α-ketoglutarate preconditioning extends the survival of engrafted adipose-derived mesenchymal stem cells to accelerate healing of burn wounds.

The application of adipose-derived stem cells (ADSCs) in treating hard-to-heal wounds has been widely accepted, while the short-term survival rate remains an obstacle in stem cell therapy. The aim of this study is to investigate the effect of preconditioning ADSCs with α-ketoglutarate (α-KG) on the healing of acid burn wounds and cell survival within wounds. Preconditioning of ADSCs was performed by treating cells at passage 3 with 3.5 mM DM-αKG for 24 h. Proliferation and migration of ADSCs was examined. An acid burn wound was created on the dorsal skin of mice. Cell suspension of ADSCs (2 × 106 cells/ml), either pre-treated with α-KG or not, was injected subcutaneously around the margin of wound. At 1,4,7,10,14 days after injection, the percentage of wound closure was evaluated. Expression of pro-angiogenic factors, matrix molecules and HIF1-α in pretreated ADSCs or in wounds was evaluated by qRT-PCR and immunohistochemistry staining, respectively. The survival rate of DiO-labelled ADSCs was determined with the in vivo bioluminescent imaging system. Treating with α-KG induced an enhancement in migration of ADSCs, while their proliferation was not affected. Expression of Vegf and Fgf-2 was significantly increased. With injection of pretreated ADSCs, healing of wounds was remarkably accelerated, along with increased ECM deposition and microvessel density. Moreover, pretreatment with α-KG resulted a prolonged survival of engrafted ADSCs was observed. Expression of HIF-1α was significantly increased in ADSCs treated with α-KG and in wounds injected with preconditioned ADSCs. Our results revealed that healing of acid burn wound was accelerated with administration of ADSCs pretreated with α-KG, which induced elevated expression of HIF-1α and prolonged survival of engrafted stem cells.

The role of exosomal circular RNA ZNF292 in intermittent hypoxia-induced AC16 cardiomyocytes injury.

BACKGROUND: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH). METHODS: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292. RESULTS: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis. CONCLUSIONS: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA.

Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis.

BACKGROUND: Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA. METHODS: The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches. RESULTS: The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome. CONCLUSIONS: This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy.

Fermentation supernatant of Staphylococcus aureus drives catabolism in chondrocytes via NF-κB signaling mediated increase of cholesterol metabolism.

Septic arthritis induced by Staphylococcus aureus (S. aureus) causes irreversible cartilage degradation and subsequent permanent joint dysfunction. Recently, cartilage degradation in osteoarthritis is recognized to be associated with metabolic disorders. However, whether cholesterol metabolism is linked to septic arthritis pathology remains largely unknown. Here, we found that exposure to fermentation supernatant (FS) of S. aureus in chondrocytes resulted in a significant increase in expression of key modulators involved in cholesterol metabolism, including lectin-type oxidized low density lipoprotein receptor 1 (LOX1), cholesterol 25-hydroxylase (CH25H), 25- hydroxycholesterol 7α-hydroxylase (CYP7B1) as well as retinoic acid-related orphan receptor alpha (RORα), a binding receptor for cholesterol metabolites. We further demonstrated that enhancement of CH25H/CYP7B1/RORα axis resulted from FS exposure was mediated by activation of NF-κB signaling, along with upregulation in catabolic factors including matrix metallopeptidases (MMP3 and MMP13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2) in chondrocytes. Exogenous cholesterol acts synergistically with FS in activating NF-κB pathway and increases cholesterol metabolism. While, the addition of tauroursodeoxycholic acid (TUDCA) which promotes cholesterol efflux, resulted in remarkable reduction of intracellular cholesterol level and restoration of balance between anabolism and catabolism in FS treated chondrocytes. Collectively, our data indicated that, in response to FS of S. aureus, NF-κB signaling activation coupled with increased cholesterol metabolism to stimulate catabolic factors in chondrocytes, highlighting cholesterol metabolism as a potential therapeutic target for treating septic arthritis.

LncRNA XR_595552 inhibition alleviates intermittent hypoxia-induced cardiomyocyte damage via activating the PI3K/AKT pathway.

