Oral oxymatrine for hepatitis B cirrhosis: A systematic review protocol.

BACKGROUND: Characterized by diffuse hepatic fibrosis and nodule formation, hepatitis B cirrhosis (HBC), an important result of chronic hepatitis B development, mainly contains compensated and decompensated stage. Compensated cirrhosis can further develop into decompensated stage and hepatocellular carcinoma with serious complications and high mortality. Antiviral therapy using interferon (IFN) or nucleos(t)ide analogs (NUCs) is essential for improving the prognosis of the disease but IFN has large side effects while NUCs often develop drug resistance. Antifibrosis is also an important strategy, but currently there is no effective antifibrosis drug. Pharmacologic studies have demonstrated that oxymatrine (OM) exhibits anti-hepatitis B virus (HBV) and antifibrosis effects. An increasing number of clinical controlled studies also have found that OM combined with conventional therapy could improve the curative effect and reduce adverse events incidence in treating HBC but there is no systematic review of it. Based on the extensive collection of literature, we will use meta-analysis to assess the efficacy and safety of OM for HBC. METHODS: PubMed, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang data, Chinese Scientific Journals Database (VIP), and China biomedical literature database will be searched to obtain the eligible studies published up to July 15, 2018. The primary outcome will be liver function indexes, liver fibrosis indexes, and Child-Pugh score. The secondary outcome will be hepatitis B virus DNA quantification, HBV DNA seroconversion rate, hepatitis B e antigen (HBeAg) seroconversion rate, and adverse events incidence. Data analysis will be conducted using RevMan 5.3 and Stata V.9.0 software. Trial sequential analysis (TSA) will be performed to assess the risk of random error and the validity of conclusion using TSA program version 0.9 beta. RESULTS: This systematic review will provide a high quality synthesis of OM for HBC from various evaluation aspects including liver function indexes, liver fibrosis indexes and Child-Pugh score, HBV DNA quantification, HBV DNA seroconversion rate, HBeAg seroconversion rate and adverse events incidence. CONCLUSION: The systematic review will provide evidence to assess the efficacy and safety of OM in the treatment of HBC. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018095275.

Further Insights into the Ciliary Gene and Protein KIZ and Its Murine Ortholog PLK1S1 Mutated in Rod-Cone Dystrophy.

We identified herein additional patients with rod-cone dystrophy (RCD) displaying mutations in KIZ, encoding the ciliary centrosomal protein kizuna and performed functional characterization of the respective protein in human fibroblasts and of its mouse ortholog PLK1S1 in the retina. Mutation screening was done by targeted next generation sequencing and subsequent Sanger sequencing validation. KIZ mRNA levels were assessed on blood and serum-deprived human fibroblasts from a control individual and a patient, compound heterozygous for the c.52G>T (p.Glu18*) and c.119_122del (p.Lys40Ilefs*14) mutations in KIZ. KIZ localization, documentation of cilium length and immunoblotting were performed in these two fibroblast cell lines. In addition, PLK1S1 immunolocalization was conducted in mouse retinal cryosections and isolated rod photoreceptors. Analyses of additional RCD patients enabled the identification of two homozygous mutations in KIZ, the known c.226C>T (p.Arg76*) mutation and a novel variant, the c.3G>A (p.Met1?) mutation. Albeit the expression levels of KIZ were three-times lower in the patient than controls in whole blood cells, further analyses in control- and mutant KIZ patient-derived fibroblasts unexpectedly revealed no significant difference between the two genotypes. Furthermore, the averaged monocilia length in the two fibroblast cell lines was similar, consistent with the preserved immunolocalization of KIZ at the basal body of the primary cilia. Analyses in mouse retina and isolated rod photoreceptors showed PLK1S1 localization at the base of the photoreceptor connecting cilium. In conclusion, two additional patients with mutations in KIZ were identified, further supporting that defects in KIZ/PLK1S1, detected at the basal body of the primary cilia in fibroblasts, and the photoreceptor connecting cilium in mouse, respectively, are involved in RCD. However, albeit the mutations were predicted to lead to nonsense mediated mRNA decay, we could not detect changes upon expression levels, protein localization or cilia length in KIZ-mutated fibroblast cells. Together, our findings unveil the limitations of fibroblasts as a cellular model for RCD and call for other models such as induced pluripotent stem cells to shed light on retinal pathogenic mechanisms of KIZ mutations.

[Evaluation of biocompatibility of modified gelatin composite membranes for corneal regeneration].

In order to investigate the feasibility of the modified chitosan-gelatin crosslinked membrane (MC-Gel) and chitosan-gelatin crosslinked membrane (CS-Gel) to be a potential biomaterial for corneal regeneration, we evaluated their physicochemical properties and intraocular biocompatibility in this study. White light transmission and permeability of these membranes were detected. Results showed that white light transmission of both membranes was above 90% at 500 nm, which was similar to that of human cornea. The glucose, tryptophan and NaCl permeability of MC-Gel membrane and CS-Gel membrane was better than or similar to those of human cornea. The methylthiazol tetrazolium (MTT) assay was used to assess cell viability and proliferation. Also, interlamellar corneal transplantation was carried out to evaluate ophthalmic biocompatibility of MC-Gel membrane and CS-Gel membrane. Results indicated that MC-Gel membranes could support the proliferation of HCEC and displayed good intraocular biocompatibility when implanted into rabbits. No severe inflammatory reaction occurred after transplantation and the implanted MC-Gel membrane degraded completely 16 weeks post-operation. Due to its good physicochemical properties and biocompatibility, MC-Gel membrane could be a promising candidate material for corneal regeneration.