SC-AIR-BERT: a pre-trained single-cell model for predicting the antigen-binding specificity of the adaptive immune receptor.

Accurately predicting the antigen-binding specificity of adaptive immune receptors (AIRs), such as T-cell receptors (TCRs) and B-cell receptors (BCRs), is essential for discovering new immune therapies. However, the diversity of AIR chain sequences limits the accuracy of current prediction methods. This study introduces SC-AIR-BERT, a pre-trained model that learns comprehensive sequence representations of paired AIR chains to improve binding specificity prediction. SC-AIR-BERT first learns the 'language' of AIR sequences through self-supervised pre-training on a large cohort of paired AIR chains from multiple single-cell resources. The model is then fine-tuned with a multilayer perceptron head for binding specificity prediction, employing the K-mer strategy to enhance sequence representation learning. Extensive experiments demonstrate the superior AUC performance of SC-AIR-BERT compared with current methods for TCR- and BCR-binding specificity prediction.

The effect of Inc parameter on VMAT radiotherapy plans quality for rectal cancer using Monaco TPS.

BACKGROUND: To investigate the effect of the Increment of gantry angle (Inc) parameter setting of the Monaco Treatment planning system (Monaco TPS) on the dosimetry and quality parameters of the volumetric modulated arc therapy (VMAT) program for rectal cancer. METHODS: A retrospective analysis was conducted on 50 patients with rectal cancer who underwent intensity modulated radiation therapy using the Monaco TPS system from 2020 to 2021. Under the same optimization function configuration and other parameter settings, the Inc parameters in the VMAT radiotherapy plan were set to 10°, 20°, 30°, and 40°. The dose-volume histogram (DVH) was used to evaluate the dose distribution of the target area and the radiation dose of the organs at risk (OAR). The differences in the dosimetry of the planning target volume (PTV) and OAR, as well as the gamma pass rate (GPR) were compared. RESULTS: In terms of target dose, D98, Dmin, HI, and conformity index (CI) of Inc10 group was significantly lower than those of Inc20, 30, and 40 groups (P < 0.05), and D2 of Inc10 group was significantly higher than that of Inc20 group (P = 0.009). We also found CI of Inc20 and 30 were significantly better than that of Inc40 (both P < 0.05). In terms of OAR dose, the study found that the Dmean, Dmin, V50%, V45%, and V40% for the bladder of the Inc10 group were lower than those of the other groups (all P < 0.05), the Dmean for femoral head of the Inc20 group was lower than that of the Inc30 group (P < 0.05), and Inc20 showed a better protective effect on the femoral head. The MUs tend to decrease as the Inc parameter setting is increased. The monitor unit (MU) in Inc10 group were significantly higher than those in Inc20, Inc30, and Inc40 groups, and the MU of Inc20 group was significantly higher than that of Inc40 group (both P < 0.05). We found that for the 3%/3 mm and 2%/2 mm standards, the GPRs of each plan were > 90%, which met clinical requirements. CONCLUSIONS: Different settings of Inc parameters have varying degrees of impact on target dose, OAR dose, and machine MU. It is important for doctors to choose different Inc parameters according to different clinical needs.

Knowledge and attitudes of medical and pharmacy students about pharmacogenomics: a systematic review and meta-analysis.

Pharmacogenomics (PGx) is rapidly growing branch of molecular genetics with high potentials to influence therapeutics. This review evaluates knowledge and attitudes of medical and pharmacy students about PGx. A literature search was conducted in electronic databases and studies were selected by following precise eligibility criteria. After quality assessment, studies were reviewed systematically, and meta-analyses of proportions were performed to estimate response rates of students. Fifteen studies (5509 students; 69% [95% confidence interval (CI): 60%, 77%] females) were included. Among students, 28% [95%CI: 12, 46] had adequate PGx knowledge; 65% [95%CI: 55, 75] were willing to have PGx test for their own risk assessment; 78% [95%CI: 71, 84] had intention to incorporate PGx in future practice; and 32% [95%CI: 21, 43] were satisfied with current PGx component of curriculum. Age, advanced year of educational program, and more time spent in PGx education were positively associated with PGx knowledge and positive attitudes.