BACKGROUND: Although the long noncoding RNAs (lncRNAs) expression profiles have been observed in previous study, the biological functions and underlying mechanisms of lncRNAs in OSA-related cardiac injury have not been elucidated. In the present study, we investigated a novel lncRNA, lncRNA XR_595552, and evaluated its role in intermittent hypoxia (IH)-induced damage in H9c2 cardiomyocytes. METHODS: H9c2 cells were exposed to IH condition. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression changes of lncRNA XR_595552 in H9c2 cells stimulated by IH. H9c2 cells were subjected to IH after transfection. CCK-8 was used to evaluate cell viability, and apoptosis was analyzed by Western blotting. Additionally, the regulatory relationship between lncRNA XR_595552 and PI3K/AKT was tested by RT-qPCR and Western blot. RESULTS: IH significantly induced injury in H9c2 cells (inhibited cell viability and promoted cell apoptosis). lncRNA XR_595552 was upregulated in a cell model of IH. Inhibition of lncRNA XR_595552 protected H9c2 cells against IH-induced damage, as the viability was increased, Bax, Caspase-9, and Caspase-3 were downregulated, and Bcl-2 was upregulated. More interestingly, lncRNA XR_595552 downregulation activated the PI3K/AKT pathway. Blocking the PI3K/AKT signal pathway by the use of LY294002 eliminated the myocardioprotective effects of lncRNA XR_595552 in H9c2 cells under IH condition. CONCLUSIONS: The results show that lncRNA XR_595552, a novel lncRNA, may play a protective role in attenuating IH-induced injury in cardiomyocytes via a regulating PI3K/AKT pathway. The findings suggest that this lncRNA could serve as a therapeutic target to treat OSA-related cardiovascular disorders.

Relationship between severity of obstructive sleep apnea and benign prostatic hyperplasia.

PURPOSE: The cause of benign prostatic hyperplasia (BPH) is controversial, local hypoxia and inflammation being the main two possibilities proposed. The aim of this study was to evaluate the relationship between obstructive sleep apnea (OSA) and BPH. METHODS: The study cohort comprised men from January 2016 to December 2020 in our Sleep Center. These patients were classified into four groups (no, mild, moderate, severe OSA) by apnea-hypopnea indexes (AHI). Logistic regression was used to identify independent risk factors for BPH, after which participants were stratified into younger (age ≤ 40 years) and older groups (age > 40 years) for further analysis. RESULTS: The study cohort comprised 467 patients including 135 younger subjects and 332 older subjects. The prevalence of BPH in the above listed AHI categories was 37.5%, 55.0%, 62.9%, and 52.3%, respectively (p = 0.075). Logistic regression analysis of all patients identified age as a risk factor for BPH (p < 0.001). Stratified analysis according to AHI category found a prevalence of BPH of 0.0%, 13.0%, 33.3%, and 43.9%, respectively, in younger group (p = 0.006), and 52.2%, 71.9%, 71.1%, and 56.3%, respectively, in older group (p = 0.038). Logistic regression analysis found age and AHI were independent risk factors for BPH in younger group (both p < 0.05), whereas only age was identified as a risk factor for BPH in older group (p < 0.001). CONCLUSIONS: Age is an independent risk factor for BPH in men with OSA. AHI is also an independent risk factor for BPH in younger men, suggesting that OSA may affect development of BPH in younger men.

The role of ferroptosis and endoplasmic reticulum stress in intermittent hypoxia-induced myocardial injury.

PURPOSE: Obstructive sleep apnea (OSA) is related to increased risk of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by iron overload and plays critical roles in myocardial injury. This study aimed to investigate the role of ferroptosis in intermittent hypoxia (IH)-induced myocardial injury involving endoplasmic reticulum stress (ERS). METHODS: AC16 human cardiomyocytes were exposed to IH or normoxia conditions. Mice were randomly grouped as follows: normal control (NC), IH, ferrostatin-1 + IH (FIH), and N-acetylcysteine + IH (AIH). The mRNA levels of GPX4, xCT, FTH1, and FACL4 in AC16 cells were detected by qRT-PCR. The protein levels of GPX4, xCT, NOX4, ATF4, CHOP, Bcl-2, and Bax in myocardial tissue were detected by Western blot analysis. RESULTS: The mRNA expression levels of GPX4 and xCT in AC16 cells were significantly lower in IH group than that of NC group. In IH mice, myocardial tissues were injured accompanied by increased level of ferroptosis and ERS. Inhibition of ferroptosis and treatment of N-acetylcysteine reduced ERS and myocardial injury in mice exposed to IH. In addition, compared to ferrostatin-1, N-acetylcysteine exerted a greater effect in relieving IH-induced myocardial damage and ERS. CONCLUSIONS: Ferroptosis was involved in IH-related myocardial injury accompanied by the activation of ERS. Inhibition of ferroptosis and acetylcysteine treatment alleviated IH-related myocardial injury, which may be a potential target for therapeutic approaches to OSA-induced myocardial injury.

