Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective To investigate the effect of c-fos gene silencing on differentially expressed proteins (DEPs) in human bronchial epithelial (HBE) cells after exposure to fine particulate matter (PM2.5).Methods HBE cells and c-fos-silenced HBE cells were exposed to 50 μg/mL PM2.5, LC-MS/MS and tandem mass tag (TMT) labeling methods were combined with bioinformatics methods, and DEPs and interaction networks were identified.Results In the HBE group, 414 DEPs were screened, of which 227 were up-regulated and 187 down-regulated. In the c-fos silenced HBE group, 480 DEPs were screened, including 240 up-regulated proteins and 240 down-regulated proteins. KEGG annotations showed that DEPs in the HBE group are mainly concentrated in the glycolysis/gluconeogenesis pathway and those in the c-fos silenced group are concentrated mainly in endoplasmic reticulum and the processing of proteins. Additionally, the abnormal expression of GPRC5C, DKK4, and UBE2C was identified in top 15 DEPs. After constructing the protein interaction network, 20 Hub proteins including HNRNPA2B1, HNRNPL, RPS15A, and RPS25 were screened from the HBE group and the c-fos silenced HBE group.Conclusion c-fos gene affected the expression of cancer-related proteins. Our results provided a scientific basis for further study of PM2.5-induced carcinogenesis mechanism.

BACKGROUND: The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). METHODS: All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence. RESULTS: Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation. CONCLUSION The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.
Animals ; Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Bridged Bicyclo Compounds, Heterocyclic ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Chromosomal Proteins, Non-Histone ; antagonists & inhibitors ; Electrophoresis, Polyacrylamide Gel ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Liver Neoplasms ; drug therapy ; surgery ; Liver Regeneration ; physiology ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; Sarcosine ; analogs & derivatives ; therapeutic use ; Xenograft Model Antitumor Assays

Objectives: To explore the clinical experience for a bridge therapy of percutaneous balloon aortic valvuloplasty (PBAV) in treating the patients with severe aortic stenosis (AS). Methods: A total of 37 patients with severe AS who were not suitable for surgical valvular replacement received PBAV in our hospital from 2011-03 to 2017-03 were retrospectively studied. The patient's mean age was (74±12) years, their clinical and anatomical features, efficacy and safety of operation were observed and the outcomes were evaluated by follow-up study. Results: Patients presented the high surgical risk and worse cardiac function, 50% of them had bicuspid leaflet morphology with severe calcification [HU850=(856.0±658.2) mm3]. Balloon size was chosen by the intra-operative supra-annular diameters; at 7 days after operation, aortic valve orifice area (AVOA) was increased from (0.37±0.10) cm2to (0.87±1.10) cm2, the mean trans-aortic valve gradient pressure decreased form (55.1±22.9) mmHg to (44.8±17.8) mmHg, P<0.001 and LVEF elevated form(35.8±14.3)% to(41.0±12.2)%,P<0.001.There were 4 patients died in hospital,1 received permanent pacemaker and 1 developed severe aortic valve regurgitation. The patients were followed-up for (16.5±11.1)months after operation, 13/37 (35.1%) patients were in transition to surgical or transcatheter aortic valve replacement (TAVR). Conclusions: PBAV may have good early clinical efficacy in severe AS patients who were not suitable for surgical valvular replacement and TAVR; PBAV could be expected to become a bridge therapy, smaller supra-annular diameter was safe and effective for patients having bicuspid leaflet with severe calcification.

Background:Laparoscopic total gastrectomy (LTG) is increasingly performed in patients with gastric cancer. However, the usage of intracorporeal esophagojejunostomy (IEJ) following LTG is limited, as the safety and efficacy remain unclear. The present meta-analysis aimed to evaluate the feasibility and safety of IEJ following LTG.

Methods:Studies published from January 1994 to January 2017 comparing the outcomes of IEJ and extracorporeal esophagojejunostomy (EEJ) following LTG were reviewed and collected from the PubMed, EBSCO, Cochrane Library, Embase, and China National Knowledge Internet (CNKI). Operative results, postoperative recovery, and postoperative complications were compared and analyzed. The weighted mean difference (WMD) and odds ratio (OR) with a 95% confidence interval (CI) were calculated using the Review Manager 5.3.

