Postoperative serum CHI3L1 level is associated with postoperative cognitive dysfunction in elderly patients after hip fracture surgery: A prospective observational study.

Objectives: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in older patients. Chitinase-3-like-1 protein (CHI3L1) is identified as a neuroinflammatory biomarker and impairs cognitive function. This study aimed to evaluate the association between serum levels of CHI3L1 and POCD and explore the levels of interleukin-6 (IL-6), IL-1ß and C-reactive protein (CRP) in the elderly after total hip arthroplasty (THA). Patients and methods: A total of 76 elderly patients undergoing THA were enrolled in the prospective observational study. Serum CHI3L1 levels were measured 1 day before and 1 day after surgery and other perioperative factors were also noted. The correlations between mediators of inflammation in the two groups were compared via Spearman correlation coefficients. The receiver operating characteristic (ROC) curves were implemented to analyze the predictive values of serum CHI3L1 and other inflammatory factors for POCD. And factors associated with POCD were analyzed by univariate and multivariate logistics. Results: POCD was observed in 31.6% of patients 1 week after surgery. Postoperative serum CHI3L1 levels were higher in POCD patients than in non-POCD patients [1348.26(778.46-1889.77) VS 2322.86(1686.88-2517.35) ng/ml, P < 0.001]. Postoperative serum CHI3L1 level was positively correlated with postoperative IL-6 level (r = 0.284, P = 0.013). Compared with IL-6, IL-1ß, and CRP, postoperative CHI3L1 level has the highest predictive value for POCD with the area under the curve (AUC) value of 0.779 according to the ROC curve. By the multivariate logistic regression analysis, elevated postoperative serum CHI3L1 level was found to be an independent risk factor for POCD 1 week after surgery (odds ratio = 1.204, 95% confidence interval = 1.087-1.332, P = 0.001). Conclusion: Postoperative elevated serum CHI3L1 level was significantly associated with the incident of POCD, and positively correlated with postoperative IL-6 level in the elderly after THA. This biomarker may have potential utility for further elucidating the etiology of POCD.

Investigating the association between maternal childbirth intention, labor epidural analgesia, and postpartum depression: A prospective cohort study.

BACKGROUND: Postpartum depression (PPD) is a general depressive episode after childbirth. Studies have shown that unmatched analgesic intention increases the risk of PPD, but the use of labor epidural analgesia (LEA) during childbirth can reduce this risk. We aimed to investigate the association between maternal childbirth intention, LEA, and PPD and risk factors that may be related to PPD. METHODS: A total of 590 mothers were included in this prospective cohort study. Demographic, prenatal, intrapartum and postpartum data were recorded. We investigated the association between childbirth intention, LEA and PPD and assessed the interactions between two factors. Logistic regression analysis was used to screen variables that might be associated with the occurrence of PPD. RESULTS: Overall, 130 of 451 women completing the study at 3 months had PPD (28.8 %). We did not find an association between unmatched childbirth intention, use of LEA and PPD (adjustOR = 0.684 CI 0.335-1.396, p = 0.296; adjustOR = 0.892, CI 0.508-1.565, p = 0.690). Chronic pain affecting daily life, prenatal EPDS, SAS, SSRS score, family accompaniment during labor, and 1-day numerical rating scale (NRS) score were significantly associated with PPD (p < 0.05). LIMITATIONS: In the 3-month follow-up, we only recorded the EPDS score, not the pain score, and did not evaluate the association between postpartum chronic pain and PPD. CONCLUSIONS: The association between maternal childbirth intention, LEA and PPD was not significant. Chronic pain affecting daily life, prenatal EPDS, SAS, SSRS score, family accompaniment during labor, and 1-day NRS score were significantly related to the occurrence of PPD (p < 0.05).

Exploring associations between postpartum depression and oxytocin levels in cerebrospinal fluid, plasma and saliva.

