[Is monitoring of anti-factor Xa levels required for low molecular weight heparin prophylaxis of venous thromboembolism in critically ill patients?]

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Xa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin III is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Xa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

Diagnostic value of Kaiser score combined with breast vascular assessment from breast MRI for the characterization of breast lesions.

Objectives: The Kaiser scoring system for breast magnetic resonance imaging is a clinical decision-making tool for diagnosing breast lesions. However, the Kaiser score (KS) did not include the evaluation of breast vascularity. Therefore, this study aimed to use KS combined with breast vascular assessment, defined as KS*, and investigate the effectiveness of KS* in differentiating benign from malignant breast lesions. Methods: This retrospective study included 223 patients with suspicious breast lesions and pathologically verified results. The histopathological diagnostic criteria were according to the fifth edition of the WHO classification of breast tumors. The KS* was obtained after a joint evaluation combining the original KS and breast vasculature assessment. The receiver operating characteristic (ROC) curve was used for comparing differences in the diagnostic performance between KS* and KS, and the area under the receiver operating characteristic (AUC) was compared. Results: There were 119 (53.4%) benign and 104 (46.6%) malignant lesions in total. The overall sensitivity, specificity, and accuracy of increased ipsilateral breast vascularity were 69.2%, 76.5%, and 73.1%, respectively. The overall sensitivity, specificity, and accuracy of AVS were 82.7%, 76.5%, and 79.4%, respectively. For all lesions included the AUC of KS* was greater than that of KS (0.877 vs. 0.858, P = 0.016). The largest difference in AUC was observed in the non-mass subgroup (0.793 vs. 0.725, P = 0.029). Conclusion: Ipsilaterally increased breast vascularity and a positive AVS sign were significantly associated with malignancy. KS combined with breast vascular assessment can effectively improve the diagnostic ability of KS for breast lesions, especially for non-mass lesions.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Preoperative dipstick albuminuria is associated with acute kidney injury in high-risk patients following non-cardiac surgery: a single-center prospective cohort study.

PURPOSE: This study aimed to investigate the association between preoperative dipstick albuminuria (DA) and acute kidney injury (AKI) in high-risk patients following non-cardiac surgery. METHODS: This was a single-center prospective cohort study. Adult patients with high risk of AKI undergoing non-cardiac surgery were enrolled. The primary outcome was AKI, defined according to KDIGO criteria within 7 days following non-cardiac surgery. DA status was determined by urinalysis performed within 24 h of hospital admission. Multivariate logistic regression model was used to analyze the association between preoperative DA and postoperative AKI. RESULTS: During the study period, 552 patients were enrolled and 8.5% of them developed postoperative AKI. The overall rate of preoperative positive DA was 26.4% with 30 and ≥ 100 mg/dL DA accounting for 19.2% and 7.2%, respectively. Patients with more severe preoperative DA had much higher rate of postoperative AKI (5.2% in patients with negative or trace DA, 13.2% in patients with 30 mg/dL DA and 30.0% in patients with ≥ 100 mg/dL DA, P < 0.001). After adjusting for several perioperative variables, preoperative 30 mg/dL DA (OR 2.575; 95% CI 1.049-6.322; P = 0.039) and ≥ 100 mg/dL DA (OR 3.868; 95% CI 1.246-12.010; P = 0.019) showed an independent association with postoperative AKI. In addition, patients with higher DA status demonstrated significantly increased level of postoperative urine biomarkers and their ratio to urine creatinine. CONCLUSIONS: Preoperative DA was independently associated with AKI in high-risk patients following non-cardiac surgery. Preoperative routine urinalysis for determination of DA status was suggested in early risk stratification.

Effect of low-dose dexmedetomidine on sleep quality in postoperative patients with mechanical ventilation in the intensive care unit: A pilot randomized trial.

