Design, synthesis, and biological activity of 9-O-cinnamoylberberines as novel lipid-lowering agents.

Berberine possesses a wide spectrum of lipid regulation, and yet it has poor physicochemical property and cytotoxicity as a drug candidate. In order to alleviate the problems, a total of twenty-one 9-O-cinnamoylberberines and twenty 9-O-cinnamoyltetrahydroberberines were designed, synthesized, and evaluated by in vitro cell viability experiment and four classical lipid-lowering assays involving with total cholesterol, triglyceride, low density lipoprotein cholesterol, and high density lipoprotein cholesterol. A structure-activity relationship study of these compounds resulted in the discovery of two promising candidate molecules (5p and 7u). Compound 5p displayed the most potent inhibitory effect for TG formation, with the inhibitory rates of 40.5% and 76.8% in 3T3-L1 cells and HepG2 cells, respectively. Compound 7u exhibited the most promoting activity for the production of HDLC, with the increasing rates of 52.6% and 70.5% in both models, respectively. These two attractive compounds can be further investigated as new lipid-lowering agents in follow-up researches.

A Comparative Study of Patients' Subjective Feelings Toward Total Hip Arthroplasty with Patient-Specific Instruments and Traditional Total Hip Arthroplasty.

OBJECTIVE: To determine whether differences exist in patients' subjective feelings, daily life, and surgical satisfaction between those who underwent surgery for developmental dysplasia of the hip (DDH) using patient-specific instruments (PSIs) and those who underwent traditional surgical total hip arthroplasty (THA). METHODS: We selected 30 adult patients with various types of DDH who underwent surgery during 2016-2017 at our hospital. The patients were divided into PSI surgery group and the traditional surgery group. All patients underwent follow-up, and we collected data on the Harris Hip Score, Oxford University Hip Score (OHS), Forgotten Joint Score (FJS-12), Visual Analogue Scale (VAS) score, patient satisfaction score, intraoperative surgical time, amount of bleeding and postoperative complications incidence for both groups. We then performed statistical analyses on the data. RESULTS: The Harris Hip Score, OHS, VAS score, patient satisfaction score, and mean bleeding volume did not differ statistically significantly (t-tests, P > 0.05). No statistically significant differences were found between surgical groups in the incidence of complication and sub-trochanteric osteotomy, or in the surgical side (chi-square tests, P > 0.05). For the experimental group, the FJS-12 score was 80.0 ± 12.0, and for the control group the score was 68.5 ± 16.1. The operative time of the experimental group was 138.4 ± 32.2 min, while that of the control group was 88.9 ± 26.8 min. The values of these data differed significantly (t-tests, P < 0.05). CONCLUSIONS: The novel PSI designed by our group has certain advantages for the short-term subjective feelings of patients after THA, but it may cause prolonged operative times.

Involvement of hydrogen sulfide in the progression of renal fibrosis.

OBJECTIVE: Renal fibrosis is the most common manifestation of chronic kidney disease (CKD). Noting that existing treatments of renal fibrosis only slow disease progression but do not cure it, there is an urgent need to identify novel therapies. Hydrogen sulfide (H2S) is a newly discovered endogenous small gas signaling molecule exerting a wide range of biologic actions in our body. This review illustrates recent experimental findings on the mechanisms underlying the therapeutic effects of H2S against renal fibrosis and highlights its potential in future clinical application. DATA SOURCES: Literature was collected from PubMed until February 2019, using the search terms including "Hydrogen sulfide," "Chronic kidney disease," "Renal interstitial fibrosis," "Kidney disease," "Inflammation factor," "Oxidative stress," "Epithelial-to-mesenchymal transition," "H2S donor," "Hypertensive kidney dysfunction," "Myofibroblasts," "Vascular remodeling," "transforming growth factor (TGF)-beta/Smads signaling," and "Sulfate potassium channels." STUDY SELECTION: Literature was mainly derived from English articles or articles that could be obtained with English abstracts. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors' files. RESULTS: The experimental data confirmed that H2S is widely involved in various renal pathologies by suppressing inflammation and oxidative stress, inhibiting the activation of fibrosis-related cells and their cytokine expression, ameliorating vascular remodeling and high blood pressure, stimulating tubular cell regeneration, as well as reducing apoptosis, autophagy, and hypertrophy. Therefore, H2S represents an alternative or additional therapeutic approach for renal fibrosis. CONCLUSIONS: We postulate that H2S may delay the occurrence and progress of renal fibrosis, thus protecting renal function. Further experiments are required to explore the precise role of H2S in renal fibrosis and its application in clinical treatment.