Uptake, translocation, and metabolism of organophosphate esters (OPEs) in plants and health perspective for human: A review.

Plant uptake, accumulation, and transformation of organophosphate esters (OPEs) play vital roles in their geochemical cycles and exposure risks. Here we reviewed the recent research advances in OPEs in plants. The mean OPE concentrations based on dry/wet/lipid weight varied in 4.80-3,620/0.287-26.8/12,000-315,000 ng g-1 in field plants, and generally showed positive correlations with those in plant habitats. OPEs with short-chain substituents and high hydrophilicity, particularly the commonly used chlorinated OPEs, showed dominance in most plant samples, whereas some tree barks, fruits, seeds, and roots demonstrated dominance of hydrophobic OPEs. Both hydrophilic and hydrophobic OPEs can enter plants via root and foliar uptake, and the former pathway is mainly passively mediated by various membrane proteins. After entry, different OPEs undergo diverse subcellular distributions and acropetal/basipetal/intergenerational translocations, depending on their physicochemical properties. Hydrophilic OPEs mainly exist in cell sap and show strong transferability, hydrophobic OPEs demonstrate dominant distributions in cell wall and limited migrations owing to the interception of Casparian strips and cell wall. Additionally, plant species, transpiration capacity, growth stages, commensal microorganisms, and habitats also affect OPE uptake and transfer in plants. OPE metabolites derived from various Phase I transformations and Phase II conjugations are increasingly identified in plants, and hydrolysis and hydroxylation are the most common metabolic processes. The metabolisms and products of OPEs are closely associated with their structures and degradation resistance and plant species. In contrast, plant-derived food consumption contributes considerably to the total dietary intakes of OPEs by human, particularly the cereals, and merits specifical attention. Based on the current research limitations, we proposed the research perspectives regarding OPEs in plants, with the emphases on their behavior and fate in field plants, interactions with plant-related microorganisms, multiple uptake pathways and mechanisms, and comprehensive screening analysis and risk evaluation.

Facile surface functionalization of triboelectric layers via electrostatically self-assembled zwitterionic molecules for achieving efficient and stable antibacterial flexible triboelectric nanogenerators.

Manipulation of the surface properties of the triboelectric layer has been proven to be one of the key parameters to achieve high-performance and stable triboelectric nanogenerators (TENG). Herein, a pragmatic surface engineering strategy that can substantially boost the performance and stability of flexible TENG is elaborated by incorporating the zwitterionic molecule dimethylethylammoniumpropane sulfonate (NDSB) as the surface modification layer. Given that zwitterionic molecules tend to form aggregated structures, realizing ordered arrangement on the substrate surface remains challenging to date. To address this issue, in this work, a combination of multiple surface treatments and molecular manipulation strategy is proposed. Our results prove that NDSB is effective in modifying the surface properties of the dielectric layer and electrode layer, leading to a remarkable power density and specific power of 2.86 W m-2 and 20.73 mW g-1 for flexible TENG, respectively. In addition, due to the strong interaction between the NDSB/dielectric and NDSB/electrode, a water-resistant long-term stable flexible TENG is realized. More encouragingly, our strategy is compatible with a cost-effective dip-coating technique, and an unprecedented demonstration of batch fabrication of TENG using NDSB to functionalize the surface of the dielectric layer and electrode layer synchronously can be realized, which is advantageous for rapid and up-scalable manufacturing of TENG. We also prove that the TENG based on zwitterionic materials reveals exceptional antibacterial properties against Escherichia coli. This study represents an important step towards the development of long-term stable flexible TENG that possesses a high output performance and excellent antibacterial activity based on a facile and economical strategy, enabling TENG technology to show bright prospects in a wide variety of application domains.

Uptake mechanism, translocation, and transformation of organophosphate esters in water hyacinth (Eichhornia crassipes): A hydroponic study.