Background: Sleep disturbances are prevalent in patients requiring invasive mechanical ventilation in the intensive care unit (ICU) and are associated with worse outcomes. Sedative-dose dexmedetomidine may improve sleep quality in this patient population but is associated with adverse events. Herein, we tested the effect of low-dose dexmedetomidine infusion on nighttime sleep quality in postoperative ICU patients with invasive ventilation. Methods: In this pilot randomized trial, 80 adult patients who were admitted to the ICU after non-cardiac surgery and required invasive mechanical ventilation were randomized to receive either low-dose dexmedetomidine (0.1 to 0.2 µg/kg/h, n = 40) or placebo (n = 40) for up to 72 h. The primary endpoint was overall subjective sleep quality measured using the Richards-Campbell Sleep Questionnaire (score ranges from 0 to 100, with a higher score indicating better quality) in the night of surgery. Secondary outcomes included sleep structure parameters monitored with polysomnography from 9:00 PM on the day of surgery to the next 6:00 AM. Results: All 80 patients were included in the intention-to-treat analysis. The overall subjective sleep quality was median 52 (interquartile 20, 66) with placebo vs. 61 (27, 79) with dexmedetomidine, and the difference was not statistically significant (median difference 8; 95% CI: -2, 22; P = 0.120). Among 68 patients included in sleep structure analysis, those in the dexmedetomidine group tended to have longer total sleep time [median difference 54 min (95% CI: -4, 120); P = 0.061], higher sleep efficiency [median difference 10.0% (95% CI: -0.8%, 22.3%); P = 0.060], lower percentage of stage N1 sleep [median difference -3.9% (95% CI: -11.8%, 0.5%); P = 0.090], higher percentage of stage N3 sleep [median difference 0.0% (95% CI: 0.0%, 0.4%); P = 0.057], and lower arousal index [median difference -0.9 (95% CI -2.2, 0.1); P = 0.091] but not statistically significant. There were no differences between the two groups regarding the incidence of adverse events. Conclusion: Among patients admitted to the ICU after surgery with intubation and mechanical ventilation, low-dose dexmedetomidine infusion did not significantly improve the sleep quality pattern, although there were trends of improvement. Our findings support the conduct of a large randomized trial to investigate the effect of low-dose dexmedetomidine in this patient population. Clinical trial registration: ClinicalTrial.gov, identifier: NCT03335527.

Association between urine microscopy and severe acute kidney injury in critically ill patients following non-cardiac surgery: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and adverse complication following non-cardiac surgery. Evidence have shown urine microscopy could help early detection, differentiating the causes and predicting the progression of AKI. However, little evidence is available on AKI after non-cardiac surgery. Thus, we investigated the association between urine microscopy and severe AKI in critically ill patients after non-cardiac surgery. METHODS: This was a single-center prospective cohort study. The primary outcome was severe AKI, defined as stage 2 or 3 according to maximal KDIGO criteria within 7 days following non-cardiac surgery. Urine microscopy immediately, 6 and 12 hours after surgical intensive care unit (SICU) admission were examined and graded by a urine microscopy score (UMS) based on the observed quantification of renal tubular cells and casts in the sediment. Then, multivariate Logistic regression models were used to analyze the associations between UMS and postoperative severe AKI. RESULTS: From May 20, 2019 to November 24, 2020, 661 patients were enrolled with 147 patients (22.2%) developing postoperative severe AKI. Multivariate Logistic regression model showed elevated UMS (≥1) 6 and 12 hours after SICU admission were independently associated with postoperative severe AKI (OR 2.200, 95% CI: 1.182-4.095, P=0.013 and OR 2.949, 95% CI: 1.657-5.248, P<0.001, respectively). Furthermore, higher UMS 6 hours after SICU admission demonstrated correlation with greater risk of severe AKI with OR 3.887 (95% CI: 1.430-10.563) for UMS ≥3 and OR 2.429 (95% CI: 1.237-4.770) for UMS =1-2. The specificity and sensitivity of UMS ≥1 for severe AKI was 93.8% (95% CI: 91.7-95.9%) and 15.6% (95% CI: 9.7-21.5%), respectively. While the negative and positive predictive value was 79.5% (95% CI: 76.3-82.7%) and 41.8% (95% CI: 28.8-54.8%), respectively. In addition, patients with higher UMS (≥3, 1-2 and 0) had significantly more postoperative complications and longer SICU stay; and they also showed a trend toward other adverse postoperative outcomes. CONCLUSIONS: Early urine microscopy was independently associated with severe AKI in critically ill patients following non-cardiac surgery with higher UMS related to greater risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03880110.

