Evaluation of the effects of 1,25VitD3 on Th17 cells and Tregs in HTLV-1 infected cell lines.

Human T-lymphotropic virus type 1 (HTLV-1) causes chronic infections of human T lymphocytes. The present study aimed to evaluate the effects of 1,25VitD3 on the proportion of Tregs and Th17 cells, the expression of related transcription factors (ROR-γt and FOXP3) and cytokines (IL-10, TGF-ß, IL-6, and IL-17 A) in the HTLV-1infected cell lines MT-2 and MT-4. MT-2 and MT-4 cells and control PBMCs were treated with 1,25VitD3 and percentages of Tregs and Th17 cells was determined by flow cytometry. Gene expression and cytokine levels were analyzed by real-time PCR and ELISA, respectively. Treatment with-1,25VitD3 increased the percentage of Tregs in MT-2 and MT-4 cells, while it decreased the percentage of Th17 cells among MT-2 cells. 1,25VitD3 treatment also significantly improved FOXP3 gene expression in MT-2 cells, while reducing ROR-γt-gene expression in MT-2 and MT-4 cells comparing to untreated cells. Treatment with 1,25VitD3 significantly improved IL-10 levels in MT-2 cells, as well as TGF-ß levels in both cell lines culture supernatants. 1,25VitD3 treatment diminished IL-6 levels in cell culture supernatants of MT-2 and MT-4 as well as IL-17 A levels in MT-2. Here we showed, that 1,25VitD3 modulated immune responses by enhancing Tregs differentiation and functions as well as inhibiting Th17 differentiation and actions in HTLV-1 infected cell lines. This suggests that VitD3 may have therapeutic effects in HTLV-1-related diseases by suppressing adverse inflammatory responses. Keywords: Tregs; Th17 cells; HTLV-1; 1, 25VitD3.

The diterpenoid adenanthin upregulates the expression of natural killer group 2D receptor ligands in hepatocellular carcinoma cells.

OBJECTIVE: The natural killer (NK) group 2D (NKG2D) receptor plays a crucial role in NK cell-mediated anti-tumor immunity. NKG2D anti-proliferative effect is mediated by direct interactions of the receptor with its ligands that may be considered as a potential target for NK-based immunotherapeutic strategy in cancer cells. METHODS: Here we report that a natural product adenanthin significantly promotes NKG2D ligands expression in hepatoma cells. The effect was determined using flow cytometry analysis. The activity of NK cell was evaluated by measuring its degranulation activity and cytotoxicity. RESULTS: Our data indicates that the induction of NKG2D ligand binding to liver cancer cell surface receptors greatly improves the killing activity of NK cells against the cancer cells. CONCLUSIONS: This is the first report of a new mechanism anti-cancer effects of adenanthin mediated by an indirect activation of NK cells. Our data suggests that adenanthin may be used to sensitize NK cells in tumor immunotherapy.

[Global gene expression responses to Iodine-125 radiation in three human gastric cancer cell lines].

OBJECTIVE: To study genome-wide gene expression changes in gastric cancer cells after iodine-125 ¹²5(I) particle irradiation. METHODS: ¹²5I particles were used to irradiate three gastric cancer cell lines of various differentiation levels:high (BGC-823) , medium (AGS) and low (NCI-N87) .Whole-genome gene expression was investigated with microarray. The gene expression in iodine-125 irradiated and untreated cancer cells was compared, and the genes with transcript levels altered for at least 2 folds (P < 0.05) were selected. The change in gene expression levels was verified by using quantitative real-time (qRT) -PCR. RESULTS: The three gastric cancer cell lines received the same dose rate of ¹²5I particle irradiation. Cluster analysis showed that the Gene Ontology (GO) categories did not change in the three cell lines, but changes in gene expression levels were evident for many genes. After ¹²5I particle irradiate NCI-N87 cells, 895 genes were up-regulated, 786 genes were down-regulated; AGS was irradiated by ¹²5I seed, there were 124 genes upregulated, 161 genes were down-regulated; BGC-823 cells were treated by ¹²5I seed irradiation, 2 412 genes upregulated, 3 243 downregulated genes. After ionizing radiation can cause very complex transcriptional regulation changes, KEGG pathway analysis shows that these differentially expressed genes overlap in a particular cell pathway. Four genes, TRAF3IP2-AS1, SDC1, RABL2B and NOM, were found having at least 2-fold difference in expression (P < 0.05) , and the gene expression alteration was confirmed by qRT-PCR. CONCLUSIONS: ¹²5I particle irradiation caused gene expression changes in gastric cancer cells. The expressions of TRAF3IP2-AS1, SDC1, RABL2B and NOM are altered significantly in all three cell lines studied, indicating that these genes may play an important role in the ¹²5I seed treatment of gastric cancer. These genes could be potential targets for developing anti-cancer drugs in the future.