Owing to their dominant wastewater origin, bioavailability, and toxicity, the occurrence and behavior of organophosphate esters (OPEs) in aquatic systems have attracted considerable attention over the past two decades. Aquatic plants can accumulate and metabolize OPEs in water, thereby playing an important role in their behavior and fate in waterbodies. However, their uptake, translocation and transformation mechanisms in plants remain incompletely characterized. We investigated the accumulation and transformation of OPEs in water hyacinth (Eichhornia crassipes) through a series of hydroponic experiments using three representative OPEs, tris(2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPP). These OPEs can not only be adsorbed onto and enter plant roots via passive diffusion pathways, which are facilitated by anion channels and/or aquaporins, but also can return to the solution when concentration gradients exist. After entry, hydrophilic TCEP showed a dominant distribution in the cell sap, strong acropetal transportability, and rapid translocation rate, whereas hydrophobic TPP was mostly retained in the root cell wall and therefore demonstrated weak acropetal transportability; TBEP with moderate hydrophilicity remained in the middle. All these OPEs can be transformed into diesters, which presented higher proportions in the cell sap and therefore have stronger acropetal transferability than their parent OPEs. TCEP exhibits the lowest biodegradability, followed by TPP and TBEP. These OPEs exerted apparent effects on plant growth, photosynthesis, and the diversity and composition of the rhizosphere microbial community.

Organophosphate esters (OPEs) in a heavily polluted river in South China: Occurrence, spatiotemporal trends, sources, and phase distribution.

In the past decade, organophosphate esters (OPEs) undergo rapid increase in production and use. Meanwhile, owing to their additive property, OPEs exhibit liability to escape from related products and therefore ubiquity in various environments. Moreover, numerous researches verify their bioavailability and negative effects on biota and human, hence their occurrence and associated risks have caught much concern, particularly those in aquatic systems. So far, however, OPEs in water are generally investigated as a whole, their phase distribution and behavior in waterbodies are incompletely characterized. We examined 25 OPEs in water (including dissolved and particulate phases), sediment, and sediment core samples from the Lian River, which flows through the Guiyu e-waste recycling zone and Shantou specific economic zone in South China. Compared to most global waterbodies, the Lian River showed high or ultrahigh OPE levels in both water and sediments, particularly in the reaches surrounded by e-waste recycling and plastic-related industries, which were the top two greatest OPE sources. Non-industrial and agriculture-related anthropogenic activities also contributed OPEs. Sediment core data suggested that OPEs have been present in waters in Guiyu since the 1960s and showed a temporal trend consistent with the local waste-recycling business. The phase distribution of OPEs in the Lian River was significantly correlated with their hydrophobicity and solubility. Owing to their wide range of physicochemical properties, OPE congeners showed significant percentage differences in the Lian River water and sediments. Generally, OPEs in water reflect their dynamic real-time inputs, while those in sediment signify their accumulative deposition, which is another cause of their phase distribution disparities in the Lian River. The physicochemical parameters of OPEs first imposed negative and then positive influences on their dissolved phase-sediment distribution, indicating the involvement of both the adsorption of dissolved OPEs and the deposition of particle-bound OPEs.

Rationale and design of a prospective, multicenter, cohort study on the evaluation of postoperative Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial).

Background: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication after abdominal surgery. The incidence of VTE after colorectal malignancy is higher than that after general surgery. Although more attention has been paid to the prevention of VTE, there is still a large gap between clinical practice and guideline recommendation. Methods: The Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial) will be a prospective, multicenter, cohort study to determine the current status of the incidence, diagnosis, treatment, and prevention of VTE after colorectal cancer surgery in China, as well as to further improve the level of prevention and treatment of VTE events in these fragile patients. In this study, 1,217 patients will be enrolled at 40 centers in China and evaluated on VTE events and adverse events related to VTE prevention at 5-9 and 21-28 days after surgery. The primary outcome is the incidence of VTE events during the follow-up, and secondary outcome is the incidence of adverse events associated with VTE prevention. Discussion: This study will comprehensively evaluate the incidence and prevention of VTE after colorectal cancer surgery in China, balance the relationship between VTE prevention and bleeding adverse events, and the formulate a guideline for the prevention of VTE after colorectal surgery that might suitable for national conditions. Trial Registration: Clinical trial registration number NCT04588805 (The CRC-VTE trial).

Questionable necessity of nitroglycerin for diagnostic coronary artery examination using 320-row multi-detector computed tomography.

