Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

In recent years, it is found that the classical IKKα and IKKβ pathway were closely relates with hematological tumors, except the classical pathogenesis, moreover the classical IKKβ pathway is deeply studied. The studies indicated that the IKKβis activated to phosphorylate the NF-κB through multiple cascades under the effect of extracellular IL-6, TNF-α and other stimulating factors. At the cellular level, the classical IKKβcan promote the tumor cell survival and proliferation, reduce the cell apoptosis, and promote the angiogenesis and cell transfer. Although the classical IKKα plays a role in regulating IKKβ activity, but its role in non-classical pathway is more prominent. This review briefly summarizes the latest advance of researches on the pathogenesis of hematological malignancies in term of IKKα and IKKβpathway, so as to provide the theoretic basis for deeply understanding and studying the pathogenesis of hematologic tumors. At present, blocking the classical IKKα and IKKβ pathway has become a new target for treatment of hematological tumors, moreover, some specific inhibitor for IKKα and IKKβpathway have been developed, for example, LY2409881, BMS 345541 and so on. Most of these drugs are in clinical trials and display some good anti-tumor effects.
Cell Survival ; Hematologic Neoplasms ; Humans ; I-kappa B Kinase/metabolism* ; NF-kappa B/metabolism* ; Signal Transduction ; Tumor Necrosis Factor-alpha

Visual fixation is an item in the visual function subscale of the Coma Recovery Scale-Revised (CRS-R). Sometimes clinicians using the behavioral scales find it difficult to detect because of the motor impairment in patients with disorders of consciousness (DOCs). Brain-computer interface (BCI) can be used to improve clinical assessment because it directly detects the brain response to an external stimulus in the absence of behavioral expression. In this study, we designed a BCI system to assist the visual fixation assessment of DOC patients. The results from 15 patients indicated that three showed visual fixation in both CRS-R and BCI assessments and one did not show such behavior in the CRS-R assessment but achieved significant online accuracy in the BCI assessment. The results revealed that electroencephalography-based BCI can detect the brain response for visual fixation. Therefore, the proposed BCI may provide a promising method for assisting behavioral assessment using the CRS-R.
Adolescent ; Adult ; Aged ; Brain ; physiopathology ; Brain-Computer Interfaces ; Consciousness Disorders ; diagnosis ; physiopathology ; Diagnosis, Computer-Assisted ; methods ; Electroencephalography ; methods ; Evoked Potentials ; Female ; Fixation, Ocular ; physiology ; Humans ; Male ; Middle Aged ; Neurologic Examination ; Pilot Projects ; Severity of Illness Index ; User-Computer Interface

OBJECTIVETo investigate the trichostain A (TSA)-induced expression of costinmulatory molecules CD80 and CD86 in HL-60, K562 and mononuclear cells (MNC) of bone marrow in AML patients and its clinical significance.

METHODSThe TSA-induced expression of costimulatory molecules CD80, CD86 in HL-60, K562 and BMMNC, and the cell viability were detected by flow cytometry; the mRNA expression of CD80 and CD86 was detected by RT-PCR; after the TSA-induced HL-60 cells and K562 cells were irradiated with 75 Gy, the effect of these cells on proliferation of PBMNC from healthy volunteers was determined with CCK-8 method.

RESULTSThe HL-60 cells and BMMNC in AML patients expressed CD86, not expressed CD80, while the K562 cells not expressed CD86 and CD80. TSA could up-regulate the expression of CD86 in HL-60 cells and BMMNC of AML patients. The TSA-induced HL-60 cells expressing costimulatory molecule CD86 showed the proliferative effect on BMMNC from healthy volunteers.

CONCLUSIONThe TSA can induce the expression of costimulatory molecule CD86 in HL-60 cells and BMMNC in AML patients, and can improve the proliferation of PBMNC in healthy volunteers.

