Macrophage biomimetic nanoparticle-targeted functional extracellular vesicle micro-RNAs revealed via multiomics analysis alleviate sepsis-induced acute lung injury.

Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

Cannulation via the external jugular vein--An alternative to conventional peripherally inserted central catheterisation for paediatric patients.

PURPOSE: This study aimed to describe a peripherally inserted central catheterisation (PICC) for paediatric patients with inaccessible access and a high risk of general anaesthesia (GA). METHODS: This was a retrospective observational study involving all paediatric inpatients who performed the PICC via an EJV approach without GA between September 2014 and September 2021 in a provincial key clinical speciality. RESULTS: A total of 290 EJV line placement attempts were performed, and 29 were excluded due to missing placement results, resulting in a sample size of 261. The anatomical localisation, punctures, and catheterisation success rates for this practice were 100%, 100%, and 90.04%, respectively. The placement success rate in children younger than one year was 93.75% (45/48). The median line duration of use was 19 days, with a median length of catheter insertion of 13 cm. The most common complications were catheter malposition (n = 20) and dislodgement (n = 7). CONCLUSION: The PICC via an EJV approach without GA is a feasible and safe practice with acceptable success and complication rates, and low costs. It might be an attractive alternative for obtaining central vascular access for paediatric patients.

Interleukin IL-5 alleviates sepsis-induced acute lung injury by regulating the immune response in rats.

To study the effect of IL-5 on the immune response and lung injury in rats with sepsis. We constructed a rat model of sepsis by cecal ligation and puncture (CLP). The rats were randomly divided into the control group, the sham group, the CLP group and the IL-5 group, with 6 rats in each group. With the induction of CLP, the lung tissue of rats was severely injured, and the water content of lung tissue was significantly increased. Moreover, the ratio of CD4+/CD8+ was significantly decreased and Th1/Th2 was significantly increased in the peripheral blood. The content of IL-6, TNF-α, and HMGB1 was found to be increased in the CLP group. However, with the injection of IL-5, the degree of lung tissue injury in CLP rats was alleviated and the water content of lung tissue was significantly reduced. The ratio of CD4+/CD8+ was increased and Th1/Th2 was significantly down-regulated in the peripheral blood and the levels of IL-6, TNF-α, and HMGB1 in serum were significantly decreased. In conclusion, IL-5 can alleviate lung injury by regulating the immune response and inhibiting the systemic inflammatory response induced by sepsis.

The influence of risk perception for COVID-19 pandemic on posttraumatic stress disorder in healthcare workers: A survey from four designated hospitals.

The aim of current study was to investigate risk perception of COVID-19 pandemic, sleep quality and time change of leisure activity and their correlations with posttraumatic stress disorder (PTSD) in healthcare workers (HCWs) from four designated hospitals in China. Medical staffs (n = 317) from three designated hospitals in Guangdong Province and one designated hospital in Guangxi Province were surveyed on their demographic information, sleep quality and time change of leisure activity, risk perception of pandemic and PTSD symptoms (by using PTSD checklist for DSM-5 (PCL-5)). Hierarchical regression and structural equation model (SEM) were used to examine the correlated factors of PTSD. The prevalence of high level of PTSD symptoms (PCL-5 > =33, a probable diagnosis of PTSD) was 10.7%. Regression analysis found that risk perception (dread: ß = 0.142, p < 0.01; familiarity: ß = 0.203, p < 0.01), sleep quality (ß = 0.250, p < 0.001), time change of leisure activity (ß = -0.179, p < 0.01), were independently correlated with PTSD severity, which was further confirmed by SEM. Locations of COVID-19-related hazards were significant different in cognitive map of risk perception between groups with high and low levels of PTSD symptoms. Risk perception of COVID-19 pandemic influenced PTSD symptoms in HCWs. Adequate time for leisure activity and good sleep quality protected some HCWs against PTSD symptoms under the influence of pandemic. More researches were warranted to understand the path from pre-factors of risk perception to its psychological consequences among HCWs.

[Comparison of different methods for drug delivery via the lumbar spinal subarachnoid space in rats].