OBJECTIVE: This study aims to analyze and compare the diagnostic effectiveness of 320-row multi-detector computed tomography for coronary artery angiography (MDCTA) in subjects with and without sublingual vasodilator (nitroglycerin). MATERIALS AND METHODS: From September 2015 to September 2016, 70 individuals without history of major cardiovascular diseases who underwent MDCTA for health examination were retrospectively categorized into sublingual nitroglycerin (NTG) and non-NTG groups. Medical history, CT dose index (CTDI), and multi-slice CT images were compared between two groups. A diameter of coronary artery (DA, mm) was computed and analyzed. RESULTS: A total of 41 males and 29 females (mean age: 55.43±8.84 years, range: 34- 76) were reviewed. Normal and abnormal MDCTA findings were noted in 54 and 16 participants, respectively, with the detection rate of coronary artery disease being 23%. There was no significant difference in inter-observer variability of coronary CTA image quality and diagnosis between the NTG and non-NTG groups among three experienced radiologists. Although the percentage dilatation of left anterior descending branch (LAD), right coronary artery (RCA) and left circumflex branch (LCX) following in the NTG group were 12.4%, 12.8% and 25.3%, respectively (p < 0.01), there was no significant difference in image quality and diagnosis between the two groups. CONCLUSIONS: Despite the recommendation of routine nitroglycerin use for subjects undergoing computed tomography for coronary artery angiography, our results showed no significant advantage of its use in improving image quality and rate of diagnosis accuracy.

Combination of a Self-Regulation Module and Mobile Application to Enhance Treatment Outcome for Patients with Acne.

Background and Objectives: Acne, an inflammatory disorder of the pilosebaceous unit associated with both physiological and psychological morbidities, should be considered a chronic disease. The application of self-regulation theory and therapeutic patient education has been widely utilized in different health-related areas to help patient with a chronic disease to attain better behavioral modification. The present study aims at investigating the treatment efficacy of combining a self-regulation-based patient education module with mobile application in acne patients. Materials and Methods: This was one-grouped pretest-posttest design at a single tertiary referral center with the enrollment of 30 subjects diagnosed with acne vulgaris. Relevant information was collected before (week 0) and after (week 4) treatment in the present study, including the Acne Self-Regulation Inventory (ASRI), Cardiff Acne Disability Index (CADI), and Dermatology Life Quality Index (DLQI) that involved a questionnaire-based subjective evaluation of the patient's ability in self-regulation and quality of life as well as clinical Acne Grading Scores (AGS) that objectively assessed changes in disease severity. To reinforce availability and feasibility, an individualized platform was accessible through mobile devices for real-time problem solving between hospital visits. Results: Thirty subjects completed the designed experiment. An analysis of the differences between scores of pretest and posttest of ASRI demonstrated substantial elevations (p < 0.001). The questionnaire survey of CADI and DLQI dropped significantly after the application of a self-regulation-based patient education module with a mobile application, revealing substantial reductions in both parameters (p < 0.001). The sign test demonstrated a remarkably significant difference in AGS (Z = -7.38, p < 0.001), indicating notable improvement in the clinical severity of acne after treatment. Conclusions: After incorporating modern mobile application, a self-regulation-based therapeutic patient education module could significantly improve treatment outcomes among acne patients.

Assessment of Prolonged Dengue Virus Infection in Dermal Fibroblasts and Hair-Follicle Dermal Papilla Cells.

Dengue virus (DENV)-mediated hair loss is one of the post-dengue fatigue syndromes and its pathophysiology remains unknown. Whether long-term or persistent infection with DENV in the scalp results in hair loss is unclear. In this study, we cultured human dermal fibroblasts (WS1 cells) and primary human hair-follicle dermal papilla cells (HFDPCs) in the long term with DENV-2 infection. The production of virion, the expression of inflammatory and anti-virus genes, and their signaling transduction activity in the infected cells were analyzed. DENV-2 NS3 protein and DENV-2 5' UTR RNA were detected in fibroblasts and HFDPCs that were subjected to long-term infection with DENV-2 for 33 days. A significant amount of DENV-2 virion was produced by both WS1 cells and HFDPCs in the first two days of acute infection. The virion was also detected in WS1 cells that were infected in the long term, but HFDPCs failed to produce DENV-2 after long-term culture. Type I and type III interferons, and inflammatory cytokines were highly expressed in the acute phase of DENV infection in HFPDC and WS1 cells. However, in the long-term cultured cells, modest levels of anti-viral protein genes were expressed and we observed reduced signaling activity, which was correlated with the level of virus production changes. Long-term infection of DENV-2 downregulated the expression of hair growth regulatory factors, such as Rip1, Wnt1, and Wnt4. This in vitro study shows that the long-term infection with DENV-2 in dermal fibroblasts and dermal papilla cells may be involved with the prolonged-DENV-infection-mediated hair loss of post-dengue fatigue syndrome. However, direct evidence for viral replication in the human hair of a dengue victim or animal infection model is required.