BACKGROUND: Postpartum depression (PPD) is a serious mental health concern affecting approximately 17.22 % of new mothers worldwide. In addition to its obstetric effects, oxytocin (OXT) has also been considered to play a role in PPD. However, most previous studies exploring associations between PPD and OXT levels focus on easier accessible compartments such as blood or saliva. STUDY AIM: To explore the possible association between PPD and OXT levels, and to assess the interaction between peripheral secretion and central release of OXT. METHODS: In this study, we prospectively measured OXT concentrations in cerebrospinal fluid (CSF), plasma and saliva of 94 women with elective cesarean section by enzyme-linked immunosorbent assay (ELISA) kits. The participants were divided into the PPD group if the score of Edinburgh Postpartum Depression Scale (EPDS) ≥ 10 at 3 months postpartum, otherwise into the non-PPD (nPPD) group. RESULTS: The incidence of PPD was 30.85 %. OXT concentrations in CSF (r = -0.518, p < 0.001), plasma (r = -0.240, p = 0.020) and saliva (r = -0.263, p = 0.010) were negatively correlated with EPDS score, and were valuable for the prediction of PPD, with AUC and 95%CI of 0.890 (0.809-0.945), 0.683 (0.579-0.775) and 0.699 (0.596-0.790), respectively. Moreover, OXT concentrations in plasma (r = 0.407, p < 0.001) and saliva (r = 0.624, p < 0.001) were positively correlated with CSF OXT concentrations. LIMITATIONS: Only full-term pregnant women undergoing elective cesarean section were included in this study, which may affect study generalizability. CONCLUSIONS: The central and peripheral release of OXT is coordinated, and OXT level measured prenatally in CSF, plasma, or saliva is valuable for the prediction of PPD.

Moderate Dose Irradiation Induces DNA Damage and Impairments of Barrier and Host Defense in Nasal Epithelial Cells in vitro.

Purpose: Radiotherapy (RT) is the mainstay treatment for head and neck cancers. However, chronic and recurrent upper respiratory tract infections and inflammation have been commonly reported in patients post-RT. The underlying mechanisms remain poorly understood. Method and Materials: We used a well-established model of human nasal epithelial cells (hNECs) that forms a pseudostratified layer in the air-liquid interface (ALI) and exposed it to single or repeated moderate dose γ-irradiation (1Gy). We assessed the DNA damage and evaluated the biological properties of hNECs at different time points post-RT. Further, we explored the host immunity alterations in irradiated hNECs with polyinosinic-polycytidylic acid sodium salt (poly [I:C]) and lipopolysaccharides (LPS). Results: IR induced DNA double strand breaks (DSBs) and triggered DNA damage response in hNECs. Repeated IR significantly reduced basal cell proliferation with low expression of p63/KRT5 and Ki67, induced cilia loss and inhibited mucus secretion. In addition, IR decreased ZO-1 expression and caused a significant decline in the transepithelial electrical resistance (TEER). Moreover, hyperreactive response against pathogen invasion and disrupted epithelial host defense can be observed in hNECs exposed to repeated IR. Conclusion: Our study suggests that IR induced prolonged structural and functional impairments of hNECs may contribute to patients post-RT with increased risk of developing chronic and recurrent upper respiratory tract infection and inflammation.

Quantitative MR evaluation of the infrapatellar fat pad for knee osteoarthritis: using proton density fat fraction and T2* relaxation based on DIXON.

OBJECTIVES: To investigate the efficacy of fat fraction (FF) and T2* relaxation based on DIXON in the assessment of infrapatellar fat pad (IFP) for knee osteoarthritis (KOA) progression in older adults. METHODS: Ninety volunteers (age range 51-70 years, 65 females) were enrolled in this study. Participants were grouped based on the Kellgren-Lawrence grading (KLG). The FF and T2* values were measured based on the 3D-modified DXION technique. Cartilage defects, bone marrow lesions, and synovitis were assessed based on a modified version of whole-organ magnetic resonance imaging score (WORMS). Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire. The differences of FF and T2* measurement and the correlation with WORMS and WOMAC assessments were analyzed. Diagnostic efficiency was analyzed by using receiver operating characteristic (ROC) curves. RESULTS: A total of 60 knees were finally included (n = 20 in each group). The values were 82.6 ± 3.7%, 74.7 ± 5.4%, and 60.5 ± 14.1% for FF is the no OA, mild OA, and advanced OA groups, and were 50.7 ± 6.6 ms, 44.1 ± 6.6 ms, and 39.1 ± 4.2 ms for T2*, respectively (all p values < 0.001). The WORMS assessment and WOMAC pain assessment showed negative correlation with FF and T2* values. The ROC showed the area under the curve (AUC), sensitivity, and specificity for diagnosing OA were 0.93, 77.5%, and 100% using FF, and were 0.86, 75.0%, and 90.0% using T2*, respectively. CONCLUSIONS: FF and T2* alternations in IFP are associated with knee structural abnormalities and clinical symptoms cross-sectionally and may have the potential to predict the severity of KOA. KEY POINTS: • Fat fraction (FF) and T2* relaxation based on DIXON imaging are novel methods to quantitatively assess the infrapatellar fat pad for knee osteoarthritis (KOA) progression in older adults. • The alterations of FF and T2* using mDIXON technique in IFP were associated with knee structural abnormalities and clinical symptoms. • FF and T2* alternations in IFP can serve as the new imaging biomarkers for fast, simple, and noninvasive assessment in KOA.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