Nrf2 plays protective role during intermittent hypoxia-induced ferroptosis in rat liver (BRL-3A) cells.

PURPOSE: Ferroptosis is reported to be involved in the chronic intermittent hypoxia (CIH)-related liver damage in vivo. Nuclear factor E2-related factor 2 (Nrf2) has an essential role in the regulation of ferroptosis. This study tested the hypothesis that intermittent hypoxia (IH) could lead to hepatocyte ferroptosis in vitro and the function of Nrf2 in IH-induced hepatocyte ferroptosis. METHODS: BRL-3A cells (rat liver cells) were exposed to normoxia or IH. The protocol of IH consisted of 32 cycles of 60-min hypoxic exposure with 30-min reoxygenation phase (nadir of 1% oxygen to peak of 20% oxygen). Ferroptosis was evaluated by cell viability, iron concentration, lipid reactive oxygen species (ROS), protein content of ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Both ferrostatin-1 (a ferroptosis inhibitor) and Nrf2 interfering RNA were applied to treat BRL-3A cells, respectively. RESULTS: IH exposure induced ferroptosis in BRL-3A cells with decreased cell viability and increased total iron content and lipid ROS levels. The protein contents of GPX4 and FTH1 in IH group were markedly lower than that in normoxic control. Ferroptosis inhibitor ferrostatin-1 alleviated IH-induced ferroptosis in BRL-3A cells. IH treatment enhanced expression of Nrf2, and Nrf2 knockdown augmented IH-induced ferroptosis in BRL-3A cells. CONCLUSIONS: The results revealed that Nrf2 played a protective role during IH-induced ferroptosis in BRL-3A cells. The finding provides a therapeutic target for obstructive sleep apnea-related liver injury.

Self-reported sleep quality and oligo/astheno/teratozoospermia among men attending an infertility clinic: a longitudinal study.

OBJECTIVE: We aimed to examine the influence of sleep disturbances on the risk of oligo/astheno/teratozoospermia (OAT) in men attending an infertility clinic. METHODS: We consecutively enrolled men attending an infertility clinic from July 2020 to June 2021. Semen parameters were obtained at initial presentation, and the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale score, and the STOP-BANG Questionnair were completed to assess sleep quality. Embryo outcomes were evaluated after infertility treatment. RESULTS: Of 466 men enrolled, 119 had OAT (OAT group) and 347 had normozoospermia (NS group). There were no differences between the two groups regarding Epworth Sleepiness Scale and STOP-BANG Questionnaire scores. The prevalence of poor sleep quality (Pittsburgh Sleep Quality Index score ≥ 5) in the OAT group was significantly higher than that in the NS group (42% vs. 29%, p = 0.009). A higher rate of poor subjective sleep quality was observed in the OAT group compared with the NS group (p = 0.005) and Pearson's correlations revealed a negative relationship between subjective sleep quality and semen quality. Logistic regression found that subjective sleep quality was independently associated with an increased risk of OAT (adjusted odds ratio = 0.610, p = 0.007). CONCLUSIONS: Men with OAT attending an infertility clinic exhibited poor subjective sleep quality. Improving sleep disturbances may be a target intervention to reduce the risk of OAT. This possibility warrants further investigation.

Relationship between Obstructive Sleep Apnea and Liver Abnormalities in Older Patients: A Cross-Sectional Study.

