[Effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats].

Objective: To investigate the effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats and its possible mechanism. Methods: Twenty-one adult male SD rats were enrolled and their right kidneys were excised. After two weeks, they were randomly assigned to 3 groups, with 7 rats in each group, namely sham-operated group (Group S), ischemia-reperfusion group (Group I/R), and normobaric hyperoxia+ischemia-reperfusion group (Group NBHO+I/R). In group S, only the left renal pedicle was isolated, but no ischemic treatment was performed. However, in group I/R and group NBHO+I/R, left renal pedicles were separated and left renal ischemia was induced by noninvasive arterial clamp for 45 min, and after 24 h of reperfusion, rats in group S and group I/R inhaled regular concentration of oxygen (21%), while rats in group NBHO+I/R inhaled high concentration of oxygen (60%), 2 h at each time, once a day for 7 days. On the 7th day after surgery, blood urea nitrogen (BUN) and creatinine (Cr) levels were measured by taking blood from the orbital veins of rats. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) was detected from the left kidney tissues. The mRNA and protein contents of Keap1 and Nrf2 gene in kidney tissues were determined by qPCR and Western Blotting, respectively. Hematoxylin-eosin staining (HE) was employed to observe the pathological changes of kidney tissue. Immunohistochemical staining was used to measure the protein expression of Keap1 and Nrf2 in kidney tissues. Results: Compared with group S, the serum BUN [(10.7±1.7) mmol/L, (8.4±1.0) mmol/L vs (6.1±1.3) mmol/L, both P<0.05] and Cr [(81.0±3.7) µmol/L, (62.9±3.4) µmol/L vs (48.3±2.9) µmol/L, both P<0.05] levels of rats in the group I/R and group NBHO+I/R increased, and the I/R group had the most significant increase. Compared with group S, the MDA content of kidney tissue in the rats of group I/R and NBHO+I/R increased [(10.5±1.0) µmol/L, (8.6±0.8) µmol/L vs (6.5±0.5) µmol/L, both P<0.05], but the MDA content in group NBHO+I/R was lower than that of group I/R (P<0.05). Compared with group S, the SOD content in the kidney tissues of rats in both group I/R and group NBHO+I/R decreased. However, the SOD content of group NBHO+I/R was higher than that of group I/R (P<0.05). Compared with group S, the mRNA and protein contents of Keap1 gene in kidney tissues of group I/R and group NBHO+I/R decreased, and group NBHO+I/R had the most significant decrease (P<0.05). However, compared with group S, mRNA and protein expressions of Nrf2 gene increased in kidney tissues of group I/R and group NBHO+I/R, and NBHO+I/R group had the most significant increase (P<0.05). Postoperative pathological results suggested that compared with group S, the pathological damage of kidney tissues in group I/R and group NBHO+I/R increased, but the degree of damage in group NBHO+I/R was lower than that in group I/R. Conclusion: Normobaric hyperoxia intervention may have protective effects on renal ischemia-reperfusion injury in rats by activating Keap1-Nrf2 signaling pathway.

[Clinical value of intact parathyroid hormone levels on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism].

Objective: To examine the value serum calcium and intact parathyroid hormone (iPTH) levels measured on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism. Methods: Totally 546 patients with thyroid cancer and benign thyroid lesions who underwent total thyroidectomy at Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University from February 2008 to December 2018 were analyzed retrospectively. There were 158 males and 388 females aging (50.9±13.2) years (range: 19.0 to 79.2 years). Serum calcium and iPTH levels were collected before surgery, on the first day and 6 months after surgery. Logistic regression was used to analyze the correlation between each data and the occurrence of permanent hypoparathyroidism after surgery.The area under the receiver operating characteristic curve was used to evaluate the predictive power of iPTH for postoperative occurrence of permanent hypoparathyroidism. Results: Among the 546 cases of total thyroidectomy, 22 cases of permanent hypoparathyroidism occurred, with an incidence of 4.0% (22/546). Multivariate analysis showed that iPTH levels on the first day after total thyroidectomy (OR=2.932, 95%CI: 1.129 to 7.616, P=0.027) and serum calcium levels (OR=2.584, 95%CI: 1.017 to 6.567, P=0.046) were independent prognosis factors for postoperative permanent hypoparathyroidism. When the threshold value of iPTH at 24 hours after total thyroidectomy was 5.51 ng/L, the AUC was 0.956 (95%CI: 0.936 to 0.972, P=0.000), sensitivity was 100%, specificity was 85.1%, positive predictive value was 22%, negative predictive value was 100%. When the threshold value of serum calcium at 24 hours after total thyroidectomy was 1.93 mmol/L, the AUC was 0.733 (95%CI: 0.694 to 0.770, P=0.000), sensitivity was 63.6%, specificity was 78.1%, positive predictive value of 10.8% and negative predictive value of 98.1%. Conclusions: Serum iPTH and calcium levels on the first day after total thyroidectomy were related to the occurrence of permanent hypoparathyroidism postoperatively. The predictive value of iPTH level is higher than that of serum calcium level.

