Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml

[Objective]We aimed to explore the diagnostic value of DNA fragmentation index(DFI)and acrosin activi-ty in male infertility.[Methods]Nine hundred and two semen samples were collected from patients and assessed for the DNA fragmentation index by sperm chromatin dispersion test,acrosin activity,as well as standard sperm parameters according to the WHO criteria. Statistical analysis was performed with SPSS.[Results]Statistically significant differences were observed in age,sperm concentration,total motility,progressive rate and acrosin activity among different group of sperm DNA dam-age(≤10%,11~20%,21~30%,≥31%).Sperm acrosin activity also showed difference in sperm concentration,total num-ber,total motility,progressive rate,normal morphology rate,teratozoospermia index(TZI)and sperm DFI.The DNA frag-mentation rate and sperm concentration,sperm motility,forward motility rate,total sperm count and acrosin activity was neg-atively correlated,while it is negative correlatd with TZI. Acrosin activity and sperm concentration,sperm motility,forward motility rate,sperm count and normal morphology rate was positively correlated,while it is negative correlated with the ab-normal rate of head,sperm deformity index,DNA fragmentation rate.[Conclusion]Sperm DNA damage and acrosin activity could partly reflect the quality of sperm. Moreover,sperm DFI maypredict the sperm motility part while the acrosin activity more likely related to sperm morphology.

OBJECTIVETo explore the correlation between JAK/STAT signaling pathways and pathogenesis of immune thrombocytopenia(ITP).

METHODSTwenty-six newly-diagnosed ITP patients was included in this study. They all meet the clinical and hematological criteria for the diagnosis of ITP, and patients with coronary heart disease, severe refractory hypertension, diabetes or with severe liver or kidney function incompetence were ruled out. 24 healthy control without autoimmune diseases, viral infectious diseases and with normal liver and kidney functions were also included. The expressions of Jak3, p-Jak3 mRNA, Stat3, and p-Stat3 were tested and the changes in levels of IL-21 mRNA, IL-21 cell secretion after DEX intervention and AG490 blockade were measured.

RESULTSCompared with the healthy control, patients with ITP had significantly high expressions of Jak3, p-Jak3 mRNA, Stat3 and p-Stat3 protein, which significantly reduced after AG490 blocking (P<0.01). The expression of IL-21 mRNA and the secretion of IL-21 obviously decreased after DEX intervention, but increased after AG490 blocking(P<0.01).

CONCLUSIONThe pathogenesis of ITP associates with the activation of JAK/STAT signaling pathways, and IL-21-mediated JAK/STAT signaling pathways play regulatory role in ITP.

Humans ; Interleukins ; Purpura, Thrombocytopenic, Idiopathic ; STAT3 Transcription Factor ; Signal Transduction

Objective To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). Methods The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). Results The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P < 0.05); however, the levels of plasma adrenaline in two groups had no statistical differences (P > 0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05). Conclusions As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.

OBJECTIVETo investigate the correlation between the HLA genes and pathogenesis of aplastic anemia (AA), so as to find the susceptible AA genes.

METHODSPolymerase chain reaction with specific sequence primers (PCR-SSP) method was used to detect the HLA typing of 50 AA patients and 183 normal healthy individuals as controls in Chinese Han population of northwestern plateau.

RESULTSThe frequency of HLA-A* 0201 (45.0%), B* 1501 (11.0%), B* 5501 (9.0%) and DRB1* 0901 (19.0%) gene frequences in AA patients were significantly higher than those in controls (Odds Ratio: OR=1.657, 2.138, 2.314 and 1.932, x2=4.882, 3.876, 3.863 and 4.473 (P<0.05). In contrast, A* 0301 gene frequency (4.0%) in AA was significantly lower than that in controls, OR=0.349, x2=4.154 (P<0.05). The male HLA-A* 0201 gene frequency was lower than that in female (38.2% vs 59.4%), and the difference was statistically significant (P<0.05). Concludsion: The HLA-A* 0201, B* 1501, B* 5501 and DRB1* 0901 genes may be considered as the risk markers while A* 0301 gene as a protective marker of AA, the HLA-A* 0201 also shows the sex differences.

