T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell transfer immunotherapy.

Background: Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation. Methods: Sixty H22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 106 T cells from HIFU treated-mice were intravenously injected into each syngeneic H22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer. Results: T cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs (p < 0.001), with a significant increase of TNF-α (p < 0.001) and IFN-γ secretion (p < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand+ and perforin+ tumor-infiltrating lymphocytes (TILs) and apoptotic H22 tumor cells were significantly higher (p < 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand+ TILs (r = 0.9145, p < 0.001) and perforin+ TILs (r = 0.9619, p < 0.001). Conclusion: T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.

Preoperative laser reduces silicone oil use in primary diabetic vitrectomy.

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.

[Effect of Different Cationic Polyacrylamide Organic Dehydrating Agents on Sludge Dewatering Performance].

To study the effect of different cationic polyacrylamide organic dehydrating agents on sludge dewatering performance, eight commercially available cationic polyacrylamides of the same series with different properties were used. Based on the different cationic degree, they were named 9101, 9102, 9103, 9104, 9106, 9108, 9110, and 9112, respectively. Their properties were characterized by instruments and chemical analysis, and the indexes of sludge after treatment were also measured. The results showed that the properties of the eight organic dehydrants were different, among which the charge density, cationicity, viscosity, and Zeta potential had homologous trends, which all increased gradually from 9101 to 9112. The four indexes of 9112 were as high as 2.98 meq·L-1, 17.42%, 85.07 mPa·s, and 67.10 mV, respectively. The dewatering performance of sludge was improved by improving the specific resistance of filtration (SRF), floc properties, viscosity, Zeta potential, the bound water content, and the distribution of extracellular polymeric substances (EPS) after dosing organic dewatering agents. The results showed that the viscosity, charge density, cationic degree, and Zeta potential of the dewatering agents had a great influence on the sludge dewatering performance. The SRF of sludge was negatively correlated with the viscosity of the organic dewatering agent, and the correlation coefficient was as high as 0.92025, indicating that the sludge dewatering performance was improved mainly through the adsorption bridging effect of the organic dewatering agent in sludge dewatering.

Risk Factors for Dysphagia after Anterior Cervical Discectomy and Fusion with the Zero-P implant system: A Study with Minimum of 2 Years Follow-up.

OBJECTIVE: To evaluate the risk factors for dysphagia after anterior cervical discectomy and fusion (ACDF) with the Zero-P Implant System by multidimensional analysis and investigated the predictive values of these risk factors for dysphagia. METHODS: A retrospective analysis of 260 patients who underwent ACDF with the Zero-P Implant System and had at least 2 year of follow-up were performed. All patients were divided into a non-dysphagia group and a dysphagia group. Sex, age, body mass index (BMI), intraoperative time, estimated blood loss, diabetes mellitus, hypertension, smoking, alcohol consumption, prevertebral soft-tissue thickness, the levels of surgery, O-C2 angle, C2-7 angle, T1 slope and segmental angle were analyzed. The Modified Japanese Orthopaedic Association (JOA) scoring system was used to determine functional status. NDI was used to evaluate neck pain and disability. The Bazaz grading system was chosen to evaluate dysphagia after surgery. Postoperative cerebrospinal fluid (CSF) leakage, infection, and dysphagia were recorded in both groups. An independent t-test was used to compare quantitative variables, a chi-square test was used to compare qualitative data between the two groups. To eliminate the influence of confounding factors, logistic regression was performed for multifactor regression of factors. The results were regarded as significant when the P-values were less than 0.05 in this study. RESULTS: In total, the non-dysphagia group comprised 70 patients and the dysphagia group comprised 190 patients, with an average age of 58.33 ± 4.68 years (ranging, 42-82 years). These patients were followed up for 28.5 ± 3.5 months (range, 24-32 months). For clinical outcomes, both groups demonstrated significant improvement in the NDI and JOA scores (P < 0.001). According to the Bazaz dysphagia grading system, mild, moderate, and severe dysphagia were found in 50, 17, and 3 patients, respectively. In total, 37.1% (n = 26) had resolved by 3 month, 38.6% (n = 27) by 6 months, and 17.1% (n = 12) by 12 months. Chi-square test results indicated that number of operated levels, operation time dT1 slope, dO-C2 angle, dC2-7 angle, segmental angle and dPSTT were associated with a high incidence of dysphagia. Multivariate logistic regression analysis showed that number of operated levels, operation time, dC2-7 angle and dPSTT were significantly associated with postoperative dysphagia. CONCLUSIONS: More operated levels, more operation time, more dC2-7 angle and dPSTT were the risk factors for postoperative dysphagia. In additional, sufficient preoperative preparation, evaluation combined with proficient and precise surgical treatment were suggested to reduce the incidence of postoperative dysphagia when ACDF was performed.