Constructing network structures to enhance stability and target deposition of selenium nanoparticles via amphiphilic sodium alginate and alkyl glycosides.

Dietary selenium (Se) supplementation has recently received increasing attention; however, Selenium nanoparticles (SeNPs) exhibit poor stability and tend to aggregate in aqueous solution. Therefore, enhancing the stability of SeNPs and their effective delivery to plants remain challenging. In this study, sodium alginate (SA) and lysozyme (LZ) were reacted via the wet-heat Maillard reaction (MR) to obtain amphiphilic alginate-based polymers (SA-LZ). Alkyl glycosides (APG) were introduced into SA-LZ to enhance the deposition of SeNPs in leaves. Thus, a renewable and degradable polysaccharide-based material (SA-LZ/APG) loaded with Se formed an amphiphilic alginate-based-based shell with a Se core. Notably, the encapsulation of SeNPs into a polysaccharide base (SA-LZ/APG) increased the stabilization of SeNPs and resulted in orange-red, zero-valent, monoclinic and spherical SeNPs with a mean diameter of approximately 43.0 nm. In addition, SA-LZ/APG-SeNPs reduced the interfacial tension of plant leaves and increased the Se content of plants compared to the blank group. In vitro studies have reported that SA-LZ/APG-SeNPs and SA-LZ-SeNPs have significantly better clearance of DDPH and ABTS than that of APG-SeNPs. Thus, we believe that SA-LZ/APG is a promising smart delivery system that can synergistically enhance the stability of SeNPs in aqueous solutions and improve the bioavailability of Se nutrient solutions.

Prognosis value of circulating tumor cell PD­L1 and baseline characteristics in patients with NSCLC treated with immune checkpoint inhibitors plus platinum­containing drugs.

Immune checkpoint inhibitors (ICIs) combined with platinum-containing chemotherapy are recommended as the standard first-line treatment for non-small cell lung cancer (NSCLC). However, specific prognostic markers for this combination therapy are yet to be identified. Evaluation of circulating tumor cells (CTCs) and cell surface programmed death-ligand 1 (PD-L1) exhibits potential in predicting the efficacy of the aforementioned combination therapy. Thus, the present study aimed to evaluate the prognostic value of CTC PD-L1 testing and other clinical characteristics in patients with NSCLC treated with combination therapy as first-line treatment. In total, 40 patients with advanced NSCLC were included in the present study, and all patients underwent CTC PD-L1 testing at initial diagnosis to determine the association between CTC PD-L1 and tissue PD-L1. The prognostic value of CTC PD-L1 and the baseline characteristics of 26 patients with NSCLC were analyzed, and the prognostic values of changes in CTC PD-L1 and baseline characteristics during 6 months of treatment were further explored. Results of the present study demonstrated that there was no association between CTC PD-L1 and tissue PD-L1 levels. After 6 months of combination therapy, tumor shrinkage, CYFA19 levels and treatment maintenance were associated with progression-free survival (PFS) of patients. Notably, CTC PD-L1 and tissue PD-L1 levels, TNM stage, nutritional score, inflammation score and other blood indicators were not associated with PFS. In conclusion, the evaluation of CTCs and CTC PD-L1 suggested that undetectable CTCs at 6 months of NSCLC treatment are associated with a good prognosis. In addition, negative CTC PD-L1 expression may change to positive CTC PD-L1 expression in line with disease progression, and this may be indicative of poor prognosis.

Case Report: Genetic and immune microenvironmental characteristics of a rectal cancer patient with MSS/PD-L1-negative recurrent hepatopulmonary metastasis who achieved complete remission after treatment with PD-1 inhibitor.