Human Amnion Epithelial Cells and Their Derived Exosomes Alleviate Sepsis-Associated Acute Kidney Injury via Mitigating Endothelial Dysfunction.

Background: Sepsis is characterized by organ dysfunction resulting from a patient's dysregulated response to infection. Sepsis-associated acute kidney injury (S-AKI) is the most frequent complication contributing to the morbidity and mortality of sepsis. The prevention and treatment of S-AKI remains a significant challenge worldwide. In the recent years, human amnion epithelial cells (hAECs) have drawn much attention in regenerative medicine, yet the therapeutic efficiency of hAECs in S-AKI has not been evaluated. Methods: Septic mice were induced by cecal ligation and puncture (CLP) operation. hAECs and their derived exosomes (EXOs) were injected into the mice via tail vein right after CLP surgery. The 7-day survival rate was observed. Serum creatinine level was measured and H&E staining of tissue sections were performed 16 h after CLP. Transmission electron microscopy was used to examine the renal endothelial integrity in CLP mice. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) and EXOs. Zonula occludens-1 (ZO-1) localization was observed by immunofluorescence staining. Expression of phosphor-p65 (p-p65), p65, vascular cell adhesion molecule-1 (VCAM-1), and ZO-1 in the kidney were determined by Western blot. Results: hAECs decreased the mortality of CLP mice, ameliorated septic injury in the kidney, and improved kidney function. More precisely, hAECs suppressed systemic inflammation and maintained the renal endothelial integrity in septic animals. EXOs from hAECs exhibited similar renal protective effects as their parental cells. EXOs maintained endothelial cell adhesion junction in vitro and inhibited endothelial cell hyperactivation in vivo. Mechanistically, EXOs suppressed proinflammatory nuclear factor kappa B (NF-κB) pathway activation in LPS-treated HUVECs and in CLP mice kidneys. Conclusion: Our results indicate that hAECs and their derived EXOs may ameliorate S-AKI via the prevention of endothelial dysfunction in the early stage of sepsis in mice. Stem cell or exosome-based therapy targeting endothelial disorders may be a promising alternative for treatment of S-AKI.

Lenalidomide attenuates post-inflammation pulmonary fibrosis through blocking NF-κB signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a pathological consequence of interstitial pulmonary diseases, and is characterized by the persistence of fibroblasts and excessive deposition of extracellular matrix (ECM). The etiology of IPF is multifactorial. Although the role of inflammation in fibrogenesis is controversial, it is still recognized as an important component and epiphenomenon of IPF. Stimulus increase production of pro-inflammatory cytokines and activation of NF-κB, which will further promote inflammation response and myofibroblast transition. Lenalidomide is an immunomodulatory drug. Previous studies have revealed its anti-tumor effects through regulating immune response. Here we investigate the effect of lenalidomide on post-inflammation fibrosis. In vitro study revealed that lenalidomide inhibited NF-κB signaling in LPS-induced macrophage, and further attenuated macrophage-induced myofibroblast activation. Meanwhile, lenalidomide could inhibit TGF-ß1-induced myofibroblast activation through suppressing TGF-ß1 downstream MAPK signaling. In vivo study showed that lenalidomide inhibited pro-inflammatory cytokines TNF-α and IL-6 while enhanced anti-fibrotic cytokines IFN-γ and IL-10 in bleomycin-induced inflammation model, and attenuated pulmonary fibrosis and collagen deposition in the following fibrosis stage. In conclusion, our results demonstrate that lenalidomide possesses potential anti-fibrotic effects through suppressing NF-κB signaling.