Background: Older age is a risk factor for obstructive sleep apnea (OSA), which is associated with the development of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the correlation between OSA and liver injury among older patients. Study Design. This is a cross-sectional study. Methods: Consecutive older (≥60 years) snoring patients were included. Subjects were divided into no OSA, mild OSA, moderate OSA, and severe OSA groups according to the apnea-hypopnea index (AHI) and were also separated into liver injury and nonliver injury groups based on liver function. Logistic regression analysis was applied to analyze the independent risk factors for liver injury. Results: We studied 227 patients (155 male, 72 female). The prevalence of liver injury exhibited an increasing trend among groups with mild-to-severe OSA. In addition, body mass index, AHI, and TG showed significant differences between the liver injury and nonliver injury groups. Logistic regression analysis revealed that AHI and TG were the major contributing factors for liver injury in older patients (adjusted odds ratio [OR] = 1.055, p=0.013, and OR = 1.485, p=0.039, respectively). Conclusions: Older patients with OSA have an increased risk of liver injury and NAFLD, and sleep apnea and high TG are important factors in contributing to the development of liver injury.

The association between obstructive sleep apnea and lung nodule, carcinoembryonic antigen.

PURPOSE: The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA. METHODS: The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI < 15/h were classified as control group. RESULTS: A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest O2 saturation (ß = - 0.256, p < 0.001), smoking status (ß = 0.156, p = 0.007) and age (ß = 0.153, p = 0.008) were independent predictors of elevated CEA. CONCLUSIONS: OSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.

Reverse traction with Kirschner wires and bilateral external fixation device combined with minimally invasive plate oseoynthesis technique for tibial plateau fractures of type Schatzker V and VI.

PURPOSE: Complex bicondylar tibial plateau fracture (TPF) has always been a tricky problem for surgeons. We created a novel external device used intraoperatively consisting of Kirschner wires, and combined with minimally invasive plate oseoynthesis (MIPO) technique to treat complex bicondylar TPFs, and the clinical effect and feasibility were further evaluated. METHODS: From March 2016 to February 2021, 49 cases (29 males and 20 females) were identified as bicondylar TPF, the mean age 47.2 (27-69). All patients adopted the device and MIPO technique. A series of score, complications, and radiographs in the follow-up period, from three months, six months, one year, and two years and the last follow-up, were recorded, from visual analogue score (VAS), hospital for special surgery (HSS), and Short-Form 36 (SF-36), containing physical (PCS) and mental (MCS), and Rasmussen score. RESULTS: Forty-seven patients showed good functional recovery. No patients were lost, mean follow-up time was 28.17 ± 2.81 (24.2-35.4) months. Operation time was 89.80 ± 13.46 (58-110) min. At the last follow-up, VAS was 1.3 ± 0.92 (0-4), HHS was 93.10 ± 2.63 (89-99), PCS was 49.20 ± 7.40 (38-65), and MCS was 50.08 ± 4.77 (43-62). Complications were as follows: cutaneous necrosis (3, 6%), asymptomatic arthritis (3, 6%), symptomatic arthritis (1, 2%), and deep venous thrombosis (1, 2%). Mean fracture healing time was 11.82 ± 1.5 (10-15.4) weeks. All patients got recovery without extra surgery and removed the implants at 12.85 ± 0.76 (11.2-15.4) months. CONCLUSION: Temporary traction device of bilateral external fixator combined with MIPO technique was simple and convenient, with a smaller soft-tissue damage, an easier operational approach, and its worth being promoted.

Berberine ameliorates aGVHD by gut microbiota remodelling, TLR4 signalling suppression and colonic barrier repairment for NLRP3 inflammasome inhibition.

Berberine (BBR), an isoquinoline alkaloid, is used to treat gastrointestinal disorders as an herbal medicine in China. The aim of this study was to investigate the anti-inflammatory activities of BBR in a mouse model with acute graft-versus-host disease (aGVHD). Mice were intravenously injected with bone marrow cells from donors combined with splenocytes to develop aGVHD. The body weight, survival rate and clinical scores were monitored. Then the levels of inflammatory cytokines, histological changes (lung, liver and colon), colonic mucosal barrier and gut microbiota were analysed. Moreover, the toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (Myd88)/nuclear factor-κB signalling pathway, NLRP3 inflammasome and its cytokines' expressions were determined. The results showed that the gavage of BBR lessened GVHD-induced weight loss, high mortality and clinical scores, inhibited inflammation and target organs damages and prevented GVHD-indued colonic barrier damage. Additionally, BBR modulated gut microbiota, suppressed the activation of the TLR4 signaling pathway and inhibited NLRP3 inflammasome and its cytokine release. This study indicated that BBR might be a potential therapy for aGVHD through NLRP3 inflammasome inhibition.