Alleles ; Anemia, Aplastic ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; HLA-DRB1 Chains ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic

OBJECTIVETo investigate the correlation of immunologic thrombocytopenia(ITP) pathogenesis with the abnormal expression of IL-21, and to explore the association of high-dose dexamethasone (HD-DEX) treatment with the IL-21 expression.

METHODS26 newly diagnosed ITP patients and 24 healthy controls were enrolled in this study. The mononuclear cells and serum were obtain from density gradient centrifugation in the newly diagnosed ITP patients before HD-DXM treatment, and the samples of healthy controls were also used for assays. The protein and mRNA expression of IL-21 on peripheral blood mononuclear cells(MNC) were determined by flow cytometry and real-time reverse-transcription polymerase chain reaction. Plasma levels of IL-21, IFN-γ and IL-4 were determined by enzyme-linked immunoabsorbent assay (ELISA).

RESULTSIL-21 expression on mononuclear cells was significantly higher in ITP patients (13.07%) than that in normal controls (8.2%), the ratio of IL-21/GAPDH mRNA expression on MNC was significantly higher in ITP patients (9.524±0.97) than that in normal controls (3.701±0.60, P<0.01). After HD-DXM therapy, the ratio of IL-21/GAPDH mRNA decreased significantly (5.87±1.21) as compared with the level before treatment. Significantly high levels of serum IL-21, IFN-γ and lower IL-4 were found in ITP patients, as compared with healthy controls. Serum IL-21 and IFN-γ levels in ITP patients decreased significantly after HD-DXM administration (P<0.01), while post-treatment levels of IL-4 were increased significantly, compared with the levels before treatment (P<0.01).

CONCLUSIONTherapeutic effect of DXM on ITP associates with down-regalation of IL-21 expression. The increased expression of IL-21 involves in the pathogenesis of ITP.

Dexamethasone ; Flow Cytometry ; Humans ; Interleukin-4 ; Interleukins ; Leukocytes, Mononuclear ; Purpura, Thrombocytopenic, Idiopathic ; RNA, Messenger

This study was purposed to investigate the effects of interferon (IFN)-γ on expression of adhesion molecules in mesenchymal stromal cells derived from human umbilical cord tissue (UC-MSC). The UC-MSC were isolated from human umbilical cord by tissue culture. The expressions of specific markers on UC-MSC were detected by flow cytometry in the physiological condition. The adipogenic and osteogenic induction of UC-MSC was detected by alizarin and Oil red O staining. UC-MSC were exposed to IFN-γ (100, 1 000, 10 000 U/ml) for 24 h, the expressions of CD54, CD58, CD44, CD49d, CD62p, CD62L, CD102 and CD106 on cell surface were detected using flow cytometry. The results showed that in physiological condition, UC-MSC extremely low expressed CD102, CD106, CD62P, CD62L, while the expression of CD54 was relatively high (41.58 ± 0.83)%. When stimulated by IFN-γ, the expression of CD102, CD106, CD62P, CD62L increased slightly, but still low (< 5%), while CD54 and CD58 upregulated concentration-dependently up to (59.66 ± 1.36)% and (43.96 ± 0.62)% respectively. The expression of CD49d upregulated to (51.33 ± 0.74)% when UC-MSC exposed to IFN-γ 100 U/ml. CD44 increased to (73.22 ± 1.93)% when UC-MSC exposed to IFN-γ 1 000 U/ml. It is concluded that IFN-γ can elevate significantly the expression of CD54, CD49d, CD44 and CD58, but has no significant effect on CD102, CD106, CD62P and CD62L expression on the surface of UC-MSC.
Cell Adhesion Molecules ; metabolism ; Cells, Cultured ; Humans ; Interferon-gamma ; pharmacology ; Mesenchymal Stromal Cells ; cytology ; drug effects ; metabolism ; Umbilical Cord ; cytology