USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination.

Background: Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism by which USP7 regulates osteoporosis remains unknown. Herein, we aimed to investigate whether USP7 regulates abnormal osteoclast differentiation in osteoporosis. Methods: The gene expression profiles of blood monocytes were preprocessed to analyze the differential expression of USP genes. CD14+ peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from osteoporosis patients (OPs) and healthy donors (HDs), and the expression pattern of USP7 during the differentiation of CD14+ PBMCs into osteoclasts was detected by western blotting. The role of USP7 in the osteoclast differentiation of PBMCs treated with USP7 siRNA or exogenous rUSP7 was further investigated by the F-actin assay, TRAP staining and western blotting. Moreover, the interaction between high-mobility group protein 1 (HMGB1) and USP7 was investigated by coimmunoprecipitation, and the regulation of the USP7-HMGB1 axis in osteoclast differentiation was further verified. Osteoporosis in ovariectomized (OVX) mice was then studied using the USP7-specific inhibitor P5091 to identify the role of USP7 in osteoporosis. Results: The bioinformatic analyses and CD14+ PBMCs from osteoporosis patients confirmed that the upregulation of USP7 was associated with osteoporosis. USP7 positively regulates the osteoclast differentiation of CD14+ PBMCs in vitro. Mechanistically, USP7 promoted osteoclast formation by binding to and deubiquitination of HMGB1. In vivo, P5091 effectively attenuates bone loss in OVX mice. Conclusion: We demonstrate that USP7 promotes the differentiation of CD14+ PBMCs into osteoclasts via HMGB1 deubiquitination and that inhibition of USP7 effectively attenuates bone loss in osteoporosis in vivo.The translational potential of this article:The study reveals novel insights into the role of USP7 in the progression of osteoporosis and provides a new therapeutic target for the treatment of osteoporosis.

[Safety of two ventilator weaning strategies after high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome: a prospective randomized controlled trial].

OBJECTIVE: To study the safety of two ventilator weaning strategies after high-frequency oscillatory ventilation (HFOV) for the treatment of neonatal respiratory distress syndrome (NRDS) in preterm infants. METHODS: A prospective randomized controlled trial was conducted for 101 preterm infants with NRDS, with a gestational age of ≤32+6 weeks or a birth weight of ≤1 500 g, who were admitted to the neonatal intensive care unit of Xiamen Maternal and Child Health Hospital from January 1, 2019 to June 30, 2020. The infants underwent HFOV as the preferred treatment. The infants were randomly divided into an observation group (50 infants with direct weaning from HFOV) and a control group (51 infants with weaning after HFOV was switched to conventional mechanical ventilation). The two groups were compared in terms of failure rate of ventilator weaning within 72 hours, changes in blood gas parameters at 2 hours before weaning and at 2 and 24 hours after weaning, respiratory support therapy, incidence rates of complications, and outcome at discharge. RESULTS: There was no significant difference in the failure rate of ventilator weaning within 72 hours (8% vs 14%, P > 0.05). The observation group had a significantly shorter duration of mechanical ventilation than the control group [(64±39) hours vs (88±69) hours, P < 0.05]. There were no significant differences between the two groups in the duration of mechanical ventilation, total oxygen supply time, blood gas parameters before and after ventilator weaning, incidence rates of complications, and outcome at discharge (P > 0.05). CONCLUSIONS: For preterm infants with NRDS, the strategy of weaning directly from HFOV is safe and reliable and can reduce the duration of invasive mechanical ventilation, and therefore, it holds promise for clinical application.

[Coagulation function and hemorrhagic diseases in preterm infants with different gestational ages].

OBJECTIVE: To study the correlation between coagulation function and gestational age in preterm infants and the possible value of coagulation function measurement in predicting hemorrhagic diseases. METHODS: The clinical data of preterm infants who were hospitalized between September 2016 and August 2017 were collected. The coagulation indicators were measured within 2 hours after birth. According to the gestational age, the preterm infants were divided into late preterm infant group (n=322), early preterm infant group (n=241) and extremely/very early preterm infant group (n=128). Coagulation function was compared among the three groups, as well as between the preterm infants with and without hemorrhagic diseases within 3 days after birth. RESULTS: There were significant differences in thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) and D-dimer (DD) among the three groups (P<0.05). APTT, PT, FDP and DD were negatively correlated with gestational age, while TT was positively correlated with gestational age (P<0.05). The preterm infants with hemorrhagic diseases had a longer APTT and a higher level of DD (P<0.05). CONCLUSIONS: Coagulation function gradually becomes mature in preterm infants with the increase in gestational age. Abnormal APTT and DD indicate that preterm infants may have a higher risk of hemorrhagic diseases.

Characterization and tissue distribution of leptin, leptin receptor and leptin receptor overlapping transcript genes in yellow catfish Pelteobagrus fulvidraco.

In the present study, full-length cDNA sequences of leptin (LEP), leptin receptor (LEPR) and leptin receptor overlapping transcript (LEPROT) were cloned from yellow catfish Pelteobagrus fulvidraco, and their tissue distribution profiles were determined. The validated cDNA of yellow catfish leptin (ycLEP), leptin receptor (ycLEPR) and LEPROT were 1119, 4195 and 827bp in length, encoding the peptide of 172, 1086 and 130 amino acid residues, respectively. The phylogenetic analysis revealed that fish LEP, LEPR and LEPROT were separated from tetrapod, and also ycLEPS were separated from other fish species. The ycLEP mRNA expression levels were highest in liver, followed by ovary, mesenteric fat and spleen, and lowest in intestine, heart, muscle, pituitary and testis. The ycLEPR mRNA levels were highest in pituitary, intermediate in mesenteric fat, liver, ovary, muscle and spleen, and lowest in heart, intestine and testis. The ycLEPROT mRNA levels were highest in pituitary, followed by spleen, mesenteric fat, heart, ovary, liver, muscle, testis and intestine. Identification and tissue distribution of yellow catfish LEP, LEPR and LEPROT genes provided initial step towards understanding their biological roles in yellow catfish.