Objective To explore the mechanism of latent human immunodeficiency ciency virus type 1 (HIV-1) infection is unclear, especially in dendritic cells (DC).We hypothesized that DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) binds with HIV-1 may activate HIV-1 provirus.Methods We generated a model by transfecting 293T cells with a DC-SIGN expression plasmid and a HIV-1 5'long terminal repeat (LTR) reporter plasmid, and then stimulated the 293T cells with HIV-1 gp120 protein, wild-type HIV-1 and VSV-G-pNL4.3 pseudotype virus ( without gp120 protein).CEM-Bru cells were transfected with the DC-SIGN expression plasmid and stimulated by HIV-1 gp120 protein.Then HIV-1 replication was detected.The involvement of the ERK, p38 and NF-κB pathways signaling in this response were determined by inhibiting the pathways specifically and detecting the phosphorylation of the signaling kinase.Results The HIV-1 5'LTR was reactivated by HIV-1 gp120 in DC-SIGN-expressing 293T cells.After HIV-1 gp120 protein stimulation of the mold of CEM-Bru cells, the increasing expression of HIV-1 Tat mRNA and HIV-1 p24,which implies early and late HIV-1 provirus replication was reactivated by the HIV-1 gp120/DC-SIGN stimulation.HIV-1 gp120/DC-SIGN stimulation reactivates latent HIV-1 provirus via the NF-κB signal pathway.Conclusion HIV-1 gp120/DC-SIGN stimulation reactivates latent HIV-1 provirus via the NF-κB signal pathway.

Pancreatitis is one of the most common inflammatory diseases of the pancreas caused by autodigestion induced by excessive premature protease activation. However, recognition of novel pathophysiological mechanisms remains a still challenge. Both genetic and environmental factors contribute to the pathogenesis of pancreatitis, and the gut microbiota is a potential source of an environmental effect. In recent years, several new frontiers in gut microbiota and genetic risk assessment research have emerged and improved the understanding of the disease. These investigations showed that the disease progression of pancreatitis could be regulated by the gut microbiome, either through a translocation influence or in a host immune response manner. Meanwhile, the onset of the disease is also associated with the heritage of a pathogenic mutation, and the disease progression could be modified by genetic risk factors. In this review, we focused on the recent advances in the role of gut microbiota in the pathogenesis of pancreatitis, and the genetic susceptibility in pancreatitis.

Objective To investigate the exposure difference of different dosage forms of mycophenolic acid (MPA) between children aged ≤12 and > 12 years old after kidney transplantation. Methods Clinical data of 73 children undergoing kidney transplantation from donation after cardiac death (DCD) were retrospectively analyzed. Postoperative immunosuppressive regimen was MPA+ tacrolimus+glucocorticoid. According to different dosage forms of MPA, all recipients were divided into group A (n=37, mycophenolate mofetil capsules), group B (n=28, enteric-coated mycophenolate sodium) and group C (n=8, mycophenolate mofetil dispersible tablets). All children were divided into ≤12 and > 12 years old groups according to the age of kidney transplantation. The daily dosage of different dosage forms was calculated. The blood concentration (C) of MPA and the area under the curve (AUC) were detected by enzyme-multiplied immunoassay technique. The MPA blood concentration was statistically compared between two age groups at different time points. The recovery of renal function and postoperative complications were assessed. Results No significant differences were observed in the dosage and blood concentration of drug at different time points among groups A, B and C (all P > 0.05). The MPA-C_{4 h} and AUC in the ≤12 years old group were significantly higher than those in the > 12 years old group (both P < 0.05). In group B, the MPA-C_{4 h} of children aged ≤12 years old was significantly higher compared with that in those aged > 12 years old (P=0.016). The MPA-C_{4 h} of children aged ≤12 years old in group B was higher than those in group A and group C, but the differences were not statistically significant (P=0.080). There was no significant difference in the incidence of acute rejection and infection among three groups (both P > 0.05). Conclusions Children of different ages who are given with different dosage forms of MPA after kidney transplantation obtain different exposure rates. The exposure rate of kidney transplant recipients aged ≤12 years old tends to be higher than that of their counterparts aged > 12 years old, mainly seen in the recipients treated with enteric-coated mycophenolate sodium. Therefore, it is necessary to monitor the exposure level of MPA, which provides significant guidance for adjusting the drug dosage of different dosage forms.

Objective:To evaluate the effect of unilateral pediatric kidney donation for adult kidney transplantation.Methods:Retrospective analysis was conducted on the cases of children who donated unilateral donor kidney for adult kidney transplantation recipients in our hospital, and those who were followed up for more than three years were included in this study. The body weight of the recipients in group A was ≤50 kg, and the body weight of the recipients in group B was ≤70 kg.The recipients were divided into 0-5 year old donor group (group A) and 6-17 year old donor group (B group). Clinical data, recipient/kidney survival, graft function and growth, and complications of the recipient were analyzed.Results:A total of 45 adult recipients were enrolled, including 12 in group A and 33 in group B. The renal survival rate at 3 years after operation was (100%, 96.9%)/(91.6%, 93.9%). One week after the operation, the early postoperative recovery of renal function in group B was better than that in group A, and the difference of serum creatinine was statistically significant ( P<0.05), while the difference of serum creatinine in other postoperative follow-up time points was not statistically significant ( P>0.05). Within a year, both groups of grafts continued to grow, reaching adult levels in one year. There was no statistical significance in the incidence of complications between the two groups ( P>0.05). The incidence of protein in the two groups was 33.3% and 6.1%, respectively, 1 case in each group still had proteinuria at 1 year after surgery, and only 1 case in the infant donor kidney recipient in group A had proteinuria at 3 years after surgery. Conclusions:Unilateral donor kidney transplantation from children can provide good results for adult patients with uremia by selecting suitable donors according to the weight of the recipient.

Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.