BACKGROUND:The rabbits were widely used as experimental animal models in the research on etiology and pathological mechanism of steroid-induced osteonecrosis of the femoral head. It is stil a valuable and realistic research topic to improve and to innovate the modeling technology nowadays. OBJECTIVE:To improve the modeling technology on osteonecrosis of the femoral head in rabbits induced by glucocorticoid combined with lipopolysaccharide, with the focus on its reduced mortality and the guaranteed successful rate of modeling. METHODS:A total of 28 New Zealand white rabbits were randomly divided into the control group (n=10) and improvement group (n=18). Models of steroid-induced osteonecrosis of the femoral head were established according to different methods. In the improvement group, rabbits were injected with sodium penicilin (5.0 mg/kg) and amikacin sulfate (1.63×104 U/kg) in the left gluteus muscle. Twenty-four hours later, al rabbits were injected with prednisolone acetate (20 mg/kg) in the right gluteus muscle. Forty-eighthours later, 5.0 μg/kg of lipopolysaccharide was intravenously injectedvia the ear. From then on, two injections of prednisolone acetate (20 mg/kg) were respectively performed alternately in the left and right gluteal muscle at an interval of each 24 hours. Sodium penicilin (5.0 mg/kg) and amikacin sulfate (1.63×104 U/kg) were intraperitonealy injected for 2 consecutiveweeks. In the control group, 10 μg/kg lipopolysaccharide was injectedvia the ear vein of rabbit. From then on, prednisolone acetate (20 mg/kg) was intramuscularly injected at an interval of each 24 hours, totaly three times. Benzylpenicilin sodium 20×104 U/rabbit was intramuscularly injected once a week. RESULTS AND CONCLUSION:Rabbit models of steroid-induced osteonecrosis of the femoral head were successfuly established in both groups. Compared with the control group, the mortality was significantly reduced after model establishment in the improvement group, and the bone lacuna and osteonecrosis of the femoral head were apparent. These findings indicated that the improved technology of model establishment of steroid-induced osteonecrosis of the femoral head could be used to aleviate the damage degree on the gluteal muscles, to guarantee the successful rate of modeling, and to noticeably reduce the mortality of rabbits.

ObjectiveTo investigate the curative effect and prognostic impact of radical resection assisted by transcatheter arterial chemoembolization (TACE) in the treatment of intrahepatic cholangiocarcinoma (ICC). MethodsThe clinical data of 80 patients with ICC who were admitted to the Department of Hepatobiliary Surgery in our hospital from January 2008 to December 2010 were retrospectively analyzed. Thirty-five patients in the control group received radical resection, while forty-five patients in the observation group received adjuvant TACE therapy following radical resection. The curative effect and survival time were compared between the two groups. Comparison of continuous data between the two groups was made by t test, and comparison of categorical data was made by chi-square test. ResultsThe observation group had significantly lower serum levels of alpha-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9, and alanine aminotransferase than the observation group at 6 months after surgery (47.35±13.76 vs 83.54±24.17 μg/L, t=19.58, P＜0.05; 30950±125.55 vs 37585±136.77 μg/L, t=101.33, P＜0.05; 20.86±10.38 vs 34.18±8.55 ng/ml, t=29.46, P＜0.05; 25.44±819 vs 58.56±22.58 U/L, t=32.25, P＜0.05). The 1-year, 2-year, and 3-year survival rates in the observation group were significantly higher than those in the control group (χ2=11.43, P＜0.05; χ2=20.15, P＜0.05; χ2=9.87, P＜0.05). The mean survival period was significantly longer in the observation group than in the control group (t=15.38, P＜0.05). According to the analysis of factors influencing the survival period in patients with ICC, patients with a tumor size larger than 5.0 cm, a low degree of differentiation, and metastasis had a significantly lower long-term survival rate and a significantly shorter mean survival period than other patients (P＜0.05). ConclusionThe adjuvant TACE therapy after radical resection is a safe and effective method in the treatment of ICC. The tumor size, degree of differentiation, portal vein tumor thrombus, and metastasis have a strong prognostic impact.

