Histological Features of Uterine Myometrial Dysfunction:Possible Involvement of Localized Inflammation

Objective The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage.Lipopolysaccharide(LPS)has been widely used to induce inflammation in animal models.Therefore,this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium,as well as the potential underlying molecular mechanisms involved.Methods In vivo,an animal model was established by intraperitoneal injection of 300μg/kg LPS in rats on gestational day 21.Hematoxylin-eosin(H&E)staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle.Enzyme-linked immunosorbent assay(ELISA)was used to detect inflammatory cytokines.Immunohistochemistry,tissue fluorescence,and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4(TLR4)and the nuclear factor kappa-B(NF-κB)signaling pathway.In vitro,human uterine smooth muscle cells(HUtSMCs)were exposed to 2μg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation.Results In this study,LPS induced uterine myometrial dysfunction in rats,leading to a disorganized arrangement,a significant increase in collagen fiber deposition,and widespread infiltration of inflammatory cells.In both in vivo animal models and in vitro HUtSMCs,LPS elevated IL-6,IL-1β,and TNF-αlevels while concurrently suppressing the expression of connexin 43(Cx43)and oxytocin receptor(OXTR).Mechanistically,the LPS-treated group exhibited TLR4 activation,and the phosphorylation levels of p65 and IκBαwere notably increased.Conclusion LPS triggered the TLR4/NF-κB signaling pathway,inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.

Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45

AIM:To clarify the role of activated Notch2 in the invasiveness of gastric cancer.METHODS:To investigate the invasiveness of silencing Notch2 gene expression,we established a Notch2small interfering RNA(siRNA) transfected cell line using the MKN-45 gastric cancer cell line.After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction(RT-PCR) and Western blotting,migration and invasion assays were employed to evaluate the aggressiveness of the gastric cancer.RT-PCR and Western blottings were employed to confirm the down-regulation of Notch2 and to evaluate the expression of epithelial mesenchymal transition-related gene matrix metallopeptidase 9(MMP9),Akt,p-Akt.To confirm the relationship between PI3KAkt and MMP9,the PI3K inhibitor LY294002 was used to treat MKN-45 cells.RESULTS:Notch2 expression was dramatically decreased after Notch2 siRNA transfection(100.00% ± 9.74% vs 11.61% ± 3.85%,P < 0.01 by qRT-PCR).There was also a marked reduction of Notch target gene Hes1(100.00% ± 4.74% vs 61.61% ± 3.58%,P < 0.05) at the mRNA,indicating an inhibition of Notch signaling.Inhibition of Notch signaling was also confirmed by the marked reduction of Notch2 intracellular domain at the protein levels(100.00% ± 9.74% vs 65.61% ± 7.58%,P < 0.05).Down-regulation of Notch2 by siRNA enhanced tumor cell invasion(100.00% ± 21.64% vs 162.22% ± 16.84%,P < 0.05) and expression of MMP9(1.56 fold,P < 0.05),and activated the pro-MMP9 protein to its active form(1.48 fold,P < 0.05).There was no significant difference in the protein levels of Akt between the two groups(100.00% ± 10.87% vs 96.61% ± 7.33%,P > 0.05),while down-regulation of Notch2 elevated p-Akt expression(100.00% ± 9.87% vs 154.61% ± 13.10%,P < 0.05).Furthermore,p-Akt and MMP9 was down-regulated in response to the inhibitor LY294002(p-Akt 100.00% ± 8.87% vs 58.27% ± 5.01%,P < 0.05;MMP9 100.00% ± 9.17% vs 50.03% ± 4.88%,P < 0.05).CONCLUSION:Notch2 may negatively regulate cell invasion by inhibiting the PI3K-Akt signaling

Extensive full-thickness eyelid reconstruction with rotation flaps through "subcutaneous tunnel" and palatal mucosal grafts

· AIM: To reconstruct the extensive full-thickness defects of eyelids is a challenge for the plastic surgeon because of their complex anatomy and special functions.This article presents and discusses an improved surgical technique in which the orbicularis oculi myocutaneous flap is rotated through a "subcutaneous tunnel" in conjunction with a palatal mucosal graft employed for lining.·METHODS: Data from 22 eyes with extensive full-thickness eyelid defects from various causes between2009 and 2013 were analyzed in this study. After the different layers of eyelid were separated completely, a temporally based orbicularis oculi myocutaneous flap was designed following fishtail lines and was mobilized,leaving the base of the pedicle intact with a submuscular tissue attachment. The flap was then rotated through a "subcutaneous tunnel" to the defect, and the donor site was closed primarily. Posterior lamellar reconstruction was performed with a mucosal graft harvested from the hard palate.·RESULTS: All the flaps were survived without any healing problems. There was no corneal irritation, flap contraction, or significant donor-site morbidity in the follow-up period. The incision scars were almost invisible.The defects were repaired completely, and the evaluations showed satisfactory function and appearance.·CONCLUSION: This technique is an improved singlestage operation and can be applied to repair large, full-thickness eyelid defects from various causes. With our method, the functional and aesthetic results can be obtained in either the upper or lower eyelids.

Timing analysis of the black hole candidate EXO 1846–031 with Insight-HXMT monitoring

We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be classified roughly into four different states.Type-C quasi-periodic oscillations(QPOs)observed by NICER(about 0.1-6 Hz)and Insight-HXMT(about 0.7-8 Hz)are also reported in this work.Meanwhile,we study various physical quantities related to QPO frequency.The QPO rms-frequency relationship in the energy band 1-10 keV indicates that there is a turning pointing in frequency around2 Hz,which is similar to that of GRS 1915+105.A possible hypothesis for the relationship above may be related to the inclination of the source,which may require a high inclination to explain it.The relationships between QPO frequency and QPO rms,hardness,total fractional rms and count rate have also been found in other transient sources,which can indicate that the origin of type-C QPOs is non-thermal.