Aim To investigate the modeling of breast cancer in zebrafish embryos and its related protein expression. Methods 48hpf wild type AB/ TG(Transgenic) zebrafishs were micro-in-jected with breast cancer cell line: MCF-7,T-47D, MDA-MB-231 respectively, the relationship between the number of tumor and model application was investigated, and the number of sub-intestinal veins(SIVs) was detected under confocal microscope, as well as the metastasis of tumor cells in embryos; then the ze-brafish xenografts of MB-231 were co-cultured with tofacitinib/ptk787 for 48 h, optical density(OD) of the cell survival and subintestinal veins(SIVs) were evaluated under confocal micro-scope, and Western blot(WB) analysis was used to test micro-circumstances related protein. Results When the number of in-oculated cells was more than 200 per embryo, xenograft model rate woule be more than 0. 90;MB-231 xenografts showed metas-tasis feature in zebrafish, which could be inhibited by tofacitinib (P < 0. 01), while the number of xenograft MB-231 cells was reduced significantly(P < 0. 01); in another zebrafish xenografts SIVs assay, the tumor could promote the proliferation of SIVs, and 4 mg·L - 1 PTK787 showed inhibiton effect( P < 0. 01). Western blot showed 4d T-47D xenograft zebrafish got more HER2 expression than AB embryos; VEGFa expression in ze-brafish MB-231 model group was higher, and model zebrafish P53 expressi was higher after treated by tofacitinib. Conclusion A zebrafish xenograft model of human brest cancer can be es-tablished, which demonstrates applicability for screening com-pounds in drug discovery studies.

As a model organism, zebrafish have many advantages over other animal models and is suitable for studies on establishment of human disease model and mechanism.In zebrafish, there are two phases of endocrine formation during early development, which are directed by concomitant activity of many signaling pathways.Zebrafish pancreas possess similar cell structure with that of other animals, which can express various endocrine hormones including insulin.The main organs required for metabolic control, such as the pancreas, islet, and insulin sensitive tissue (muscle, liver) are conserved in zebrafish, and the mechanisms of glucose regulation in zebrafish is similar to that seen in mammalian models.These render it an excellent model to study glucose metabolism.Hyperglycemia in zebrafish model can be induced by administration of the diabetogenic drug, streptozotocin (STZ), alternatively immersion of the fish in glucose solution and water, or disturbing of signaling pathways associated with glucose metabolism.Glucose levels in adult zebrafish blood or embryo tissue and phenotype of retinal cell layers or retinal vasculature are the commonly used measurement organs in zebrafish diabetic models.

Aim To study the effect of rhein on renal damage induced by aristolochic acid. Methods Ze-brafish model of aristolochic acid nephropathy, genera-ted by treating zebrafish larvae with aristolochic acid for 24 h, was treated with rhein simultaneously . Mor-pholigical changes were observed and the creatinine level in larvae tissue was measured. And mRNA ex-pression levels of inflammatory factor cox2 a and fibrosis factor TGF-β1 in larvae tissue were detected using qPCR. Results Some larvae show periocular edema and circulation system defection e. g. weak heart beat, narrow cardiac vesicle, decreased blood flow and even blockage , with a dose-response relationship after expo-sure to aristolochic acid for 24 h. The creatinine level in larvae tissue of the treated group was significantly higher than that of the control larvae. And the expres-sion levels of cox2 a and TGF-β1 in larvae tissue of the treated group were also significantly increased. Per-centage of abnormal larvae and creatinine level in lar-vae tissue were decreased when treated with rhein sim-ultaneously. And the expression levels of cox2a was down-regulated by rhein compared with the aristolochic acid treated group. But rhein had no effect on TGF-β1 expression. Conclusion To some extent rhein can protect renal from damage induced by aristolochic acid.

