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AIM: To evaluate the outcomes and elucidate the failure factors for trabeculectomy with mitomycin C (MMC) in Southwest Chinese patients. METHODS: A retrospective correlational study was conducted on the glaucomatous patients who underwent initial trabeculectomy with MMC in Southwest Hospital and had been followed up for 1-3y. A complete success for surgery is defined as a postoperative intraocular pressure (IOP) >5 and ≤21 mm Hg and 20% reduction of IOP compared to preoperative, without IOP-lowering medications. A qualified success for surgery is defined as the abovementioned postoperative IOP with or without IOP-lowering medications. The primary outcomes were IOP, the number of IOP-lowering medications, and cumulative success rate. The secondary outcomes included best corrected visual acuity (BCVA), mean deviation (MD) of visual field, major complications, and risk factors for surgical failure. RESULTS: A total of 325 eyes of 261 glaucomatous patients had been included in our study. Both the mean IOP and the number of IOP-lowering medications were significantly decreased from 32.9±12.0 to 16.4±5.7 mm Hg (P<0.0001) and 3.0±0.9 to 0.9±1.0 (P<0.0001), respectively, at the last visit. The cumulative complete success rate and qualified success rate were 77.8% and 92.0% at 1-year follow-up, and 47.2% and 77.7% at 3-year follow up. There were no significant differences in surgical outcomes between primary angle-closure glaucoma (PACG) and primary open angle glaucoma (POAG). In PACG patients, the success rates of trabeculectomy were comparable with those of phacotrabeculectomy. Hypertension (HR=1.904, P=0.011), encapsulated bleb (HR=2.756, P<0.001), and more preoperative topical medications (HR=2.475, P=0.008) were risk factors for surgical failure. CONCLUSION: The qualified success rate of trabeculectomy with MMC in glaucomatous patients in the cohort is 92.0% at 1-year, and 77.7% at 3-year follow up. Hypertension, encapsulated bleb, and more preoperative topical medications are associated with surgical failure.

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Flue gas not only contains carbon dioxide (CO2) but also air pollutants (sulfur oxides (SOx) and nitrogen oxides (NOx)). The effective utilization of flue gas could help us to reduce the cost of microalgal biomass production. This study assessed and explored the utilization of flue gas for the absorption characteristics of different components and their biological effect in microalgal culture systems. In abiotic absorption experiments, the absorptivity of CO2 was reduced by a maximum of 3.1%, and the concentration of the available carbon source in the culture medium was decreased by 6.7% when sulfur dioxide (SO2, at 100 mg/m3) was presented in the flue gas. Meanwhile, the presence of oxygen (O2, at 4%) in the flue gas improved the absorptivity of nitric oxide (NO). When Scenedesmus dimorphus was cultured using bisulfites and nitrites (at 10 mmol/L and 8 mmol/L, respectively) as the sulfur and nitrogen sources, SOx and NOx in the flue gas did not significantly affect growth of microalgal cells and the carbohydrate, lipid, and protein content. The consumption rates of nutrient elements were calculated, which could provide an adjustment strategy for the initial gas source when culturing microalgae with the flue gas. This study indicates that the flue gas used for microalgal culture should be partially desulfurized, so that the SOx and CO2 concentrations can optimize growth of microalgal cells, while the denitrification might not be needed since the flue gas can be oxidized to utilize the NO. KEY POINTS: • The concentration of the available carbon source in the culture medium was decreased when SO2 was presented in the flue gas, and the presence of O2 in the flue gas improved the absorptivity of NO. • An adjustment strategy for the initial gas source when culturing microalgae with the flue gas was firstly proposed. • For flue gas containing 10% CO2 and 60 mg/m3 of SO2, growth of Scenedesmus dimorphus showed no difference in cell growth in normal culture conditions.