This study was aimed to elucidate the expression of costimulatory molecule CD80 and CD86 in HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Acute myelocytic leukemia cell line HL-60 and chronic myelocytic leukemia cell line K562 were cultured. The viability of the cells was measured by flow cytometry. Proteasome inhibitor MG132 at the concentrations of 2 or 3 µmol/L was used to stimulate the HL-60 cell cultured for 24 h and 48 h respectively, and the Annexin V/7-AAD staining and flow cytomotry were used to detect the apoptosis of the HL-60 cells. HL-60 and K562 cells were treated with 1 µmol/L MG132 for 24 h and 48 h respectively, then CD80 and CD86 antibodies were added, finally the expression of CD80 and CD86 was analysed by flow cytomery. The mRNA expression of CD86 in the HL-60 cells treated with 1 µmol/L MG132 was detected by RT-PCR. HL-60 and K562 cells were treated by 1 µmol/L MG132 and then underwent irradiation of 75 Gy (60)Co to kill the cells with their antigenicity preserved. Peripheral blood mononuclear cells (PBMNCs) of healthy volunteers, as reactive cells, were isolated and inoculated into the (60)Co irradiated HL-60 cells of different concentrations, as stimulating cells, CCK-8 was added and then the A value of absorbance was measured at the wave length of 450 nm in an enzyme labeling instrument. The results showed that the cell viability of the HL-60 cells treated with 1 µmol/L MG132 for 24 h an d 48 h was 92.95% and 85.87% respectively. The apoptotic rates of the HL-60 cells treated with MG132 increased in dose-and time-dependent manner. High-concentration of MG132 directly killed HL-60 cells. Before MG132 treatment K562 cells did not express CD86, but the CD86 expression of the HL-60 cells was up-regulated time-dependently after MG132 treatment (P < 0.01). The mRNA expression of CD86 in the HL-60 treated with MG132 was up-regulated time-dependently (P < 0.01). CCK-8 test showed that the proliferation level of PBMNC gradually increased along with the concentration of HL-60 cells treated with MG132 and reached its peak when the concentration of the HL-60 cells was 1×10(5) (P < 0.01). No remarkable proliferation of PBMNC was observed in the K562 groups no matter if the HL-60 cells had been treated with MG132. It is concluded that the high concentration of MG132 can directly kill HL-60 cells, low-concentration of MG132 can induce the expression of costimulatory molecule CD86 in HL-60 cells, also can improve the proliferation of PBMNC.
Apoptosis ; B7-2 Antigen ; immunology ; Cell Survival ; Flow Cytometry ; HL-60 Cells ; Humans ; K562 Cells ; Leukocytes, Mononuclear ; drug effects ; Leupeptins ; pharmacology ; Lymphocyte Culture Test, Mixed ; Proteasome Inhibitors ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation

The purpose of this study was to elucidate the apoptosis, apoptotic pathway of HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Apoptosis of HL-60 cells was detected by flow cytometry, the expression of P21, P27 and P53 proteins in HL-60 cells treated with MG132 was assayed by Western blot. The HL-60 cells were treated with 1 µmol/L MG132 for 48 h, and irradiated by 75 Gy of (60)Co γ-ray, but their antigenicity was preserved. The effect of irradiated HL-60 cells treated with MG132 on proliferation of peripheral blood mononuclear cells (PBMNC) was measured by CCK-8 method. The results showed that the apoptotic rate of MG132-treated HL-60 cells increased in dose-and time-dependent manner. No significant changes in MG132-induced apoptosis were observed after inhibiting caspase-8 and caspase-9 pathway. The expression of P21 and P27 protein increased after treatment of HL-60 cells with MG132. CCK-8 test showed that HL-60 cells induced with low-dose of MG132 displayed the enhancing effect on proliferation of PBMNC. It is concluded that high dose of MG132 can induce the apoptosis of HL-60 cells, and has direct killing effect on HL-60 cells, but this inducing apoptotic effect on HL-60 cells can not be realized through caspase-8 and caspase-9 pathway. The P21 and P27 protein may be involved in MG132 induced HL-60 cell apoptosis. Low dose of MG132 promotes the proliferation of PBMNC in healthy individuals and enhance the immunity of organism.
Apoptosis ; drug effects ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; HL-60 Cells ; Humans ; Leupeptins ; pharmacology ; Proteasome Inhibitors ; pharmacology

The present study was aimed to investigate the function of diffusion weight imaging (DWI) combining with magnetic resonance spectroscopy (MRS) in the grading of brain gliomas. 12 cases low grade and 17 cases high grade of brain gliomas patients were examined with DWI and MRS, with all tumors confirmed by pathology in advance. The apparent diffusion coefficient (ADC) values, their corresponding metabolite ratios of Cho/Cr, Cho/NAA and tumor cellularities of tumor solid enhanced parts were measured. The ratios of Cho/Cr and Cho/NAA and their corresponding ADC values had significant differences between their high and low grade gliomas values, respectively. The ADC values demonstrated a negative correlation with Cho/Cr, Cho/NAA, and a significant negative correlated with Cho/Cr. And the ADC values demonstrated strong negative correlations with tumor cellularities. DWI combining with MRS could provide more valuable information in evaluating gliomas grading.
Adolescent ; Adult ; Aged ; Brain Neoplasms ; diagnosis ; pathology ; Child ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Glioma ; diagnosis ; pathology ; Humans ; Hydrogen ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Neoplasm Grading ; Young Adult