Knockdown of KIF23 alleviates the progression of asthma by inhibiting pyroptosis.

BACKGROUND: Asthma is a chronic disease affecting the lower respiratory tract, which can lead to death in severe cases. The cause of asthma is not fully known, so exploring its potential mechanism is necessary for the targeted therapy of asthma. METHOD: Asthma mouse model was established with ovalbumin (OVA). H&E staining, immunohistochemistry and ELISA were used to detect the inflammatory response in asthma. Transcriptome sequencing was performed to screen differentially expressed genes (DEGs). The role of KIF23 silencing in cell viability, proliferation and apoptosis was explored by cell counting kit-8, EdU assay and flow cytometry. Effects of KIF23 knockdown on inflammation, oxidative stress and pyroptosis were detected by ELISA and western blot. After screening KIF23-related signalling pathways, the effect of KIF23 on p53 signalling pathway was explored by western blot. RESULTS: In the asthma model, the levels of caspase-3, IgG in serum and inflammatory factors (interleukin (IL)-1ß, KC and tumour necrosis factor (TNF)-α) in serum and bronchoalveolar lavage fluid were increased. Transcriptome sequencing showed that there were 352 DEGs in the asthma model, and 7 hub genes including KIF23 were identified. Knockdown of KIF23 increased cell proliferation and inhibited apoptosis, inflammation and pyroptosis of BEAS-2B cells induced by IL-13 in vitro. In vivo experiments verified that knockdown of KIF23 inhibited oxidative stress, inflammation and pyroptosis to alleviate OVA-induced asthma mice. In addition, p53 signalling pathway was suppressed by KIF23 knockdown. CONCLUSION: Knockdown of KIF23 alleviated the progression of asthma by suppressing pyroptosis and inhibited p53 signalling pathway.

Circular RNA hsa_circ_0005939 Regulates UHRF1BP1L Expression by Targeting miR-4693-3p to Promote Colorectal Cancer Progression.

INTRODUCTION: Colorectal cancer (CRC) is the second most common and fatal cancer in China. circRNAs are different expressed between tumor and non-tumor tissues, and they are proved to be correlated with tumorigenesis and cancer progression. OBJECTIVE: We aimed to explore the biological and molecular function of hsa_circ_0005939 in CRC. METHODS: We collected and compared ten CRC tissues and four noncancerous tissues and performed circRNA sequencing. We investigated the hsa_circ_0005939 expression in fresh tissues from CRC and adjacent tissues by qPCR. Meanwhile, functional roles of hsa_circ_0005939 in CRC cells were explored by CCK-8, colony formation, wounding healing, cell apoptosis and western blot assays. RNA-FISH was used to confirm the cellular distribution of hsa_circ_0005939. Bioinformatic prediction and luciferase reporter assay were used to determine the mechanisms of hsa_circ_0005939. RESULTS: Our results indicated that hsa_circ_0005939 was up-regulated in CRC tissues and cells. Up-regulation of hsa_circ_0005939 was associated with the occurrence and the number of lymph node metastasis of CRC. Hsa_circ_0005939 down-regulation inhibited cell proliferation, increased cell apoptosis and caused G2 phase arrest of CRC cells. Mechanistically, luciferase assay revealed that hsa_circ_0005939 acts as a molecular sponge for miR-4693-3p and then enhanced Ubiquitin Like With PHD And Ring Finger Domains 1 binding protein 1 like (UHRF1BP1L) expression. CONCLUSION: Our findings indicated an oncogenic role of hsa_circ_0005939 in CRC, and it enhanced malignant phenotypes of CRC cells through miR-4693-3p/UHRF1BP1L axis. Our study may offer promising biomarkers and therapeutic targets for CRC.

