Generation of a Predictive Clinical Model for Isolated Distal Deep Vein Thrombosis (ICMVT) Detection.

BACKGROUND Isolated distal deep vein thrombosis (ICMVT) increases the risk of pulmonary embolism. Although predictive models are available, their utility in predicting the risk is unknown. To develop a clinical prediction model for isolated distal calf muscle venous thrombosis, data from 462 patients were used to assess the independent risk variables for ICMVT. MATERIAL AND METHODS The area under curve (AUC) for Model A and Model B were calculated and other risk factors were based on age, pitting edema in the symptomatic leg, calf swelling with least 3 cm larger than the asymptomatic leg, recent bed rest for 3 days or more in the past 4 weeks, requiring general or major surgery with regional anesthesia, sex, and local tenderness distributed along the deep venous system as independent predictors of calf muscle venous thrombosis. Model A includes the risk variables for C-reactive protein and D-dimer. RESULTS The area under ROC curve for Model A training set was 0.924 (95% CI: 0.895-0.952), the area under ROC curve for Model B training set was 0.887 (95% CI: 0.852-0.922), and the AUC difference between the 2 models was statistically significant (P<0.001); the area under ROC curve for Model A obtained in the validation set was 0.902 (95% CI: 0.844-0.961), the area under ROC curve for Model B was 0.842 (95% CI: 0. 0.773-0.910), and the difference between the 2 models was statistically significant (P=0.012). CONCLUSIONS Predictive Model A better predicts isolated calf muscle venous thrombosis and is able to help clinicians rapidly and early diagnose ICMVT, displaying higher utility for missed diagnosis prevention and disease therapy.

Short-Term Clinical Response and Changes in the Fecal Microbiota and Metabolite Levels in Patients with Crohn's Disease After Stem Cell Infusions.

Recent studies have shown a close relationship between the gut microbiota and Crohn's disease (CD). This study aimed to determine whether mesenchymal stem cell (MSC) treatment alters the gut microbiota and fecal metabolite pathways and to establish the relationship between the gut microbiota and fecal metabolites. Patients with refractory CD were enrolled and received 8 intravenous infusions of MSCs at a dose of 1.0 × 106 cells/kg. The MSC efficacy and safety were evaluated. Fecal samples were collected, and their microbiomes were analyzed by 16S rDNA sequencing. The fecal metabolites at baseline and after 4 and 8 MSC infusions were identified by liquid chromatography-mass spectrometry (LC--MS). A bioinformatics analysis was conducted using the sequencing data. No serious adverse effects were observed. The clinical symptoms and signs of patients with CD were substantially relieved after 8 MSC infusions, as revealed by changes in weight, the CD activity index (CDAI) score, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). Endoscopic improvement was observed in 2 patients. A comparison of the gut microbiome after 8 MSC treatments with that at baseline showed that the genus Cetobacterium was significantly enriched. Linoleic acid was depleted after 8 MSC treatments. A possible link between the altered Cetobacterium abundance and linoleic acid metabolite levels was observed in patients with CD who received MSCs. This study enabled an understanding of both the gut microbiota response and bacterial metabolites to obtain more information about host-gut microbiota metabolic interactions in the short-term response to MSC treatment.

A Case-Control Study of 40 Patients with Piriformis Muscle Syndrome to Evaluate Diagnostic Findings Using Two-Dimensional Ultrasound and Shear Wave Elastography.

BACKGROUND Piriformis muscle syndrome (PMS) is a neuropathy caused by compression of the sciatic nerve by the piriformis muscle. This case-control study included 40 patients with PMS and aimed to evaluate the diagnostic findings using two-dimensional ultrasound and shear wave elastography (SWE), as non-invasive and cost-effective diagnostic methods. MATERIAL AND METHODS In order to evaluate the value of two-dimensional ultrasound diagnosis, a new imaging technique called shear wave elastography (SWE) was used in the screening of PMS, with a total of 40 PMS patients and 40 healthy individuals participating in our study. We analyzed the correlation and area under the curve (AUC) of changes in thickness (mm) and Young's modulus (kpa) of the bilateral piriformis muscle (PM). RESULTS We found that PM thickness and Young's modulus on the lesion sides were significantly higher in PMS patients than in controls (P<0.05). Also, we determined that there was a positive correlation between PM thickness and Young's modulus (r=0.454, P<0.05). Using two-dimensional ultrasonic diagnosis and the SWE technique, a specificity of 95.8% and sensitivity of 78.8% were demonstrated in the clinical diagnosis of PM. CONCLUSIONS Two-dimensional ultrasound with SWE technology has demonstrated its superior sensitivity and specificity in diagnosing PMS in the clinic.

Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial.

BACKGROUND AND AIMS: Liver transplantation (LT) is the primary curative option for cirrhotic patients with early-stage hepatocellular carcinoma (HCC). However, tumor recurrence occurs in 15-20% of cases with unfavorable prognosis. We have developed a library of T cell receptors (TCRs) specific for different hepatitis B virus (HBV) antigens, restricted by different molecules of human leucocyte antigen (HLA)-class I, to redirect T cells against HBV antigens (Banu in Sci Rep 4:4166, 2014). We further demonstrated that these transiently functional T cells specific for HBV obtained through messenger RNA (mRNA) electroporation can eliminate HCC cells expressing HBV antigens in vitro and in vivo (Kah in J Clin Invest 127:3177-3188, 2017). A phase I clinical trial for patients with HCC recurrence post-liver transplant was conducted to assess the safety, tolerability, and anti-tumor efficacy of transiently functional HBV-TCR T cells. Here, we report the clinical findings with regard to the safety and anti-tumor efficacy of mRNA electroporated HBV-specific TCR-T cells. (ClinicalTrials.gov identifier: NCT02719782). PATIENTS AND METHODS: A total of six patients with HBV-positive recurrent HCC post-liver transplant and HLA-matched to TCR targeting hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) (HLA-A*02:01/HBsAg, HLA-A*11:01/HBcAg, HLA-B*58:01/HBsAg or HLA-C*08:01/HBsAg) were enrolled in this study. The primary objective was to assess the safety of short-lived mRNA electroporated HBV-TCR T cells based on the incidence and severity of the adverse event (AE) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. The secondary objective was to determine the effectiveness of HBV-TCR T cells as per RECIST 1.1 criteria. Patients were followed up for survival for 2 years post-end of treatment. RESULTS: The median age of the six patients was 35.5 years (range: 28-47). The median number of HBV-TCR T cell infusions administered was 6.5 (range: 4-12). The treatment-related AE included grade 1 pyrexia. This study reported no cytokine release syndrome nor neurotoxicity. One patient remained alive and five were deceased at the time of the data cutoff (30 April 2020). CONCLUSION: This study has demonstrated that multiple infusions of mRNA electroporated HBV-specific TCR T cells were well-tolerated in patients with HBV-positive recurrent HCC post-liver transplant.

Human Mitochondrial Protein HSPD1 Binds to and Regulates the Repair of Deoxyinosine in DNA.

The generation of deoxyinosine (dI) in DNA is one of the most important sources of genetic mutations, which may lead to cancer and other human diseases. A further understanding of the biological consequences of dI necessitates the identification and functional characterizations of dI-binding proteins. Herein, we employed a mass spectrometry-based proteomics approach to detect the cellular proteins that may sense the presence of dI in DNA. Our results demonstrated that human mitochondrial heat shock protein 60 (HSPD1) can interact with dI-bearing DNA. We further demonstrated the involvement of HSPD1 in the sodium nitrite-induced DNA damage response and in the modulation of dI levels in vitro and in human cells. Together, these findings revealed HSPD1 as a novel dI-binding protein that may play an important role in the mitochondrial DNA damage control in human cells.

Differentiating dreaming and waking reports with automatic text analysis and Support Vector Machines.