[Factors associated with sleep quality during first and second trimester in Chinese pregnant woman].

Objective: To investigate sleep quality in pregnant women during their first and second trimester and to identify risk factors. Methods: Data was from the Chinese Pregnant Women Cohort Study. A total of 3 618 pregnant women were included, with the exclusion 346 women who had missing information. Sociodemographic, health-related behavior, depression and sleep quality information were collected and analyzed. Logistic regression analysis were used to explore the influencing factors of sleep quality in pregnant women. Results: Among the 3 618 pregnant woman 28.2% had poor sleep quality in their first trimester and 28.7% in the second trimester. 15.2% pregnant women had progressively worse sleep and 13.0% had persistently poor sleep had pregnant women were generally suffered from poor sleep quality, difficulty falling asleep, sleep disorders and daily fatigue. Regular diet (OR=0.75, 95%CI: 0.62-0.92) and work (OR=0.84,95%CI: 0.71-0.99) in the first trimester were protective factors of sleep quality in pregnant women. Age ≥30 year old (OR=1.19, 95%CI: 1.03-1.37), passive smoking (OR=1.18, 95%CI: 1.02-1.36) and depression (OR=2.25, 95%CI: 1.95-2.61) in the first trimester were risk factors. Conclusions: The rate of poor sleep quality are high among Chinese pregnant woman during their first and second trimester. The risk factors of sleep quality are multiple. Regular diet and work, reduction of tobacco exposure, alleviation of depression symptom may help improve sleep quality among pregnant women.

[Risk factors for preterm birth, low birth weight and small for gestational age: a prospective cohort study].

Objective: To study the relationship between exposure factors in early pregnancy and preterm birth (PB), low birth weight (LBW) and small for gestational age (SGA) of neonates. Methods: A total of 3 172 pregnant women who were enrolled in the project of Chinese Pregnant Women Cohort Study-Peking Union Medical College (CPWCS-PUMC) from July 25, 2017 to July 24, 2018 and delivered before December 31, 2018 were selected as subjects in this study. The relationship between exposure factors in early pregnancy and adverse outcomes of neonatal delivery was analyzed by using binary logistic regression analysis. Results: The incidence rates of PB, LBW and SGA were 4.76%, 3.53% and 5.74%, respectively. In terms of PB, the analysis results showed that the gestational weight gain (GWG) and living in northern China were protective factors, while premature rupture of membranes, gestational hypertension, dental examination or treatment within 1-3 years and family with 3-4 members were risk factors. In the respect of LBW, GWG and daily consumption of milk and dairy products were the protective factors, while premature rupture of membranes, gestational hypertension, sedentary working time more than 6 hours, dental examination or treatment within 1-3 years and passive smoking were risk factors. For SGA, baby girl, passive smoking, peanut oil consumption and unsalted taste were risk factors, while folic acid supplementation was protective factor. Conclusion: The risk factors for PB, LBW and SGA were multifactorial, and relevant specific measures should be taken to reduce the occurrence of adverse neonatal outcomes.

[The inflammatory pattern and the characteristics of mucous remodeling in different immune type of nasal polyps].