Long non-coding RNA MALAT1 affects intermittent hypoxia-induced endothelial injury by regulating miR-142-3p/HMGB1.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is strongly linked to endothelial cell functions. However, the function of MALAT1 in intermittent hypoxia (IH) associated vascular endothelial injury has not been explored yet. The current study makes great attempts to investigate the function of MALAT1 in IH-induced endothelial injury and its latent control network. METHODS: To mimic the effect of OSA, we cultured the human umbilical vein endothelial cells (HUVECs) under intermittent hypoxia. Western blot was applied to measure the expression level of associated proteins including capase-3, Bax, Bcl-2 while qRT-PCR was used in measurement of MALAT1 and miR-142-3p. Cell Counting Kit-8 (CCK-8) was carried out in assessing cell viability. Dual-luciferase reporter assay was applied to verify the relationships among high mobility group box (HMGB)1 and MALAT1, miR-142-3p. RESULTS: IH treatment significantly reduced cell viability but enhanced cell apoptosis in HUVECs. Concomitantly, MALAT1 was significantly upregulated in IH-treated HUVECs. Further experiment showed that MALAT1 knockdown augmented IH-induced injury of HUVECs. In addition, it was confirmed by dual-luciferase reporter assay that MALAT1 interacted with miR-142-3p directly. Besides, inhibition of miR-142-3p alleviated damage induced by MALAT1 knockdown in IH-treated HUVECs. Finally, miR-142-3p interacted with HMGB1 directly and inhibition of HMGB1 protein expression mediated by MALAT1 knockdown was reversed by miR-142-3p inhibitor. CONCLUSIONS: IH resulted in increased expression of MALAT1 in HUVECs. MALAT1 knockdown augmented IH-induced injury of HUVECs. MALAT1 exerted its effects on IH-treated HUVECs via miR-142-3p/HMGB1.

Obstructive sleep apnea and the risk of mortality in patients with lung cancer: a meta-analysis.

PURPOSE: Prior reports have examined the relationship between obstructive sleep apnea (OSA) and the mortality rate of lung cancer. However, the findings remain controversial. The present meta-analysis was performed to assess the relationship between OSA and increased risk of mortality in patients with lung cancer. METHODS: PubMed, Web of Science, and Embase were systematically searched for the correlative studies. Data were analyzed and pooled to evaluate odds ratios (ORs) of lung cancer mortality related to OSA. RESULTS: From 249 identified studies, 3 met inclusion criteria and were analyzed, including 67 patients with lung cancer and comorbid OSA and 45 patients with lung cancer and no OSA. The meta-analysis indicated that OSA was not significantly correlated with mortality rate in lung cancer (OR = 2.005, 95% CI = 0.703 to 5.715, z = 1.30, p = 0.193). There was no significant publication bias according to Begg's tests (p = 0.296) and Egger's tests (p = 0.097). CONCLUSION: This meta-analysis suggests that OSA is not significantly correlated with the mortality rate in lung cancer.

The role of platelet-related parameters for the prediction of NAFLD in OSAHS patients.

PURPOSE: As the detection of non-alcoholic fatty liver disease (NAFLD) is imperative for the prevention of its complications, we aimed to explore the predictive value of platelet to lymphocyte count ratio (PLR) and white blood cell count to mean platelet volume ratio (WBC/MPV) in relation to the occurrence of NAFLD among patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: This was a cross-sectional study consisting of 351 patients with OSAHS (279 with and 72 without NAFLD). The logistic regression analysis was performed to estimate associations between PLR, WBC/MPV, and NAFLD. Finally, the receiver operating characteristic curve (ROC curve) was used to analyze the efficacy of PLR and WBC/MPV in NAFLD prediction. RESULTS: Compared to the OSAHS-only group, there was a rising trend in AHI and TS90% in the OSAHS + NAFLD group. And the logistic regression analysis identified average oxygen saturation (MaSO2), WBC/MPV and PLR as predicted factors (odds ratio [OR] = 1.134, P = 0.031; OR = 7.559, P = 0.018, OR = 0.980, P < 0.001, respectively) for NAFLD in OSAHS patients. Moreover, compared with WBC/MPV, PLR, FLI, and APRI, a combination of WBC/MPV and PLR presented the largest AUC for the detection of NAFLD in BMI < 28 kg/m2 (0.753, 95% CI 0.684-0.822), and in age ≥ 60 years subgroup (0.786, 95% CI 0.692-0.880) in ROC analysis. Meanwhile, a combination of WBC/MPV and PLR presented the second largest AUC for the detection of NAFLD in all subjects (0.743, 95% CI 0.708-0.831), as well as in the age < 60 years subgroup (0.729, 95% CI 0.652-0.806), only ranked after FLI, suggesting the combination of WBC/MPV and PLR has a good predictive value for NAFLD in OSAHS patients. CONCLUSION: We confirmed that the levels of WBC/MPV, PLR, and MaSO2 were closely related to the occurrence of NAFLD among OSAHS patients. Furthermore, our results highlighted the clinical combination of WBC/MPV and PLR levels could act as a simple and effective biomarker for screening NAFLD in patients with OSAHS.