OBJECTIVE To investigate the role of PDE4 inhibition in astrocyte swelling caused by cerebral ischemic/reperfusion(I/R)injury and the molecular mech-anisms.METHODS SD rats were subjected to 2 h of focal cerebral ischemia induced by middle cerebral artery occlusion/reperfusion(MCAO/R).Roflumilast(Roflu)was intraperitoneally injected 2 h after MCAO.At 24 h after reperfusion,a high-resolution MRI was performed and using the wet-dry weighting method to measure the water content.The oxygen-glucose deprivation/reoxygenation(OGD/R)model was established in primary astrocytes for 2 h.After 24 h of reoxygenation,CellMask? plasma membrane stain was used to label the plasma membrane to calculate cell volume.The protein expressions insides astrocytes and penumbra were detected by Western blot-ting.To investigate the role of Akt/FoxO3a in mediating the effect of Roflu on the expression of AQP4.The astro-cytes were treated with an Akt inhibitor MK2206 before treatment with Roflu and the activation of Akt,the expres-sion of AQP4 and cell volume were determined as described above.In addition,an IL-1β-stimulated cell model was established in astrocytes,the expression of AQP4 and the activation of Akt/FoxO3a were detected by Western blotting.The change of AQP4 expression inside astrocytes and penumbra were visualized by immunofluo-rescence staining.RESULTS Roflu reduced MCAO/R-induced water contents,the expression of AQP4 and the phsophorylation of Akt and FoxO3a in the brains of MCAO/R rats.Inhibition of PDE4 decreased the cell volume and the expression of AQP4 in primary astro-cytes subjected to OGD/R.PDE4 inhibition activated Akt/FoxO3a,and inhibition of Akt by MK2206 blocked the protective effect of Roflu against OGD/R induced astro-cyte swelling.PDE4B knocking down reduced the expres-sion of AQP4,while PDE4B overexpression reversed the effect of PDE4B siRNA in astrocytes.Roflu exert-ed similar protective effect in IL-1β-cultured astrocytes,and importantly overexpression of FoxO3a remarkably increased the expression of AQP4 in IL-1β-stimulated astrocytes.CONCLUSION Our findings indicate that PDE4 inhibition limits I/R-induced brain edema and astro-cyte swelling via the Akt/FoxO3a/AQP4 pathway.PDE4 inhibition is a promising strategy for the treatment of brain edema after I/R injury.

Objective To review the clinical characteristics and risk factors of Pseudomonas aeruginosa bloodstream infections. Methods The clinical data of P. aeruginosa bloodstream infections in the First Affiliated Hospital of Soochow University from January 2007 to December 2016 were analyzed retrospectively. Results Of the 251 patients identified, APACHE Ⅱ score on admission was 11.5±5.2. Majority (98.4％, 247/251) of the patients had fever. Leukopenia was found in 125 patients, leukocytosis in 87 patients, neutropenia in 122 patients, agranulocytosis in 113 patients, anemia in 193 patients, and hypoalbuminemia in 120 patients. Overall, 219 patients had at least one underlying disease, primarily hematological malignancy, or malignant solid tumor. Most (229) patients received invasive procedures such as deep venous catheter, urinary catheter, mechanical ventilation before blood sampling. P. aeruginosa was isolated from 108 of the 173 deep venous catheters. In addition, 130 patients received radiation or chemotherapy. Immunosuppressive agents were used in 124 patients. Among the 251 strains of P. aeruginosa, 87.3％ were susceptible to amikacin, followed by ciprofloxacin (85.7％) and cefepime (81.6％). Multidrug-resistant P. aeruginosa was isolated from 36 (14.3％) patients, and extensively drug resistant strain was isolated from 7 patients. All the 251 patients were treated withantimicrobial agents, mainly β-lactam/β-lactamase inhibitor combinations, carbapenems or fluoroquinolones. Overall, 20 (8.0％) of the 251 patients died, 37 (14.7％) refused further therapy due to worsening condition, and 194 (77.3％) improved. Binary logistic regression analysis showed that high APACHE Ⅱ score on admission, anemia and hypoalbuminemia were risk factors for poor outcome of bloodstream infectionscaused by P. aeruginosa. Conclusions P. aeruginosa bloodstream infection occurs more readily in immunocompromised patients. High APACHE Ⅱ score on admission, anemia and hypoalbuminemia are associated with poor prognosis. Appropriate empiric antimicrobial treatment as early as possible can improve the prognosis of P. aeruginosa bloodstream infection.

Aim To investigate the anti-angiogenesis and anti-xenograftes of UA in zebrafish larvaes. Meth-ods 24 hour post-fertilization ( hpf ) TG zebrafish was treated with different concentration of UA for 24h, and the number of intersegmental vessels( IVS) were detec-ted under fluorescent microscope respectively;then the models of AB/TG zebrafish xenografts were established by be micro-injected with SMMC-7721 or HT-29 cell at 48hpf respectively, and after cocultured with UA for 48h, optical density (OD) of the SMMC-7721 cell and subintestinal veins ( SIVs) induced by HT-29 were e-valuated under confocal microscope. Results ISV as-say showed that UA could cause IVS missing or disap-perance, inhibition ratio reaching 20. 25% and 26. 65%. UA blocked the spread of SMMC-7721 cells in zebrafish and OD value,and inhibition ratios at three concentrations were 38. 01%, 54. 69%, 61. 88%, re-spectively; in another SIVs assay induced by xeno-grafts, UA at concentration 10 and 15mg·L-1 showed that SIVs were inhibited (P<0. 01) obviously. Con-clusion UA could inhibit the angiogenesis and the growth of SMMC-7721/HT-29 xenografts,and the anti-tumor mechanism may be related with VEGFR2 expres-sion.