p63+Krt5+ basal cells are increased in the squamous metaplastic epithelium of patients with radiation-induced chronic Rhinosinusitis.

BACKGROUND: Squamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls. METHODS: We assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36), CRSsNP (n = 33) and controls (n = 28). RESULTS: The prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium. CONCLUSION: SM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.

Long-term defects of nasal epithelium barrier functions in patients with nasopharyngeal carcinoma post chemo-radiotherapy.

BACKGROUND AND PURPOSE: Chronic and recurrent upper respiratory tract infection and inflammation is common in patients with nasopharyngeal carcinoma (NPC) post chemo-radiotherapy (CRT). Whether it is due to intrinsic (e.g., host-defense mechanisms of the epithelium), epigenetic or extrinsic factors is not fully understood. MATERIALS AND METHODS: Tissue biopsies of the middle turbinate (MT) and inferior turbinate (IT) from NPC patients after CRT (mean of 3 years, n = 39) were compared with the IT biopsies from healthy subjects (n = 44). The epithelial ultrastructure was examined by transmission electron microscope (TEM). mRNA and protein expressions of epithelial stem/progenitor cells markers, as well markers of cell proliferation and differentiation markers was analyzed. RESULTS: Abnormal epithelial architecture was observed in all tissue samples of NPC patients. Significantly decreased expression levels of mRNA and protein levels for p63 (basal cells), Ki67 (cell proliferation), p63+/KRT5+ (epithelial stem/progenitor cells), MUC5AC and MUC5B (secretary proteins from goblet cells), alpha-tubulin, beta-tubulin and TAp73 (ciliated cells), DNAH5 and DNAI1 and RSPH4A (microtubule assemblies of motile cilia), FOXJ1 and CP110 (ciliogenesis-associated markers) were evident in MT and IT biopsies from NPC patients when compared to healthy controls. CONCLUSION: CRT causes long-term defects of epithelial barrier functions and increases the susceptibility of these patients to upper respiratory tract infection and inflammation.

Host Antiviral Response Suppresses Ciliogenesis and Motile Ciliary Functions in the Nasal Epithelium.

BACKGROUND: Respiratory viral infections are one of the main drivers of development and exacerbation for chronic airway inflammatory diseases. Increased viral susceptibility and impaired mucociliary clearance are often associated with chronic airway inflammatory diseases and served as risk factors of exacerbations. However, the links between viral susceptibility, viral clearance, and impaired mucociliary functions are unclear. Therefore, the objective of this study is to provide the insights into the effects of improper clearance of respiratory viruses from the epithelium following infection, and their resulting persistent activation of antiviral response, on mucociliary functions. METHODS: In order to investigate the effects of persistent antiviral responses triggered by viral components from improper clearance on cilia formation and function, we established an in vitro air-liquid interface (ALI) culture of human nasal epithelial cells (hNECs) and used Poly(I:C) as a surrogate of viral components to simulate their effects toward re-epithelization and mucociliary functions of the nasal epithelium following damages from a viral infection. RESULTS: Through previous and current viral infection expression data, we found that respiratory viral infection of hNECs downregulated motile cilia gene expression. We then further tested the effects of antiviral response activation on the differentiation of hNECs using Poly(I:C) stimulation on differentiating human nasal epithelial stem/progenitor cells (hNESPCs). Using this model, we observed reduced ciliated cell differentiation compared to goblet cells, reduced protein and mRNA in ciliogenesis-associated markers, and increased mis-assembly and mis-localization of ciliary protein DNAH5 following treatment with 25 µg/ml Poly(I:C) in differentiating hNECs. Additionally, the cilia length and ciliary beat frequency (CBF) were also decreased, which suggest impairment of ciliary function as well. CONCLUSION: Our results suggest that the impairments of ciliogenesis and ciliary function in hNECs may be triggered by specific expression of host antiviral response genes during re-epithelization of the nasal epithelium following viral infection. This event may in turn drive the development and exacerbation of chronic airway inflammatory diseases.