We analyzed similarities and differences between dream and waking reports in a collection by Kahan and Sullivan (2012). We compared word frequencies in the reports using the automatic text analysis software, Linguistic Inquiry and Word Count (LIWC). Social words were more frequent in dream than waking reports, support for Social Simulation Theory. Positive emotion words were less frequent in dream than waking reports, support for Threat Simulation theory. Amount of cognition was the same in dream and waking reports, i. e., the number of words in the summary category "Cognitive Processes" was not significantly different. But specific categories of cognitive words differed in frequency. We also applied a machine learning technique to dream research and built a support vector machine to achieve binary characteristics detection (here, whether a report is about waking or dream) based on LIWC word counts. Performance metrics for the support vector machine were high.

Blood exosome PD-L1 is associated with PD-L1 expression measured by immunohistochemistry, and lymph node metastasis in lung cancer.

BACKGROUND: Previous observations illustrated that programmed cell death ligand 1 in exosomes (Exo-PD-L1) may lead to immunosuppression. This study proposed to investigate the significance of Exo-PD-L1 and the results of PD-L1 immunohistochemistry (IHC) assay in the clinical diagnosis and treatment of lung cancer. METHODS: 29 lung cancer patients were enrolled. Exosomes were extracted from the blood of patients and purified, and the extracts were identified by Western blot and transmission electron microscope. Next, the levels of Exo-PD-L1 and PD-L1 in tumor tissue were evaluated by enzyme-linked immunosorbent assay (ELISA) and IHC, respectively. The correlation between Exo-PD-L1, IHC PD-L1 status and pathological features of patients was analyzed by applying Chi-square test. After immune checkpoint inhibitor (ICI) treatment, the objective response rate (ORR) was calculated, and drug response prediction in lung cancer patients by using Exo-PD-L1 alone, IHC PD-L1 alone, and their combined detection were analyzed. RESULTS: This study confirmed that lung cancer patients had much expression of PD-L1 in blood exosomes and that Exo-PD-L1 level was associated with IHC PD-L1 status. The expression level of Exo-PD-L1 was evidently related to the positive lymph node metastasis of lung cancer patients, while IHC PD-L1 status was not correlated with clinicopathological features of patients. Moreover, Exo-PD-L1 and IHC PD-L1 alone or their combined detection could be utilized to predict the efficacy of ICI therapy in lung cancer patients. CONCLUSION: The correlation between Exo-PD-L1 and IHC PD-L1 status was indicated, and Exo-PD-L1 could assist in determining the suitable lung cancer patients suitable for ICI therapy using IHC PD-L1. This study provides references for the application of Exo-PD-L1 as an effective predictor of ICI therapy.

Isolation and Identification of Efficient Malathion-Degrading Bacteria from Deep-Sea Hydrothermal Sediment.

The genetic and metabolic diversity of deep-sea microorganisms play important roles in phosphorus and sulfur cycles in the ocean, distinguishing them from terrestrial counterparts. Malathion is a representative organophosphorus component in herbicides, pesticides, and insecticides and is analogues of neurotoxic agent. Malathion has been one of the best-selling generic organophosphate insecticides from 1980 to 2012. Most of the sprayed malathion has migrated by surface runoff to ocean sinks, and it is highly toxic to aquatic organisms. Hitherto, there is no report on bacterial cultures capable of degrading malathion isolated from deep-sea sediment. In this study, eight bacterial strains, isolated from sediments from deep-sea hydrothermal regions, were identified as malathion degradators. Two of the tested strains, Pseudidiomarina homiensis strain FG2 and Pseudidiomarina sp. strain CB1, can completely degrade an initial concentration of 500 mg/L malathion within 36 h. Since the two strains have abundant carboxylesterases (CEs) genes, malathion monocarboxylic acid (MMC α and MMC ß) and dibasic carboxylic acid were detected as key intermediate metabolites of malathion degradation, and the pathway of malathion degradation between the two strains was identified as a passage from malathion monocarboxylic acid to malathion dicarboxylic acid.

Development of an Endonuclease V-Assisted Analytical Method for Sequencing Analysis of Deoxyinosine in DNA.