Objective:The aim of this study is to study the different immune-type of polyps and valuate mucosal inflammatory pattern and remodeling features between in IL-5 positive vs.IL-17 positive nasal polyps.Method:Nasal polyp or nasal turbinate tissue was obtained from 88 CRSwNP patients during endonasal sinus surgery or 18 non-atopic control subjects during septoplasty,respectively.Assessment of pro-inflammatory cytokines and mediators by ELISA.Additionally,the distribution of IL-5 positive or IL-17 positive cells and inflammatory cells(eosinophil,neutrophil,etc.) were examined using immunohistochemistry(IHC).Result:Overall more than half amount of polyp tissue did not express any TH cells key cytokine.However there are 21% polyp present IL-5 positive and 16% of IL-17 positive as well as 9% of IFN-γ positives.Amount of them that IL-17 positive polyps by synthesis of mediators promoting neutrophilic inflammation[myeloperoxidase(MPO),IL-1ß,IL-6 and IL-8)] and staining infiltration of MPO positive with IL-17 positive cells,whereas IL-5 positive nasal polyps were characterized by synthesis of mediators promoting eosinophilic inflammation(IL-5,ECP,TIgE,and SAE-IgE) and infiltrating of eosinophils and IL-5 positive cells.Meanwhile TGF-ß1 and MMP7 protein levels enhanced in IL-17 positive polyps and decreased in IL-5 positive than control.Conclusion:Nasal polyps presenting as different immune types and there were characterized with different inflammatory and remodeling patterns.Amount of them that IL-17 positive polyps presenting as a neutrophilic inflammation with remodeling biased.Whereas IL-5 positive nasal polyps were characterized by eosinophilic inflammation and absence of remodeling tendency.

Caspase-dependent deubiquitination of monoubiquitinated nucleosomal histone H2A induced by diverse apoptogenic stimuli.

Enzymatic deubiquitination of mono-ubiquitinated nucleosomal histone H2A (uH2A) and H2B (uH2B) is closely associated with mitotic chromatin condensation, although the function of this histone modification in cell division remains ambiguous. Here we show that rapid and extensive deubiquitination of nucleosomal uH2A occurs in Jurkat cells undergoing apoptosis initiated by anti-Fas activating antibody, staurosporine, etoposide, doxorubicin and the proteasome inhibitor, N-acetyl-leucyl-leucyl-norlucinal. These diverse apoptosis inducers also promoted the accumulation of slowly migrating, high molecular weight ubiquitinated proteins and depleted the cellular pool of unconjugated ubiquitin. In apoptotic cells, ubiquitin was cleaved from uH2A subsequent to the appearance of plasma membrane blebbing, and deubiquitination of uH2A closely coincided with the onset of nuclear pyknosis and chromatin condensation. Nucleosomal uH2A deubiquitination, poly (ADP-ribose)polymerase (PARP) cleavage and chromatin condensation were prevented in cells challenged with apoptosis inducers by pretreatment with the pan-caspase inhibitor, zVAD-fmk, or by over-expressing anti-apoptotic Bcl-xL protein. These results implicate a connection between caspase cascade activation and nucleosomal uH2A deubiquitination. Transient transfection of 293 cells with the gene encoding Ubp-M, a human deubiquitinating enzyme, promoted uH2A deubiquitination, while an inactive mutated Ubp-M enzyme did not. However, Ubp-M-promoted deubiquitination of uH2A was insufficient to initiate apoptosis in these cells. We conclude that uH2A deubiquitination is a down-stream consequence of procaspase activation and that unscheduled cleavage of ubiquitin from uH2A is a consistent feature of the execution phase of apoptosis rather than a determining or initiating apoptogenic event. Nucleosomal uH2A deubiquitination may function as a cellular sensor of stress in situations like apoptosis through which cells attempt to preserve genomic integrity.

A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division.

A new ubiquitin-processing protease (Ubp-M) has been identified in mammalian cells that is phosphorylated at the onset of mitosis and dephosphorylated during the metaphase/anaphase transition. The carboxyl-terminal domain of this 823-aa protein can be phosphorylated in vitro with either extracts of mitotic cells or purified cdc-2/cyclin B complexes. Recombinant Ubp-M is able to deubiquitinate histone H2A in vitro, and the phosphorylated form is also enzymatically active. Wild-type Ubp-M, transiently expressed as green fluorescent protein-fusion proteins, localizes in the cytoplasm of cultured cells, but mutant forms, lacking an active-site cysteine, associate closely with mitotic chromosomes during all stages of cell division and remain within the nucleus during the postmitotic period. Cells transfected with plasmids containing mutant Ubp-M genes stop dividing and eventually undergo apoptosis. Ubp-M may deubiquitinate one or more critical proteins that are involved in the condensation of mitotic chromosomes, possibly acting selectively on histones H2A and H2B, the major ubiquitinated proteins of chromatin.