Noise reduction in low-dose computed tomography with noise equivalent image and deep learning / 中华放射医学与防护杂志

Objective:To investigate the method of simulating low-dose CT (LDCT) images using routine dose level scanning mode to generate LDCT images with correspondence to the routine dose CT (RDCT) images in the training sets for deep learning model, which would be used for LDCT noise reduction.Methods:The CT images reconstructed by different algorithms in Philips CT Big Core had different noise levels, where the noise was larger with iDose 4 algorithm and lower with IMR(knowledge-based iterative model reconstruction)algorithm. A new method of replacing LDCT image with noise equivalent reconstructed image was proposed. The uniform module of CTP712 was scanned with the exposure of 250 mAs for RDCT, 35 mAs for LDCT. The images were reconstructed using IMR algorithm for LDCT images and iDose 4 algorithm at multiple noise reduction levels for RDCT images, respectively. The noise distribution of each image set was analyzed to find the noise equivalent images of LDCT. Then, RDCT images, those selected images were used for training cycle-consistent adversarial networks (CycleGAN)model, and the noise reduction ability of the proposed method on real LDCT images of phantom was tested. Results:The RDCT images generated with iDose 4 level 1 could substitute the LDCT images reconstructed with IMR algorithm. The radiation dose was reduced by 86% in low dose scanning. Using CycleGAN model, the noise reduction degree was 45% for uniform module, and 50%, 13%, 7% for CIRS-SBRT 038 phantom in the specific regions of brain, spinal cord, bone, respectively. Conclusions:Equivalent noise level reconstructed images could potentially serve as the alternative of LDCT images for deep learning network training to avoid additional radiation dose. The generated CT images had substantially reduced noise relative to that of LDCT.

NS1: A Key Protein in the "Game" Between Influenza A Virus and Host in Innate Immunity.

Since the influenza pandemic occurred in 1918, people have recognized the perniciousness of this virus. It can cause mild to severe infections in animals and humans worldwide, with extremely high morbidity and mortality. Since the first day of human discovery of it, the "game" between the influenza virus and the host has never stopped. NS1 protein is the key protein of the influenza virus against host innate immunity. The interaction between viruses and organisms is a complex and dynamic process, in which they restrict each other, but retain their own advantages. In this review, we start by introducing the structure and biological characteristics of NS1, and then investigate the factors that affect pathogenicity of influenza which determined by NS1. In order to uncover the importance of NS1, we analyze the interaction of NS1 protein with interferon system in innate immunity and the molecular mechanism of host antagonism to NS1 protein, highlight the unique biological function of NS1 protein in cell cycle.

Artificial dermis combined with KCI negative pressure suction device in repair of skull exposure after scalp malignant tumor surgery / 中华医学美学美容杂志

Objective:To investigate the effect of artificial dermis combined with KCI negative pressure suction device in the repair of scalp defect with skull exposure after the operation of scalp malignancy.Methods:From January 2016 to June 2018, 18 patients with scalp defect and skull exposure after scalp malignant tumor surgery were treated with artificial dermis combined with KCI negative pressure suction device.Results:Eighten patients had good wound healing after the first stage of surgery, and no infection occurred. The time for artificial dermis to complete granulation was 10-14 days, with an average of 12.1 days. After the second stage of skin grafting, the skin graft had a survival rate of 100%, with uniform color and good elasticity, without obvious scar hyperplasia or contracture. The postoperative follow-up period was 6 to 2 months, all the patients healed well without tumor recurrence, with good skin elasticity and friction-resistant, and they were satisfied.Conclusions:Artificial dermis combined with KCI negative pressure suction device is an effective and simple method to repair the scalp defect with skull exposure after tumor surgery.