Efficient complete denture metal base design via a dental feature-driven segmentation network.

BACKGROUND AND OBJECTIVE: Complete denture is a common restorative treatment in dental patients and the design of the core components (major connector and retentive mesh) of complete denture metal base (CDMB) is the basis of successful restoration. However, the automated design process of CDMB has become a challenging task primarily due to the complexity of manual interaction, low personalization, and low design accuracy. METHODS: To solve the existing problems, we develop a computer-aided Segmentation Network-driven CDMB design framework, called CDMB-SegNet, to automatically generate personalized digital design boundaries for complete dentures of edentulous patients. Specifically, CDMB-SegNet consists of a novel upright-orientation adjustment module (UO-AM), a dental feature-driven segmentation network, and a specific boundary-optimization design module (BO-DM). UO-AM automatically identifies key points for locating spatial attitude of the three-dimensional dental model with arbitrary posture, while BO-DM can result in smoother and more personalized designs for complete denture. In addition, to achieve efficient and accurate feature extraction and segmentation of 3D edentulous models with irregular gingival tissues, the light-weight backbone network is also incorporated into CDMB-SegNet. RESULTS: Experimental results on a large clinical dataset showed that CDMB-SegNet can achieve superior performance over the state-of-the-art methods. Quantitative evaluation (major connector/retentive mesh) showed improved Accuracy (98.54 ± 0.58 %/97.73 ± 0.92 %) and IoU (87.42 ± 5.48 %/70.42 ± 7.95 %), and reduced Maximum Symmetric Surface Distance (4.54 ± 2.06 mm/4.62 ± 1.68 mm), Average Symmetric Surface Distance (1.45 ± 0.63mm/1.28 ± 0.54 mm), Roughness Rate (6.17 ± 1.40 %/6.80 ± 1.23 %) and Vertices Number (23.22 ± 1.85/43.15 ± 2.72). Moreover, CDMB-SegNet shortened the overall design time to around 4 min, which is one tenth of the comparison methods. CONCLUSIONS: CDMB-SegNet is the first intelligent neural network for automatic CDMB design driven by oral big data and dental features. The designed CDMB is able to couple with patient's personalized dental anatomical morphology, providing higher clinical applicability compared with the state-of-the-art methods.

Treating colon cancer with injectable PLGA-PEG-PLGA as a carrier for iodine-125.

PURPOSE OF WORK: Provide a safer way for treating various cancers with PLGA-PEG-PLGA (PPP)-embedded iodine-125. To improve the safety of iodine treatment for colon cancer, iodine-125 solution was embedded into PLGA-PEG-PLGA (PPP) (synthesized by bulk co-polymerization of DL-polylactide glycolide and PEG). Xenograft-carrying nude mice were then treated with iodine-125-PPP. Proliferating cell nuclear antigen and Terminal Transferase dUTP Nick-End Labeling were used to measure proliferation and apoptosis in the tumors, respectively. Simultaneously, immunohistochemistry SP was used to detect the expression levels of p53. In addition, the microvessel density (MVD) of the tumors was recorded. PPP-embedded iodine-125 induced apoptosis by increasing the expression of p53, and by decreasing the levels of VEGF and MVD in the colon cancer tumors (P < 0.01). Significant inhibition of tumor growth is seen with iodine-125 from 0.4 to 0.8 mCi. PPP-embedded iodine-125 has a similar inhibitory efficiency to using the iodine-125 seeds for the treatment of colon tumors (P > 0.05). The findings therefore provide a potentially safer method for treating various tumors with radioactive iodine.

Activation of periodate by N-doped iron-based porous carbon for degradation of sulfisoxazole: Significance of catalyst-mediated electron transfer mechanism.