Angiogenic and osteogenic regeneration in rats via calcium phosphate scaffold and endothelial cell co-culture with human bone marrow mesenchymal stem cells (MSCs), human umbilical cord MSCs, human induced pluripotent stem cell-derived MSCs and human embryonic stem cell-derived MSCs.

Angiogenesis is a limiting factor in regenerating large bone defects. The objective of this study was to investigate angiogenic and osteogenic effects of co-culture on calcium phosphate cement (CPC) scaffold using human umbilical vein endothelial cells (hUVECs) and mesenchymal stem cells (MSCs) from different origins for the first time. hUVECs were co-cultured with four types of cell: human umbilical cord MSCs (hUCMSCs), human bone marrow MSCs (hBMSCs) and MSCs from induced pluripotent stem cells (hiPSC-MSCs) and embryonic stem cells (hESC-MSCs). Constructs were implanted in 8 mm cranial defects of rats for 12 weeks. CPC without cells served as control 1. CPC with hBMSCs served as control 2. Microcapillary-like structures were successfully formed on CPC in vitro in all four co-cultured groups. Microcapillary lengths increased with time (p < 0.05). Osteogenic and angiogenic gene expressions were highly elevated and mineralization by co-cultured cells increased with time (p < 0.05). New bone amount and blood vessel density of co-cultured groups were much greater than controls (p < 0.05) in an animal study. hUVECs co-cultured with hUCMSCs, hiPSC-MSCs and hESC-MSCs achieved new bone and vessel density similar to hUVECs co-cultured with hBMSCs (p > 0.1). Therefore, hUCMSCs, hiPSC-MSCs and hESC-MSCs could serve as alternative cell sources to hBMSCs, which require an invasive procedure to harvest. In conclusion, this study showed for the first time that co-cultures of hUVECs with hUCMSCs, hiPSC-MSCs, hESC-MSCs and hBMSCs delivered via CPC scaffold achieved excellent osteogenic and angiogenic capabilities in vivo. The novel co-culture constructs are promising for bone reconstruction with improved angiogenesis for craniofacial/orthopaedic applications. Copyright © 2017 John Wiley & Sons, Ltd.

Identification of a critical basic residue on the ecotropic murine leukemia virus receptor.

Susceptibility to ecotropic murine leukemia viruses (MLV) is restricted to mice and rats at the level of virus binding to the host cell receptor. Asparagine 232, valine 233, tyrosine 235, and glutamic acid 237 in the third extracellular domain (EL3) of the receptor are critical determinants of the host range difference between mice and humans. However, placing these residues in the human homolog confers only partial binding, indicating that other divergent sequences are involved. We sought to determine if the other sequences lie within or outside EL3. Here we report the identification of lysine 234 as another critical residue that influences virus binding and infection, as well as evidence that the unidentified sequences lie outside EL3. Each of the four basic residues in the third extracellular domain were changed to an acidic residue and initially examined in combination with a change at position 235 or position 237. Substitution of lysine 211, 215, or 222 combined with substitution of the critical tyrosine 235 or glutamic acid 237 did not affect virus infection. However, combined substitution of lysine 234, a conserved residue between mice and humans, and tyrosine 235 resulted in a marked decrease in virus infection and binding. A lysine 234 change alone reduced virus binding, contrary to previous observations that at least two of the other four residues must be changed before binding is reduced. Interestingly, there was no decrease in infection when lysine 234 was replaced in combination with glutamic acid 237. This result suggests that residue 234 may act by influencing the local structure of residues 233 to 235, whereas the presence of a glycine at position 236 may prevent this influence from extending to residue 237. With this report, the involvement of all the residues divergent between mice and humans in the third extracellular domain has been ruled out, suggesting that as yet unidentified determinants lie in other extracellular domains.