Application of visual feedback coaching bar in deep inspiration breath holding during left breast cancer radiotherapy / 中华放射肿瘤学杂志

Objective:To evaluate the application of visual feedback coaching method, which is embedded in an optical surface monitoring system, in deep inspiration breath holding during the radiotherapy in left breast cancer patients after breast-conserving surgery.Methods:Thirty patients with left breast cancer, who were scheduled to receive the whole breast radiotherapy after breast-conserving surgery, met the requirements of deep inspiration breath holding after respiratory coaching with the visual feedback coaching module in the optical surface monitoring system. Active breathing control equipment was used to control breath-holding state and CT simulation was performed. During treatment, optical surface monitoring system was used to guide radiotherapy. All patients were randomly divided into two groups. In group A ( n=15), visual feedback respiratory training method was utilized and not employed in group B ( n=15). In group A, the visual feedback coaching bar of the optical surface monitoring system was implemented, while audio interactive method was employed to guide patients to hold their breath. Real-time data of optical body surface monitoring were used to compare the interfraction reproducibility and intrafraction stability of breath holding fraction between two groups. Besides, the number of breath holding and treatment time per fraction were also compared. GraphPad prism 6.0 software was used for data processing and mapping, and SPSS 21.0 software was used for analyzing mean value and normality testing. Results:Compared with the control group, the reproducibility in the experiment group was reduced from 1.5 mm to 0.7 mm, the stability was reduced from 1.1 mm to 0.8 mm, the mean number of breath holding required per fraction was decreased from 4.6 to 2.4, the mean beam-on time per fraction from 336 s to 235 s, and the treatment time per fraction was shortened from 847 s to 602 s (all P<0.05), respectively. Conclusions:The application of visual feedback coaching method can improve the reproducibility and stability of breath holding during radiotherapy for left breast cancer, and it can also effectively reduce the number of breath holding and shorten the treatment time per fraction.

Association of University Reopening Policies with New Confirmed COVID-19 Cases in the United States

ImportanceReopening of universities in the U.S. has been controversial in the setting of the coronavirus disease 2019 (COVID-19) pandemic. ObjectiveTo investigate (1) the association between new COVID-19 cases since September 1st with the number of students returning to campus in each county across the U.S. and (2) how different reopening policies at universities correlated with new COVID-19 cases. DesignObservational cohort study using publicly available data sources. Multivariable regression models estimated both effects of university reopening and different reopening policies. Settings and ParticipantsPopulations in U.S. counties reporting new confirmed COVID-19 cases from August 1st to October 22nd. Exposures(1) total enrollment of students under the in-person or hybrid policies per county population and (2) proportion of online and hybrid enrollment within each county. Main Outcomes and MeasuresMean number of daily new confirmed COVID-19 cases per 10,000 county population from September 1st to October 22nd. ResultsFor 2,893 counties included in the study, mean number of daily confirmed cases per 10,000 county population rose from 1.51 from August 1st to August 31st to 1.98 from September 1st to October 22nd. Mean number of students returning to universities was 2.1% (95% CI, 1.8% to 2.3%) of the county population. The number of students returning to campus had an increased association ({beta} = 2.006, P < 0.001) with new confirmed COVID-19 cases within the local county region where the institution resided. For 1,069 U.S. counties with universities, the mean proportion of online enrollment within each county was 40.1% (95% CI, 37.4% to 42.8%), with most students enrolling in-person or hybrid mode. In comparison to holding classes in-person, reopening universities online ({beta} = -0.329, P < 0.001) or in a hybrid mode ({beta} = -0.272, P = 0.012) had a decreased association with new confirmed COVID-19 cases. Conclusions and RelevanceA higher number of students returning to campus in U.S. counties was associated with an increase in new confirmed COVID-19 cases; reopening online or partially online was associated with slower spread of the virus, in comparison to in-person reopening. Key PointsO_ST_ABSQuestionC_ST_ABSAre students returning to universities and specific reopening policies associated with new confirmed coronavirus cases in United States? FindingsIn this cohort study of 2,893 U.S. counties, the number of students returning to campus was significantly associated with a higher number of new confirmed COVID-19 cases. In 1,069 U.S. counties with universities, online or hybrid reopening was significantly associated with a lower risk of new cases compared with in-person reopening. MeaningAn increased risk of coronavirus infection was seen in surrounding regions after universities reopened last fall, and this effect was largest in those holding in-person classes.

Effect of inhibitor of differentiation 1 deficiency on ocular neovascularization / 上海交通大学学报（医学版）

Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.

