Objective To investigate the biological behavior and expression of intergrin-linked kinase (ILK) after exposure to transforming growth factor beta 2 (TGF-β32) in human Tenon fibroblasts (HTFs).Methods The primary ceils of HTFs were cultured by tissue attached culture method and identified by immunofluorescence analysis with Vimentin and keratin.The proliferation levels of HTFs induced by different concentrations of TGF-β2 were analyzed by MTT.The α-smooth muscle actin (α-SMA) and ILK mRNA expression were analyzed by quantitative Real-time PCR.The protein expression of α-SMA,ILK and E-cadherin were analyzed by Western Blot,and the protein expression of α-SMA and E-cadherin were also analyzed by immunofluorescence staining.Results MTT analysis showed that the optical density levels of 5.0 μg · L-1 and 10.0 μg · L-1 TGF-β2 were significantly higher than those of 0.1 μg · L 1,1.0 μg · L-1 and the control after exposure for 48 hours and 72 hours,and all these optical density levels were significantly higher than that for 24 hours (all P ＜0.05).The expression of α-SMA and ILK mRNA increased significantly when cells were treated with 5.0 μg · L-1 TGF-β2 for 48 hours in comparison with the control group (all P ＜ 0.05).The protein of α-SMA,ILK and E-cadherin were expressed both in TGF-β2 treated groups and control group,and TGF-β2 up-regulated the expression of them.There were significant differences when compared with the control group (all P ＜ 0.05).Immunofluorescent staining showed that α-SMA and E-cadherin were detected in TGF-β2 treated groups.α-SMA expressed in cytoplasm,while E-cadherin both in cytoplasm and nucleus.Conclusion TGF-β2 can induce the proliferation,transdifferentiation and adhesion of HTFs,and up-regulate the expression of ILK in vitro,suggests that ILK may play a role in the process of scar formation after glaucoma filtration surgery.

Objective To evaluate the efficacy of patients with stage T2 bladder cancer who underwent combined treatment of bladder-preserving surgery and adjuvant intra-arterial chemotherapy.Methods The survival data of bladder cancer paients from January 2000 to December 2014 with stage T2N0M0 were retrospectively analyzed.Thirty-five patients of cT2N0M0 receive combined treatment of bladder-preserving surgery and adjuvant intra-arterial chemotherapy(group A),and 80 patients of pT2N0M0 underwent radical cystectomy (RC) (group B).The pathological diagnosis of all patients was urothelial carcinoma.In group A,there were 33(94.2％) males and 2 (5.8％) females;20 (57.1％) tumor size less than 3 cm and 15 (42.9％) larger than 3 cm;24 (68.6％) with single tumor and 11 (31.4％) with multiple tumors;11 (31.4％) patients with primary tumors and 24 (68.6％) recurrent tumors.In group B,there were 71 (88.7％) males and 9 (11.3％) females;35 (43.8％) tumor size less than 3 cm and 45(56.2％) larger than 3 cm;44 (55.0％) with single tumors and 36 (45.0％) with multiple tumors;22(27.5％) patients with primary tumors and 58 (72.5％) recurrent tumors.Results Groups A and B consisted of 35 and 80 patients and median follow-up time was 68 (13-157)and 67 (4-198)months,respectively.There was no significantly statistical difference in disease-specific survival (DSS) between the two groups(P =0.888),76.5％ for group A and 60.6％ for group B respectively.In group A,26 (74.3％) patients achieved complete response (CR) to intra-arterial chemotherapy.Additionally,amounts of 21 (60.0％) patients preserve their functional bladder successfully and their median follow-up time was 69 (13-134)months.8 patients receive delayed radical cystectomy when suffered tumor recurrence and none of them had lymph node metastases.Of those pathological stage was presented as stage T2 5 cases,T3 2 cases and T4 1 case.Importantly,the 8 patients who receive delayed RC did not confer worse DSS when compared with those underwent immediate RC in group B (P =0.809).Cox proportional hazards model showed that tumor number and CR to intra-arterial chemotherapy was independent prognostic factor for disease-free survival (HR =0.238,P =0.007) and DSS(HR =0.085,P =0.004) respectively.During the period of intra-arterial chemotherapy,we did not observe hematological toxicity of grade Ⅳ and the hematological toxicity of grade Ⅰ-Ⅲ was 9 (25.7％),6 (17.1％) and 4 (11.4％).Conclusions For patients with T2N0M0,combined treatment of bladder-preserving surgery and adjuvant intra-arterial chemotherapy could be a therapy with long-term survival outcome and safety.The therapy could be offered as alternative treatment option for patients who were unsuitable for receiving RC.