Currently, microsatellite high instability (MSI-H)/mismatch repair protein deletion (dMMR) has become a crucial biomarker for utilizing immune checkpoint inhibitors in patients with advanced colorectal cancer (mCRC). However, the proportion of MSI-H/dMMR in advanced patients is only about 5% and mCRC patients with microsatellite stability (MSS)/proficient mismatch repair (pMMR) exhibit poor responses to immunotherapy. Although diverse immune combination therapy regimens have been examined in patients with advanced colorectal cancer who demonstrate MSS/pMMR, these approaches have not yielded favorable efficacy and only a limited proportion of patients have benefited, especially for advanced colorectal cancer patients with liver metastases. Therefore, the mechanism of benefit and potential biomarkers of immunotherapy in patients with MSS/pMMR mCRC deserve more in-depth exploration. Here, we present a case study of a rectal cancer patient with MSS and PD-L1-negative recurrent hepatopulmonary metastases who attained complete remission (CR) and sustained benefits with immunotherapy after systemic therapy had failed. The analysis of the patient's genetic and immune microenvironmental characteristics revealed that mutations in DNA damage repair (DDR) pathway genes and the existence of abundant tumor-infiltrating lymphocytes could contribute to his potential benefit.

Development of an Indirect Enzyme-Linked Immunosorbent Assay Based on the Yeast-Expressed CO-26K-Equivalent Epitope-Containing Antigen for Detection of Serum Antibodies against Porcine Epidemic Diarrhea Virus.

Porcine epidemic diarrhea (PED) is a severe contagious intestinal disease caused by the porcine epidemic diarrhea virus (PEDV), which leads to high mortality in piglets. In this study, by analyzing a total of 53 full-length spike genes and COE domain regions of PEDVs, the conserved COE fragment of the spike protein from the dominant strain SC1402 was chosen as the target protein and expressed successfully in Pichia pastoris (P. pastoris). Furthermore, an indirect enzyme-linked immunosorbent assay (iELISA) based on the recombinant COE protein was developed for the detection of anti-PEDV antibodies in pig sera. The results showed that under the optimized conditions, the cut-off value of COE-based indirect ELISA (COE-iELISA) was determined to be 0.12. Taking the serum neutralization test as standard, the relative sensitivity of the COE-iELISA was 94.4% and specificity 92.6%. Meanwhile, no cross-reactivity to other porcine pathogens was noted with this assay. The intra-assay and inter-assay coefficients of variation were less than 7%. Moreover, 164 vaccinated serum samples test showed that overall agreement between COE-iELISA and the actual diagnosis result was up to 99.4%. More importantly, the developed iELISA exhibited a 95.08% agreement rate with the commercial ELISA kit (Kappa value = 0.88), which suggested that the expressed COE protein was an effective antigen in serologic tests and the established COE-iELISA is reliable for monitoring PEDV infection in pigs or vaccine effectiveness.

DeepAIR: A deep learning framework for effective integration of sequence and 3D structure to enable adaptive immune receptor analysis.

Structural docking between the adaptive immune receptors (AIRs), including T cell receptors (TCRs) and B cell receptors (BCRs), and their cognate antigens are one of the most fundamental processes in adaptive immunity. However, current methods for predicting AIR-antigen binding largely rely on sequence-derived features of AIRs, omitting the structure features that are essential for binding affinity. In this study, we present a deep learning framework, termed DeepAIR, for the accurate prediction of AIR-antigen binding by integrating both sequence and structure features of AIRs. DeepAIR achieves a Pearson's correlation of 0.813 in predicting the binding affinity of TCR, and a median area under the receiver-operating characteristic curve (AUC) of 0.904 and 0.942 in predicting the binding reactivity of TCR and BCR, respectively. Meanwhile, using TCR and BCR repertoire, DeepAIR correctly identifies every patient with nasopharyngeal carcinoma and inflammatory bowel disease in test data. Thus, DeepAIR improves the AIR-antigen binding prediction that facilitates the study of adaptive immunity.

A retrospective study of postoperative targeted therapy in ALK-positive lung cancer.

In this study, we aim to investigate the therapeutic effect and safety of ALK inhibitor in ALK-positive lung cancer patients. 59 patients with ALK-positive lung cancer from August 2013 to August 2022 were retrospectively recruited. The basic information, pathological type, clinical stage and treatment strategy were collected. These patients were divided into two groups, including 29 patients of conventional adjuvant chemotherapy, and 30 cases of targeted therapy. The patients in the targeted therapy group underwent adjuvant targeted therapy with crizotinib for 2 years. The observation indicators include curative effects and adverse events. The disease-free survival (DFS) and overall survival (OS) were also analyzed. We analyzed the pathological stages after adjuvant chemotherapy and targeted therapy in lung cancer, no significant difference in the p stage N and T was found between the two therapeutic groups. However, the DFS events, DFS median time and OS median time showed significant improvement in the targeted therapy group when compared with adjuvant chemotherapy (all P < 0.05). Besides, the patients under both therapeutic regimens presented some adverse events, among them elevated aspartate transaminase/alanine aminotransferase was the most common adverse event in all the patients, followed by nausea and vomiting. Our study identified that crizotinib-based postoperative targeted therapy helps improve the prognosis of patients with ALK-positive lung cancer, confirming that postoperative targeted therapy can be considered an effective and feasible therapeutic alternative.