Advances of optimized neoadjuvant therapy in the treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Neoadjuvant chemoradiotherapy is the current standard of care for locally advanced rectal cancer. However, this modality is facing more and more challenges. The research progress on this issue around the world can be summarized into three aspects. The first is to increase the intensity of treatment to obtain better tumor regression, such as adding a second drug during the neoadjuvant chemoradiotherapy, prolonging the interval and receiving sufficient chemotherapy before surgery. Current research data are not sufficient to support strategies for adding drugs or receiving sufficient chemotherapy before surgery, but it may be worth looking forward to adding irinotecan during neoadjuvant chemoradiotherapy, and an appropriate extension of the interval before surgery may also be a good option. Secondly, we can reduce the intensity of treatment to improve the quality of life of patients with a non-inferior clinical outcome, such as non-surgical approach, local excision rather than total mesorectal excision and removal of preoperative radiotherapy. The data of the International Watch & Wait Database (IWWD) suggest that patients with a Watch & Wait strategy have similar long-term survival outcomes as those who have undergone surgery and have pathologic complete response, meanwhile the data are still inadequate to support using local excision instead of total mesorectal excision, or removal of preoperative radiotherapy strategies. Finally, to achieve a precise individual treatment, some potential biomarkers are investigated via genomics, metabolomics and radiomics. But so far, there is no recognized biomarker for clinical treatment in the field of neoadjuvant therapy for rectal cancer. This article summarizes the clinical research progress of locally advanced rectal cancer in recent years from the above three aspects.

Fudan experience of neoadjuvant treatment for rectal cancer / 中华胃肠外科杂志

Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. Fudan University Shanghai Cancer Center has carried out multiple series of studies to explore the optimization of the neoadjuvant therapy since 2005. On the one hand, the "addition" method refers to a higher intensity treatment at the neoadjuvant stage to obtain better tumor regression. On the other hand, the "subtraction" method reduces some unnecessary treatment from the current triad of surgery, radiotherapy and chemotherapy to improve the quality of life of patients. However, locally advanced rectal cancer is associated with great heterogeneity, and therefore, any single treatment mode will not be optimal for all. Notably, the treatment decision-making should be based on clinical presentations, imaging findings, and molecular biology to precisely stratify patients. Besides, the scheme should be dynamically adjusted according to the therapeutic response, so as to realize the dual goals of prolonging patients′ life and improving their quality of life. Meanwhile, the treatment decision-making for target population under the guidance of biomarker should be dynamically and self-adaptively adjusted based on the therapeutic effect. This approach will become the future development direction and objective for the precise medical treatment for rectal cancer.

Clinical analysis of the correlation between transverse sinus drainage dominance and aneurysm formation and rupture / 中国神经精神疾病杂志

To investigate the clinical correlation between transverse sinus classification and variation and aneurysm formation and rupture and to determine the risk factors of intracranial aneurysm rupture. Methods A retrospective data analysis was conducted on a total of 345 cases of intracranial aneurysms from January to December 2018. Clinical characteristics were compared between ruptured aneurysm group (RAG, n=230) and unruptured aneurysms group (URAG, n=115). Logistic regression analysis was performed to analyze the anatomy of venous sinus and clinical features including smoking history, hypertension, diabetes, location and size of the aneurysm in patients with intracranial aneurysm rupture. Results There were significant differences in had statistical significance with the patients' drinking history, smoking history, hypertension, diabetes, location and size of the aneurysm, as well as the dominant venous sinus on the same side as the aneurysm between rupture of intracranial aneurysm group and unruptured aneurysms group (P＜0.05). Multivariate logistic regression analysis suggested that diabetes (OR=10.567), anterior communication (OR=2.214), posterior communication (OR=2.932), small aneurysms (OR=3.841), dominant venous sinus on the same side as the aneurysm (OR=1.736) were independent risk factors for rupture of the unruptured aneurysm. In addition, the dominant side of transverse sinus were more likely to form intracranial aneurysms (P＜0.001). Conclusion The predisposing factors for rupture of intracranial aneurysms are anterior communication, posterior communication, small aneurysms and dominant lateral venous sinuses on the same side as aneurysms. Ipsilateral aneurysms are more likely to form in patients with dominant venous sinuses and can be used to accurately predict aneurysm rupture.

Irinotecan plus cisplatin compared with etoposide plus cisplatin in patients with previously untreated extensive-stage small cell lung cancer: A meta-analysis.

