[A retrospective controlled study of TACE-HAIC-targeted-immune quadruple therapy for intermediate and advanced-stage hepatocellular carcinoma].

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ2 test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.

[Role of imbalance of M1/M2 subsets of bone marrow macrophages in the pathogenesis of immune-mediated aplastic anemia in mice].

Objective: To investigate the role of macrophages (Mø) in the pathogenesis of modified immune-mediated aplastic anemia (AA) mice model. Methods: Before the establishment of the F1 AA mice model by total-body irradiation combined with allogeneic lymphocyte infusion, the mice of the CLO+AA group were treated with clodronate (CLO) liposomes to remove macrophages, and those of the PBS+AA group were treated with phosphate-buffered saline (PBS) liposomes and used as control. The severity of AA was observed by bone marrow (BM) pathological examination and peripheral blood cell count. Flow cytometry (FCM) was used to detect the CD4(+)/CD8(+) T lymphocyte subsets in the BM and Mø subsets in the BM and spleen of each group. The levels of IFN-γ, TNF-α, G-CSF, GM-CSF, EPO, and TPO in the peripheral blood were detected using enzyme-linked immunosorbent assay. Finally, the relationships between inflammatory factors and Mø subsets were analyzed. Results: The BM fatty conversion of mice in the CLO+AA group was significantly alleviated compared with the PBS+AA group. Hemoglobin counts were (91.50±31.63) and (110.65±24.15) g/L, respectively, and the platelet counts were (90.85±121.90) × 10(6)/L and (461.13±483.45) ×10(6)/L, respectively. The differences were all statistically significant (all P<0.05) . After removing macrophages, the proportions of CD4(+) and CD8(+) T lymphocytes in BM of mice in the CLO+AA group decreased, but the reduction of CD8(+) T cells was more significant. The proportions of CD4(+) T cells and CD8(+) T cells in BM of the PBS+AA group were (18.5±10.17) % and (36.23±6.40) %, respectively, and in the CLO+AA group were (7.58±8.00) % and (6.67±5.78) %, respectively. Similarly, the percentage of macrophages in the spleen and BM in the CLO+AA group was significantly reduced compared with the PBS+AA group, most of which were M1 macrophages (P<0.05) . The levels of IFN-γ in peripheral blood of the PBS+AA and CLO+AA groups were (602.37±104.62) ng/L and (303.01±87.22) ng/L, respectively, the levels of TNF-α were (34.46±1.42) ng/L and (23.25±4.21) ng/L, respectively, the levels of GM-CSF were (9.32 ± 2.00) ng/L and (64.85±12.25) ng/L, respectively, the levels of G-CSF were (5 891.78±2 632.39) ng/L and (17 784.16±488.36) ng/L, respectively, the levels of EPO were (9 667.31±4 501.95) ng/L and (2 078.02±897.56) ng/L, respectively, and the levels of TPO were (6.36±2.09) ng/L and (11.67±2.86) ng/L, respectively (all P<0.05) . Conclusions: This study confirmed that macrophages were involved in the pathogenesis of AA, and the degree of BM damage in AA mice was improved by removing macrophages in advance. The imbalance of M1/M2 macrophages and the changes of IFN-γ and TNF-α may be important mechanisms that eventually lead to AA.

Clinical features and treatment outcomes of eosinophilic gastroenteritis : an analysis of 28 cases.

BACKGROUND: Eosinophilic gastroenteritis (EG) is uncommon disease, and the pathogenesis of this disease have yet to be fully clarified. AIM: This study was to describe the clinical manifestations, endoscopic features and treatment outcomes of a cohort of patients with EG. METHOD: This retrospective study was included 28 consecutive patients who were diagnosed EG between January 2011 and December 2015 in Taizhou Hospital. The patients' clinical manifestations, endoscopic features and treatment outcomes were reviewed from a prospectively maintained database. RESULTS: Twenty-eight patients with EG were enrolled in the study (median age 54 years). The main symptoms were abdominal pain (78.6%), abdominal distension (50.0%), nausea and vomiting (28.6%) and diarrhea (25.0%). Laboratory examinations showed the elevation of blood eosinophil count (85.7%), serum IgE (71.4%). Endoscopic findings included small patchy mucosal erythema or erosions (75.0%), mucosal fold thickening (17.9%), submucosal nodules (21.4%), small gastroduodenal ulcers (14.3%). Twenty patients were treated and responded to prednisolone but five patients (25.0%) relapsed during the follow-up. The other 8 patients were treated with loratadine, proton pump inhibitors and dietary modification, 5 patients had clinical resolution during the follow-up. The other 3 patients did not achieve clinical remission, and then were given prednisone treatment. CONCLUSION: For some patients with gastrointestinal symptoms and peripheral eosinophilia, a high suspicion of EG is necessary and multiple endoscopic examinations might be helpful in diagnosis of EG. Most patients with EG could achieve remission after with the treatment of steroid or dietary elimination therapy.

The roles of cytochrome P450 and P-glycoprotein in the pharmacokinetics of florfenicol in chickens.

