Identification of qualitative characteristics of immunosuppression in sepsis based on immune-related genes and immune infiltration features.

Objective: Sepsis is linked to high morbidity and mortality rates. Consequently, early diagnosis is crucial for proper treatment, reducing hospitalization, and mortality rates. Additionally, over one-fifth of sepsis patients still face a risk of death. Hence, early diagnosis, and effective treatment play pivotal roles in enhancing the prognosis of patients with sepsis. Method: The study analyzed whole blood data obtained from patients with sepsis and control samples sourced from three datasets (GSE57065, GSE69528, and GSE28750). Commonly dysregulated immune-related genes (IRGs) among these three datasets were identified. The differential characteristics of these common IRGs in the sepsis and control samples were assessed using the REO-based algorithm. Based on these differential characteristics, samples from eight Gene Expression Omnibus (GEO) databases (GSE57065, GSE69528, GSE28750, GSE65682, GSE69063, GSE95233, GSE131761, and GSE154918), along with three ArrayExpress databases (E-MTAB-4421, E-MTAB-4451, and E-MTAB-7581), were categorized and scored. The effectiveness of these differential characteristics in distinguishing sepsis samples from control samples was evaluated using the AUC value derived from the receiver operating characteristic curve (ROC) curve. Furthermore, the expression of IRGs was validated in peripheral blood samples obtained from patients with sepsis through qRT-PCR. Results: Among the three training datasets, a total of 84 common dysregulated immune-related genes (IRGs) were identified. Utilizing a within-sample relative expression ordering (REOs)-based algorithm to analyze these common IRGs, differential characteristics were observed in three reverse stable pairs (ELANE-RORA, IL18RAP-CD247, and IL1R1-CD28). In the eight GEO datasets, the expression of ELANE, IL18RAP, and IL1R1 demonstrated significant upregulation, while RORA, CD247, and CD28 expression exhibited notable downregulation during sepsis. These three pairs of immune-related marker genes displayed accuracies of 95.89% and 97.99% in distinguishing sepsis samples among the eight GEO datasets and the three independent ArrayExpress datasets, respectively. The area under the receiver operating characteristic curve ranged from 0.81 to 1.0. Additionally, among these three immune-related marker gene pairs, mRNA expression levels of ELANE and IL1R1 were upregulated, whereas the levels of CD247 and CD28 mRNA were downregulated in blood samples from patients with sepsis compared to normal controls. Conclusion: These three immune-related marker gene pairs exhibit high predictive performance for blood samples from patients with sepsis. They hold potential as valuable auxiliary clinical blood screening tools for sepsis.

miR-29b-1-5p exacerbates myocardial injury induced by sepsis in a mouse model by targeting TERF2.

Myocardial damage is a critical complication and a significant contributor to mortality in sepsis. MicroRNAs (miRNAs) have emerged as key players in sepsis pathogenesis. In this study, we explore the effect and mechanisms of miR-29b-1-5p on sepsis-induced myocardial damage. Sepsis-associated Gene Expression Omnibus datasets (GSE72380 and GSE29914) are examined for differential miRNAs. The mouse sepsis-induced cardiac injury was established by Lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). LPS-treated HL-1 mouse cardiomyocytes simulate myocardial injury in vitro. miR-29b-1-5p is co-upregulated in both datasets and in cardiac tissue from sepsis mouse and HL-1 cell models. miR-29b-1-5p expression downregulation was achieved by antagomir transduction and confirmed by real-time quantitative reverse transcription PCR. Survival analysis and echocardiography examination show that miR-29b-1-5p inhibition improves mice survival cardiac function in LPS- and CLP-induced sepsis mice. Hematoxylin and eosin and Masson's trichrome staining and Immunohistochemistry analysis of mouse myocardial α-smooth muscle actin show that miR-29b-1-5p inhibition reduces myocardial tissue injury and fibrosis. The inflammatory cytokines and cardiac troponin I (cTnI) levels in mouse serum and HL-1 cells are also decreased by miR-29b-1-5p inhibition, as revealed by enzyme-linked immunosorbent assay. The expressions of autophagy-lysosomal pathway-related and apoptosis-related proteins in the mouse cardiac tissues and HL-1 cells are evaluated by western blot analysis. The sepsis-induced activation of the autophagy-lysosomal pathway and apoptosis are also reversed by miR-29b-1-5p antagomir. MTT and flow cytometry measurement further confirm the protective role of miR-29b-1-5p antagomir in HL-1 cells by increasing cell viability and suppressing cell apoptosis. Metascape functionally enriches TargetScan-predicted miR-29b-1-5p target genes. TargetScan prediction and dual luciferase assay validate the targeting relationship between miR-29b-1-5p and telomeric repeat-binding factor 2 (TERF2). The expression and function of TERF2 in HL-1 cells and mice are also evaluated. MiR-29b-1-5p negatively regulates the target gene TERF2. TERF2 knockdown partly restores miR-29b-1-5p antagomir function in LPS-stimulated HL-1 cells. In summary, miR-29b-1-5p targetedly inhibits TERF2, thereby enhancing sepsis-induced myocardial injury.