OBJECTIVE: To systematically review the effect and safety of irinotecan plus cisplatin (IP) compared with etoposide plus cisplatin (EP) in patients with previously untreated extensive-stage small cell lung cancer (E-SCLC). MATERIALS AND METHODS: Databases including PubMed, The Cochrane Library, EMBASE, China National Knowledge Infrastructure, VIP, and WanFang Data were searched for the randomized controlled trials (RCTs) about IP compared with EP in patients with previously untreated E-SCLC from the establishment to June 2016. Two reviewers independently screened literature, extracted data and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.3 software (Cochrane Collaboration, Oxford, UK). RESULTS: A total of 12 RCTs involving 2030 patients were finally included. Meta-analysis showed that compared with EP regimen, IP regimen significantly improved the 1- and 2-year survival rates of the patients with previously untreated E-SCLC (risk ratio [RR] = 1.16, 95% confidence interval [CI] [1.03-1.31], P = 0.02; RR = 1.79, 95% CI [1.22-2.61], P = 0.003, respectively). However, there was no significant difference between IP regimen and EP regimen in the objective response rate (ORR) (RR = 1.07, 95% CI [0.99-1.15], P = 0.10) and disease control rate (DCR) (RR = 1.03, 95% CI [0.96-1.10], P = 0.38). The incidence of Grade 3/4 leukopenia, neutropenia, anemia, and thrombocytopenia of IP regimen was sigificantly lower than EP regimen (all P < 0.05), the incidence of Grade 3/4 nausea/vomiting and diarrhea of IP regimen was sigificantly higher than EP regimen (all P < 0.05). CONCLUSION: IP regimen significantly improves the 1- and 2-year survival rates, but not significantly improves the ORR and DCR, compared with EP regimen in patients with previously untreated E-SCLC. IP regimen has less Grade 3 or 4 hematological adverse events. IP regimen is an alternative of EP regimen in patients with previously untreated E-SCLC.

Down regulation of G protein-coupled receptor 137 expression inhibits proliferation and promotes apoptosis in leukemia cells.

BACKGROUND: G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment. MATERIALS AND METHODS: In this study, lentivirus-mediated RNA interference (RNAi) was employed to investigate the role of GPR137 in two leukemia cell lines K562 and HL60. The gene expression of GPR137 was analyzed by RT-PCR and its protein expression was determined by Western blot. Flow cytometry and Annexin V/7-AAD Apoptosis Detection Kit was used respectively in cell cycle and apoptosis analysis. The protein expression of CyclinD1, CDK4, BCL-2 and caspase-3 were also determined. RESULTS: There was high level of constitutive expression of GPR137 in leukemia cancer cell lines K562 and HL60. Lentivirus-mediated RNAi could significantly down-regulate gene and protein expression of GPR137 in both cell lines. Down regulation of GPR137 was associated with the reduction in proliferation rate and colony forming capacity. In addition, down regulation of GPR137 arrested cells in the G0/G1 phase of cell cycle and induced apoptosis in both leukemia cell lines K562 and HL60. CONCLUSIONS: The expression of GPR137 is associated with the proliferation of leukemia cell lines. Down regulation of GPR137 could inhibit proliferation and promote apoptosis in leukemia cells, which makes it a promising bio-marker and therapeutic target to treat patients with leukemia.

Knockdown of immature colon carcinoma transcript 1 induces suppression of proliferation, S-phase arrest and apoptosis in leukemia cells.

Immature colon carcinoma transcript 1 (ICT1), a human mitochondrial translation release factor, is a ribosome-dependent codon-independent peptidyl-tRNA hydrolase. ICT1-deficiency has been recognized as a cell growth inhibitor of hepatoblastoma and glioblastoma multiforme. To explore the role of ICT1 in human leukemia, 2 short hairpin RNAs (shRNAs) targeting ICT1 sequences were designed in leukemia U937 cells. The successful infection of ICT1 in the U937 cells was observed under a fluorescence microscope and further quantified by western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tetrazolium dye (MTT) assay revealed a significant decrease in proliferation of ICT1-knockdown U937 cells on the fourth and fifth day as compared with the control. Depletion of ICT1 resulted in an increase in S phase and sub-G1 (representing cell apoptosis) fractions. Annexin V-APC/7-AAD staining assay confirmed that knockdown of ICT1 played a crucial role in boosting early and late apoptotic programs in U937 cells. Downregulation of ICT1 also altered cyclin A2 transcription expression, caspase-3 activity and p21 protein expression. Additionally, decreased levels of heat shock protein 27 (HSP27) phosphorylation at Ser78 was correlated with knockdown of ICT1 in U937 cells. Thus, we concluded that the regulatory role of ICT1 in leukemia may be used as a potential therapeutic target for the treatment of leukemia.

Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells.

Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia.

