Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Objective:To explore the effect of teach-back method combined with follow-up nursing on the adherence of glucocorticoid medication in patients with uveitis.Methods:From July to December 2021, 243 patients with uveitis admitted to the Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University were selected as the study subject by convenience sampling. A total of 120 patients admitted from July to September 2021 were set as the control group, and 123 patients admitted from October to December 2021 were set as the intervention group. The control group received routine medication guidance and follow-up nursing, while the intervention group received medication guidance and follow-up nursing using the teach-back method. The adherence of two groups of patients to glucocorticoid medication before and three months after intervention were compared.Results:Before intervention, there was no statistically significant difference in medication adherence between the two groups of patients ( Z=-0.382, P=0.702). After intervention, the medication adherence of the intervention group patients was better than that of the control group, with a statistically significant difference ( Z=-8.854, P<0.001) . Conclusions:The combination of teach-back method and follow-up nursing can effectively improve the adherence of patients with uveitis to glucocorticoid medication.

Objective To analyze the molecular characteristic and trace the resource of dengue virus in Zhuhaidistrict of Guangzhou during 2012-2015.Methods Collected the cases data of dengue fever in Zhuhai district from 2012-2015 and analyzed the epidemical characteristic.DENV strains were isolated by C6/36 cells,the E gene was amplified from the positive specimen by RT-PCR.The PCR products were sequenced and then analyzed by bio-information software.Results Total of 6 260 DENV infection cases were reported,and the cases happened in every age group;57.78％ of the cases occurred in October.16 virus strains were isolated from 48 samples and the whole E genes were successfully amplified,the virus strains from 2013 and 2014 were the same one and the nucleotide sequence 99.93％ identify with DENV-1 in 2009.Phylogenetic analysis showed that DENV-1 belonged to the G1 genotype,genetically close to the strains from Thailand;strains from 2015 were the same one and belonged to the Cosmopolitan genotype of DENV-2,most similar with the strains from India.Conclusions The DENV-1 outbreak in Haizhu district of Guangzhou during 2012-2015 were belonged to G1 that originated from Thailand and might indigenous in 2009;DENV-2 was belonged to Cosmopolitan genotype which was imported.

Objective To explore the expression of Survivin in colorectal cancer tissue and its relationship with clinicopathological features.Methods In situ hybridization was used to examine the expression of Survivin mRNA,and immunohistochemical method was used to detect the expression of Survivin protein in 60 cases of colorectal cancer and 30 cases of colorectal normal mucos tissue.The relationship of the expression of Survivin protein with clinicopathological features of colorectal cancer was analyzed.Results The positive expression rate of Survivin protein in colorectal normal mucos tissue (10.00％,3/30) was lower than that in colorectal cancer tissue (73.33％,44/60),and there was significant difference (P ＜ 0.05).The positive expression rate of Survivin mRNA in colorectal normal mucos tissue (6.67％,2/30) was lower than that in colorectal cancer tissue (63.33％,38/60),and there was significant difference (P ＜ 0.05).The expression of Survivin mRNA was positively correlated with depth of invasion,lymph node metastasis,liver metastasis,peritoneal micrometastasis and TNM stage in patients with colorectal cancer (P ＜ 0.01),but had no correlation with gender,age,tumor size,location,degree of differentiation and histological type (P ＞ 0.05).Conclusions The specific high expression of Survivin protein has a high correlation with the occurrence,development,infiltration of colorectal cancer.Survivin may be used as a marker for prognosis of patients with colorectal cancer.

Objective To investigate the protection of agmatine on blood brain barrier (BBB) permeability and the effect on the expression of aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) in ischemic reperfusion injury rats.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into normal control group (NC),model group and agmatine group,and there were 20 rats in each group.Normal control group was treated with intraperitoneal injection of saline in 2 hours after incision and suture of skin.Model group was treated with intraperitoneal injection of saline in 2 hours after the establishment of middle cerebral artery occulation (MCAO) model.Agmatine group was treated with intraperitoneal injection of agmatine (AGM) in 2 hours after the establishment of MCAO model.The damage of blood brain barrier was detected by measuring the permeability of blood brain barrier.The infarct size of brain was observed with TTC staining.The morphological changes of neurons were observed with electron microscope.The expressions of AQP4 and MMP9 were detected using immunohistochemical method.Results The permeability of BBB of agmatine treatment group (0.31±0.10) decreased significantly compared with the model group (0.46±0.09) (P＜0.05),but was still significantly higher than the normal control group (0.24±0.12) (P＜0.05).There was no infarction area in normal control group and the infarction areas of agmatine group decreased obviously compared with the model group.Compared with model group,the number of neurons with morphological changes reduced significantly and the degree of pathological changes of neurons was obviously improved in agmatine group.Compared with normal control group,the expression of AQP4 and MMP9 in ischemic penumbra of left cerebral hemisphere parietal cortex in the rats of model group and agmatine group increased significantly(P＜0.05).And the expression of AQP4 and MMP9 in model group was significantly higher than that of agmatine group(P＜0.05).Conclusion Agmatine has a protective effect on BBB with ischemia-reperfusion injury due to its down-regulation the expression of AQP-4 and MMP-9.

Objective To explore the influence of life quality for the breast cancer patients receiving chemotherapy after the cog-nitive ,behavioral and psychological intervention to their spouse .Methods 120 breast cancer patients received standardized chemo-therapy and their spouses ,and divided into control and intervention groups .The intervention group receive the routine care and health guidance .Before and after chemotherapy ,the life quality of patients was investigated .The data was analyzed statistically .Re-sults The result by the breast cancer patients Quality of Life Questionnaire in Chinese (FACT-B) show that ,the scores of the con-trol and intervention groups in the physiological status ,social/family status ,emotional status ,functional status ,additional attention andtotalscorewere(18.77±4.18,16.48±4.60,17.35±4.41,16.04±4.80,20.81±6.02,89.45±6.34 ;22.46±3.57,19.03± 4 .83 ,18 .58 ± 3 .96 ,18 .59 ± 4 .48 ,24 .73 ± 5 .63 ,103 .39 ± 8 .91) .The scores of intervention groups was increased significantly than the control group .The data was analyzed statistically .Conclusion The quality of life of patients was improved by the cognitive ,be-havioral and psychological guidance and intervention to the spouse of breast cancer chemotherapy patients.