Results:Seven nonrandomized studies with 785 patients were included. Compared with EEJ, IEJ has less blood loss (WMD: -13.52 ml; 95% CI: -24.82--2.22; P = 0.02), earlier time to first oral intake (WMD: -0.49 day; 95% CI: -0.83--0.14; P < 0.01), and shorter length of hospitalization (WMD: -0.62 day; 95% CI: -1.08--0.16; P < 0.01). There was no significant difference between IEJ and EEJ regarding the operation time, anastomotic time, number of retrieved lymph nodes, time to first flatus, anastomosis leakage rate, anastomosis stenosis rate, and proximal resections (all P > 0.05).

ConclusionsCompared with EEJ, IEJ has better cosmesis, milder surgical trauma, and a faster postoperative recovery. IEJ can be performed as safely as EEJ. IEJ should be encouraged to surgeons with sufficient expertise.

Esophagostomy ; adverse effects ; methods ; Esophagus ; surgery ; Gastrectomy ; adverse effects ; methods ; Humans ; Jejunostomy ; adverse effects ; methods ; Laparoscopy ; adverse effects ; methods ; Stomach Neoplasms ; surgery ; Treatment Outcome

BACKGROUNDIt remains controversial whether patients with Stage II colorectal cancer would benefit from adjuvant chemotherapy after radical resection. The aim of this study was to establish two mathematical models to identify the suitable patients for adjuvant chemotherapy.

METHODSThe current study comprised of two steps. In the first step, 353 patients with Stage II colorectal cancer who underwent surgical procedures at the Third Affiliated Hospital of Sun Yat-sen University between June 2006 and December 2015 were entered and followed up for 6-120 months. Their clinical data were collected and enrolled into the database. We established two mathematical models by univariate and multivariate Cox regression analysis to identify the target patients; in the second step, 230 patients under the same standard between January 2012 and December 2016 were entered and followed up for 3-62 months to verify the two models' validation.

RESULTSIn the first step, totally 340 surgical patients with Stage II colorectal cancer were finally enrolled in this study. Statistical analysis showed that tumor differentiation (TD) (P < 0.001), lymphovascular invasion (LVI) (P < 0.001), uncertain or positive margins (UPM) (P < 0.001), and fewer lymph nodes (LNs) (<12) retrieved (P < 0.001) were correlated with the overall survival (OS) and disease free survival (DFS). We obtained two models: (1) OS risk score = 1.116 × TD + 2.202 × LVI + 3.676 × UPM + 1.438 × LN - 0.493; (2) DFS risk score = 0.789 × TD + 2.074 × LVI + 3.183 × UPM + 1.329 × LN - 0.432. According to the models and cutoff points [(0.07, 1.33) and (-0.04, 1.30), respectively], patients can be divided into three groups: low-risk, moderate-risk, and high-risk. Moreover, the high-risk group patients could benefit from adjuvant chemotherapy. In the second step, totally 221 patients were finally used to verify the models' validation. The results proved that the models were accurate and feasible (P< 0.05).

CONCLUSIONSAccording to the predictive models, patients with Stage II colorectal cancer in the high-risk group are strongly recommended for adjuvant chemotherapy, thus facilitating the individualized and precise treatment.

OBJECTIVECentral obesity is considered to be a central component of metabolic syndrome. Waist circumference (WC) has been widely used as a simple indicator of central obesity. This study is aimed to evaluate the sensitivity of WC cut-off values for predicting metabolic risk factors in middle-aged Chinese.

METHODSThe study involved 923 subjects aged 40-65 years. The metabolic risk factors were defined according to the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. WC cut-off 85-90 cm and ⋝90 cm were used as cut-off values of central pre-obesity and central obesity in males, respectively, while WC 80-85 cm and ⋝85 cm were used as cut-off values of central pre-obesity and central obesity in females.

RESULTSFirst, WC values corresponding to body mass index (BMI) 24 kg/m2 and visceral fat area (VFA) 80 cm2 were 88.55 cm and 88.51 cm in males, and 81.46 cm and 82.51 cm in females respectively. Second, receiver operating characteristic curves showed that the optimal WC cut-off of value was 88.75 cm in males, higher than that in females (81.75 cm). Third, the subjects with higher WC values were more likely to have accumulating metabolic risk factors. The prevalence of metabolic risk factors increased linearly and significantly in relation to WC levels.

