Dectin-1 participates in the immune-inflammatory response to mouse Aspergillus fumigatus keratitis by modulating macrophage polarization.

Aim: The aim of this study was to investigate whether Dectin-1 influences the immune-inflammatory response in A. fumigatus keratitis by modulating macrophage polarization. Methods: 1. The models of 1-day, 3-day, and 5-day of fungal keratitis were established in SPF C57BL/6 mice after stimulation by A. fumigatus. Dectin-1 agonist (curdlan) and antagonist (laminaran) were injected separately in the mouse subconjunctivae for 1 day in the established mouse model of A. fumigatus keratitis; PBS was used as the control. Inflammation of the mouse cornea was observed under a slit lamp to obtain a clinical score. 2. The expression of M1 (TNF-α, INOS, IL-6, IL-12) and M2 (Arg-1, IL-10, Fizz-1, Ym-1) cytokine-encoding mRNAs was quantified by RT-PCR. 3. Changes in the number of macrophages and expression of M1 and M2 macrophages in mouse corneas detected by immunofluorescence and flow cytometry. 4. Pre-treatment of RAW264.7 cells with MAPK cell signaling pathway inhibitors SB203580 (p38 inhibitor, 10µM), U0126 (ERK inhibitor, 20µM), SP600125 (JNK inhibitor, 10µM) and DMSO separately for 2 h, and stimulated by A. fumigatus for 12 h. Changes in the mRNA expression of M1 and M2 cytokines in the macrophages were quantified by RT-PCR. Results: 1. With curdlan pre-treatment, mouse corneal inflammation worsened, and the clinical score increased after infection. In contrast, in the laminaran pre-treated group, corneal inflammation was alleviated and the clinical score decreased significantly compared to the PBS group after infection. 2. Compared with the control group, the expression levels of macrophage phenotype-related M1 and M2 cytokine mRNAs increased significantly 1, 3, and 5 days after A. fumigatus infected the corneas of mice. 3. With curdlan pre-treatment, the expression of mRNAs encoding M1 cytokines increased, while those encoding M2 cytokines decreased in the cornea compared to the PBS group. In contrast, after infection, mRNA levels for M1 cytokines decreased significantly and those for M2 cytokines increased in the cornea of the laminaran pre-treated group compared to the PBS group. 4. The number of macrophages in the corneal stroma of mice in the curdlan pretreatment group increased significantly compared with the PBS group, while in the laminaran pretreatment group this number decreased significantly. 5. The results of flow cytometry showed that after 3 days of mouse corneal A. fumigatus infection, the number of macrophages in the mouse A. fumigatus model in the curdlan pretreatment group was increased (10.4%) and the number of macrophages in the mouse A. fumigatus model in the laminaran pretreatment group (6.31%), when compared with the AF+FBS group (7.91%). The proportion of M1-type macrophages was increased in the curdlan pretreated group (55.6%) compared to the AF+FBS group (51.2%), the proportion of laminaran pretreatment group had a decreased proportion of M1-type macrophages (46.8%); while M2-type macrophages were the opposite of M1-type: the proportion of M2-type macrophages was 49.2% in the AF+FBS group, the proportion of M2-type macrophages was decreased in the curdlan pretreatment group (44.0%), and the proportion of M2-type macrophages was increased in the laminaran pretreatment group (53.5%). 6. Expression of M1 and M2 cytokine-encoding mRNAs decreased and increased, respectively, after infection, in the RAW264.7 cells pre-treated with MAPK pathway inhibitors, compared to the control. Conclusion: In a mouse model of A. fumigatus keratitis, Dectin-1 can affect macrophage recruitment and polarization, may regulate macrophage phenotype-associated factor changes through the MAPK signaling pathway.

Vascular Reactivity Index as an Effective Predictor of Mortality in Patients With Septic Shock: A Retrospective Study.

BACKGROUND: Sepsis is a serious complication that occurs after trauma, burns, and infections, and it is an important cause of death in intensive care unit (ICU) patients. Despite many new measures being proposed for sepsis treatment, its mortality rate remains high; sepsis has become a serious threat to human health, and there is an urgent need to carry out in-depth clinical research related to sepsis. In recent years, it has been found that septic shock-induced vasoplegia is a result of vascular hyporesponsiveness to vasopressors. Therefore, this study intended to establish an objective formula related to vasoplegia that can be used to assess the prognosis of patients and guide clinical treatment. MATERIALS AND METHODS: A retrospective cohort study was conducted using data from 106 septic shock patients admitted to the ICU of Jining No. 1 People's Hospital from January 2020 to December 2022. The patients were divided into mortality and survival groups based on 28-day survival, and hemodynamics were monitored by the pulse index continuous cardiac output system. The dose and duration of vasopressors, major hemodynamic parameters, lactic acid (Lac) levels, and Sequential Organ Failure Assessment scores were recorded within 48 h of hospital admission. Multifactorial logistic regression was used to analyze the independent risk factors affecting the prognosis of patients, and the predictive value of the vascular response index (VRI) was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: The differences between the survival and mortality groups in terms of age, sex ratio, body weight, ICU length of stay, distribution of infection sites, underlying disease conditions, baseline Lac levels, and some hemodynamic parameters were not statistically significant (P > .05). The results of multifactorial logistic regression showed that the admission Acute Physiology and Chronic Health Evaluation II score, Lac level at 24 h of treatment, maximal vasoactive inotropic score at 24 h (VISmax24), maximal vasoactive inotropic score at 48 h (VISmax48), and VRI were independent risk factors affecting 28-day mortality. Within 48 h of receiving vasopressor therapy, the VRI was lower in the mortality group than in the survival group. The area under the ROC curve for the VRI was 0.86, and the best cutoff value of the VRI for predicting 28-day mortality was 32.50 (YI = 0.80), with a sensitivity of 0.90, a specificity of 0.90, and a better prediction of mortality than the other indicators. CONCLUSIONS: The VRI is a good predictor of mortality in patients with septic shock, and a lower VRI indicates more severe vasoplegia, poorer prognosis, and higher mortality in patients with septic shock.