Golden bifid treatment regulates gut microbiota and serum metabolites to improve myocardial dysfunction in cecal ligation and puncture-induced sepsis mice.

Myocardial damage is a major consequence and a significant contributor to death in cases of sepsis, a severe infection characterized by a distinct inflammatory response and a potential threat to the patient's life. Recently, the effects of intestinal microbiota and serum metabolites on sepsis have garnered increasing attention. Herein, the effects of golden bifid treatment upon cecal ligation and puncture (CLP)-induced sepsis in mice as a model for myocardial dysfunction were explored. Our results demonstrated that golden bifid treatment partially improved myocardial dysfunction and apoptosis, cardiac inflammation and oxidative stress, and intestinal mucosal permeability and barrier dysfunction in CLP-induced sepsis mice. The intestinal microbiota diversity and abundance were also altered within sepsis mice and improved by golden bifid treatment. Mucispirillum schaedleri, Acinetobacter baumannii and Lactobacullus intestinalis were significantly correlated with heart damage markers, inflammatory factors, or oxidative stress indicators. Serum differential metabolite levels were also significantly correlated with these parameters. Altogether, golden bifid treatment might be an underlying approach for treating sepsis-induced myocardial dysfunction and highlight the underlying effect of intestinal microbiota and serum metabolites on the pathogenesis and treatment of sepsis-triggered myocardial dysfunction.

DLK1 overexpression improves sepsis-induced cardiac dysfunction and fibrosis in mice through the TGF-ß1/Smad3 signaling pathway and MMPs.

Sepsis is a serious inflammatory disease caused by bacterial infection. Cardiovascular dysfunction and remodeling are serious complications of sepsis, which can significantly affect sepsis patients' mortality. Delta-like homologue 1 (DLK1) has been reported could inhibit cardiac myofibroblast differentiation. However, the function of DLK1 in sepsis is unknown. In the present study, the DLK1 expression was first identified based on the online dataset GSE79962 analysis and cecal ligation and puncture (CLP)-induced sepsis mouse model. DLK1 expression was significantly reduced in septic heart tissues. In septic mouse heart, CLP operation decreased the fractional shortening (EF) (%) and ejection fraction (FS) (%) and caused significant edema, disordered myofilament arrangement, and degradation and necrosis in myocardial cells; CLP operation also increased collagen deposition and elevated the protein levels of fibrotic markers (α-SMA and F-actin). DLK1 overexpression in septic mice could effectively increase EF (%) and FS (%), attenuate CLP-caused ECM degradation and deposition and partially inhibit the CLP-induced TGF-ß1/Smad signaling activation. In conclusion, DLK1 expression was poorly expressed in the CLP-induced septic mouse heart. DLK1 overexpression partially alleviated sepsis-induced cardiac dysfunction and fibrosis, with the involvement of the TGF-ß1/Smad3 signaling pathway and MMPs.

Mental health changes in elderly patients undergoing non-cardiac surgery during the COVID-19 pandemic in China.

BACKGROUND: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic. METHODS: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery. RESULTS: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic. LIMITATION: The absence of data from the early days of the COVID-19 outbreak. CONCLUSIONS: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period.

Preemptive parasternal intercostal nerve block for patients undergoing off-pump coronary artery bypass grafting: a double-blind, randomized, controlled trial.