Deoxyinosine (dI) is a highly mutagenic lesion that preferentially pairs with deoxycytidine during replication, which may induce A to G transition and ultimately contribute to carcinogenesis. Therefore, finding the site of dI modification in DNA is of great value for both basic research and clinical applications. Herein, we developed a novel method to sequence the dI modification site in DNA, which utilizes endonuclease V (EndoV)-dependent deamination repair to specifically label the modification site with biotin-14-dATP that allows the affinity enrichment of dI-bearing DNA for sequencing. We have achieved efficient determination of the location of the modified nucleotide in dI-bearing plasmid DNA with the assistance of EndoV-dependent deamination repair. We have also successfully applied this approach to locate the dI modification sites in the mitochondrial DNA of human cells. Our method should be generally applicable for genome-wide sequencing analysis of dI modifications in living organisms.

A Novel Organophosphorus Acid Anhydrolase from Deep Sea Sediment with High Degradation Efficiency for Organophosphorus Pesticides and Nerve Agent.

Organophosphorus compounds (OPCs), including highly toxic nerve agents and pesticides, have been used widely in agricultural and military applications. However, they have aroused widespread concern because they persistently pollute the environment and threaten human life. Organophosphorus acid anhydrolase (OPAA) is a promising enzyme that can detoxify OPCs. Here, a novel OPAA (OPAA114644) was isolated and characterized from deep-sea sediment (-3104 m). It exhibited excellent alkaline stability, and the loss of activity was less than 20% in the pH range 5.0-9.0, even after being incubated for 30 d at 4 °C. It also exhibited high salt tolerance, and its enzymatic activity increased by approximately fourfold in the presence of 20% NaCl (w/v). Additionally, OPAA114644 exhibited high degradation efficiency for soman, dichlorvos, paraoxon, coumaphos, and chlorpyrifos with a concentration of up to 250 mg/L, with the degradation rate being 100%, 100%, 100%, 80% and 51%, respectively, in 20 min under optimal conditions. Notably, OPAA114644 dissolved in different solutions, such as 20% NaCl, 1 mM SDS, 0.05% soap, 10% methanol, and tap water, could efficiently decontaminate the residual paraoxon on the surfaces of glasses, cotton tissues, and apples. These results indicate that OPAA114644 has excellent potential for the biodegradation and bioremediation of OPCs pollution and represents a real application of OPAA in the decontamination and detoxification of foods and clothes, and in the remediation of sites such as floors. Deep-sea sediment might also be an abundant resource for various functional microorganisms and enzymes.

Pre-exposure to Aerosolized Polyvalent Bacterial Lysates Protects Against Bleomycin-Induced Pulmonary Fibrosis in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. No therapeutic modalities can reverse or stop its ever-deteriorating course. The stimulation of lung innate immunity using bacterial lysates was found to protect against lethal pulmonary infection. Hence, this study aimed to explore whether the immune-stimulating enhancement by pretreatment with bacterial lysates led to protection against bleomycin-induced pulmonary fibrosis. C57BL/6 mice were randomly divided into 4 groups with 20 mice in each group. The mice were exposed to an aerosolized mixture of polyvalent bacterial lysates (PVBL) or phosphate-buffered saline (PBS) three times on separate days. Twenty-four hours after the last exposure, the lungs were intratracheally infused with bleomycin (BLM) or normal saline (NS). The pulmonary morphology, Ashcroft's scale of pulmonary fibrosis, and levels of pro-inflammatory cytokines such as interferon (IFN)-γ and interleukin (IL)-4 were evaluated 14 days after the intratracheal infusion. The exposure to PVBL did not induce any discernible structural abnormalities in the lungs, while the IFN-γ/IL-4 ratio increased. BLM-induced pulmonary fibrosis was associated with an overwhelming downregulation of IFN-γ and IL-4 expression. Pre-exposure to PVBL protected against BLM-induced pulmonary fibrosis, which was demonstrated by a greater reduction of Ashcroft's fibrotic score and a greater decrease in the hydroxyproline level in the lungs. Although the PVBL pre-exposure did not restore the BLM-induced downregulation of IL-4 and IFN-γ levels, the IFN-γ/IL-4 ratio was still maintained greater than the animals with BLM infusion. BLM-induced murine pulmonary fibrosis is associated with downregulation of IFN-γ and IL-4 levels. Pre-exposure to the aerosolized PVBL protects against BLM-induced pulmonary fibrosis.

Impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation.

Chronic obstructive pulmonary disease (COPD) often tends to respond poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2 (HDAC-2) activity is an important mechanism behind this GC insensitivity. In this study, we investigated the effects of three phosphodiesterase inhibitors (PDEIs), with an anti-inflammatory propensity, on cigarette smoke (CS)-induced pulmonary inflammation and HDAC-2 activity. Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course of 30 weeks. Administration of the PDEIs commenced from the 29th week and followed a schedule of once daily treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was administered intragastrically (5 mg·kg-1 ), while pentoxifylline (PTX) (10 mg·kg-1 ) and theophylline (THEO) (10 mg·kg-1 ) were administered intraperitoneally, either alone or in combination with a GC (triamcinolone acetonide or TRI, 5 mg·kg-1 , i.m., single injection). Lung morphometry, as well as the activity of HDAC-2, pro-inflammatory cytokines and reactive oxygen species (ROS) were assessed at the end of the 30-week course. CS exposure was associated with a reduction in HDAC-2 activity and the up-regulation of ROS expression. PTX, ROF, and THEO administration led to the partial restoration of HDAC-2 activity, which was favorably associated with the reduction of ROS expression. However, combining TRI to any of these PDEIs did not synergistically augment HDAC-2 activity. Inactivation of HDAC-2 due to long-term CS exposure is closely related to exaggerated oxidative stress, and this reduced HDAC-2 activity could partially be restored through the use of PDEIs. This finding provides a potential novel approach for further clinical research.

Chemical proteomic profiling of UTP-binding proteins in human cells.

Nucleotide-binding proteins play important roles in a variety of biological processes. While ATP- and GTP-binding proteins have been well studied, the systematical identification of UTP-interacting proteins remains under investigated. Here, we developed a chemical proteomic strategy using a biotinylated UTP affinity probe coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) method to enrich, identify and quantify UTP-binding proteins at the entire proteome scale. By performing labeling reactions with high vs low concentrations of UTP probe (100 and 10 µM) or with the UTP probe in the presence of free UTP in stable isotope labeling by amino acids in cell culture (SILAC) experiments, we identified more than 70 potential UTP-binding proteins which are involved in multiple cellular processes, such as translational elongation and protein folding. We also validated the UTP-binding capability of the cytoskeletal protein ACTB by using cellular thermal shift assay (CETSA). Together, we performed a high-throughput chemical proteomics-based analysis to identify, for the first time, UTP-binding proteins in human proteome, which should be applicable for the identification and quantification of UTP-binding proteins in other organisms.

Could Wealth Make Religiosity Less Needed for Subjective Well-Being? A Dual-Path Effect Hypothesis of Religious Faith Versus Practice.

Religiosity is important for religious people to maintain their subjective well-being (SWB). We propose a dual-path effect hypothesis to explore different working mechanisms of religious faith and practice on benefiting people's SWB. Religious faith can promote SWB mainly via an intrinsic meaning-making path although religious practice can promote SWB via both an intrinsic meaning-making path and an extrinsic capital-accumulating path. If the dual-path effect hypothesis stands, then the role of religious practice in influencing SWB should be partly substituted by good economic status, but the role of religious faith should not. Then, only the effect of religious practice would be moderated by wealth. Results show that people's individual income and national GDP have significant moderating effects on the relationship between religious practice and SWB, but they had no moderating effect on the association between religious faith and SWB, indicating wealth could be an alternative source of accumulating capital and social resources between religious practice and SWB. Results provide important evidence for the dual-path effect hypothesis. The findings uniquely contribute to the literature of religiosity, SWB, and their connections with wealth. Implications for future research are also discussed.

[The value of cytochrome P4502C19 gene assay for anti-platelet therapy after PCI in stable angina patients with left main coronary artery lesions].