Objective: We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

AIM: To investigate the possible use of anti-FGF-2 nanobody for the treatment of pathological neovascularization. METHODS: SD rats were divided into a sham operation group, a control group (3 mm diameter circular filter paper soaked with 1 mol/L NaOH solution was applied to the central part of the cornea of rats for 30 s to prepare the rat model of alkali-burn angiogenesis) and a treatment group (treated with a drop of 3 mg/mL anti-FGF-2 nanobody 7 days after the operation. Repeat application 3x/day for 14 days). Corneal angiogenesis was measured by stereoscopic microscopy and CD31 immunohistochemical staining. The mRNA and protein expression levels of VEGF and FGF-2 were detected by quantitative fluorescence PCR (qPCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.RESULTS: (1) Blood vessel: The area of the treatment group was significantly reduced compared with the model group, and the vascular lumen was narrower (P<0.05). The difference was the most significant after 14 days of drug intervention; (2) Expression level of FGF-2 mRNA and protein: the model group had similar results to the treatment group (P>0.05); (3) Expression levels of VEGF mRNA and protein: The treatment group was significantly higher than the model group (P<0.05). In addition, the expression of VEGF also increased significantly in the continuous administration of the sham operation group. CONCLUSION: Anti-FGF-2 nanobody can be used for the treatment of angiogenesis. However, the expressions of VEGF will compensatorily increase after blocking FGF-2 in normal or pathological rats.

BACKGROUNDAntihypertensive drugs have been linked to new-onset osteoporotic fracture (NOF), and different classes of antihypertensive drugs may alter the risk for the development of NOF; however, the classic effect of different antihypertensive drugs on the development of NOF in the elderly has not been well studied during long-term follow-up.

METHODSIn this study, we investigated the association between different classic antihypertensives and the development of NOF in the elderly. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance in Central Taiwan, China including case patients with NOF aged 65-80 years from January 2002 to December 2012 and non-NOF controls. Prescriptions for antihypertensives before the index date were retrieved from a prescription database. We estimated the hazard ratios (HR s) of NOF associated with antihypertensive use. Non-NOF controls served as the reference group.

RESULTSA total of 128 patients with NOF were identified from among 1144 patients with hypertension during the study period. The risk of NOF after adjusting age, sex, comorbidities, and concurrent medications was higher among the users of angiotensin-converting enzyme (ACE) inhibitors (HR, 1.64; 95% confidence interval [CI], 1.01-2.66) than among nonusers. Patients who took calcium channel blockers (CCBs) (HR, 0.70; 95% CI, 0.49-0.99) were at a lower risk of developing NOF than nonusers. Loop diuretics, thiazide diuretics, angiotensin receptor blocker, beta-blocker, and alpha-blocker were not associated with the risk of NOF.

CONCLUSIONSElderly with hypertension who take CCBs are at a lower risk of NOF and that the use of ACE inhibitors was associated with a significantly increased risk of developing NOF during the 11-year follow-up.

Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Antihypertensive Agents ; adverse effects ; therapeutic use ; Calcium Channel Blockers ; adverse effects ; therapeutic use ; Cohort Studies ; Female ; Humans ; Hypertension ; drug therapy ; Longitudinal Studies ; Male ; Osteoporotic Fractures ; chemically induced ; epidemiology ; Retrospective Studies ; Risk Factors ; Taiwan ; epidemiology