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AIM: To investigate the clinical characteristics and predictive factors of pediatric ocular trauma patients with vitrectomy. METHODS: Pediatric ocular trauma patients (aged 14y or younger) who received vitrectomy in Southwest Hospital between January 2007 and December 2017 were reviewed retrospectively. Age, gender, mechanism of injury, final visual acuity (VA), and prognostic factors were analyzed. RESULTS: A total of 139 eyes in 139 pediatric patients were included in the study. The mean age was 7.4±3.7 years old and the male-to-female ratio was 5:1. There were 104 (74.8%) open globe injuries and 35 (25.2%) closed globe injuries. The top one traumatic eye injuries were penetrating injuries occur through sharp metal objects (43.9%). After vitrectomy, 116 patients had favorable anatomic outcome at the last follow-up, and 30 eyes (21.6%) achieved VA of 20/200 or better. Following univariate analysis, we found zone III injuries (P=0.021), poor initial VA (P=0.005), endophthalmitis (P=0.024), and recurrent retinal detachment (P<0.001) were poor prognostic factors for pediatric ocular trauma. After Logistic regression analysis, the poor initial VA (odds ratio: 8.276, 95%CI: 1.597-42.897, P=0.012) and recurrent retinal detachment (odds ratio: 6.455, 95%CI: 2.372-17.562, P<0.001) were significantly correlated with unfavorable vision outcome in pediatric ocular trauma. CONCLUSION: The treatment of vitrectomy for severe ocular trauma results in favorable anatomic outcomes, but VA improvement is not as good as anatomic outcomes. Initial VA and recurrent retinal detachment are the independent prognostic indicators for unfavorable visual outcome of severe pediatric ocular trauma.

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Eosinophil asthma is characterized by the infiltration of eosinophils to the bronchial epithelium. The toxic cationic protein released by eosinophils, mainly major basic protein (MBP), is one of the most important causative factors of epithelium damage. Poly-L-Arginine (PLA) is a kind of synthetic cationic polypeptides, which is widely used to mimic the effects of MBP on epithelial cells in vitro. However, little is known about the changes of differentially expressed genes (DEGs) and transcriptome profiles in cationic protein stimulated epithelial cells. In this study, we compared the expression of DEGs and transcriptome profiles between PLA-treated airway epithelial cells NCI-H292 and control. The results showed that there were a total of 230 DEGs, of which 86 were upregulated and 144 were downregulated. These DEGs were further analyzed using gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results showed that the upregulated DEGs were involved in cholesterol synthesis, protein binding, and composition of cellular membranes, mainly enriched in metabolic and biosynthesis pathways. While downregulated DEGs were implicated in cell adhesion, extracellular matrix (ECM) composition and cytoskeleton and were enriched in ECM pathway. In conclusion, our research provided the mechanism of the cationic polypeptides acting on the airway epithelial cells on the basis of transcriptomic profile, and this could be regarded as important indications in unveiling the pathologic role of natural cationic proteins in the damage to epithelial cells of asthmatics.

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BACKGROUND: Suppression of histone deacetylase 11 (HDAC11) can promote IL-10 expression in mouse macrophages RAW264.7 and induce immune tolerance. This study is to further investigate the role of HDAC11 in tolerance induction via Kupffer cells (KCs) following orthotopic liver transplantation (OLT) in rats. MATERIALS AND METHODS: KCs isolated from BALB/c mice were divided into pHDAC11, adHDAC11, and pCV group (treated with HADC11-shRNA, adenovirus encoding HDAC11, and control vector, respectively). IL-10 expression was determined after lipopolysaccharide treatment. The expression of MHC-II and co-stimulatory molecules on KCs surface was evaluated by flow cytometry. T cell proliferation was measured by [(3)H]-thymidine incorporation after culturing with aforementioned three groups, treated KCs, respectively. OLT was performed in rats after Ad-HDAC11 and pHDAC11 treatment. Blood samples were collected for biochemical studies, and postoperative survival was examined. RESULTS: IL-10 expression was inhibited and promoted by Ad-HDAC11 and HDAC11-shRNA in KCs, respectively. MHC-II and co-stimulatory molecules on KCs surface as well as T cell proliferation were significantly inhibited and induced in pHDAC11 and Ad-HDAC11 compared with pCV, respectively. Serum IL-2, TNF-α, and IFN-γ levels were significantly lower in pHDAC11 and higher in Ad-HDAC11 compared with pCV, respectively, while IL-4 and IL-10 were the reverse. Postoperative survival, liver function, and histology were different among the three groups. CONCLUSIONS: Suppression of HDAC11 can promote IL-10 expression in KCs and induce tolerance following OLT in rats. Consequently, HDAC11 may be a key component of this immune regulation system and a promising target for development of novel drugs of gene therapy for inducing tolerance in clinical liver transplantation.