Periodate (PI) has recently been studied as an excellent oxidant in advanced oxidation processes, and its reported mechanism is mainly the formation of reactive oxygen species (ROS). This work presents an efficient approach using N-doped iron-based porous carbon (Fe@N-C) to activate periodate for the degradation of sulfisoxazole (SIZ). Characterization results indicated the catalyst has high catalytic activity, stable structure, and high electron transfer activity. In terms of degradation mechanism, it is pointed out that the non-radical pathway is the dominant mechanism. In order to prove this mechanism, we have carried out scavenging experiments, electron paramagnetic resonance (EPR) analysis, salt bridge experiments and electrochemical experiments, which demonstrate the occurrence of mediated electron transfer mechanism. Fe@N-C could mediate the electron transfer from organic contaminant molecules to PI, thus improving the efficiency of PI utilization, rather than simply inducing the activation of PI through Fe@N-C. The overall results of this study provided a new understanding into the application of Fe@N-C activated PI in wastewater treatment.

Diagnostic and prognostic predictive values of triggering receptor expressed on myeloid cell-1 expression in neonatal sepsis: A meta-analysis and systematic review.

Objective: The purpose of this systematic review was to explore the value of the expression level of the triggering receptor expressed on myeloid cell-1 (TREM-1) in the diagnosis and prognosis of neonatal sepsis. Methods: A comprehensive search was performed to identify the diagnostic and prognostic predictive values of the TREM-1 expression level in neonatal sepsis. Based on the retrieval strategy, Cochrane Library, Embase, Ovid, ProQuest, PubMed, Scopus, and Web of Science databases were searched from inception to February 2022. Studies were included if they assessed the accuracy of TREM-1 expression in the diagnosis of neonatal sepsis and distinguished survival and death in neonatal sepsis. Two authors independently evaluated the study and extracted the data, including the first author of the literature, country, total study population, basic population characteristics of the study group and the control group, study design (observational studies), type of sample, sepsis onset, type of biomarker, assay method, cut-off, sensitivity, specificity, true positives (TP), false positives (FP), false negatives (FN), and true negatives (TN). A third party will be consulted if disputed. The accuracy of TREM-1 expression in the diagnosis and prognostic prediction of neonatal sepsis was evaluated by a bivariate mixed-effects model. The source of heterogeneity was explored through meta-regression analysis. Results: Thirteen articles that met the research criteria were included in qualitative analysis, and 11 of them were included in quantitative analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operator characteristic (SROC) curve of soluble TREM-1 (sTREM-1) were 0.94 (95% CI: 0.82, 0.98), 0.87 (95% CI: 0.70, 0.95), 7.36 (95% CI: 2.75, 19.74), 0.07 (95% CI: 0.02, 0.24), 111.71 (95% CI: 13.24, 942.92), and 0.96 (95% CI: 0.94, 0.98), respectively. Meta-regression and subgroup analysis were used to investigate the heterogeneity, owing to non-threshold effects caused by types of test sample and research design. sTREM-1 as a biomarker for distinguishing survival and death in neonates with sepsis had pooled sensitivity, specificity, area under the SROC curve, PLR, NLR, and DOR of 0.95 (95% CI: 0.83, 0.99), 0.98 (95% CI: 0.68, 1.00), 0.99 (95% CI: 0.97, 0.99), 39.28 (95% CI: 2.13, 723.99), 0.05 (95% CI: 0.01, 0.19), and 789.61 (95% CI: 17.53, 35,560.72), respectively. Conclusion: The study showed that TREM-1 was a potential biomarker for the diagnosis and prognosis of neonatal sepsis. The biggest advantage of this study is that it is the first to comprehensively explore the role of TREM-1 expression in the diagnosis and prognosis of neonatal sepsis. However, there are some limitations in this study, such as the reduced number of clinical studies on TREM-1 expression as a biomarker of neonatal sepsis, regional bias, and differences in detection methods. Hence, more large-scale and high-quality studies are needed to improve diagnostic accuracy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022338041.