The role of ferroptosis in chronic intermittent hypoxia-induced lung injury.

PURPOSE: Chronic intermittent hypoxia (CIH) causes lung injury but the mechanism is unclear. Ferroptosis is a novel form of programmed cell death. In this research, we attempted to explore the role of ferroptosis in CIH-induced lung injury both in vitro and in vivo. METHODS: Sprague-Dawley rats were randomly separated into control group, CIH group and CIH + ferrostatin-1 group (CIH + Fer-1). Rats in the CIH group and CIH + Fer-1 group were exposed to intermittent hypoxia for 12 weeks. Human bronchial epithelial cell line (BEAS-2B) was cultivated for 24 h in either conventional culture medium or under CIH conditions. Fer-1 was applied to observe its treatment effects. Histological changes were evaluated by Hematoxylin-eosin (HE) staining and masson staining. The expression levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) were detected via qRT-PCR or Western blot. Cell counting kit-8 (CCK-8) was used to assess cell viability. The apoptotic rate and reactive oxygen species (ROS) was calculated by flow cytometry. RESULTS: Histology showed that CIH treatment induced lung injury and pulmonary fibrosis in lung tissue. After Fer-1 treatment, the pathological changes caused by CIH alleviated. The mRNA and protein levels of GPX4 decreased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA and protein levels of ACSL4 increased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA levels of IL-6 and TNFα in BEAS-2B increased after CIH treatment, (p < 0.05). Cell viability decreased, apoptosis rate and ROS increased in CIH-treated BEAS-2B, (p < 0.05). Cotreatment with Fer-1 reversed CIH-induced apoptosis, cell viability, ROS accumulation, mRNA and protein levels of GPX4, ACSL4, IL-6 and TNFα both in vitro and in vivo (p < 0.05). CONCLUSIONS: Ferroptosis occurred in CIH-induced lung injury, both in vitro and in vivo. The ferroptosis inhibitor Fer-1 alleviated cell injury and ferroptosis in CIH-treated BEAS-2B and lung tissues of rats.

Application of logistic differential equation models for early warning of infectious diseases in Jilin Province.

BACKGROUND: There is still a relatively serious disease burden of infectious diseases and the warning time for different infectious diseases before implementation of interventions is important. The logistic differential equation models can be used for predicting early warning of infectious diseases. The aim of this study is to compare the disease fitting effects of the logistic differential equation (LDE) model and the generalized logistic differential equation (GLDE) model for the first time using data on multiple infectious diseases in Jilin Province and to calculate the early warning signals for different types of infectious diseases using these two models in Jilin Province to solve the disease early warning schedule for Jilin Province throughout the year. METHODS: Collecting the incidence of 22 infectious diseases in Jilin Province, China. The LDE and GLDE models were used to calculate the recommended warning week (RWW), the epidemic acceleration week (EAW) and warning removed week (WRW) for acute infectious diseases with seasonality, respectively. RESULTS: Five diseases were selected for analysis based on screening principles: hemorrhagic fever with renal syndrome (HFRS), shigellosis, mumps, Hand, foot and mouth disease (HFMD), and scarlet fever. The GLDE model fitted the above diseases better (0.80 ≤ R2 ≤ 0.94, P <  0. 005) than the LDE model. The estimated warning durations (per year) of the LDE model for the above diseases were: weeks 12-23 and 40-50; weeks 20-36; weeks 15-24 and 43-52; weeks 26-34; and weeks 16-25 and 41-50. While the durations of early warning (per year) estimated by the GLDE model were: weeks 7-24 and 36-51; weeks 13-37; weeks 11-26 and 39-54; weeks 23-35; and weeks 12-26 and 40-50. CONCLUSIONS: Compared to the LDE model, the GLDE model provides a better fit to the actual disease incidence data. The RWW appeared to be earlier when estimated with the GLDE model than the LDE model. In addition, the WRW estimated with the GLDE model were more lagged and had a longer warning time.