Prevention of deep venous thrombosis in patients undergoing knee arthroplasty by intermittent pneumatic compression apparatus.

OBJECTIVE: This study discussed and analyzed the preventive value of intermittent pneumatic compression combined with early rehabilitation training for deep vein thrombosis (DVT) in patients undergoing total knee arthroplasty (TKA). METHODS: During January 2019 to April 2020, 85 patients who underwent TKA in our hospital were selected as subjects, and were randomly divided into an observation group (n=44) and control group (n=41) by table of random numbers. The control group patients received conventional nursing care after TKA surgery, while the observation group received combinative treatment of intermittent pneumatic compression therapy and early rehabilitation training like the conventional treatment in the control group. Subsequently, the circumference and mobility of knee joint, hemorrheologic indexes and the incidence of DVT between the two groups of patients before and after surgery were compared. RESULTS: The knee circumferences of the two groups on 3 d and 7 d preoperatively were higher than 1 d before surgery (P<0.05), and the indexes of the observation group on 3 d and 7 d preoperatively were lower than that of the control group (P<0.05). The range of motion (ROM) of the two groups 3 d postoperatively were higher than that before surgery (P<0.05), the ROM in observation group 7 d postoperatively was increased than 3 d postoperatively (P<0.05), and the observation group had higher ROM on 3 d and 7 d postoperatively than that of control group (P<0.05). The two groups of patients had insignificant difference in knee function before treatment (P>0.05); the knee function of the two groups after treatment was better than pretreatment (P<0.05), and the observation group was better than the control group (P<0.05). The observation group had lower DVT incidence than the control group (P<0.05). CONCLUSION: Combinative treatment of intermittent pneumatic compression and early rehabilitation training can effectively improve the postoperative knee function of patients undergoing TKA, promote recovery, and effectively prevent DVT. In conclusion, the combinative treatment is worthy of clinical application.

Clevudine attenuates bleomycin-induced early pulmonary fibrosis via regulating M2 macrophage polarization.

Pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease. It is a growing clinical problem which can result in breathlessness or respiratory failure and has an average life expectancy of 3 years from diagnosis. Predominantly accumulation of M2 macrophages accelerates fibrosis progression by secreting multiple cytokines that promote fibroblast to myofibroblast transition and aberrant wound healing of epithelial cells. Targeting activated macrophages to inhibit the pro-fibrotic phenotype is considered as an approach for the potential treatment of PF. Clevudine is s a purine nucleoside analogue which in an oral formulation is approved for treatment of patients with hepatitis B virus (HBV). Here, we found that clevudine is capable of suppressing pro-fibrotic phenotype (i.e., CD206, Arg1 and YM1) of M2 macrophages while enhancing anti-fibrotic phenotype (i.e., CD86, IL-6 and IL-10) by inhibiting PI3K/Akt signaling pathway. This effect further alleviates M2-induced myofibroblast activation and epithelial-to-mesenchymal transition (EMT), thus resulting in a decline of collagen deposition, pro-fibrotic cytokines secretion, with a concomitant recover ofpulmonary functions in vivo. Less infiltration of M2 macrophages between α-SMA + cells was also found in clevudine treated mice. Our findings indicate a potential anti-fibrotic effect of clevudine by regulating macrophage polarization and might be meaningful in clinical settings.

[Relationship between postoperative immediate serum albumin level and postoperative acute kidney injury after major abdominal surgery in critically ill patients].