Innate Immune Evasion by Human Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infection in young children. Nearly all individuals become infected in their early childhood, and reinfections with RSV are common throughout life. Primary infection with RSV is usually involved in the symptom of bronchiolitis and pneumonia in the lower respiratory tract, which accounts for over 3 million hospitalizations and approximately 66,000 deaths annually worldwide. Despite the widespread prevalence and high morbidity and lethality rates of diseases caused by RSV infection, there is currently no licensed RSV vaccine. During RSV infection, innate immunity plays the first line of defense to suppress RSV infection and replication. However, RSV has evolved multiple mechanisms to evade the host's innate immune responses to gain a window of opportunity for efficient viral replication. This review discusses the comprehensive interaction between RSV infection and the host antiviral innate immunity and updates recent findings on how RSV modulates the host innate immune response for survival, which may provide novel insights to find potent drug targets and vaccines against RSV.

[Therapeutic effect of hydrocortisone combined with vitamin C and vitamin B1 on patients with sepsis: a Meta-analysis].

OBJECTIVE: To systematically evaluate the effect of hydrocortisone combined with vitamin C and vitamin B1 on the efficacy of patients with sepsis or septic shock. METHODS: Databases including CNKI, Sino Med, VIP, Wanfang, PubMed, the Cochrane Library, and Embase were searched from inception to January 2021 for the randomized controlled trial (RCT) about hydrocortisone combined with vitamin C and vitamin B1 to treat sepsis or septic shock. The experimental group was given intravenous injection of hydrocortisone, vitamin B1 and vitamin C based on conventional treatment; the control group was given conventional treatment or placebo/hydrocortisone/hydrocortisone+vitamin B1 based on conventional treatment. Outcome indicators included sequential organ failure assessment (SOFA), mortality, the duration of vasoactive drugs, new acute kidney injury (AKI) patients, length of stay in intensive care unit (ICU) and in hospital. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.3 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias. RESULTS: A total of 6 articles involving 816 patients were included, with 411 patients in the experimental group and 405 patients in the control group. The Meta-analysis results showed that the duration of vasoactive drugs in the experimental group was significantly shorter than that in the control group [mean difference (MD) = -24.02, 95% confidence interval (95%CI) was -32.36 to -15.68, P < 0.000 01]. However, there were no significant differences in SOFA, mortality, new AKI patients, the length of ICU stay and hospital stay between the two groups [SOFA: MD = -0.14, 95%CI was -1.15 to 0.87, P = 0.79; mortality: relative risk (RR) = 0.99, 95%CI was 0.81 to 1.21, P = 0.92; new AKI patients: RR = 1.10, 95%CI was 0.42 to 2.87, P = 0.84; length of ICU stay: MD = 1.33, 95%CI was -2.22 to 4.89, P = 0.46; length of hospital stay: MD = 1.02, 95%CI was -0.66 to 2.69, P = 0.23]. The funnel plot showed that most of the points were symmetrical and showed an inverted funnel shape, suggesting that the publication bias among the studies was small. There was no significant publication bias on this Meta-analysis. CONCLUSIONS: Hydrocortisone combined with vitamin C and vitamin B1 can shorten the duration of vasoactive drugs in patients with sepsis or septic shock, but it cannot effectively reduce the SOFA score, mortality, new AKI patients, length of stay in ICU and in hospital. Limited by the number and quality of the included studies, further large-scale, multi-center, blinded, RCT are still needed for verification.

A New Method for Screening Natural Products to Stimulate IFN-γ Production in Jurkat Human T Lymphocytes.

Interferon-γ (IFN-γ) is a critical cytokine in the defense against viral and bacterial infection. It is mainly produced by natural killer cells and activated T cells. Given its regulatory role in coordinating cellular and humoral immune responses, IFN-γ is considered to be an effective therapeutic agent in the treatment of viral infection. Here we established a fluorescence-based high-content screening model to find small molecules that can stimulate the production of IFN-γ in human Jurkat cells. After a primary screening of 267 natural products, two hits, Astragalus polyphenols and 6-shogaol, were identified to promote the activity of the IFN-γ promoter and subsequently validated by the flow cytometry assay. Obviously, both Astragalus polyphenols and 6-shogaol exhibited potential to induce the transcription and expression of IFN-γ in a dose-dependent manner. These results indicated that our high-content screening model could be a credible and useful platform to contribute to the discovery of novel molecules to promote the expression of IFN-γ and provide leading compounds for the treatment of viral infectious diseases.