Background: Parasternal intercostal nerve block has been increasingly used for postoperative analgesia and has shown that this technique can provide effective postoperative analgesia. This study aimed to investigate the effect of preemptive parasternal intercostal nerve block on the opioid and vasoactive drug dose required for intraoperative hemodynamic stability and postoperative analgesia in patients undergoing off-pump coronary artery bypass grafting. Methods: In this prospective, randomized controlled study, 64 participants aged 45-75 years scheduled for off-pump coronary artery bypass grafting at The Second Xiangya Hospital of Central South University. Patients were randomized into two groups and preoperatively administered ropivacaine (group R) and saline (group S), in the parasternal intercostal spaces with ultrasound-guided bilateral nerve block. Results: The primary outcome was intraoperative sufentanil and vasopressor dosage. The secondary outcomes were intraoperative hemodynamics, postoperative pain scores, and anesthesia recovery, postoperative use of rescue dezocine, stay in intensive care unit, and length of hospital stay. The consumption of intraoperative sufentanil and vasopressor was significantly lower in group R than in group S. The visual analog score in group R was significantly lower than that in group S up to 12 h postoperatively. The time to anesthesia recovery was significantly less in group R than in group S. Most patients in group S required rescue dezocine, whereas most patients in group R did not. The hemodynamic variables were stable in all patients. Conclusions: A preemptive parasternal intercostal nerve block effectively reduced the required intraoperative sufentanil and norepinephrine dose and provided adequate analgesia for the first 12 h after surgery. Therefore, a preemptive parasternal intercostal nerve block is a good option for patients undergoing off-pump coronary artery bypass grafting. Clinical trial registration: chictr.org.cn, identifier ChiCTR1800017210.

Intraoperative Fraction of Inspired Oxygen and Lung Injury in Coronary Artery Bypass Grafting: Study Protocol for a Randomised Controlled Trial.

OBJECTIVE: Postoperative pulmonary complications are a series of disorders that can contribute to respiratory distress and prolonged mechanical ventilation postoperatively. We hypothesise that a liberal oxygenation strategy during cardiac surgery leads to a higher incidence of postoperative pulmonary complications than a restrictive oxygenation strategy. METHODS: This study is a prospective, observer-blinded, centrally randomised and controlled, international multicentre clinical trial. RESULTS: After obtaining a written informed consent, 200 adult patients undergoing coronary artery bypass grafting will be enrolled and randomised to receive either restrictive or liberal oxygenation perioperatively. The liberal oxygenation group will receive 1.0 fraction of inspired oxygen throughout the intraoperative period, including during cardiopulmonary bypass. The restrictive oxygenation group will receive the lowest fraction of inspired oxygen required to maintain arterial partial pressure of oxygen between 100 and 150 mmHg during cardiopulmonary bypass and a pulse oximetry reading of 95% or greater intraoperatively, but no less than 0.3 and not higher than 0.80 (other than induction and when the oxygenation goals cannot be reached). When patients are transferred to the intensive care unit, all patients will receive an initial fraction of inspired oxygen of 0.5, and then fraction of inspired oxygen will be titrated to maintain a pulse oximetry reading of 95% or greater until extubation. The lowest postoperative arterial partial pressure of oxygen/fraction of inspired oxygen within 48 hours of intensive care unit admission will be the primary outcome. Postoperative pulmonary complications, length of mechanical ventilation, intensive care unit stay, hospital stay, and 7-day mortality after cardiac surgery will be analysed as secondary outcomes. CONCLUSION: This is one of the first randomised controlled observer-blinded trials that prospectively evaluates the influence of higher inspired oxygen fractions on early postoperative respiratory and oxygenation outcomes in cardiac surgery patients using cardiopulmonary bypass.

Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£è€ å’ŒåŒ»åŠ¡äººå‘˜çš„å¿ƒç†ç¤¾ä¼šå±æœºå¹²é¢„ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS: Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.

Silencing MYOT Expression May Inhibit Autophagy in Human Skeletal Muscle Cells.

