Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective:To investigate the clinical efficacy of ventriculo-peritoneal shunt (VPS) in acquired immunodeficiency syndrome (AIDS) patients with cryptococcal neoformans meningitis (CNM).Methods:Patients with AIDS and CNM who were hospitalized in Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2015 to June 2020 were included and divided into VPS group and conventional treatment group.The data including symptoms and signs of meningitis, cerebrospinal fluid (CSF) pressure, CSF routine examination, ink staining, Cryptococcus culture and Cryptococcus culture negative time were obtained, and the clinical efficacy compared between the two groups after six and 48 weeks of treatment.Two independent samples t test or chi-square test was used for statistical analysis. Results:Among 66 AIDS patients with CNM, 26 cases in VPS group were (35.7±11.9) years, and 11 cases (42.3%) had CSF pressure> 330 mmH 2O (1 mmH 2O=0.009 8 kPa) at admission, 25 cases (96.2%) were positive for ink staining, and 20 cases (76.9%) had positive culture of Cryptococcus neoformans in CSF. There were 40 cases in the conventional treatment group with age of (38.9±12.9) years, 15 cases (37.5%) had CSF pressure>330 mmH 2O, 32 cases (80.0%) were positive for ink staining, and 31 cases (77.5%) were positive for culture of Cryptococcus neoformans in CSF. There were no significant differences of age, the proportion of patients with CSF pressure>330 mmH 2O, positive rate of ink staining, positive rate of Cryptococcus culture between the two groups ( t=-1.02, χ2=0.15, 3.49 and 0.00, respectively; all P>0.050). All patients were administrated with antifungal treatment, decreasing CSF pressure treatment, nutritional support and symptomatic treatment after admission. VPS was performed in patients with poor responses after medical conservative treatment in VPS group. At week six of treatment, the recovery rate of CSF pressure in VPS group was 57.7%(15/26), and the partial remission rate was 73.1%(19/26), which were both higher than those in conventional treatment group (31.0%(9/29) and 47.5%(19/40), respectively). The differences were both statistically significant ( χ2=3.96 and 4.22, respectively, both P<0.050). At week 48 of treatment, the recovery rate of CSF pressure in VPS group was 92.3%(24/26), the negative rate of Cryptococcus culture in CSF was 100.0%(20/20), and the complete remission rate was 46.2%(12/26), which were all higher than those in conventional treatment group (37.9%(11/29), 67.7%(21/31) and 20.0%(8/40), respectively). The differences were all statistically significant ( χ2=17.52, 8.03 and 5.10, respectively, all P<0.050). In VPS group, 22 cases were complete or partial remission, four cases were ineffective, and no death occurred, while there were 23 cases of complete or partial remission, 12 cases of ineffective and five cases of death in the conventional treatment group. The proportion of ineffective or death in the VPS group was 15.4%(4/26), which was lower than 42.5%(17/40) in the conventional treatment group. The difference was statistically significant ( χ2=5.34, P=0.021). Conclusions:VPS in AIDS patients with CNM could significantly improve the treatment outcomes, and reduce the rates of treatment failure and mortality.

Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease that begins with injury to hepatic sinusoidal endothelial cells, and has a fatality rate of over 80% in its severe form. Therefore, early diagnosis and treatment are crucial to delay HSOS progression and reduce mortality. However, clinicians' understanding of the disease is still insufficient, and the clinical manifestations of the disease are similar to liver diseases caused by other etiologies, resulting in a high rate of misdiagnosis. This article mainly introduces the HSOS recent developments in the etiology and pathogenesis, clinical manifestations and auxiliary examinations, diagnostic criteria, treatment, and prevention.

Breeding and quality control of SPF nude mice involves many links and works .The quality and quantity of animals are directly affected by breeding management and quality control .A standardized breeding system of SPF BALB/c nude mice were gradually established at the center after 2007.This paper introduces specific practices and experience in facilities, stock, breeding management , and quality control of SPF BALB/c nude mice, in order to provide the reference for related breeding and study in SPF BALB/c nude mice.

Objective To establish a spontaneous abortion rat model for a syndrome in traditional chinese medicine, kidney deficiency, and observe the changes of physiological indicators and related cytokine expression in the model. Methods 40 female and 20 male rats were used in this study. The female and male rats were mated (mating ratio 2:1). The day of vaginal smear with a large number of sperm was considered as the first day of pregnancy. The rats were randomly divided into control group and model group. The model group received 450 mg/kg hydroxyurea every day. Mifepristone was given on the eighth day in a dose of 3.75 mg/kg. The diet amount, the diameter index of kidney, ovary and embryos were analyzed. The mRNA expression of Th1/Th2 cytokine was detected by RT-PCR, and the expression of co-stimulating factors CD80, CD86, CD28, CTLA-4 were determined by flow cytometry.Results Comparing the model group with control group on the eighth day, there were significant differences between the model and control groups in quantity of food and water intake, and weight increase (P<0.05), and also in the embryonic diameter index, average of abortion rate, Th1/Th2 type cytokines, co-stimulating factor CD80, CD86, CD28, and CTLA-4 (P<0.05). Conclusion A rat model of spontaneous abortion due to kidney deficiency can be successfully established with hydroxyurea and mifepristone. The high expression of Th1 (TNF-α, IFN-γ) may cause abortion and be harmful to pregnancy. Th2 type (IL-4, IL-10) may facilitate pregnancy. The expression co-stimulating factor CD80, CD86, CD28, CTLA-4 may be relevant to the spontaneous abortion.