[Effects of 37 centigrade volume resuscitation on coagulation function and blood lactic acid in neonates with septic shock].

OBJECTIVE: To investigate the effect of volume resuscitation with normal saline (NS) at 37 centigrade on the coagulation function and microcirculation of neonates with septic shock. METHODS: Children with septic shock admitted to neonatal intensive care unit (NICU) of the First Affiliated Hospital of Gannan Medical University were enrolled. Twenty-four newborns with septic shock were divided into two groups by random number table method (12 in each group), and were resuscitated with 10 mL/kg at 25 centigrade NS and 37 centigrade NS respectively on the basis of routine treatment. Factor II, V, VII, VIII, IX, X, and prothrombin time (PT), thrombin Time (TT), fibrinogen (FIB), activated partial thromboplastin time (APTT), D-Dimer (DD), lactic acid (Lac) were detected before treatment and 6 hours and 12 hours after treatment. RESULTS: The levels of coagulation factors II, V, VII, VIII, IX, X were not significantly changed before and after treatment in the two groups, and there was no significant difference between the two groups. After treatment, PT and APTT in both groups were gradually shortened, DD and Lac were gradually decreased, FIB were gradually increased, while TT had no significant change. Among them, PT, APTT, DD and Lac at 6 hours after treatment in 37 centigradeNS group were significantly lower than those before treatment [PT (s): 14.07±1.02 vs. 17.08±1.54, APTT (s): 54.83±12.39 vs. 69.17±16.36, DD (mg/L): 2.40±0.63 vs. 4.18±0.88, Lac (mmol/L): 2.84±0.82 vs. 5.98±1.17, all P < 0.05]; DD and Lac at 6 hours after treatment in 25 centigrade NS group were significantly lower than those before treatment [DD (mg/L): 3.13±0.84 vs. 4.16±1.04, Lac (mmol/L): 4.83±0.64 vs. 5.69±0.74, both P < 0.05], and PT at 12 hours after treatment was significantly shorter than that before treatment (s: 14.63±1.14 vs. 16.48±1.61, P < 0.01); FIB in both 25 centigrade NS group and 37 centigrade NS group at 12 hours after treatment were significantly higher than those before treatment (g/L: 2.83±0.83 vs. 1.58±0.43, 2.87±0.87 vs. 1.47±0.41, both P < 0.01), but TT had no significant change. The comparison between groups showed that PT, DD and Lac in the 37 centigrade NS group were significantly lower than those in the 25 centigrade NS group at 6 hours after treatment [PT (s): 14.07±1.02 vs. 15.69±1.21, DD (mg/L): 2.40±0.63 vs. 3.13±0.84, Lac (mmol/L): 2.84±0.82 vs. 4.83±0.64, all P < 0.05]; at 12 hours after treatment, PT, APTT and DD in the 37 centigrade NS group were significantly lower than those in the 25 centigrade NS group [PT (s): 13.26±0.91 vs. 14.63±1.14, APTT (s): 37.08±10.43 vs. 54.75±14.96, DD (mg/L): 1.20±0.59 vs. 2.06±0.69, all P < 0.01], and FIB was significantly higher than that in the 25 centigrade NS group (g/L: 2.87±0.87 vs. 2.83±0.83, P < 0.05). CONCLUSIONS: Volume resuscitation at 37 centigrade can improve the coagulation function and microcirculation of newborns with septic shock.

Combination of Permanent Interstitial 125I-Seed Brachytherapy and Surgery for the Treatment of Large Hepatocellular Carcinoma.