The effects of three selective oral inhibitors, fluvoxamine (FLU), ketoconazole (KET), and verapamil (VER), on the pharmacokinetics (PK) of florfenicol (FFC) were investigated in chickens. The chickens were administered orally with saline solution (SAL), FLU (60 mg/kg), KET (25 mg/kg), or VER (9 mg/kg) for 7 consecutive days. Florfenicol was given to the chickens at a single dose of 30 mg/kg orally. Blood samples were collected from each chicken at 0 to 12 h post-administration of FFC. The plasma concentration of FFC was analyzed by high-performance liquid chromatography (HPLC). The AUC of FFC increased and the CLs of FFC decreased with oral co-administration of KET in chickens, and the Cmax of FFC increased with VER. While the AUC, the CLs and the Cmax of FFC were all invariable with FLU. These data suggested that CYP 3A played a key role in the PK of FFC in chickens, however, P-glycoprotein (P-gp) and CYP 1A did not. The results imply that the adverse drug-drug interaction may occur in the use of FFC if the co-administrated drugs are the substrates, inducers or inhibitors of CYP 3A or/and P-gp.

Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer.

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study is to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia.

Critical Ovarian Hyperstimulation Syndrome After In Vitro Fertilization Treatment in a Renal Transplant Recipient: A Case Report.

OBJECTIVE: The study sought to describe a case of critical ovarian hyperstimulation syndrome (OHSS) after in vitro fertilization treatment in a renal transplant recipient. PATIENT: A 35-year-old woman with a 5-year history of renal transplantation underwent in vitro fertilization treatment with a midluteal pituitary downregulation regimen. RESULT: There are only 7 cases published regarding successful pregnancies outcomes after in vitro fertilization treatment in renal transplant recipients. In the most of the case reports, there was no deterioration of graft function. However, our patient developed critical OHSS. After effective treatment, her serum creatinine level decreased from 668 µmol/L to baseline. CONCLUSIONS: Our case demonstrates that the highly specialized care and close cooperation of transplantation and perinatology teams are required when undergoing in vitro fertilization treatment in renal transplant recipients.

First Report of Alternaria Blight of Potato Caused by Alternaria tenuissima in China.

Potato (Solanum tuberosum L.) is grown worldwide as a major food crop. Potato early blight is an important disease caused by Alternaria solani (4). In 2011, diseased potato leaves with blight symptoms were collected from 21 sites (incidence averaged 60% for about 2,000 ha of potato fields examined) in Gansu Province, northwest China. Small pieces of tissue taken from the margin between healthy and diseased tissues were surface-disinfected in 0.3% NaOCl for 2 min, rinsed with sterilized, distilled water, then placed on potato dextrose agar (PDA) at 25°C in the dark. Two of 24 Alternaria isolates from single-spore cultures were identified preliminarily as A. tenuissima, and the remaining isolates as A. solani or A. alternata, based on morphological traits. Colony appearance on potato carrot agar (PCA) was loosely cottony under a day/night cycle of 8 h fluorescent light/16 h dark at 22°C for 7 days (3). The isolates were characterized by formation of unbranched conidial chains up to 12 conidia in length, with one or two lateral branches forming occasionally. Conidia were typically ovoid to obclavate, and ranged from 20.4 to 42.4 × 7.7 to 13.2 µm. Transverse septa and longitudinal septa of conidia varied from 1 to 6 and 0 to 2, respectively. Short conidiophores arose singly and were 15.1 to 76.8 µm long by 2.4 to 6.2 µm wide. The internal transcribed spacer (ITS) region of rDNA and partial coding sequence of a histone gene were amplified from genomic DNA of the two A. tenuissima isolates using the ITS1/ITS4 and H3-1a/H3-1b primers (2), respectively. The ITS sequences of the two isolates (GenBank Accession Nos. JX495165 and JX495166) were 100% identical to those of A. tenuissima strains sdau 07-100 and BL08-3 (GQ871507 and AB470887), as well as to other Alternaria species, but the partial histone gene sequences (JX495167 and JX495168) were 99% identical to those of A. tenuissima isolates CR27, MA1, MA6, and CN-L-01 (AF404622, AF404633, AF404634, and EF371552, respectively) with less similarity to those of other Alternaria spp. Therefore, the isolates were identified as A. tenuissima based on morphological and molecular characteristics. Pathogenicity tests were conducted by inoculating detached leaves (30 per isolate) from 45-day-old plants of potato cv. Favorita with 20 µl drops (one drop per leaf) of a conidial suspension containing 106 conidia/ml in sterilized, distilled water. Thirty control leaves were inoculated similarly with sterilized, distilled water. Inoculated leaves were incubated in chambers at 25°C and 90% RH with a 12-h photoperiod/day. After 7 days, symptoms on the inoculated leaves were similar to those naturally occurring on the original plants, and the two cultures were reisolated consistently from those leaves, and the species identity was confirmed by morphological and molecular characteristics, fulfilling Koch's postulates. The control leaves remained asymptomatic and Alternaria was not isolated from those leaves. Alternaria blight of potato caused by A. tenuissima was previously detected in Iran (1). To our knowledge, this is the first report of A. tenuissima causing blight on potatoes in China. References: (1) S. T. Ardestani et al. Iran. J. Plant Pathol. 45:83, 2010. (2) N. L. Glass and G. C. Donaldson. Appl. Environ. Microbiol. 61:1323, 1995. (3) E. G. Simmons. Alternaria. An Identification Manual. CBS Fungal Biodiversity Centre, Utrecht, the Netherlands, 2007. (4) J. E. van der Waals et al. Plant Dis. 88:959, 2004.

