Synthesis of iridium-based nanocomposite with catalase activity for cancer phototherapy.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted attention due to its enhanced tumor therapy effect. This study proposes a novel nanoenzyme-based theranostic nanoplatform, IrO2@MSN@PDA-BSA(Ce6), for the combined PTT and PDT of tumors. IrO2 was prepared by a simple hydrolysis method and coated with a thin layer of mesoporous silica (MSN) to facilitate the physical adsorption of Chlorin e6 (Ce6). The PDA coating and IrO2 NPs of the nanoplatform demonstrated an improved photothermal conversion efficiency of 29.8% under NIR irradiation. Further, the Ce6 loading imparts materials with the ability to produce reactive oxygen species (ROS) under 660 nm NIR laser irradiation. It was also proved that the IrO2 NPs could catalyze the hydrogen peroxide (H2O2) in the tumor microenvironment (TME) to generate endogenous oxygen (O2), thereby enhancing the efficiency of PDT. The in vitro and in vivo experiments indicated that the nanocomposite was highly biocompatible and could produce a satisfactory tumor therapeutic effect. Thus, the findings of the present study demonstrate the viability of using theranostic nanoenzymes for translational medicine.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Protocol for a gallbladder cancer registry study in China: the Chinese Research Group of Gallbladder Cancer (CRGGC) study.

INTRODUCTION: Gallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population. METHODS AND ANALYSIS: The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers. ETHICS AND DISSEMINATION: The protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019-085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT04140552, Pre-results.

Down-regulation of dihydrofolate reductase inhibits the growth of endothelial EA.hy926 cell through induction of G1 cell cycle arrest via up-regulating p53 and p21(waf1/cip1) expression.

Folic acid supplementation may meliorate cardiovascular disease risk by improving vascular endothelial structure and function. However, the underlying mechanisms are still lack of a global understanding. To be used, folic acid must be converted to 7,8-dihydrofolate by dihydrofolate reductase to generate one-carbon derivatives serving as important cellular cofactors in the synthesis of nucleotides and amino acids required for cell growth. Therefore, this study explored the effect of dihydrofolate reductase knockdown on endothelial EA.hy926 cell growth and the mechanism involved. We found that down-regulation of dihydrofolate reductase inhibited EA.hy926 cell proliferation, and induced G1 phase arrest. Meanwhile, the expression of regulators necessary for G1/S phase transition, such as cyclin-dependent kinases CDK2, CDK4 and CDK6, were remarkably down-regulated; by contrast, the cell cycle inhibitors p21(waf/cip1), p27(Kip1) and p53 were significantly up-regulated after dihydrofolate reductase knockdown. Furthermore, supplementation of 5-methyltetrahydrofolate to the dihydrofolate reductase knockdown cells could weaken the inhibitory effect of dihydrofolate reductase knockdown on cell proliferation, simultaneously, inducing the expression of p53 and p21(waf/cip1) falling back moderately. Our findings suggest that attenuating dihydrofolate reductase may cause imbalanced expression of cell cycle regulators, especially up-regulation of p53-p21(waf/cip1) pathway, leading to G1 cell cycle arrest, thereby inhibiting the growth of endothelial EA.hy926 cells.

Protective effects of Radix Astragali injection on multiple organs of rats with obstructive jaundice.

OBJECTIVE: To investigate the protective effects and mechanisms of Radix Astragali Injection on multiple organs of rats with obstructive jaundice (OJ). METHODS: A total of 180 rats were randomly divided into the sham-operated, model control and treated groups (60 in each group). On 7, 14, 21 and 28 days after operation, the serum contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), r-glutamyl transpeptidase (r-GT), total bilirubin (TBil), direct bilirubin (DBil), blood urine nitrogen (BUN), and creatinine (CREA) were determined. And the pathological changes of livers, kidneys and lungs, and protein expressions of toll-like receptor-4 (TLR-4) of livers, intercellular adhesion molecule-1 (ICAM-1) of lungs, Bax and nuclear factor-kappa B (NF-κB), as well as apoptotic indexes of multiple organs were observed, respectively. RESULTS: The pathological severity scores of multiple organs (including livers on 7, 14, 21 and 28 days, kidneys on 14 and 28 days, and lungs on 14 days), serum contents of ALT (14 and 21 days), AST (14 days), TBil (7, 14, 21 and 28 days), DBil (14 and 21 days), BUN (28 days), protein expressions of TLR-4 (in livers, 28 days), Bax (in livers and kidneys, 21 days), and apoptotic indexes in livers (7 and 21 days) in the treated group were significantly lower than those in the model control group (P<0.05 or P<0.01). CONCLUSION: Radix Astragali Injection exerts protective effects on multiple organs of OJ rats by improving the pathological changes of lung, liver and kidney, decreasing the serum index of hepatic and renal function as well as inhibiting the protein expression of TLR-4 and Bax in the livers and Bax in the kidneys.