin and braces. RESULTS: Thirty-two patients were followed up for 8 to 18 months with an average of 12 months. All fractures were healing without complications. According to modified Gartland-Werley scoring system (GWSS), the total score was 1.12 +/- 0.45, the remain deformity was 0, subjective evaluation was 0.50 +/- 0.30, objective evaluation was 0.30 +/- 0.21, complications was 0.40 +/- 0.09; the result was excellent in 21 cases, good in 11 cases. CONCLUSION: The location of ulnar lateral mass in distal radial fractures is one of the important prognostic factors in wrist function and surgical treatment is an effective method of fixing ulnar lateral mass in distal radial fractures.

[Minimally invasive percutaneous plate osteosynthesis for the treatment of intertrochanteric femoral fractures of Evans IlI and IV in elderly patients].

OBJECTIVE: To study therapeutic effects of minimally invasive percutaneous plate osteosynthesis for the treatment of intertrochanteric femoral fractures of Evans III, IV in elderly patients. METHODS: From December 2007 to April 2010, 23 patients with intertrochanteric femoral fractures were reviewed. Among the patients, 11 patients were male and 12 patients were female,ranging in age from 62 to 90 years, with a mean of 72.8 years. According to Evans classification, 13 patients were type III and 10 patients were type IV. All the patients were treated with proximal femoral locking plate (minimally invasive percutaneous plate osteosynthesis, MIPPO) surgery. RESULTS: The operative time ranged from 45 to 60 min, with an average of 50 min. The blood loss ranged from 60 to 100 ml, averaged 80 ml. All the patients were followed up,and the duration ranged from 9 to 18 months, with an average of 11 months. The healing time based X-ray ranged from 3 to 6 months, with an average of 4 months. According to hip scoring criteria evaluation: 18 patients got an excellent results, 5 good. CONCLUSION: For the treatment of intertrochanteric femoral fractures of Evans III, IV in elderly patients, MIPPO has advantages such as small trauma, reliable fixation, which has good clinical application.