Epidermal growth factor receptor (EGFR) inhibitor induced purpuric drug eruption: Three case reports.

INTRODUCTION: Purpuric drug eruption (PDE) is an uncommon, clinically distinct side effect of epidermal growth factor receptor (EGFR) inhibitors. PATIENT CONCERNS: Unlike acneiform eruption, which arises from hair follicles mainly in the head and neck area, PDE starts from xerosis cutis, primarily in the lower extremities and is not associated with hair follicles. Herein, we report 3 cases of 3 patients who had received EGFR inhibitor and were hospitalized for PDE later. The cases were characterized by painful late-onset palpable purpura with identifiable bacterial pathogens. DIAGNOSIS: The patients were diagnosed with characteristic clinical presentations, that is, late onset, PDE locations mainly in the lower extremities, nonfollicular centricity, and laboratory findings with identifiable bacterial pathogens. INTERVENTIONS: Systemic antibiotics and intensive moisturizer application were prescribed. OUTCOMES: All the patients were successfully treated within 6 to 9 days without discontinuation of EGFR inhibitors. CONCLUSION: Systemic antibiotics, topical emollient, and skin barrier repair should be included in the treatment regimens for PDE.

Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study.

BACKGROUND: Sorafenib is the standard treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). However, the treatment outcome is not satisfactory. We retrospectively analyzed whether adding transarterial embolization/chemoembolization (TA(C)E)-based locoregional therapy to sorafenib can further improve treatment efficacy. PATIENTS AND METHODS: We included 147 BCLC stage C HCC patients with Child-Turcotte-Pugh class A liver function and treated with sorafenib for analysis. Through propensity score matching, we divided patients into the combined treatment group (n = 63; patients received TA(C)E-based locoregional treatment and sorafenib) and the sorafenib monotherapy group (n = 63). We analyzed the effects of patients' clinical and tumor-related factors on their overall survival (OS) and time to tumor progression. RESULTS: The OS was better in the combined treatment group than in the sorafenib monotherapy group (419 vs. 223 days, p = 0.028). In the Cox regression model, combined treatment, a lower baseline α-fetoprotein (AFP) level < 400 ng/mL, tumors without main portal venous tumorous thrombosis, and age ≥60 years were identified as independent factors for OS. Subgroup analysis demonstrated that patients with a higher baseline AFP level > 400 ng/mL, age < 60 years, tumors with branched portal venous tumorous thrombosis only or without extrahepatic metastasis benefited the most from combined treatment. CONCLUSION: Combining TA(C)E-based locoregional treatment with sorafenib resulted in better OS in patients with BCLC stage C HCC compared with sorafenib alone. TA(C)E-based locoregional treatment can be an adjunctive treatment to sorafenib for patients with advanced HCC and a satisfactory liver functional reserve.

Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells.

Anti-angiogenesis is one of the most general clinical obstacles in cancer chemotherapy. Kaempferol is a flavonoid phytochemical found in many fruits and vegetables. Our previous study revealed that kaempferol triggered apoptosis in human umbilical vein endothelial cells (HUVECs) by ROS­mediated p53/ATM/death receptor signaling. However, the anti­angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF­stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF­stimulated HUVEC viability. Kaempferol treatment also inhibited cell migration, invasion, and tube formation in VEGF­stimulated HUVECs. VEGF receptor­2 (VEGFR­2), and its downstream signaling cascades (such as AKT, mTOR and MEK1/2­ERK1/2) were reduced as determined by western blotting and kinase activity assay in VEGF­stimulated HUVECs after treatment with kaempferol. The present study revealed that kaempferol may possess angiogenic inhibition through regulation of VEGF/VEGFR­2 and its downstream signaling cascades (PI3K/AKT, MEK and ERK) in VEGF-stimulated endothelial cells.