OBJECTIVE: To investigate the relationship between albumin (ALB) level immediately after major abdominal surgery and postoperative acute kidney injury (AKI) in critically ill patients. METHODS: A retrospective cohort study was conducted. Patients who accepted the major abdominal surgery admitted to the department of intensive care unit (ICU) of the Peking University First Hospital from June 2017 to July 2018 were enrolled. Clinical data including the postoperative ALB level and renal function were collected. Patients were divided into postoperative AKI group and postoperative non-AKI group according to the AKI diagnosis and staging criteria of Kidney Disease: Improving Global Outcomes (KIDGO). The risk factors of perioperative AKI occurrence were analyzed, and multivariate Logistic regression analysis was performed. The receiver operator characteristic curve (ROC curve) was plotted for the ALB level to predict the occurrence of AKI and to determine the ALB cut-off value. The Kaplan-Meier survival curve of postoperative survival of patients was drawn. RESULTS: A total of 363 critically ill patients underwent major abdominal surgery, and 105 patients (28.9%) suffered from AKI. Compared with the non-AKI group, the patients in the AKI group were older (t = -2.794, P = 0.005), preoperative proportions of diabetes and chronic kidney disease were higher (χ21 = 4.613, χ22 = 5.427, both P < 0.05), the proportion of American Society of Anesthesiologists (ASA) grades and V was higher (χ2 = 19.444, P < 0.001), baseline serum creatinine (SCr) and preoperative brain natriuretic peptide (BNP) levels were higher (U1 = 2.859, U2 = 2.283, both P < 0.05), preoperative ALB level was lower (t = 3.226, P = 0.001), the proportion of preoperative use of contrast media was higher (χ2 = 7.431, P = 0.006), the proportions of emergency surgery and using vasopressor during surgery were higher (χ21 = 4.211, χ 22 = 4.947, both P < 0.05), non-renal SOFA score and acute physiology and chronic health evaluation (APACHE) within 24 hours after ICU admission were higher (U = 2.233, t = 3.130, both P < 0.05), and the proportion of postoperative immediate ALB less than 32 g/L was higher (χ2 = 7.601, P = 0.006). ROC curve analysis showed that the cut-off value of immediate postoperative ALB for predicting postoperative AKI was 32 g/L, with the sensitivity was 86.7%, and the specificity was 28.3%. Multivariate Logistic regression analysis showed that ASA grade, use of contrast before surgery, baseline SCr and postoperative immediate serum ALB level below 32 g/L were independent risk factors for AKI [odds ratio (OR) and 95% confidence interval (95%CI) were 2.248 (1.458-3.468), 2.544 (1.332-4.857), 1.018 (1.008-1.027) and 2.685 (1.383-5.212), respectively, all P < 0.01]. Compared with the non-AKI group, the proportion of patients with AKI undergoing mechanical ventilation in ICU was higher (χ2 = 13.635, P < 0.001), mechanical ventilation duration, length of ICU stay, postoperative hospital stay were longer (U1 = 2.530, U2 = 5.032, U3 = 3.200, all P < 0.05), more postoperative complications except AKI (U = 4.799, P < 0.001), and in-hospital mortality and total hospitalization cost were higher (χ2 = 11.681, U = 3.537, both P < 0.001). Compared with the group with postoperative immediate serum ALB ≥ 32 g/L, the proportion of mechanical ventilation in ICU of the ALB < 32 g/L group was higher (χ2 = 33.365, P < 0.001), the length of ICU stay and postoperative hospital stay were longer (U1 = 3.246, U2 = 4.563, both P < 0.001), more postoperative complications except AKI (U = 3.328, P = 0.001), total hospitalization cost was higher (U = 4.127, P < 0.001). CONCLUSIONS: For critically ill patients underwent major abdominal surgery, the postoperative immediate serum ALB level below 32 g/L significantly increased the risk of AKI, which was related to the poor prognosis of the patients.

Fedratinib Attenuates Bleomycin-Induced Pulmonary Fibrosis via the JAK2/STAT3 and TGF-ß1 Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with multiple causes, characterized by excessive myofibrocyte aggregation and extracellular matrix deposition. Related studies have shown that transforming growth factor-ß1 (TGF-ß1) is a key cytokine causing fibrosis, promoting abnormal epithelial-mesenchymal communication and fibroblast-to-myofibroblast transition. Fedratinib (Fed) is a marketed drug for the treatment of primary and secondary myelofibrosis, targeting selective JAK2 tyrosine kinase inhibitors. However, its role in pulmonary fibrosis remains unclear. In this study, we investigated the potential effects and mechanisms of Fed on pulmonary fibrosis in vitro and in vivo. In vitro studies have shown that Fed attenuates TGF-ß1- and IL-6-induced myofibroblast activation and inflammatory response by regulating the JAK2/STAT3 signaling pathway. In vivo studies have shown that Fed can reduce bleomycin-induced inflammation and collagen deposition and improve lung function. In conclusion, Fed inhibited inflammation and fibrosis processes induced by TGF-ß1 and IL-6 by targeting the JAK2 receptor.