OBJECTIVE: To compare 3 commonly used methods for drug delivery via the lumbar spinal subarachnoid space in rats. METHODS: We compared the effects of 3 methods for drug delivery via the lumbar spinal subarachnoid space in Sprague Dawley rats, namely acute needle puncture, chronic catheterization via laminectomy, and non-laminectomized catheterization. Body weight changes of the rats were measured, and their general and neurological conditions were assessed after the surgeries. The motor function of the rats was examined using rota rod test both before and after the surgeries. Nociceptive tests were performed to assess nociception of the rats. HE staining was used to examine local inflammation caused by the surgeries in the lumbar spinal cord tissue, and lidocaine paralysis detection and toluidine blue dye assay were used to confirm the precision of drug delivery using the 3 methods. RESULTS: Both needle puncture and catheterization via laminectomy resulted in a relatively low success rate of surgery and caused neurological abnormalities, severe motor dysfunction, hyperalgesia, allodynia and local inflammation. Catheterization without laminectomy had the highest success rate of surgery, and induced only mild agitation, slight cerebral spinal fluid leakage, mild sensory and motor abnormalities, and minimum pathology in the lumbar spinal cord. Catheterization without laminectomy produced less detectable effects on the behaviors in the rats and was well tolerated compared to the other two methods with also higher precision of drug delivery. CONCLUSIONS: Catheterization without laminectomy is a safe, accurate and effective approach to lumbar drug delivery in rats.

[Ultrasound, abdominal X-ray and dual-source CT in the diagnosis of colon tumor mechanical obstruction].

OBJECTIVE: To study the value of ultrasound, abdominal X-ray, and dual-source CT (DSCT) in the diagnosis of colon tumor obstruction. METHODS: A retrospective analysis was conducted among 45 patients who were admitted to our department between October 2010 and August 2011 for abdominal pain. All the patients underwent ultrasound, abdominal X-ray and DSCT examinations and subsequent surgical interventions, which confirmed the diagnosis of colon tumor obstruction. RESULTS: DSCT diagnosis was obviously more efficient than ultrasound and X-ray in detecting colon obstruction by neoplasms, and could better predict the position of the obstruction. Complete information of the vessels in the surgical field could be obtained by DSCT imaging three-dimensional reconstruction. CONCLUSIONS: Compared with ultrasound and X-ray, DSCT is more effective in the diagnosis of colon tumor obstruction by acquiring more thorough information by imaging reconstruction and should be considered for a rapid and accurate diagnosis.

[Clinical analysis of 286 cases of abdominal trauma with gastrointestinal tract laceration].

OBJECTIVE: To improve the diagnosis and treatment of abdominal injury. METHODS: The clinical data of 286 patients with gastrointestinal tract laceration admitted between 2004 and 2009 to our hospital was analyzed. RESULTS: The duration after trauma was 15 min to 2 days. Of the 286 patients eventually confirmed by laparotomy, 273 were cured, 3 showed improvement and 10 died. CONCLUSION: Abdominal trauma in patients with gastrointestinal tract laceration, Abdominal puncture diagnosis and orthostatic abdominal X-ray are rapid and effective diagnostic methods for gastrointestinal tract laceration in patients with abdominal trauma. Laparotomy is the primary treatment measures and should be performed as early as possible.

[Application of intraoperative colon irrigation in primary resection and anastomosis of left colorectal cancer with intestinal obstruction].

OBJECTIVE: To study the application of intraoperative irrigation of the colon in primary resection and anastomosis of left colorectal cancer with intestinal obstruction. METHODS: The clinical data were analyzed in 58 patients with left colon rectal cancer and intestinal obstruction undergoing intraoperative irrigation of the colon for primary anastomosis, and the results were compared with 58 patients receiving conventional primary tumor resection. RESULTS: The mean intraoperative blood loss or postoperative hospital stay was comparable between the two groups, but the patients undergoing colon irrigation had significantly delays in the recovery of bowel movement. CONCLUSION: With strict control of the surgery indication, intraoperative colon irrigation can be safe and feasible in primary resection and anastomosis of left colorectal cancer with intestinal obstruction.

[Traditional Chinese and Western medicine treatment of mycoplasmal pneumonia in children and the serum cytokine changes].

OBJECTIVE: To observe the therapeutic effect of traditional Chinese medicine (TCM) and Western medicine (WM) treatments on mycoplasmal pneumonia in children and the changes in the serum cytokines. METHODS: Ninety children with mycoplasmal pneumonia were randomly divided into the treatment group and the control group. TCM was given orally and azithromycin at the daily dose of 10 mg/kg was administered intravenously in the treatment group. In the control group, only intravenous azithromycin was given. After a 7-day treatment, the response rate, time of symptom disappearance, and serum levels of IL-6, IL-8 and TNF-alpha were observed. RESULTS: The total response rate was 93.33% in the treatment group and 73.33% in the control group, showing a significantly better therapeutic effect in the treatment group (P<0.05). The combined treatments also showed better effects in alleviating fever, coughing and rales (P<0.05), and resulted in more obvious reduction in the serum levels of cytokines (P<0.05). CONCLUSION: Combined treatment with TCM and WM produce good therapeutic effects in children with mycoplasmal pneumonia.