Identification of a novel autophagy signature for predicting survival in patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most commonhistological lung cancer subtype, with an overall five-year survivalrate of only 17%. In this study, we aimed to identify autophagy-related genes (ARGs) and develop an LUAD prognostic signature. METHODS: In this study, we obtained ARGs from three databases and downloaded gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used TCGA-LUAD (n = 490) for a training and testing dataset, and GSE50081 (n = 127) as the external validation dataset.The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature. We performed gene set enrichment analysis (GSEA) and immune cell analysis between the high- and low-risk groups. A nomogram was built to guide the individual treatment for LUAD patients. RESULTS: We identified a total of 83 differentially expressed ARGs (DEARGs) from the TCGA-LUAD dataset, including 33 upregulated DEARGs and 50 downregulated DEARGs, both with thresholds of adjusted P < 0.05 and |Fold change| > 1.5. Using LASSO and multivariate Cox regression analyses, we identified 10 ARGs that we used to build a prognostic signature with areas under the curve (AUCs) of 0.705, 0.715, and 0.778 at 1, 3, and 5 years, respectively. Using the risk score formula, the LUAD patients were divided into low- or high-risk groups. Our GSEA results suggested that the low-risk group were enriched in metabolism and immune-related pathways, while the high-risk group was involved in tumorigenesis and tumor progression pathways. Immune cell analysis revealed that, when compared to the high-risk group, the low-risk group had a lower cell fraction of M0- and M1- macrophages, and higher CD4 and PD-L1 expression levels. CONCLUSION: Our identified robust signature may provide novel insight into underlying autophagy mechanisms as well as therapeutic strategies for LUAD treatment.

Co-Occurring Alteration of NOTCH and DDR Pathways Serves as Novel Predictor to Efficacious Immunotherapy in NSCLC.

Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the most patients produce an ultra-rapid progressive disease. Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. One hundred six NSCLC patients treated with immunotherapy were combined from Rizvi et al. and Hellman et al. studies (whole exon sequencing). Two independent validation datasets consisted of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [22.1 vs 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2-0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [Cohort 2: 13 vs 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31-0.96; Cohort 3: 21 vs 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18-1.1]. By analyzing TCGA cohort, we found patients with coexisting NOTCH+/co-DDR+ pathway had a higher TMB, more infiltration of CD4+T cells. Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.

[Scleral buckling combined with intravitreal gas injection for treatment of retinal detachment in vitrectomized eyes without silicon oil tamponade].

OBJECTIVE: To evaluate the effects of scleral buckling combined with intravitreal gas injection for the treatment of retinal detachment in selected eyes which had undergone vitrectomy but without silicon oil tamponade. METHODS: This was a retrospective observational case series. Including 52 eyes of 52 selected patients. All patients had undergone vitrectomy without silicon oil tamponade as the first surgery for the treatment of various vitreoretinal diseases. After the failure of the first surgery, scleral buckling combined with intravitreal gas injection were performed for the treatment of retinal detachment in Xijing Hospital between January 2001 and May 2004. The scleral buckling was used in all surgeries and using radial placement of a silicon sponge or circumferential placement of solid silicon combined with an encircling band. During the surgery, all breaks were carefully marked to ensure they were on the crest or anterior slope of the buckle. Air or C(3)F(8) gas was injected intravitreously. The reattachment rate, visual outcome, and postoperative complications were investigated. RESULT: After a six-month to three-year follow-up period, the reattachment rate was 69.2% (36/52 cases). Further vitrectomy surgeries were needed for other 16 eyes. The visual acuity was improved in 32 eyes (61.5%), three eyes (23.1%) with no change, and 8 eyes (15.4%) decreased. Macular epiretinal membrane happened postoperatively in one eye, and cataract was found in another case. There is no serious complications. CONCLUSIONS: Scleral buckling combined with intravitreal gas injection is an effective procedure for the treatment of retinal detachment in vitrectomized eyes without silicon oil tamponade. The rate of secondary vitrectomy also can be reduced.