The development and validation of an acne self-regulation inventory.

BACKGROUND: Acne, an inflammatory disease of the pilosebaceous unit, is now recognized and investigated as a chronic disease. Since the physiological and psychosocial impact of acne may be long-lasting, the treatment of acne vulgaris poses a formidable challenge for dermatologists. OBJECTIVE: The present study aims at investigating the validity and reliability of a self-developed instrument "acne self-regulation inventory" (ASRI) based on self-regulation theory in assessing the selfregulation ability of acne patients as part of the therapeutic strategy. METHODS: All proposed items to be included in ASRI, which consisted of four subscales (i.e., self-monitoring, self-judgment, self-reaction, and self-motivation), were first reviewed by 5 experts in the field. Pilot testing of scale reliability and validity of ASRI were then performed by recruiting 144 acne patients, followed by conduction of formal questionnaire survey by enrolling other 90 acne patients to complete a questionnaire comprising the refined ASRI, Cardiff Acne Disability Index (CADI), and Dermatology Life Quality Index (DLQI) to obtain constructive validity to evaluate the associations of ASRI with clinical acne grading scores, CADI, and DLQI. RESULTS: Expert review resulted in the inclusion of totally 31 items for pilot testing (i.e., self-monitoring 6 items, self-judgment 6 items, self-reaction 12 items, and self-motivation 7 items). The differentiating ability of each item was confirmed by significant difference between the higher third scorers and those of the lower third using t-test for independent means (all p<0.001). Moreover, Cronbach's α indicated that deletion of a single item in ASRI did not elevate mean value above 0.958 and removal of each item in the four subscales did not increase the mean value of the set Cronbach's α value for each subscale (i.e., 0.886; 0.860; 0.895; 0.907, respectively), suggesting suitability of the 31 items. A high Cronbach's α coefficient of the whole scale as well as the four subscales (i.e., 0.958; 0.886, 0.860, 0.895, and 0.907) demonstrated a high reliability of the ASRI. Pearson's correlation demonstrated moderate to high discriminant validity of ASRI with coefficients between each pair of the four subscales ranging from 0.637-0.798. Formal questionnaire survey demonstrated significant difference between the higher third ASRI scorers and those of the lower third in comparison with clinical acne grading scores, CADI, and DLQI, using t-test for independent means (both p=0.001). CONCLUSION: The results of the present study demonstrated the usefulness of a self-developed ASRI as an assessment tool to be included in the treatment strategy for acne patients.

Validity of combination active specific immunotherapy for colorectal cancer: a meta-analysis of 2993 patients.

BACKGROUND AIMS: The aim of this study was to investigate whether active specific immunotherapy (ASI) is able to demonstrate therapeutic efficacy against colorectal cancer. METHODS: We conducted a systematic review of published papers from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors who used predefined database templates. The effects of ASI were compared with those of surgery alone, and a pooled analysis was performed with the use of the data from random- or fixed-effect models. RESULTS: Twelve trials matched our inclusion criteria (n = 2993, including 1842 control subjects). The overall analysis showed a significant survival benefit [1-, 2-, 3-, 4-, 5-, 6- and 7-year overall survival (OS), P < 0.05; 10-year OS, P < 0.001] in favor of ASI immunotherapy combined with surgery, but there was not an improvement in the 8- or 9-year OS (P > 0.05). The disease-free survival (DFS) rate was improved after the combination of ASI immunotherapy (2-, 3-, 5- and 10-year DFS, P < 0.05), but no significant improvement was noted for the 1-, 4-, 6-, 7-, 8- or 9-year DFS (P > 0.05). In addition, the disease-specific survival (DSS) was improved at some time points after the combination of ASI immunotherapy and surgery (2-, 3-, 4-, 5- and 6-year DSS, P < 0.05, but not the 1-, 7-, 8- or 9-year DSS, P > 0.05). An improved 2-, 3-, 4-, 5- and 6-year recurrence-free interval (RFI) (P < 0.05) was also observed in patients who received ASI therapy, but this was not observed for the 1-year RFI (P > 0.05). Furthermore, an analysis of the recurrence-free survival (RFS) showed that it was significantly increased in the ASI plus surgery group (1-, 2-, 3-, 4-, 5- and 6-year RFS, P < 0.001). The funnel plots showed that the analyses were relatively reliable and the publication bias was small. CONCLUSIONS: The combination of ASI immunotherapy and surgery was superior in prolonging the overall survival time and enhancing the recurrence-free survival rate compared with surgery alone.

Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis.

OBJECTIVES: Our meta-analysis performed a systematic evaluation on the therapeutic efficacy and safety of tumour vaccines for the treatment of advanced non-small cell lung cancer (NSCLC). DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCT). DATA SOURCES: PubMed, the Cochrane Center Register of Controlled Trials, Science Direct and EMBASE were searched from January 1980 until January 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RCT were included; the control arm had to receive either placebo or chemotherapy or no treatment. MAIN OUTCOME MEASURES: The quality of the data from individual papers was assessed for overall survival (OS), clinical response rate and side effects. RESULTS: Overall, 11 RCT of advanced NSCLC with a total of 3986 patients were conducted for meta-analysis. The results showed that the vaccine arm significantly extended primary endpoint median overall survival compared with control group (p<0.00001) (HR 0.760; 95% CI 0.644 to 0.896; p=0.001). Three subgroup patients with tumour vaccine at 1-year, 2-year and 3-year survival rates also gained significant benefits compared with their corresponding control group (p=0.0004, 0.03 and 0.19, respectively). Besides, a significant improvement in median time to progression (TTP), median progression-free survival (PFS) and a trend of improvement in objective response rate were observed after tumour vaccine treatment (p=0.001, 0.005 and 0.05, respectively; median PFS HR 0.842; 95% CI 0.744 to 0.954; p=0.007). A few severe adverse effects occurred in the tumour vaccine group, but fewer side effects were observed in the vaccine group compared with the control group (p<0.00001). CONCLUSIONS: Taken together, NSCLC tumour vaccines markedly prolong median OS (p<0.00001), median TTP (p=0.001) and median PFS (p=0.005), improve clinical response rate (p=0.05) and lessen adverse side effects (p<0.00001). Our meta-analysis suggests tumour vaccines improve the efficacy of the treatment, and also provide superiority in treatment of patients with advanced NSCLC among a variety of immunotherapy strategies.

Adoptive immunotherapy of cytokine-induced killer cell therapy in the treatment of non-small cell lung cancer.

AIM: The aim of this study was to systemically evaluate the therapeutic efficacy of cytokine-induced killer (CIK) cells for the treatment of non-small cell lung cancer. MATERIALS AND METHODS: A computerized search of randomized controlled trials for CIK cell-based therapy was performed. The overall survival, clinical response rate, immunological assessment and side effects were evaluated. RESULTS: Overall, 17 randomized controlled trials of non-small cell lung cancer (NSCLC) with a total of 1172 patients were included in the present analysis. Our study showed that the CIK cell therapy significantly improved the objective response rate and overall survival compared to the non-CIK cell-treated group. After CIK combined therapy, we observed substantially increased percentages of CD3+, CD4+, CD4+CD8+, CD3+CD56+ and NK cells, whereas significant decreases were noted in the percentage of CD8+ and regulatory T cell (Treg) subgroups. A significant increase in Ag-NORs was observed in the CIK-treated patient group (p = 0.00001), whereas carcinoembryonic antigen (CEA) was more likely to be reduced to a normal level after CIK treatment (p = 0.0008). Of the possible major side effects, only the incidence of fever in the CIK group was significantly higher compared to the group that received chemotherapy alone. CONCLUSION: The CIK cell combined therapy demonstrated significant superiority in the overall survival, clinical response rate, and T lymphocytes responses and did not present any evidence of major adverse events in patients with NSCLC.

Cytokine-induced killer cells in the treatment of patients with renal cell carcinoma: a pooled meta-analysis.

Cytokine-induced killer cells (CIKs) have been applied in multifarious cancer. Here, we address the connection between immune therapy and clinical responses by a systematic meta-analysis. A total of 385 patients (including 183 controls) were identified for renal cell cancer (RCC) in the seven selected trials. The estimated pooled complete response and partial response showed a significant improvement for patients receiving CIK immunotherapy compared with non-CIK therapy (p < 0.0001), which was up to 62% of clinical response. The overall analysis showed a significant survival benefit (1-year overall survival [OS]: p = 0.0002; 3-year OS: p < 0.0001) in favor of CIK-based therapy in RCC, thus a statistically significant effect of OS and clinical response was demonstrated in RCC patients.