[Immunohistochemical study of tumor necrosis factor-alpha expression in the lungs and small intestines in hyperthermia-LPS co-stressed rats].

OBJECTIVE: To investigate the effects of co-exposure to hyperthermia and lipopolysaccharides (LPS) on tumor necrosis factor-alpha (TNF-alpha) expression in the lungs and small intestines of rats. METHODS: Male pathogen-free Wistar rats were randomly assigned into saline-injected normothermic control (C), saline heat exposure (H), LPS normothermic control (L), and LPS plus heat exposure (HL) groups. The rats in H and HL groups were exposed in a chamber at an ambient dry bulb temperature (Tdb) of 35.0-/+0.5 degrees celsius;, and those in C and L groups to 26-/+0.5 degrees celsius;. In L and HL groups, the rats were given an intravenous injection of LPS 10 mg/kg via the tail vein to induce endotoxemia, and those in C and H group received 10 ml/kg injection. The plasma levels of sTNFrI and sTNFrII were detected at different time points using ELISA. The expression of TNF-alpha in the lungs and small intestines was detected by immunohistochemical SABC method, and the damage of the lungs and small intestines evaluated histologically 120 min after the treatment. RESULTS: Co-exposure to hyperthermia and LPS caused significantly enhanced expressions of TNF-alpha and its receptor sTNFrI and sTNFrII in the plasma and tissues and obvious histopathological damage in the lung and small intestines. CONCLUSION: Co-stress of hyperthermia and LPS-induced toxicity is associated with the expression of TNF-alpha in the lung and small intestines.

[Changes of the sodium channel in alveolar type II cells in pulmonary water transport in rats with oleic acid-induced acute lung injury].

OBJECTIVE: To determine the capability of alveolar fluid clearance and the changes of sodium channel in alveolar type II cells (ATII) in oleic acid-induced acute lung injury. METHODS: Forty four male Sprague-Dawley (SD) rats were randomized into a control group and an acute lung injury (ALI) group, with 22 rats in each group. The ALI model was established by oleic acid. The ATII cells were acutely isolated and purified, and the ATII cellular ultrastructure was observed by transmission electron microscope. In each group, the mRNA expression of 3 epithelial sodium channel (ENaC) subunits in acute isolated ATII cells from 8 rats were detected by reverse transcription-polymerase chain reaction (RT-PCR), while the extravascular lung water (EVLW) content was quantified in 7 rats by gravimetric measurement, and the lung histopathological changes were studies in 7 rats. RESULTS: In the ALI group, Smith lung injury score (7.6 +/- 0.8) and EVLW (0.80 +/- 0.17) ml were significantly higher than those in the control group [Smith score: (1.1 +/- 0.2), t = -20.859, P < 0.01; EVLW: (0.52 +/- 0.10) ml, t = -3.851, P < 0.01]. The transmission electron microscopic observation showed that there were degeneration, apoptosis, and lamellar body vacuolar changes in the ATII cells from the ALI rats. RT-PCR demonstrated that the alpha-subunit of the ENaC mRNA expression was the highest among the 3 subunits (F = 4.40, P = 0.02). In the ALI group, mRNA expressions of all the 3 ENaC subunits in acutely isolated ATII cells were decreased as compared to those in the control group [alpha-subunit: (51 +/- 9)% vs (82 +/- 7)%, t = 7.61, P < 0.01; beta-subunit: (13 +/- 7)% vs (25 +/- 4)%, t = 4.53, P < 0.01; gamma-subunit: (31 +/- 15)% vs (40 +/- 17)%, t = 3.01, P < 0.05; respectively]. CONCLUSIONS: The capacity of alveolar fluid clearance was attenuated in oleic acid-induced acute lung injury. The ENaC subunit mRNA levels of ATII cells were significantly decreased in ALI rats.

[Epithelial sodium channel subunit mRNA expression in acutely isolated rat alveolar type II cells].

OBJECTIVE: To investigate the epithelial sodium channel (ENaC) subunit mRNA expression in acutely isolated rat alveolar type II (ATII) cells. METHODS: Acutely isolated ATII cells from 20 SD rats were purified and ENaC alpha, beta, gamma-subunit mRNA levels were determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: mRNA expressions of all the subunits were detected in the ATII cells, and ENaC alpha-subunit mRNA showed significantly higher expression than beta- and gamma-subunit mRNAs, and the expressions of the latter two mRNAs were comparable. CONCLUSION: As the predominant ENaC subunit expressed at the mRNA level in rat ATII cells, the alpha-subunit of ENAC plays an important role in alveolar fluid clearance.