Modified percutaneous iliosacral screw and anterior internal fixator technique for treating unstable pelvic fractures: a retrospective study.

BACKGROUND: The commonly used technique for treating unstable pelvic fractures with sacroiliac screws and anterior internal fixator (INFIX) is prone to complications, such as injury to the pelvic vasculature and nerves, life-threatening bleeding, lateral femoral cutaneous neuritis, and wound infection. This study investigated the clinical effects of using a modified percutaneous iliosacral screw and INFIX technique for treating unstable pelvic fractures. METHODS: A retrospective analysis of minimally invasive internal fixation using modified incision of an anterior-ring INFIX application combined with modified percutaneous iliosacral screw placement was performed for 22 cases of unstable pelvic fractures from January 2017 to December 2018. Based on the Tile classification, there were 4 type B1, 7 type B2, 5 type B3 and 6 type C1 injuries. Preoperatively, the length and orientation of the internal fixation were computer-simulated and measured. On postoperative day 3, pelvic radiographs and three-dimensional computed tomograms were used to assess fracture reduction and fixation. All patients were regularly followed up at 4 weeks, 12 weeks, 6 months, 12 months, 24 months and annually thereafter. Fracture healing, complications, visual analogue scale (VAS) scores, the quality of fracture repositioning and Majeed score were assessed during follow-up. RESULTS: All patients were followed up for a mean of 25.23 ± 1.48 months. All fractures healed without loss of reduction and no patient showed evidence of delayed union or nonunion. Two years postoperatively, the mean VAS score was 0.32 ± 0.09 and the mean Majeed score was 94.32 ± 1.86. CONCLUSION: The modified percutaneous iliosacral screw technique increases the anterior tilt of the sacroiliac screw by shifting the entry point posteriorly to increase the safety of the screw placement. Downward modification of the INFIX incision reduces the risk of lateral femoral cutaneous nerve injury. This technique is safe, effective and well tolerated by patients.

Assessment of bone mineral density and bone metabolism in young men with obstructive sleep apnea: a cross-sectional study.

BACKGROUND: Hypoxia in obstructive sleep apnea (OSA) patients during sleep may have an effect on bone metabolism. Few data regarding evaluation of bone metabolism in young individuals diagnosed with OSA. In this study, we aim to identify the association between bone mineral density and OSA in young men (≤ 40 years old of age). METHODS: Consecutive male subjects who underwent polysomnography were enrolled. Serum calcium, 25-hydroxyvitamin-D3, ß-isomerized form C-terminal telopeptide of type I collagen, osteocalcin and procollagen type 1 N-propeptide were measured in all participants, and bone mineral density (BMD) at lumbar spine (L1-L4), femoral neck and hip total were determined by dual energy X-ray absorption (DXA). RESULTS: The population consisted of 85 subjects (mean age 35.53 years). The BMD at lumbar spine (L1-L4) in moderate OSA patients was higher than control and severe OSA group significantly (p = 0.036). After adjustment for confounding factors, stepwise multiple linear regression analyses showed LaSO2 (ß = 0.340, p = 0.008) as an independent explanatory variable for Lumbar L1-L4 BMD, LaSO2 (ß = 0.304, p = 0.037), BMI (ß = 0.393, p = 0.008) for femur neck BMD and BMI (ß = 0.720, p = 0.002) for hip total BMD. CONCLUSIONS: Our finding indicated that there was a relationship between OSA and bone metabolism in younger men, and moderate OSA-related hypoxia positively related with BMD. This study also showed that different degrees of recurrent hypoxia had different effects on bone metabolism, a finding that required further investigation.