Deglycosylated Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis via the TGF-ß1 Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease characterized by the proliferation of myofibroblasts and deposition of extracellular matrix that results in irreversible distortion of the lung structure and the formation of focal fibrosis. The molecular mechanism of IPF is not fully understood, and there is no satisfactory treatment. However, most studies suggest that abnormal activation of transforming growth factor-ß1 (TGF-ß1) can promote fibroblast activation and epithelial to mesenchymal transition (EMT) to induce pulmonary fibrosis. Deglycosylated azithromycin (Deg-AZM) is a compound we previously obtained by removing glycosyls from azithromycin; it was demonstrated to exert little or no antibacterial effects. Here, we discovered a new function of Deg-AZM in pulmonary fibrosis. In vivo experiments showed that Deg-AZM could significantly reduce bleomycin-induced pulmonary fibrosis and restore respiratory function. Further study revealed the anti-inflammatory and antioxidant effects of Deg-AZM in vivo. In vitro experiments showed that Deg-AZM inhibited TGF-ß1 signaling, weakened the activation and differentiation of lung fibroblasts, and inhibited TGF-ß1-induced EMT in alveolar epithelial cells. In conclusion, our findings show that Deg-AZM exerts antifibrotic effects by inhibiting TGF-ß1-induced myofibroblast activation and EMT.

Novel approach of rigid bronchoscopy concurrent with cesarean section and bronchial arterial embolism for patients with massive hemoptysis during pregnancy: case reports and literature review.

Massive hemoptysis can be life-threatening and is frequently encountered in clinical practice, but rare during pregnancy. There have been limited case reports of massive hemoptysis in pregnancy in patients with conditions such as Takayasu's arteritis, bronchiectasis, bronchial carcinoid tumor, and tuberculosis. The most important management is early control of the hemorrhage and airway protection. We report on 2 patients at 33 and 27 gestational weeks who were admitted to the emergency department because of massive hemoptysis. Therapeutic rigid bronchoscopy with the application of high-frequency jet ventilation was performed under general anesthesia during cesarean section to control potential bleeding and stabilize the airway; this was then followed by bronchial artery embolization (BAE) postsurgically. The lives of both mothers and infants were saved. At the 16- and 11-month follow-ups, the patients showed no symptoms. To our knowledge, this is the first report on the application of therapeutic rigid bronchoscopy concurrent with cesarean section in order to protect the airway and reduce the side effects of the subsequent treatment for both mother and fetus in hemoptysis cases. By reporting these cases and conducting a literature review, we present a novel treatment method for massive hemoptysis in pregnant patients that may improve patients' outcomes.

Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing evidence suggests that exosomes may act as critical cell-cell communicators. Accordingly, we assessed the therapeutic potential of hAECs and their derived exosomes (hAECs-EXO) in ischemia reperfusion mouse model of AKI and explored the underlying mechanisms. METHODS: The hAECs were primary cultured, and hAECs-EXO were isolated and characterized. An ischemic-reperfusion injury-induced AKI (IRI-AKI) mouse model was established to mimic clinical ischemic kidney injury with different disease severity. Mouse blood creatinine level was used to assess renal function, and kidney specimens were processed to detect cell proliferation, apoptosis, and capillary density. Macrophage infiltration was analyzed by flow cytometry. hAEC-derived exosomes (hAECs-EXO) were used to treat hypoxia-reoxygenation (H/R) injured HK-2 cells and mouse bone marrow-derived macrophages to evaluate their protective effect in vitro. Furthermore, hAECs-EXO were subjected to liquid chromatography-tandem mass spectrometry for proteomic profiling. RESULTS: We found that systematically administered hAECs could improve mortality and renal function in IRI-AKI mice, decrease the number of apoptotic cells, prevent peritubular capillary loss, and modulate kidney local immune response. However, hAECs showed very low kidney tissue integration. Exosomes isolated from hAECs recapitulated the renal protective effects of their source cells. In vitro, hAECs-EXO protected HK-2 cells from H/R injury-induced apoptosis and promoted bone marrow-derived macrophage polarization toward M2 phenotype. Proteomic analysis on hAECs-EXO revealed proteins involved in extracellular matrix organization, growth factor signaling pathways, cytokine production, and immunomodulation. These findings demonstrated that paracrine of exosomes might be the key mechanism of hAECs in alleviating renal ischemia reperfusion injury. CONCLUSIONS: We reported hAECs could improve survival and ameliorate renal injury in mice with IRI-AKI. The anti-apoptotic, pro-angiogenetic, and immunomodulatory capabilities of hAECs are at least partially, through paracrine pathways. hAECs-EXO might be a promising clinical therapeutic tool, overcoming the weaknesses and risks associated with the use of native stem cells, for patients with AKI.

Thymidine phosphorylase promotes angiogenesis and tumour growth in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer, and thymidine phosphorylase (TP) is a regulator of angiogenesis. To investigate the biological activities of TP in ICC, we established human cholangiocarcinoma RBE cell lines overexpressing TP or silencing TP. Overexpression of TP enhanced viability, suppressed apoptosis and increased tube formation in human umbilical vein endothelial cells, while downregulation of TP reversed these effects. Moreover, an orthotopic xenograft mouse model of ICC was built to further explore TP's function in ICC in vivo. Histological analysis using H&E, TUNEL and Ki67 staining showed that TP promoted tumour growth and inhibited cell apoptosis. Immunostaining for CD31 revealed an elevation in microvessel density in the presence of TP. Besides, upregulation of TP increased the expression of vascular endothelial growth factor, basic fibroblast growth factor, interleukin-8 and tumour necrosis factor alpha. In contrast, TP knockdown inhibited tumour growth, suppressed microvessel formation and decreased the expression of angiogenesis-related proteins. Therefore, we suggest that TP promotes angiogenesis and tumour growth in ICC, which can be a potent therapeutic target for ICC treatment.

Intraoperative hypotension is associated with increased postoperative complications in patients undergoing surgery for pheochromocytoma-paraganglioma: a retrospective cohort study.

BACKGROUND: Dramatic hemodynamic fluctuation occurs frequently during surgery for pheochromocytoma or paraganglioma. However, the criteria of intraoperative hemodynamic instability vary widely, and most of them were defined arbitrarily but not according to patients' prognosis. The objective was to analyze the relationship between different thresholds and durations of intraoperative hyper-/hypotension and the risk of postoperative complications in patients undergoing surgery for pheochromocytoma or paraganglioma. METHODS: This was a retrospective single-center cohort study performed in a tertiary care hospital from January 1, 2005 to December 31, 2017. Three hundred twenty-seven patients who underwent surgery for pheochromocytoma or paraganglioma, of which the diagnoses were confirmed by postoperative pathologic examination, were enrolled. Those who were less than 18 years, underwent surgery involving non-tumor organs, or had incomplete data were excluded. The primary endpoint was a composite of the occurrence of AKI or other complications during hospital stay after surgery. Multivariate Logistic regression models were used to analyze the association between different thresholds and durations of intraoperative hyper-/hypotension and the development of postoperative complications. RESULTS: Forty three (13.1%) patients developed complications during hospital stay after surgery. After adjusting for confounding factors, intraoperative hypotension, defined as systolic blood pressure (SBP) of ≤95 mmHg for ≥20 min (OR 3.211; 99% CI 1.081-9.536; P = 0.006), SBP of ≤90 mmHg for ≥20 min (OR 3.680; 98.8% CI 1.107-12.240; P = 0.006), SBP of ≤85 mmHg for ≥10 min (OR 3.975; 98.3% CI 1.321-11.961; P = 0.003), and SBP of ≤80 mmHg for ≥1 min (OR 3.465; 95% CI 1.484-8.093; P = 0.004), were associated with an increased risk of postoperative complications. On the other hand, intraoperative hypertension was not significantly associated with the development of postoperative complications. CONCLUSIONS: For patients undergoing surgery for pheochromocytoma or paraganglioma, intraoperative hypotension is associated with increased postoperative complications; and the harmful effects are level- and duration-dependent. The effects of intraoperative hypertension need to be studied further.

Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-ß signaling via targeting HSP90ß.

Idiopathic pulmonary fibrosis is a progressive-fibrosing lung disease with high mortality and limited therapy, which characterized by myofibroblasts proliferation and extracellular matrix deposition. Myricetin, a natural flavonoid, has been shown to possess a variety of biological characteristics including anti-inflammatory and anti-tumor. In this study we explored the potential effect and mechanisms of myricetin on pulmonary fibrosis in vivo and vitro. The in vivo studies showed that myricetin effectively alleviated bleomycin (BLM)-induced pulmonary fibrosis. KEGG analysis of RNA-seq data indicated that myricetin could regulate the transforming growth factor (TGF)-ß signaling pathway. In vitro studies indicated that myricetin could dose-dependently suppress TGF-ß1/Smad signaling and attenuate TGF-ß1-induced fibroblast activation and epithelial-mesenchymal transition (EMT). Molecular docking indicated that heat shock protein (HSP) 90ß may be a potential target of myricetin, and MST assay demonstrated that the dissociation constant (Kd) of myricetin and HSP90ß was 331.59 nM. We demonstrated that myricetin interfered with the binding of HSP90ß and TGF-ß receptor II and impeded fibroblast activation and EMT. In conclusion, myricetin impedes TGF-ß1-induced lung fibroblast activation and EMT via targeting HSP90ß and attenuates BLM-induced pulmonary fibrosis in mice.

EZH2 inhibition promotes ANGPTL4/CREB1 to suppress the progression of ulcerative colitis.

AIMS: Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. MAIN METHODS: Lipopolysaccharide (LPS)-treated Caco-2 cells and dextran sodium sulfate (DSS)-treated mice were used as model of ulcerative colitis. The levels of EZH2, angiopoietin-like 4 (ANGPTL4) and cyclic adenosine monophosphate response element-binding protein 1 (CREB1) were tested via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability and apoptosis was measured via 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide or flow cytometry. The abundances of inflammatory cytokines were examined via qRT-PCR and enzyme-linked immunosorbent assay. The association between EZH2 and ANGPTL4 was explored via chromatin immunoprecipitation. The colon damage in DSS-treated mice was investigated by colon length, histological analysis, inflammatory response and apoptosis. KEY FINDINGS: LPS induced viability inhibition, inflammatory response and apoptosis in Caco-2 cells. EZH2 expression was increased but ANGPTL4 and CREB1 levels were decreased in LPS-challenged Caco-2 cells. Overexpression of ANGPTL4 or CREB1 suppressed LPS-induced damage in Caco-2 cells. EZH2 could target ANGPTL4 to mediate CREB1 expression. Inhibition of EZH2 suppressed LPS-caused injury. Moreover, knockdown of ANNGPTL4 or CREB1 attenuated the role of EZH2 inhibition. DSS caused the reduced colon length and increased inflammatory response as well as apoptosis. EZH2 expression was up-regulated but ANGPTL4 and CREB1 expression were down-regulated in DSS-treated mice. SIGNIFICANCE: Inhibition of EZH2 declined LPS-induced injury in Caco-2 cells by mediating ANGPTL4 and CREB1, indicating the potential of EZH2 in treatment of ulcerative colitis.