The treatment methods available for large primary hepatocellular carcinomas (diameter >5 cm) are inadequate. Here, we report the successful management of 80 cases of large hepatocellular carcinoma, using a combination of custom-designed permanent interstitial iodine-125 seed brachytherapy and palliative surgery. Patients were enrolled in the study between 2011 and 2014. All patients underwent surgical treatment along with permanent interstitial iodine-125 seed brachytherapy; for the latter, patients received minimum doses covering 90% of the target (D90 s) of iodine-125 seeds ranging from 100 to 160 Gy (median: 110 Gy). All patients received 6 cycles of chemotherapy and were followed up at 6, 12, 24, and 36 months postoperatively. The clinical symptom remission rate was 95.3% (61 of 64). Alanine aminotransferase and aspartate aminotransferase levels decreased to normal in 80% (50 of 60) and 75% of the patients (45 of 60), respectively. The posttreatment alpha-fetoprotein levels decreased by 50% in 80% of the patients (40 of 50). The effective therapy rates were 80% (76 of 95) for 95 tumor nodules (diameters 5-10 cm) and 78.6% (33 of 42) for 42 tumor nodules (diameters >10 cm). The 3-year disease-free survival rate was 66.6%. Palliative surgery plus permanent interstitial iodine-125 seed brachytherapy appears to be a reasonable therapeutic alternative for large hepatocellular carcinoma.

Interleukin 2 and interleukin 10 function synergistically to promote CD8+ T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.

The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8+ T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8+ T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8+ T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8+ T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8+ T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8+ T cells but could significantly enhance IL-2-mediated promotion of CD8+ T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8+ T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4+CD25+ regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8+ T cells, an effect suppressible by CD4+CD25+ Treg cells.

Sensitization of hepatocellular carcinoma cells to irradiation by miR­34a through targeting lactate dehydrogenase­A.

Radiation is a therapeutic strategy for the treatment of cancer, and is also used for the treatment of hepatocellular carcinoma. MicroRNAs (miRs) are endogenous, non­coding single­stranded RNA molecules, which regulate gene expression at the post­transcriptional level. In the present study, the roles of miR­34a­mediated glycolysis in radiation sensitivity were investigated. By establishing a radioresistant liver cancer cell line, the present study compared the expression level of miR­34a from radiosensitive and radioresistant cells using the reverse transcription­quantitative polymerase chain reaction. The glucose uptake and lactate production were also compared between the two types of cells. The results demonstrated that miR­34a acted as a tumor suppressor in human hepatocellular cancer cells. Following comparison of radiosensitive and radioresistant cancer cells, the results of the present study demonstrated that miR­34a was negatively correlated with radiation resistance; and levels of miR­34a were significantly downregulated in the HepG2 radioresistant cells. Furthermore, the rate of glycolysis in the radioresistant cells was elevated, and there was evidence that glucose uptake and lactate production increased. Lactate dehydrogenase A (LDHA), which is a key enzyme in the glycolysis signaling pathway, was found to be a target of miR­34a in hepatocellular cancer cells. Notably, the overexpression of miR­34a re­sensitized HepG2 radioresistant cells to radiation treatment by inhibiting LDHA. The results of the present study revealed a negative correlation between miR­34a and glycolysis, caused by the targeting of LDHA­34a, providing a novel mechanism for miR­34a­mediated radioresistance.

[125I seed implantation in sphincter preservation for treatment of low rectal cancer].

OBJECTIVE: To evaluate the effects of (125)I seed implantation in sphincter preservation for treatment of low rectal cancer. METHODS: Seventy-six patients with low rectal cancer were randomly divided into 2 group: group A, 17 males and 13 females, aged 48.5 +/- 2.4, receiving rectostomy and anal sphincter preservation and group B, 24 males and 22 females, aged 49.4 +/- 2.6, receiving modified TME and anal sphincter preservation combined with brachytherapy by (125)I seed implantation. Two to four weeks after operation chemotherapy with 5-FU/CF were performed. Follow-up was carried out 6, 12, 24, and 36 months after operation. RESULTS: The local recurrence rates 6, 12, 24, and 36 months after operation were 0%, 11.1%, 14.3%, and 23% respectively in the group A, and all 0% in the group B (P < 0.05 for the rate 36 months later). The survival rates 6, 12, 24, and 36 months after operation were 100%, 100%, 85.7%, and 76.7% respectively in the group A, and were 100%, 100%, 97.1%, and 93% respectively in the group B (P < 0.05 for the rate 36 months later). The functions of defecation and erection were better in the group B and the symptom of pain was improved better in the group A too (all P < 0.05). CONCLUSIONS: Safe, simple, and effective, surgery with sphincter preservation combined with brachytherapy in low rectal cancer is one of the ideal methods for treatment of low rectal cancer.