Killing effect of CIK cells combined with Gemcitabine on QBC939 cells / 中国现代普通外科进展

Objective:To investigate the anti-tumor effects of cytokine-induced kill cells(CIK)methods combined with chemotherapeuticdrug Gemcitabine against Cholangiocarcinoma cancer cell lines QBC-939.Methods:Peripheral blood mononuclear cells(PBMC) of healthy people were stimulated by different cytokines,and were induced into CIK cells.CIK cells were cultured for 14 days as effector cells.The phenotype of CIK cells were analyzed by flow cytometer.QBC939 cells were cultured with the CIK cells at different effector-target ratio or various concentrations of Gemcitabine for 24 and 48 hours.The antitumor effects were measured by CCK8 methods.The expression of Bax was detected by using Western blot.Results:The CD3+CD4+,CD3+CD8+,CD3+HLA-DR+,CD3+CD56+,CD4+CD25+ double positive cel1 was up to 10.89％,60.27％,71.82％,9.03％ and 4.01％ after 14 days' cultivation.The killing effect of CIK and Gemcitabine increased with the increase of effector-target ratio and drug concentration or the extension of time.The killing effect of combination of CIK and Gemcitabine was obviously higher than that of each single factor.The protein levels detected hints of CIK cells and gemcitabine can up-regulated the expression of Bax,and the joint action of both is more significant.Conclusions:CIK cells have strong anti-tumor effect against QBC939 cells by inducing apoptosis of QBC939 cells,and it can enhance the anti-tumor effects of Gemcitabine against QBC939 cells when CIK and Gemcitabine are combined together.

Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia.

BACKGROUND: Pharmacological management of acute leukemia remains a challenge. A seashell protein Haishengsu (HSS) has been found to exert anticancer activities in recent in vitro studies. The aim of this study was to determine whether the addition of HSS to the conventional chemotherapies would increase chemosensitivity and improves quality of life in patients with acute leukemia. METHODS: Two hundred and forty-eight patients with acute leukemia were enrolled in a double-blind, and placebo-controlled study. In addition to conventional chemotherapy, 142 patients received HSS and 106 received placebo. In an in vitro study, the expression of P-gp was evaluated by flow cytometry in a drug-resistant leukemia cell line (K562/ADM cells). Sorcin was examined by Western blot. RESULTS: The complete remission rates in the HSS treatment group were all higher than in the placebo group with non-relapsing leukemia and relapsed leukemia (p<0.05). Less patients in the HSS group experienced gastrointestinal side effects from chemotherapy, whereas more patients had increased food take and an increase in Karnofsky performance status (KPS) score (p<0.01). In vitro, the expression of P-gp and sorcin in the HSS treated cells were lower than in the control group cells (p<0.01). CONCLUSION: When added to conventional chemotherapy, HSS improves the complete remission rates and quality of life in patients with acute leukemia. The in vitro findings indicate that suppression of P-gp and sorcin genes in leukemia cells may be involved in the beneficial effects of HSS.

Safety and Efficacy of a Mouth-Rinse with Granulocyte Colony Stimulating Factor in Patients with Chemotherapy-Induced Oral Mucositis.

OBJECTIVE: To assess the safety and effectiveness of a mouth-rinse with G-CSF (JiSaiXin, produced by NCPC Biotechnology Co., Ltd) in treating patients with chemotherapy-induced oral mucositis (CIM). METHOD: A consecutive cohort of patients with advanced cancers and CIM were treated with mouth-rinse G-CSF. All chemotherapy for patients with advanced cancers was adopted from regimens suggested by NCCN guidelines. The mouth-rinse with G-CSF at a dose of 150-300ug plus 100ml-500ml normal saline was started from the time of oral mucositis was confirmed and continuously used for at least 7 days as one course. After at least two courses of treatment, safety and efficacy were evaluated. RESULTS: There were 7 female and 7 male patients with advanced cancer and CIM recruited into this study, including 5 with colorectal, 2 with lung, 1 patient with gastric, 1 with cervical and 1 with pancreatic cancer, as well as 2 patients with diffuse large B cell lymphomas, 1 with nasopharyngeal and 1 with gastric cancer. The median age was 57 (41-79) years. Grade 1 to 2 myelosuppression was observed in 3/14 patients, and Grade 4 myelosuppression in 1/14. Adverse effects on the gastrointestinal tract were documented in 5/14 patients, and were Grade 1 to Grade 3. No treatment related death was documented. Regarding CIM, the median response time to mouth rinse of G-CSF was 2 (1-5) days, and all patients with CIM demonstrated a positive response. CONCLUSIONS: Mouth-rinse with G-CSF proved to be safe and effective in treating patients with advanced cancers and CIM. However, further randomized controlled studies should be conducted to clarify the effectiveness of this treatment with other lesions.