Thymidylate synthase gene polymorphism predicts disease free survival in stage II-III rectal adenocarcinoma patients receiving adjuvant 5-FU-based chemotherapy.

BACKGROUND: The objective is to investigate whether thymidylate synthase gene TS 5'-UTR polymorphism of peripheral blood mononuclear cells are associated with clinical outcomes of patients with stage II-III rectal adenocarcinoma treated with adjuvant 5-fluorouracil (5-FU) chemotherapy in Chinese population. METHODS: One hundred and seventeen pathologically diagnosed colorectal adenocarcinoma patients with stage II-III, who underwent curative resection and received 5-fluoropyrimidine-based adjuvant chemotherapy were enrolled to this study. The 5'-TSER polymorphisms determined from the peripheral blood mononuclear cells were measured by Direct Sequencing. Kaplan-Meier curves and log-rank tests were used for survival analysis. The independent prognostic factors influencing DFS and OS were estimated by Cox proportional hazards model. RESULTS: The distribution of TS 5'-UTR polymorphisms ware 2.6% 2R/2R, 31.6% 2R/3R and 65.8% 3R/3R respectively, which was fitted with Hard-Weinberg equilibrium (χ2=0.345, P=0.558). Stage, N stage, number of mesenteric lymph node metastasis, KPS, and 5'-UTR polymorphisms (2R/2R/2R/3R vs. 3R/3R, P<0.001) were significantly associated with DFS. Meanwhile, gender (female vs. male, P=0.025) and adjuvant radiotherapy (yes vs. no, P=0.025) were significantly associated with OS. Multivariate Cox regression showed that KPS score (HR =0.947, P=0.007), TS 5'-UTR polymorphism (HR =0.455, P=0.004) were independent prognostic factors for DFS. Whereas, KPS score was the only independent prognostic factors for OS (HR =0.910, P=0.005). CONCLUSIONS: TS 5'-UTR tandem repeat polymorphisms had potential utilization for personalized therapy in Chinese population.

Identification and characterization of a spotted-leaf mutant spl40 with enhanced bacterial blight resistance in rice.

BACKGROUND: Spotted leaf mutants show typical necrotic lesions that appear spontaneously in the absence of any pathogen attack. These mutants are often characterized to exhibit programmed cell death (PCD) and activation of plant defense responses resulting in enhanced disease resistance to multiple pathogens. Here, we reported a novel spotted-leaf mutant, spl40 that showed enhanced disease resistance response. RESULTS: Initially lesions appeared at leaf tips during seedling stage and gradually covered the whole leaf at the tillering stage. The lesion development was light-dependent. spl40 showed obvious cell death at and around the lesion, and burst of reactive oxygen species (ROS) was accompanied by disturbed ROS scavenging system. Photosynthetic capacity was compromised as evidenced by significant reductions in chlorophyll content, important photosynthesis parameters and downregulated expression of photosynthesis-related genes which ultimately led to poor performance of major agronomic traits. spl40 exhibited enhanced resistance to 14 out of 16 races of bacterial blight pathogen of rice, caused by Xanthomonas oryzae pv. oryzae, most probably though activation of SA and JA signaling pathways, owing to upregulated expression of SA and JA signaling genes, though the exact mechanism remain to be elucidated. The spotted-leaf phenotype was controlled by a novel single recessive nuclear gene. Genetic mapping combined with high throughput sequencing analysis identified Os05G0312000 as the most probable candidate gene. Sequencing of ORF revealed a single SNP change from C to T that resulted in non-synonymous change in amino acid residue from leucine to phenylalanine. Interestingly, the complementation plants did not display lesions before heading but showed lesions at the heading stage and the transgenic T1 progenies could be classified into 3 categories based on their lesion intensity, indicating the complex genetic nature of the spl40 mutation. CONCLUSION: The results obtained here clearly show that genes related to defense and PCD were upregulated in accordance with enhanced disease resistance and occurrence of PCD, whereas the photosynthetic capacity and overall ROS homeostasis was compromised in spl40. Our data suggest that a novel spotted-leaf mutant, spl40, would help to elucidate the mechanism behind lesion development involving programmed cell death and associated defense responses.