[The relationship between hypoxia inducible factor-1 alpha expression and novoendotheliasis after autogenous vein grafting].

OBJECTIVE: To elucidate the relationship between the level of hypoxia inducible factor-1alpha (HIF-1alpha) expression and novoendotheliasis after autogenous vein grafting. METHODS: 40 Wistar rats underwent right internal jugular vein to common jugular artery interposition grafting. Twenty rats were killed 7 and 14 days after the grafting respectively and the grafted veins were harvested respectively. Twenty rats not undergoing grafting were used as controls. The expressions of HIF-1alpha mRNA and protein and vascular endothelial growth factor (VEGF) mRNA and protein were examined by using reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry. Electron microscope was used to observe the process of vascular novoendotheliasis. RESULTS: The percentage of HIF-1alpha positive cells 7 days after grafting was 20.5 +/- 6.2%, significantly higher than that 14 days after (12.3 +/- 3.7, P < 0.01) and that of the controls (0.5 +/- 0.1%, P < 0.01). The percentage of HIF-1alpha positive cells 14 days after grafting was significantly higher than that of the controls too (P < 0.01). The expression of HIF-1alphamRNA 7 days after grafting was 53.2 +/- 9.3, significantly higher than that 14 days after grafting (43.2 +/- 6.3, P < 0.01) and that in the control (29.4 +/- 5.6, P < 0.01). The expression of HIF-1alpha7 mRNA 14 days after grafting was significantly higher than that of the controls too (P < 0.01). The expression of HIF-1alpha protein 7 days after grafting was 5.6 +/- 0.4, significantly higher than that 14 days after grafting (3.5 +/- 0.2, P < 0.01) and that in the control (0.8 +/- 0.1, P < 0.01). The expression of VEGF protein 7 days after grafting was 2.2 +/- 0.1, significantly higher than that of the control (0.5 +/- 0.1, P < 0.01). Novoendotheliasis was seen 7 days after grafting and decreased 14 days after. The expression of HIF-1alpha was positively correlated with the expression of VEGF (r = 0.903, P < 0.01). CONCLUSION: HIF-1 alpha is closely related to novoendotheliasis. The deficiency of HIF-1 alpha expression plays an important role in intima hyperplasia.

[Iodine-125 interstitial brachytherapy for malignant tumor].

OBJECTIVE: To assess the clinical effects of (125)I interstitial brachytherapy for malignant tumors. METHODS: One hundred and twelve patients with malignant tumors of stage II stage and III under went radical resection combined with (125)I intraoperative implantation. Seven days and three month after operation WBC count and immune markers were observed. Blood biochemistry ultrasonography and X-ray were performed to observe recurrence and metastasis of tumors per three months. RESULTS: In the 112 patients, 3 died of tumor recurrence in six months, and others survived with the longest time of 35 months. CONCLUSION: (125)I interstitial brachytherapy for malignant tumor is simple, safe and effective.

Meta-analysis of the MDM2 T309G polymorphism and gastric cancer risk.

BACKGROUND: Mdm2 binds to the amino-terminus of p53 to induce its degradation and a single nucleotide polymorphism in the MDM2 promoter region (T309G) has been reported to increase the risk of several carcinomas, such as gastric cancer. However, the results of published studies to analyze the association between MDM2 T309G and gastric cancer havve often conflicted. METHODS: To better illustrate the filiation between MDM2 T309G and gastric cancer, we performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the relationship. The pooled ORs were performed for 4 models, additive, recessive, co-dominant model, and dominant. RESULTS: Nine published case-control studies including 3,225 gastric cancer cases and 4,118 controls were identified. The MDM2 T309G polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR=1.57; 95%CI=1.57-2.12; p=0.003) and GG versus GT/TT, OR=1.52; 95%CI=1.217-1.90; p<0.001). Furthermore, Egger