Bipolar optical forces on dielectric and metallic nanoparticles by evanescent wave.

We numerically show that both repulsive and attractive (bipolar) optical forces can be exerted on a dielectric or metallic cylindrical nanoparticle by a totally internal refracted wave. This requires that the particles possesses either a whispering gallery (WG) resonance or a localized surface plasmon (LSP) resonance. We further explore the force spectrum that is governed by competition between the separation-dependent resonant Q factor and the coupling strength of the nanoparticle to the evanescent wave. In spite of a much smaller Q of the LSP as compare to the WG resonances, the metallic particle gains much stronger trapping force.

Multimedia model of atrazine in plant-soil-groundwater system with a fugacity approach.

The application of atrazine in China during the last ten years has led to some environmental problems. In this paper, the multimedia model of atrazine in soil-plant-groundwater system at Baiyangdian Lake area in Northern China was established using a fugacity approach, and verified with observed values. The model involved 7 environmental compartments which are air, groundwater, soil, corn roots, corn stem, corn leaf and kernel of corn. The results showed that the relative errors between calculated and observed values have a mean value of 24.7%, the highest value is 48% and the lowest value is 1.4%. All these values indicated that this multimedia model can be used to simulate the environmental fate of atrazine. Both the calculated and observed values of concentrations of atrazine in plant compartments are in the following order: in corn roots > in corn stem > in kernel of corn > in corn leaf, it exhibited a good regularity. The prediction results indicated that concentrations of atrazine in the groundwater and kernel of corn will override the limitation of 3 micrograms/L and 0.05 mg/kg respectively.

Distribution of atrazine in a crop-soil-groundwater system at Baiyangdian Lake area in China.

In this paper, the concentration distribution and environmental fate of atrazine in a crop-soil-groundwater system at Baiyangdian Lake area of North China were studied. The concentration of the herbicide in spatial and vertical soils, and in roots, stem, leaf, corncob and kernel of corn, and in groundwater were measured by HPLC. The results showed that the variation of spatial concentration of atrazine in soil can be described by first-order kinetics equation which has a half-life of 360 days and a rate constant of 0.0019 d-1. The vertical variation of atrazine concentration with soil depth follows the exponential decay law. After 120 days following atrazine application, the mass distributions of this herbicide in crop-soil-groundwater system are 71% in soil, 20% in groundwater and 1% in crop respectively, and 8% due to loss by degradation or often removal processes. The order of atrazine concentration in every part of corn crop is in roots > in corncob > in kernel of corn > in leaf.

Identification of UV photoproducts and hydrolysis products of butachlor by mass spectrometry.

The photoproducts and hydrolysis products of butachlor in water were identified by gas chromatography/mass spectrometry. When exposed to UV light, butachlor in aqueous solution was rapidly degraded, giving at least 11 photoproducts as a result of dechlorination with subsequent hydroxylation or cyclization processes. The chemical structures of nine degradation compounds were identified on the basis of mass spectrum interpretation and literature data. Major photoproducts are identified as 8-ethyl-1-butoxymethyl-4-methyl-2-oxo-1,2,3,4-tetrahydro-quinoline, 2-hydroxy-2',6'-diethyl-N-(butoxymethyl) acetanilide, and a compound related to butachlor. Minor photoproducts are identified as 2,6-diethylaniline; 1-acetyl-7-ethylindole; N-(2,6-diethylphenyl)-N-(butoxymethyl)acetamide; 2-oxo-N-(2,6-diethyl-phenyl)-N-(butoxymethyl)acetamide; 1-hydroxyacetyl-2-butoxyl-3-methyl-7-ethylindole; 1-acetyl-2-butoxyl-3-methyl-7-ethylindole; and two compounds with the chemical structure unknown. The half-lives of butachlor UV photolysis were 7.54, 10.56, and 12.22 min in deionized water, river water, and paddy water, respectively. The half-lives of butachlor hydrolysis at pH 4, 7, and 10 were 630, 1155, and 1155 days at 25 +/- 1 degrees C, respectively. A hydrolysis product at pH 4 was identified by GC/MS to be 2-hydroxy-2',6'-diethyl-N-(butoxymethyl) acetanilide.

The 42K protein of rice dwarf virus is a post-translational cleavage product of the 46K outer capsid protein.

The outer capsid protein (P8) heterogeneity of rice dwarf virus (RDV) exists not only in purified virus particles, but also in RDV-infected rice, transgenic rice expressing P8, E. coli expression of P8 product and the in vitro translation products of S8. N-terminal amino acid sequencing revealed that P8 is a cleavage product of P8'. The cleavage occurs specifically at the residues of Asp362 and Pro363. The function of the proteolytic processing is unknown.