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BACKGROUND: Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive human tumors. At present, surgical resection is the only potentially curative treatment. Early neck division is inadequate when invasion of the superior mesenteric artery (SMA) is suspected or in cases of replaced or accessory right hepatic artery. Malignant periampullary tumors often invade retroperitoneal peripancreatic tissues and a positive resection margin is associated with a poor long-term survival. DATA SOURCES: English-language medical databases, PubMed, ELSEVIER and SPRINGERLINK, were searched for articles on "posterior approach pancreaticoduodenectomy", "superior mesenteric artery first approach", "retroperitoneal tissue", "hanging maneuver", and related topics. RESULTS: The modification allowed the surgeon to early identify the nonresectability of a replaced right hepatic artery if present, enabling complete dissection of the right side of the SMA and portal vein as well as complete excision of the retroportal pancreatic lamina. CONCLUSION: Pancreaticoduodenectomy with early retropancreatic dissection is a useful and safe technical variant, which is indicated for the improvement of the safety and curative effect of the procedure.

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OBJECTIVE: To develop human papillomavirus (HPV) 16 DNA vaccine for the treatment of HPV16 infection and its related tumors. METHODS: HPV16 oncogene E7 was modified by combined approaches including insertion and replication of specific region of E7 gene, murine codon optimization, and point-mutation at transforming regions of the E7 protein. The resulting artificial gene, named as mE7, was obtained by gene synthesis. The mE7 gene was then genetically fused to murine CD40 ligand (CD40L) by overlapping PCR to form the mE7/CD40L fusion gene. The mE7/CD40L gene was inserted into pVR1012 plasmid and then immunized C57/BL6 mice intramuscularly. The E7-specific IFN-gamma-secreting CD8+ T cells were analyzed with EIISPOT, and E7-specific antibody was measured by indirect ELISA. FACS assays were performed to analyze the activation of E7-specific Th cells. Mice were vaccinated, followed by tumor challenged or challenged before immunization. Tumor growth was observed. RESULTS: The mE7 DNA vaccine elicited an increased E7-specific antibody level (P < 0.01), E7-specific IFN-gamma-secreting CD8+ T (P < 0.01), and CD4+ T cells number (P < 0.05), compared with those of mice immunized with wE7 gene. Furthermore, the mE7/CD40L DNA vaccine elicited an increased number of E7-specific IFN-gamma secreting CD8+ T cell compared with that of mice immunized with mE7 gene (P < 0.01); however, no significant differences were found between mice immunized with the mE7 gene and mE7/CD40L fusion gene in the E7-specific antibody production and Th cell activation. In the preventive experiment, all mice received the mE7 or mE7/CD40L remained tumor-free 7 weeks after challenges with TC-1 tumor cells, while the wE7 group exhibited tumor growth within 2 weeks. In the therapeutic experiment, all the mice in the wE7 group exhibited tumor growth within 8 days, while among mice receiving the mE7 and mE7/CD40L, 30% and 45% of mice remained tumor-free after TC-1 challenge, respectively. HE staining of tumor tissues showed copious lymphocytes infiltration around tumor cells in mE7 and mE7/CD40L mice with regression of tumor growth. CONCLUSIONS: The mE7 DNA vaccine increases the E7-specific humoral and cellular immune responses, and the fusion of CD40L to mE7 gene enhances the specific immune responses and anti-tumor effects against HPV16 E7-expressing murine tumors. mE7/CD40L may therefore be a suitable and promising target for HPV16 therapeutic vaccine.