CONCLUSIONWC cut-off values of central pre-/central obesity are optimal to predict multiple metabolic risk factors.

Aged ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Intra-Abdominal Fat ; physiopathology ; Male ; Metabolic Syndrome ; diagnosis ; epidemiology ; physiopathology ; Middle Aged ; Obesity ; diagnosis ; ROC Curve ; Waist Circumference

Aged ; Autoimmune Diseases ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis ; diagnosis ; drug therapy ; surgery ; Prednisone ; therapeutic use

OBJECTIVETo investigate effects of glucose excursion on the oxidative/antioxidative system in subjects with different types of glucose regulation.

METHODSA total of 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR) and 27 subjects with newly diagnosed type 2 diabetes mellitus (T2DM) were selected and recruited for 3 days' continuous glucose monitor system (CGMS) assessment. The data from CGMS was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), area under the ROC curve when the blood glucose >5.6 mmol/L within 24 h (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE). In all groups, the content or activity of malondialdehyde (MDA), total antioxidation capacity (TAOC) and glutathione peroxidase (GSH-Px) were detected.

RESULTSGlucose excursion parameters of subjects with T2DM or IGR were higher than those of NGR subjects (P<0.05 or 0.01). Moreover, Glucose excursion parameters of T2DM subjects were higher than those of IGR subjects (P<0.05 or 0.01). Subjects with T2DM or IGR had significant higher MDA levels and lower GSH-Px/MDA and TAOC/MDA levels compared to NGR subjects (P<0.01). T2DM subjects had even higher MDA levels and lower GSH-Px/MDA levels than IGR (P<0.05 or 0.01). According to the median of normal population for MAGE, T2DM and IGR subjects were divided into MAGE>2.6mmol/L Group and MAGE ≤ 2.6mmol/L Group. MAGE>2.6mmol/L Group had higher levels of MDA and lower levels of GSH-Px/MDA than MAGE ≤ 2.6mmol/L Group (P<0.05). There was no significant difference between the two groups (P>0.05) in terms of the levels of TAOC/MDA. Pearson correlation analysis showed that MDA was positively correlated with FPG, 2hPG, MAGE, and SBP. GSH-Px/MDA was negatively correlated with MAGE and TC. TAOC/MDA was negatively correlated with FPG. Partial correlation analysis showed that the relationship between MDA and MAGE, GSH-Px/MDA, and MAGE remained significant after adjustments for the other differences among groups.

CONCLUSIONGlucose excursion contributed significantly to promoting lipid peroxidation and decreasing antioxidation capacity than chronic sustained hyperglycemia did in the subjects with different types of glucose regulation.

Adult ; Antioxidants ; metabolism ; Blood Glucose ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Oxidation-Reduction

BACKGROUNDAlthough thrombolytic therapy with rescue percutaneous coronary intervention (PCI) is a common treatment strategy for ST-segment elevation acute myocardial infarction (STEMI), scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study.

METHODSThis multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients (age < or = 70 years) with STEMI who presented within 12 hours of symptom onset (mean interval > 3 hours). Patients were randomized to three groups: primary PCI group (n = 101); recombinant staphylokinase (r-Sak) group (n = 104); and recombinant tissue-type plasminogen activator (rt-PA) group (n = 106). For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery (IRA) patency; rescue PCI was performed in cases with TIMI flow grade < or = 2. Bare-metal stent implantation was planned for all patients.

RESULTSAfter randomization it required an average of 113.4 minutes to start thrombolytic therapy (door-to-needle time) and 141.2 minutes to perform first balloon inflation in the IRA (door to balloon time). Rates of IRA patency (TIMI flow grade 2 or 3) and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure (70.5% vs. 98.0%, P < 0.0001, and 53.0% vs. 85.9%, P < 0.0001, respectively). Rescue PCI with stenting was performed in 117 patients (55.7%) in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group (88.9% vs. 97.9%, P = 0.0222, and 68.4% vs. 85.0%, P = 0.0190, respectively). At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group (7.1% vs. 0, P = 0.0034). Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group (10.0% vs. 1.0%, P = 0.0380, and 28.10% vs. 8.91%, P = 0.0001, respectively).

CONCLUSIONSThrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Thrombolytic Therapy