Clinical efficacy of tumor antigen-pulsed DC treatment for high-grade glioma patients: evidence from a meta-analysis.

BACKGROUND: The effectiveness of immunotherapy for high-grade glioma (HGG) patients remains controversial. To evaluate the therapeutic efficacy of dendritic cells (DCs) alone in the treatment of HGG, we performed a systematic review and meta-analysis in terms of patient survival with relevant published clinical studies. MATERIALS AND METHODS: A total of 409 patients, including historical cohorts, nonrandomized and randomized controls with HGG, were selected for the meta-analysis. RESULTS: The treatment of HGG with DCs was associated with a significantly improved one-year survival (OS) (p<0.001) and 1.5-, 2-, 3-, 4-, and 5-year OS (p<0.001) compared with the non-DC group. A meta-analysis of the patient outcome data revealed that DC immunotherapy has a significant influence on progression-free survival (PFS) in HGG patients, who showed significantly improved 1-,1.5-, 2-, 3- and 4-year PFS (p<0.001). The analysis of Karnofsky performance status (KPS) demonstrated no favorable results for DC cell therapy arm (p = 0.23).The percentages of CD3+CD8+ and CD3+CD4+ T cells and CD16+ lymphocyte subset were not significantly increased in the DC group compared with the baseline levels observed before treatment (p>0.05), whereas CD56+ lymphocyte subset were significantly increased after DC treatment (p = 0.0001). Furthermore, the levels of IFN-γ in the peripheral blood of HGG patients, which reflect the immune function of the patients, were significantly increased after DC immunotherapy (p<0.001). CONCLUSIONS: Thus, our meta-analysis showed that DC immunotherapy markedly prolongs survival rates and progression-free time, enhances immune function, and improves the efficacy of the treatment of HGG patients.

Efficacy of autologous bone marrow mononuclear cell therapy in patients with peripheral arterial disease.

AIM: Peripheral arterial disease (PAD), particularly critical limb ischemia (CLI), is a severe cause of amputation and mortality. More than 50% of diabetic patients with CLI die within four to five years. The development of novel stem cell therapies may bring new hope to these patients. We aimed to assess the efficacy of autologous bone marrow cell therapy for treating CLI using a meta-analysis. METHODS: We searched the literature in PubMed, the Cochrane Central Registry of Controlled Trials, the Elsevier database and EBSCO for trials of autologous cell therapy in patients with severe PAD published before October 30, 2013. We chose objective clinical endpoints to assess the efficacy of therapy in the meta-analysis, including changes in the ankle-brachial index (ABI), transcutaneous oxygen tension (TcO2), pain scale (0-10 scale) and amputation-free survival (AFS). RESULTS: Thirty-one articles reporting clinical trials involving a total of 1,214 patients treated with bone marrow stem cell-based therapy were collected for the meta-analysis, in which the randomized controlled trials (RCTs) and other trials (non-RCTs) were classified into two groups. Regarding the efficacy of stem cell therapy, the ABI showed significant increases (P＜0.05) at 12 , 24 and 48 weeks after therapy in the non-RCT and RCT groups, but not after four to eight weeks in the non-RCT group. The TcO2 values also increased in the RCT group at four to eight weeks after therapy and 24 weeks after therapy (P＜0.001) and in the non-RCT group at four to eight weeks after therapy (P= 0.01), although no significant increases were observed in the RCT group at 12 weeks after therapy or the non-RCT group at 24 weeks after therapy. Meanwhile, pain was significantly reduced (P＜0.05) at four to eight weeks and 24 weeks after therapy in both the non-RCT and RCT groups, but not at four to eight weeks or 12 weeks after therapy in the RCT group. In addition, the long-term clinical trials demonstrated that the AFS rate improved after therapy with bone marrow stem cells (one-year AFS, P＜0.00001; three-year AFS, P=0.0003). CONCLUSIONS: The present results suggest that autologous bone marrow stem cells have an advantageous therapy effect in PAD patients who are not eligible for revascularization.