[The distribution and phenotype of bone marrow-derived cells in mice's eyes after induction of choroidal neovascularization by laser photocoagulation].

OBJECTIVE: To investigate the phenotype feature of bone marrow-derived cells in mice's eyes after induction of choroidal neovascularization by laser photocoagulation. METHODS: It was a experimental study. Green fluorescent protein (GFP) chimeric mice were developed by transplanting bone marrow cells from GFP +/+ transgenic mice to adult C57BL/6J mice. The chimeric mice underwent laser rupture of Bruch membrane to induce CNV. Fluorescein fundus angiography and histopathological study were used to confirm the stable formation of CNV. Then the eyes were enucleated and processed for immunofluorescence to detect the distribution and phenotype of GFP + cells. RESULTS: The development of CNV has stabled by the 14th day after lasering. GFP-labelled cells appeared in CNV lesions (including choroid beneath CNV lesion), neurosensory retina over CNV, corneoscleral limbus, ciliary body, optic disc and sclera, retina and choroid distant from CNV. GFP + cells, which were immunoreactive for alphaSMA or CD31, appeared in lesions only. However, F4/80 + green cells can be also detected in neurosensory retina over CNV, corneoscleral limbus and ciliary body. CONCLUSIONS: BMC which differentiated into vascular cells presented in CNV lesions only. Some BMC appearing in other positions might be macrophages or dendritic cells. There may be other functions apart from contributing to choroidal neovascularization for BMC in the eyes.

FGFR inhibitor AZD4547 can enhance sensitivity of esophageal squamous cell carcinoma cells with epithelial­mesenchymal transition to gefitinib.

Activation of fibroblast growth factor receptor (FGFR) signaling occurs in various cancers, including esophageal squamous cell carcinoma (ESCC), however, the effect of targeting FGFR in ESCC is not clear. Herein, we examined the phosphorylation level of FGFR1Y654 (p­FGFR1) in ESCC cell lines and tumor tissues, as well as the cancer cell killing effects of gefitinib and FGFR inhibitor AZD4547 in combination form or alone in ESCC cells. Immunohistochemistry staining was used to detect the expression level of p­FGFR1 in 87 ESCC specimens. The effects of gefitinib and FGFR inhibitor AZD4547 on ESCC cells were analyzed by CCK­8 assay, flow cytometry and western blotting assays. Twenty­six patients diagnosed with esophageal squamous cell carcinoma (ESCC) (29.9%) were observed with a high level of p­FGFR1. The proportion of lesions located in the lower segment of the esophagus was significantly higher in the high p­FGFR1 level group (26.9 vs. 8.2%, P=0.003). The IC50 values of gefitinib alone and in combination with 500 nM AZD4547 were 22.9±2.1 and 4.13±0.12 µM in TE10 cells, and 9.85±5.5 and 3.21±0.76 µM in EC9706 cells, respectively. The combination of AZD4547 and gefitinib induced robust apoptosis and decreased clone formation ability compared to gefitinib monotherapy in the TE10 cells. TE10 cells exhibited a mesenchymal phenotype, with a higher level of p­FGFR1 and p­AKT than that in EC9706 cells. AZD4547 and gefitinib co­treatment resulted in a significant decrease in the level of p­AKT in TE10 cells and a complete inhibition of phosphorylation of ERK1/2 in EC9706 cells. Collectively, AZD4547 can improve sensitivity of ESCC cells to gefitinib.

Intravitreal injection of bevacizumab alone or with triamcinolone acetonide for treatment of macular edema caused by central retinal vein occlusion.