OBJECTIVE: To evaluate the efficacy and safety of different antiplatelet therapies for stable angina patients with complicated left main coronary artery lesions and intermediate metabolizer Cytochrome P450 2C19 gene (CYP2C19) undergoing PCI. METHODS: A total of 247 patients diagnosed with stable angina in cardiology department of Fujian union hospital from February 2015 to February 2017 were retrospectively analyzed, among them, the elective PCI were performed on the left main coronary artery and the CYP2C19 gene poly-morphism were intermediate metabolize, they were divided into ticagrelor treatment group(aspirin combined with ticagrelor, n=95)and clopidogrel treatment group(aspirin combined with clopidogrel, n=152) according to the different antiplatelet treatment programs. Both groups were given aspirin 300 mg and clopidogrel 300 mg orally before PCI; the ticagrelor group were given the maintenance dose of ticagrelor (90 mg orally, twice a day) after PCI, while those in clopidogrel group were clopidogrel 75 mg orally (once a day) after PCI; both groups were given the maintenance dose of aspirin (100 mg orally, once a day)after PCI. The major adverse cardiovascular events (MACE) were observed within 12 months after PCI. RESULTS: At 12 months after PCI, the incidence of MACE in the ticagrelor treatment group was significantly lower than that in the clopidogrel treatment group, the difference was statistically significant (2.1% vs 15.1%, P=0.001).There were no significant differences between the two groups in the restenosis rates of non- revascularized target vessel, recurrent rates of angina pectoris(but not myocardial infarction), recurrent rates of myocardial infarction, and revascularization rates of target vessel (P > 0.05). There were also no significant differences between the two groups in bleeding. CONCLUSIONS: For stable angina patients with complicated left main coronary artery lesions and intermediate metabolizer CYP2C19 gene, aspirin combined with ticagrelor antiplatelet therapy after PCI is effective, the effect of ticagrelor is better than clopidogrel on MACE, and ticagrelor does not seem to increase the risk of bleeding.

Generation of hepatocyte-like cells from human urinary epithelial cells and the role of autophagy during direct reprogramming.

Somatic cells can be directly reprogrammed into other cell lineages, which holds great promise for regenerative medicine. However, low efficiency and obscure mechanism hinder the application of direct reprogramming. Here, we show that overexpressing the hepatic-specific transcription factors (TFs) HNF1α, FOXA3, and GATA4 was sufficient to convert human urinary epithelial cells (hUCs) into induced hepatocyte-like cells (iHeps). The obtained iHeps were confirmed to express various hepatocyte-specific genes with multiple mature hepatocyte functions. Moreover, autophagy-related genes P62, ULK1, BECN1, VPS34, and LC3B were upregulated in the early stage of reprogramming and knockout of P62 and BECN1 in hUCs with CRISPR/Cas9 technology increased the efficiency of direct reprogramming. Collectively, we established a non-invasive approach to convert hUCs into iHeps and provided a glimpse into the role of autophagy in this process.

Effect of neutrophil CD64 for diagnosing sepsis in emergency department.

BACKGROUND: The aim of this study is to investigate the diagnostic and prognostic value of neutrophil CD64 (nCD64) as a novel biomarker in sepsis patients. METHODS: One hundred fifty-one adult patients diagnosed with sepsis and 20 age-matched healthy controls were enrolled in the study. Patients with sepsis were further subdivided into a sepsis group and a septic shock group. nCD64 expression, serum procalcitonin (PCT) level, C-reactive protein (CRP) level, and white blood cell (WBC) count were obtained for each patient, and Sequential Organ Failure Assessment (SOFA) scores were calculated. RESULTS: nCD64 expression was higher in the sepsis group with confirmed infection than in the control group. The receiver operating characteristic (ROC) curve of nCD64 was higher than those of SOFA score, PCT, CRP and WBC for diagnosing infection. The area under the curve (AUC) of nCD64 combined with SOFA score was the highest for all parameters. The AUC of nCD64 for predicting 28-day mortality in sepsis was significantly higher than those of PCT, CRP, and WBC, but slightly lower than that of SOFA score. The AUC of nCD64 or PCT combined with SOFA score was significantly higher than that of any single parameter for predicting 28-day mortality. CONCLUSION: nCD64 expression and SOFA score are valuable parameters for early diagnosis of infection and prognostic evaluation of sepsis patients.

