Heme oxygenases (HO) are rate-limiting enzymes which degrade heme into carbon monoxide,biliverdin and free iron. HO-1 is the inducible form of HO. Induction and over-expression of HO-1 or inhibition of HO-1 degradation have been shown to interfere with replication of hepatitis B and C viruses,acute and chronic liver inflammation,and progression to fibrosis. HO-1 as well as its reaction products of heme degradation has been linked to cytoprotection by its anti-inflammatory,antioxidative and anti-apoptotic effects,displayed a broad range of protective effects against hepatic damage,and showed beneficial effects on ischemia-reperfusion injury,acute/chronic graft rejection and graft survival rate in liver transplantation. However,HO-1 has been found to be over-expressed in tumor cells. Inhibition of HO-1 expression can promote tumor cell apoptosis,decrease growth of HCC and reduce angiogenesis, suggesting that HO-1 is a potential target in the treatment of hepatic cancer. To validate the target property of HO-1,this review analyzed the effects and mechanism of action of HO-1 and its products in viral hepatitis,liver injury,hepatic fibrosis,liver transplantation and hepatocellular carcinoma. Given HO-1′s marked anti-viral,anti-inflammatory and hepatoprotective properties,the inhibitory effect of its down-modulation on hepatic cancer and the strategy to target HO-1 may promise new areas in both drug development and clinical therapy of liver diseases.

Objective:To analyze the characteristics of eyes with congenital optic disc pits (ODPs) through multimodal imaging.Methods:A cross-sectional study was conducted.Thirty-eight patients (38 eyes) diagnosed with congenital ODPs in the Second Hospital of Hebei Medical University from January 2009 to January 2020 were enrolled.A comprehensive summary analysis of the imaging results including fundus photography, spectral domain-optical coherence tomography (SD-OCT), infrared imaging, fundus autofluorescence (FAF), fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA) was performed.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The Second Hospital of Hebei Medical University (No.2021-P011). Written informed consent was obtained from each subject prior to any medical examination.Results:Among the 38 eyes, there were 32 eyes with ODPs located in or below the temporal side of optic disc, 4 eyes with ODPs located above the temporal side of optic disc, and 2 eyes with ODPs located at the center of optic disc, which were round or quasi-circular pale depression, and dark red eminences with clear or unclear boundaries between milk spots were found in 29 eyes with optical-disc macular degeneration (ODP-M) by fundus photography.SD-OCT examination showed that the structure of lamina cribrosa in the lesion area in all ODPs patients was incomplete, which presented a dark area with no tissue reflection, and the fissure led to the deep optic nerve.Fluid was found in the outer nuclear layer in all ODP-M patients, and there were 27 eyes with fluid in the inner nuclear layer, 13 eyes in the ganglion cell layer, and 4 eyes under the inner limiting membrane.Among the 29 eyes with ODP-M, there were 21 eyes with retinoschisis in outer layer, 27 eyes with neuroepithelial detachment.In the 27 eyes with neuroepithelial detachment, spot-like high reflection and reduced or disappeared ellipsoid band reflectance were seen above the neuroepithelium in 18 eyes.In infrared images, there were circular or quasi-circular low-reflection areas in the temporal side of the optic disc, and the lesion of ODP-M eyes presented low-reflection areas.FAF examination showed that in 27 eyes with ODP-M, there was a hypofluorescent region at the posterior pole consistent with the lesion range, among which, there was a granular or sheet-like hyperfluorescence at the center of the hypofluorescent region in 18 eyes.FFA showed that the optic disc depression in the arterial phase of patients was in a localized hypofluorescence state.During the venous phase, fluorescein dye extravasation along the temporal side of the optic disc could be found.A strong fluorescent arc with unclear boundaries at the temporal edge of the optic disc was formed in the late stage of angiography.Among the 29 eyes with ODP-M, the area of the macular lesion showed hyperfluorescence during the late stage of angiography in 27 eyes with neuroepithelial detachment, and no extension of dye toward the macula was found.ICGA showed that the optic disc depression of ODPs patients presented a localized hypofluorescence, and the lesion showed hyperfluorescence in 27 of the 29 ODP-M eyes with neuroepithelial detachment.Conclusions:Multimodal imaging can be helpful to realize the early diagnosis, etiology analysis of ODPs and make treatment plan.

ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.