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BACKGROUND: Human papillomaviruses (HPVs) can infect squamous or mucosal epithelia and cause cervical cancer or genital warts. Coinfection with multiple HPV types is a common finding of many epidemiological studies. Therefore, it is necessary to develop a vaccine, which can eradicate established HPV infections and prevent other HPV infections. In this study, we generated chimeric virus like particles (cVLPs) composed of HPV-6b L1, HPV-6b L2 and one artificial HPV-16 mE7 proteins. METHODS: The artificial HPV-16 mE7 gene was designed by codon modification, point mutation and gene shuffling then chemically synthesized and subcloned behind HPV-6b L2. HPV-6b L1 and L2-mE7 were expressed in insect cells by using Bac-to-Bac system. The generated cVLPs were purified by CsCl gradient ultracentrifuge and analyzed by immunoblot, electron microscope and haemagglutination assay. RESULTS: The HPV-6b L1 and L2-mE7 proteins were well expressed in insect cells and could selfassemble into cVLPs, whose diameter was about 55 nm and similar to that of HPV-6b L1/L2 VLPs. Intact cVLPs could be recognized by H6.M48 neutralizing monoclonal antibody and HPV-6b L2 polyclonal antibody, while the denatured cVLPs, but not the intact cVLPs, were reactive to HPV-16 E7 polyclonal antibody. HPV-6b L1/L2-mE7 cVLPs haemagglutinated mouse erythrocytes as efficiently as HPV-6b L1/L2 VLPs did. CONCLUSIONS: The insertion of the 158 amino acid HPV-16 mE7 protein behind L2 did not disrupt the correct assembling of cVLPs. The morphological characteristics and haemagglutinating activity of cVLPs were similar to those of HPV-6b L1/L2 VLPs. The cVLPs retained conformational B cell epitopes of HPV-6 VLPs and HPV-16 mE7 protein had an internal location in the cVLPs. Therefore, large modified E7 protein with higher immunogenicity could be incorporated into cVLPs by fusing to the C-terminus of L2, which would help to improve the therapeutic effects of L1/L2-E7 cVLPs.

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OBJECTIVE: To investigate the immune responses and protection from virus challenge, induced by the coinjection of IL-2cDNA with herpes simplex virus type 1 (HSV-1) glycoprotein-D (gD) DNA vaccine. METHODS: Two DNA vaccines (pgD and pIL-2) were constructed by inserting the gD gene and IL-2 cDNA into the eukaryotic expression vector pcDNA3.1, respectively. The BALB/c mice were inoculated intramuscularly three times at 2-week intervals. Two weeks after the final immunization, mice were bled for antibody assay and spleen cells were separated for Th cell proliferation and cytokine assays. Delayed type hypersensitivity (DTH) response was detected by the pinna-swelling test. Corneal protection under HSV-1 virus challenge was continuously observed with slit-lamp microscope. RESULTS: IL-2 cDNA coinjection remarkably enhanced the specific IgG2a level when compared with gD plasmid vaccination alone. Th cell proliferation and secretion of cytokines (IL-2 and IFN-gamma) were significantly increased by IL-2 cDNA coinjection. However, the production of IL-10 was inhibited. The DTH response was also enhanced by IL-2 coinjection. When the mice were challenged with HSV-1, the cornea epithelial lesions were significantly alleviated by IL-2 coinjection as compared with gD vaccination alone. CONCLUSION: IL-2 cDNA can enhance both the humoral and cellular immune responses, and thus increase the vaccine potency.

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