Long non-coding RNA MM2P suppresses M1-polarized macrophages-mediated excessive inflammation to prevent sodium taurocholate-induced acute pancreatitis by blocking SHP2-mediated STAT3 dephosphorylation.

M1 macrophage-mediated excessive inflammatory response plays a key role in the onset and progression of acute pancreatitis (AP), and this study aimed to investigate the role and underlying mechanisms by which the macrophage polarization-related long noncoding RNA (lncRNA) MM2P participated in the regulation of AP progression. By performing quantitative reverse-transcription PCR (qRT-PCR) assay, lncRNA MM2P was found to be downregulated in both sodium taurocholate-induced AP model mice tissues and lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and gain-of-function experiments confirmed that overexpression of lncRNA MM2P counteracted inflammatory responses, reduced macrophage infiltration and facilitated M1-to-M2 transformation of macrophages to ameliorate AP development in vitro and in vivo. Further mechanical experiments revealed that lncRNA MM2P inhibited Src homology 2 containing protein tyrosine phosphatase 2 (SHP2)-mediated signal transducer and activator of transcription 3 (STAT3) dephosphorylation to activate the STAT3 signaling, and silencing of SHP2 suppressed M1 type skewing in LPS-induced RAW264.7 cells. Interestingly, our rescuing experiments verified that lncRNA MM2P-induced suppressing effects on M1-polarization of LPS-treated RAW264.7 cells were abrogated by co-treating cells with STAT3 inhibitor stattic. Collectively, our data for the first time revealed that lncRNA MM2P suppressed M1-polarized macrophages to attenuate the progression of sodium taurocholate-induced AP, and lncRNA MM2P might be an ideal biomarker for AP diagnosis and treatment.

Intraoperative triggered electromyographic monitoring of pedicle screw efficiently reduces the lumbar pedicle breach and re-operative rate-a retrospective analysis based on postoperative computed tomography scan.

BACKGROUND: To investigate whether intraoperative triggered electromyographic (T-EMG) monitoring could effectively reduce the breach rate of pedicle screws and the revision rate. METHODS: Patients with posterior pedicle screw fixation from L1-S1 were enrolled between June 2015 and May 2021. The patients in whom T-EMG was utilized were placed in the T-EMG group, and the remaining patients were considered in the non-T-EMG group. Three spine surgeons evaluated the images. The two groups were divided into subgroups based on screw position (lateral/superior and medial/inferior) and breach degree (minor and major). Patient demographics, screw positions, and revision procedures were reviewed. RESULTS: A total of 713 patients (3403 screws) who underwent postoperative computed tomography (CT) scans were included. Intraobserver and interobserver reliabilities were perfect. The T-EMG and non-T-EMG groups had 374(1723 screws) and 339 (1680 screws) cases, respectively. T-EMG monitoring efficiently reduced the overall screw breach (T-EMG 7.78% vs. non-T-EMG 11.25%, p = 0.001). in the subgroup analysis, the medial/inferior breach rate was higher in the T-EMG group than in the non-T-EMG group (T-EMG 6.27% vs. non-T-EMG 8.93%, p = 0.002); however, no difference was observed between the lateral and superior breaches (p = 0.064). A significant difference was observed between the minor (T-EMG 6.21% vs. non-T-EMG 8.33%, p = 0.001) and major (T-EMG 0.06% vs. non-T-EMG 0.6%, p = 0.001) medial or inferior screw breach rates. Six screws (all in the non-T-EMG group) underwent revision, with a significant difference between the groups (T-EMG 0.0% vs. non-T-EMG 3.17%, p = 0.044). CONCLUSIONS: T-EMG is a valuable tool in improving the accuracy of screw placement and reducing the screw revision rate. The screw-nerve root distance is vital in causing symptomatic screw breach. TRIAL REGISTRATION: The study is retrospective registered in China National Medical Research Registration and Archival information system in Nov 17th 2022.

Delayed Hemorrhage Followed by Vertebral Artery Injury during Cervical Anterior Controllable Antedisplacement and Fusion Surgery: Case Report and Literature Review.

BACKGROUND: Vertebral artery injury (VAI) during cervical spine surgery is rare. Anterior controllable ante-displacement and fusion (ACAF) surgery is a novel technique for treating degenerative cervical spine disorders, especially ossification of the posterior longitudinal ligament. To date, there have been no reports of VAI during cervical ACAF surgery. Here, we report a rare case of perioperative complication of VAI during ACAF surgery. The available English literature that provides treatment instructions were reviewed. CASE PRESENTATION: A patient diagnosed with mixed ossification of the posterior longitudinal ligament (OPLL) underwent ACAF surgery from C2-C6. Two level transverse foramina were ruptured, and severe bleeding was encountered during ACAF osteotomy. Hemostatic tamponade was performed using bone waxes. The patient had delayed hemorrhage on postoperative day 6. Emergence angiography revealed two vertebral artery pseudoaneurysms in the ruptured transverse foramina. A balloon-expandable covered stent was deployed to treat the pseudoaneurysm. The patient recovered without complications. CONCLUSION: ACAF surgery is a good choice for multiple-level OPLL disease, but special attention should be paid to VAI in the perioperative period. Intraoperative tamponade with bone wax and postoperative digital subtraction angiography (DSA) are effective in preventing disaster-related hemorrhage.