AIM: To compare the efficacy and safety of intravitreal bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with macular edema caused by central retinal vein occlusion (CRVO) in Chinese patients. METHODS: Seventy-five eyes of 75 patients were enrolled in this prospective, randomized, consecutive study. Thirty-six patients in group 1 were treated with an intravitreal injection of bevacizumab (1.25mg/0.05mL), and 39 patients in group 2 were treated with intravitreal bevacizumab (1.25mg/0.05mL) combined with triamcinolone acetonide (2mg/0.05mL). The main outcomes of the mean best corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) were measured. RESULTS: In group 1, the mean BCVA improved from 37.78±6.14 (baseline) to 48.06±3.86, 46.48±4.77 and 44.18±5.78 at four, six and twelve weeks post-injection, respectively (P<0.01, P=0.03, P=0.04). In group 2, the mean BCVA improved from 35.92±6.20 (baseline) to 50.69±4.22, 48.76±5.59 and 45.70±6.56 at the same time points (P<0.01 each). However, there was no significant differences in the mean BCVA (F=0.043, P=0.836) and CRT (F=0.374, P=0.544) between these two groups. During the follow-up, five patients in group 1 and six patients in group 2 with high IOP were controlled with anti-glaucoma drugs. CONCLUSION: Intravitreal injection of bevacizumab alone or combined with triamcinolone acetonide has a short beneficial effect in Chinese patients with macular edema caused by CRVO, but there is no significant difference between the two groups.

Intravitreal bevacizumab combined with/without triamcinolone acetonide in single injection for treatment of diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME) is a common manifestation of diabetic retinopathy (DR) that forms the main cause of central visual impairment. This study aimed to compare the efficacy and safety of a single intravitreal injection of bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with diabetic macular edema (DME). METHODS: A total of 40 eyes in 40 Chinese patients (22 male and 18 female) diagnosed with diabetic macular edema were enrolled in this prospective, randomized, consecutive study. Among them, 21 patients in group 1 were treated with intravitreal injection of bevacizumab (1.25 mg/0.05 ml), and the other 19 patients in group 2 accepted intravitreal bavacizumab (1.25 mg/0.05 ml) combined with triamcinolone acetonide (2 mg/0.05 ml). All patients were examined at baseline and followed up at 4, 6 and 12 weeks after the injection. Changes in mean best correct visual acuity (BCVA) using ETDRS chart, central retina thickness (CRT) measured by optical coherence tomography (OCT), and intraocular pressure (IOP) were focused on. RESULTS: In group 1, mean BCVA improved from (41.76 ± 15.59) letters (baseline) to (56.24 ± 18.56) letters, (52.57 ± 12.31) letters and (48.41 ± 17.90) letters at 4, 6 and 12 weeks post-injection, respectively (P = 0.004, P = 0.011 and P = 0.026, respectively). Mean CRT decreased from (525.76 ± 184.10) µm (baseline) to (270.33 ± 202.67)µm, (303.12 ± 168.43) µm and (402.26 ± 196.21) µm, respectively (P = 0.009, P = 0.016 and P = 0.030, respectively). In group 2, mean BCVA improved from (39.89 ± 12.27) letters (baseline) to (55.31 ± 19.27) letters, (51.25 ± 13.48) letters and (46.97 ± 16.23) letters at 4, 6 and 12 weeks after injection, respectively (P = 0.003, P = 0.010 and P = 0.027, respectively). Mean CRT decreased from (554.50 ± 169.05) µm (baseline) to (292.76 ± 196.05) µm, (323.46 ± 164.05) µm and (426.38 ± 169.05) µm, respectively (P = 0.009, P = 0.014 and P = 0.028, respectively). However, there was no significant difference between these two groups with regard to mean BCVA (F = 1.602, P = 0.216) and CRT (F = 0.412, P = 0.526). At 12 weeks after the injection, 11 of the patients in group 1 and nine patients in group 2 appeared recurrent macular edema and needed repeat injections. There was one patient in group 2 appeared transient intraocular pressure increases. CONCLUSIONS: Intravitreal injection of bevacizumab combined with/without triamcinolone acetonide had a beneficial effect on DME. However, the significant effect was not permanent. Our results showed that no significant differences were detected between intravitreal bevacizumab combined with/without triamcinolone acetonide for the eyes with diabetic macular edema in Chinese patients.