Objective:To investigate the risk factors and predictive value of early neurological deterioration (END) in patients with minor stroke caused by middle cerebral artery occlusion.Methods:Consecutive patients with minor stroke caused by middle cerebral artery occlusion admitted to Zhangjiagang Hospital Affiliated to Soochow University from October 2021 to May 2023 were retrospectively included. Minor stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 at admission, and END was defined as an increase of ≥4 from baseline in the NIHSS score within 24 h of admission (excluding intracranial hemorrhage). Multivariate logistic regression analysis was used to determine independent risk factors for END. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of various risk factors on END. Results:A total of 130 patients with minor stroke caused by middle cerebral artery occlusion were included, of which 33 (25.4%) had END and 97 (74.6%) did not. Univariate analysis showed that there were statistically significant differences in NIHSS scores, volume with cerebral blood flow <30%, CT perfusion mismatch volume, baseline blood glucose, and baseline white blood cell count between the END and non-END groups (all P<0.05). Multivariate logistic regression analysis showed that CT perfusion mismatch volume (odds ratio [ OR] 1.010, 95% confidence interval [ CI] 1.003-1.017; P=0.007) and baseline white blood cell count ( OR 1.582, 95% CI 1.200-2.085; P=0.001) were the independent risk factors for END. ROC curve analysis showed that the area under the curves of CT perfusion mismatch volume and baseline white blood cell count for predicting END were 0.748 (95% CI 0.660-0.835; P<0.001) and 0.757 (95% CI 0.659-0.854; P<0.001), respectively. The area under the curve of combined predicting END was 0.821 (95% CI 0.738-0.905; P<0.001). Conclusions:CT perfusion mismatch volume and baseline white blood cell count are independent risk factors for the occurrence of END patients with minor stroke caused by middle cerebral artery occlusion, and the combination of the two has good predictive value for END.

Objective:To explore changes in high-risk sexual behaviors and associated factors in HIV-infected men who have sex with men (MSM) in industrial workers, and provide evidence for designing behavioral interventions for this population.Methods:In this observational study, HIV-infected MSM were recruited in industrial workers using convenient sampling during August to September 2021. The sample size was estimated to be 530. A questionnaire was used and combined with routine follow-up to collect socio-demographic characteristics, high-risk sexual behaviors, partner notification, viral load testing and history of sexually transmitted diseases before and after diagnosis of HIV infection. The χ2 test was used to analyze the changes in high-risk sexual behaviors before and after diagnosis and logistic regression was conducted to identify factors associated with high-risk sexual behaviors. Results:A total of 560 HIV-infected MSM in industrial workers were recruited in this study. Of whom, 32.1% (180/560) had unprotected anal intercourse (UAI) within 12 months after diagnosis . The proportions of those having UAI with casual, commercial and regular same-sex partners significantly decreased from 73.4% (381/519), 75.1% (187/249) and 69.5% (207/298) within 12 months before diagnosis to 36.2% (146/403), 40.2% (86/214) and 34.2% (67/196) within 12 months after diagnosis , respectively. Educational level of college or above (a OR=0.41, 95% CI:0.23-0.71), passive anal sex (a OR=0.40, 95% CI:0.19-0.85), both active and passive anal sex after diagnosis (a OR=0.40, 95% CI:0.20-0.83) and no unprotected oral sex (a OR=0.02, 95% CI:0.01-0.05) were negatively associated with UAI within 12 months after diagnosis. Whereas, not considering necessary to use condom consistently after having repeated undetectable viral load (a OR=3.02, 95% CI:1.37-6.69) was positively associated with UAI within 12 months after diagnosis. Conclusions:Compared with that before diagnosis of HIV infection, although the prevalence of UAI seemed to decrease in HIV-infected MSM in industrial workers after diagnosis, nearly one third of them had high-risk sexual behaviors. Therefore, relevant interventions should be strengthened to reduce high-risk sexual behaviors.

【Objective】 To explore the effect of nifedipine controlled-release tablets on left wrist pulse wave transit time (PWTT) in hypertensive patients. 【Methods】 We selected 262 essential hypertensive patients hospitalized at Chinese PLA General Hospital Hainan Branch from August 2021 to December 2022. The patients were divided into observation group (n=140) and control group (n=122) according to whether or not taking nifedipine controlled release tables. The left wrist PWTT at 0.5 h, 2.5 h, 4.5 h, 6.5 h and 8.5 h after administration of the medicine was collected with a smart watch for statistical analysis. 【Results】 ①The PWTT in the observation group (93±15, 93±13, 87±15, 85±15, 84±10) and the control group (98±18, 92±16, 90±10, 89±8, 89±9) decreased gradually with the extension of time (F=11.448, P<0.001). ②The PWTT decreased by the same amplitude (F=2.206, P>0.05). ③There was no significant difference in PWTT between the observation group and the control group at five time points (F=1.164, P>0.05). 【Conclusion】 Administration of nifedipine controlled-release tablets does not affect PWTT of primary hypertensive patients’ left wrist.