A ROS-responsive and scavenging hydrogel for postoperative abdominal adhesion prevention.

Postoperative abdominal adhesion (PAA) widely occurs after abdominal surgery, which often produces severe complications. However, there were still no satisfactory anti-adhesive products including barriers and anti-adhesive agents. Herein, we developed a ROS-responsive and scavenging hydrogel barrier, termed AHBC/PSC, wherein the monomer AHBC was synthesized by phenylboronic acid (PBA)-modified hyaluronic acid (HA-PBA) further grafted with adipic dihydrazide (ADH) and PBA-based chlorogenic acid (CGA) via ROS-sensitive borate ester bond, and the other monomer PSC was constructed by polyvinyl alcohol (PVA) grafted with sulfated betaine (SB) and p-hydroxybenzaldehyde (CHO). Further, the double crosslinked AHBC/PSC hydrogel was successfully fabricated between AHBC and PSC via forming dynamic covalent acylhydrazone bonds and borate ester bonds. Results showed that AHBC/PSC hydrogel had in situ gelation behavior, satisfactory mechanical properties (storage modulus of about 1 kPa and loss factor Tan δ of about 0.5), suitable wet tissue adhesion strength of about 2.3 kPa on rat abdominal wall, and good biocompatibility, achieving an ideal physical barrier. Particularly, CGA could be responsively released from the hydrogel by breakage of borate ester bonds between CGA and PBA based on high reactive oxygen species (ROS) levels of damaged tissue and exhibited great ROS scavenging capability to regulate inflammation and promote the polarization of macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Moreover, the grafted SB as a zwitterionic group could reduce protein adsorption and fibroblast adhesion. Finally, the in vivo experiments revealed that AHBC/PSC hydrogel with good safety and in vivo retention behavior of about 2 weeks, effectively prevented PAA by regulating the inflammatory microenvironment and alleviating the fibrosis process. In brief, the versatile AHBC/PSC hydrogel would provide a more convenient and efficient approach for PAA prevention. STATEMENT OF SIGNIFICANCE: Postoperative abdominal adhesion (PAA) widely occurs after surgery and is often accompanied by severe complications. Excessive inflammation and oxidative stress are very crucial for PAA formation. This study provides a ROS-responsive and scavenging hydrogel with suitable mechanical properties, good biocompatibility and biodegradability, and resistance to protein and fibroblast. The antioxidant and anti-inflammatory active ingredient could be responsively released from the hydrogel via triggering by the high ROS levels in the postoperative microenvironment thereby regulating the inflammatory balance. Finally, the hydrogel would effectively regulate the development process of PAA thereby achieving non-adhesion wound healing.

Clinical and genetic risk factors for the prediction of hepatotoxicity induced by a docetaxel, epirubicin and cyclophosphamide regimen in breast cancer patients.

Aim: To screen clinical and genetic risk factors and examine their combined effect on docetaxel, epirubicin and cyclophosphamide (TEC) regimen-induced liver injury (TEC-ILI). Patients & methods: We enrolled 396 breast cancer patients, and TEC-ILI-associated factors were screened by logistic regression analyses. Results:SOD2 rs4880 and ABCG2 rs2231142 polymorphisms correlated with an increased risk of TEC-ILI. Multivariate analysis incorporating clinical and genetic factors revealed that ABCC1 rs246221 (CC) and SOD2 rs4880 (AG/GG) increased the risk of TEC-ILI. Patients with at least two risk factors among nonalcoholic fatty liver disease, high low-density lipoproteinemia levels and the rs246221 or rs4880 adverse genotypes exhibited a significantly increased risk of developing TEC-ILI. Conclusion: The combination of clinical and genetic risk factors had higher predictive value for TEC-ILI than the interclinical risk factors alone.

High Serum Estradiol Reduces Acute Hepatotoxicity Risk Induced by Epirubicin Plus Cyclophosphamide Chemotherapy in Premenopausal Women with Breast Cancer.

Aim: We evaluated whether acute drug-induced liver injury (DILI) caused by adjuvant chemotherapy with epirubicin plus cyclophosphamide for early breast cancer was associated with estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Methods: Reproductive hormone test results of breast cancer patients were collected in the first chemotherapy cycle. E2, LH, and FSH levels were loge-transformed to normally distributed variables and were assessed using Student's t-test to determine significant differences between the case and control groups. Hormone levels were classified according to the interquartile range and analyzed by logistic regression to determine their association with DILI caused by chemotherapy. Results: Among the 915 enrolled patients (DILI group: 204; control group: 711), menopausal status, along with serum E2, LH, and FSH levels, did not substantially differ between case and control groups. However, in the premenopause subgroup (n = 483), we found a significant difference in the E2 level between the case and control groups (p = 0.001). After adjusting for age and body mass index, premenopausal patients with 152-2,813 pg/mL E2 showed a lower risk of chemotherapy-induced DILI than patients with ≤20 pg/mL E2 (odds ratio: 0.394; 95% confidence interval: 0.207-0.748). The linear trend χ2 test revealed that E2 levels in premenopausal patients with breast cancer were inversely associated with the development of DILI. Conclusion: High serum E2 levels are associated with a reduced DILI risk in premenopausal patients with breast cancer undergoing epirubicin plus cyclophosphamide adjuvant chemotherapy.

catena-Poly[[dichloridocopper(II)]-µ-4,4'-bis-(benzimidazol-1-yl)biphen-yl].

In the title compound, [CuCl(2)(C(26)H(18)N(4))](n), the Cu(II) ion is four-coordinated by two N atoms from two 4,4'-bis-(benzo-imidazol-1-yl)biphenyl ligands and two chloride anions, in a slightly distorted tetra-hedral environment. The biphenyl ligand acts as a linear bidentate ligand, connecting the metal atoms into an infinite chain parallel to [101]. In the biphenyl ligand, the two benzene rings make a dihedral angle of 33.19 (7)°.