Efficacy of cytokine-induced killer cell-based immunotherapy for hepatocellular carcinoma.

In attempts to delay tumor progression after surgery or minimally invasive local treatments, multidisciplinary strategies have been broadly studied in patients with hepatocellular carcinoma (HCC). The objective of this present study was to evaluate the efficacy of autologous transplantations of cytokine-induced killer (CIK) cells as an adjuvant therapy for patients with HCC. A total of 264 patients with HCC were enrolled in this retrospective study. Of these patients, 165 received either CIK cell therapy alone or as adjuvant therapy to surgery, transcatheter arterial chemoembolization (TACE), or TACE-based comprehensive treatments (CT). The remaining 99 patients received only surgery or TACE. Kaplan-Meier analysis and the Chi-squared test were used to analyze the overall survival (OS), progression-free survival (PFS), and clinical characteristics of the patients in the different treatment subgroups. Kaplan-Meier analysis suggested that patients in the Surgery+CIK group had a significantly improved OS compared with those in the other three groups (P < 0.001). Furthermore, patients who developed a fever after the CIK cell treatments manifested a likely better OS (P = 0.028). Subgroup analysis indicated that patients in the Surgery+CIK group likely had an improved PFS but a similar OS compared with the patients in the Surgery-alone group (P = 0.055 for PFS, and P = 0.746 for OS). Further subgroup analysis showed that the OS in both the TACE+CIK and CT+CIK groups was prolonged significantly compared with that in the TACE-alone group (P = 0.015 and P = 0.018, respectively). However, similar OS was observed between the TACE+CIK and CT+CIK groups (P = 0.686). Autologous transplantation of CIK cells as an adjuvant therapy was associated with better survival for patients with HCC, especially for those who had also undergone TACE. A fever reaction might be a potential event for assessing the curative effect of the CIK treatment.

MicroRNA­192 acts as a tumor suppressor in colon cancer and simvastatin activates miR­192 to inhibit cancer cell growth.

Colon cancer is one of the most common malignant tumors worldwide. Understanding the underlying molecular mechanisms is crucial for the development of therapeutic strategies for the treatment of patients with colon cancer. In the present study, a novel tumor suppressive microRNA, miR­192, was demonstrated to be markedly downregulated in colon cancer cells compared with normal colon cells. By overexpressing miR­192 in colon cancer HCT­116 cells, the results of the present study revealed that miR­192 inhibits cell proliferation, migration and invasion. Bioinformatics were used to determine the target gene of miR­192 and Ras­related protein Rab­2A (RAB2A) was identified as a downstream target of miR­192. Following the determination of the role of the miR­192­RAB2A pathway in colon cancer, small molecules that may regulate miR­192 were screened and the results demonstrated that simvastatin is an activator of miR­192. Furthermore, simvastatin upregulated miR­192 and inhibited the expression of downstream targets of miR­192, which subsequently led to suppressed proliferation, migration and invasion of colon cancer cells. In conclusion, the present study identified a novel colon cancer cell suppressor, as well as a small­molecule activator of the tumor suppressor miR­192, which may represent a therapeutic strategy for the treatment of patients with colon cancer.

Engineering a 3D DNA-Logic Gate Nanomachine for Bispecific Recognition and Computing on Target Cell Surfaces.

Among the vast number of recognition molecules, DNA aptamers generated from cell-SELEX exhibit unique properties for identifying cell membrane biomarkers, in particular protein receptors on cancer cells. To integrate all recognition and computing modules within a single structure, a three-dimensional (3D) DNA-based logic gate nanomachine was constructed to target overexpressed cancer cell biomarkers with bispecific recognition. Thus, when the Boolean operator "AND" returns a true value, it is followed by an "ON" signal when the specific cell type is presented. Compared with freely dispersed double-stranded DNA (dsDNA)-based molecular circuits, this 3D DNA nanostructure, termed DNA-logic gate triangular prism (TP), showed better identification performance, enabling, in turn, better molecular targeting and fabrication of recognition nanorobotics.