Muscle diseases are closely related to autophagy disorders. Studies of autophagy inhibition indicated the importance of autophagy in muscle regeneration, while activation of autophagy can restore muscle function in some myopathies. Previous studies have revealed that mutations in the MYOT gene may lead to several kinds of hereditary myopathies. However, whether the autophagy played a crucial role in hereditary myopathy caused by MYOT mutations was still not clear. In this study, we established the MYOT knockdown human skeletal muscle cell models (HSkMCs) by small interfering RNA. Real-time PCR and Western blot studies found that the expression of p62 and LC3B-II was decreased dramatically, which suggested that silencing MYOT expression may regulate the autophagy in HSkMCs. Further immunofluorescence study on Ad-mCherry-GFP-LC3B adenovirus transfection and monodansylcadaverine (MDC) staining revealed that knocking down the expression of MYOT may inhibit the autophagy. Next, we used the autophagy inducer Earle's balanced salt solution (EBSS) and late-autophagy inhibitor bafilomycin A1 (BAF A1) to treat the HSkMCs, respectively, and found that silencing MYOT expression can inhibit the activation of autophagy by EBSS and aggravate the inhibition of autophagy by BAF A1. Finally, we also found that silencing MYOT expression can downregulate the expression of ATG7 and ATG5, two important autophagy regulatory molecules. Hence, our study may first reveal that knocking down the expression of MYOT may inhibit the autophagy. Hereditary myopathies caused by MYOT mutations may partly result from the inhibition of autophagy in HSkMCs.

Effect of Ice Slush on Reducing the Oculocardiac Reflex During Strabismus Surgery.

BACKGROUND: The aim of this study was to explore whether ice slush (IS) causing local hypothermia can effectively inhibit the oculocardiac reflex (OCR) during strabismus surgery. METHODS: This prospective, randomized, double-blind study included 58 patients with concomitant strabismus scheduled for lateral rectus (LR) recession under general anesthesia. Patients were randomly allocated to receive IS (IS group) or standard treatment (control group) with sterile saline at room temperature before surgery. OCR was defined as a sudden decrease in heart rate (HR) of >15% from baseline. If one incidence of the OCR was found in 1 patient in any stage (0/I/II/III), the patient was defined as an OCR responder, and the incidence of overall OCR was the incidence of OCR responders. The primary outcome was the incidence of overall OCR during all stages of the surgery, which was analyzed by the Z test and computed based on the absolute risk difference with 2-sided 95% confidence intervals (CIs) using the Newcombe method. RESULTS: The overall OCR occurred in 19 of 29 patients (62.5% [95% CI, 45.7-82.1]) in the IS group and 28 of 29 patients (96.6% [95% CI, 82.2-99.9]) in the control group (absolute risk difference, -31.0% [95% CI, -49.4 to -11.0]; Z test, P < .001), which demonstrated that the incidence of overall OCR in IS group was significantly lower than that in the control group. CONCLUSIONS: IS on the ocular surface causing local hypothermia is a promising and easily accessible method to reduce the overall OCR, which can improve the safety of strabismus surgery.

A de novo mutation (p.S1419F) of Retinoic acid induced 1 is responsible for a patient with Smith-Magenis syndrome exhibiting schizophrenia.

Smith-Magenis syndrome (SMS, OMIM# 182290) is a rare congenital disorder which characterized by multiple abnormalities involving in craniofacial, skeletal, otorhinolaryngolocial, neurological, behavioral and others. 17p11.2 microdeletion and RAI1 mutations have been proven to be genetic lesions of this disease. However, the relationship between RAI1 variants and different phenotypes is still unclear. The discoveries of more RAI1 mutations in patients with different phenotypes will help to elucidate the pathogenesis of the RAI1 gene. Here, we describe a young patient with schizophrenia and headache as the main clinical presentation, with SMS-like features including depression, sleep disturbance and pain-free status. Whole exome sequencing and Sanger sequencing suggested that a de novo mutation (NM_030665.3: c.4256C > T/p.S1419F) of RAI1 may be the genetic lesion of the patient. The bioinformatic program predicted that the new mutation (p.S1419F), located in an evolutionarily conserved site of RAI1, was deleterious. Further, western blot analysis suggested that the novel mutation may decrease the protein levels of RAI1 in the patient. Hence, we reported a novel mutation of RAI1 in a patient with SMS, schizophrenia and headache. Our study may expand the spectrum of RAI1 mutations which may further contribute to the mechanisms underlying SMS, schizophrenia and headache.

KLF13 overexpression protects sepsis-induced myocardial injury and LPS-induced inflammation and apoptosis.

Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The caecal ligation and puncture (CLP) -induced sepsis mouse model was established and the septic mice were examined using standard histopathological methods. KLF13 expression was detected in the septic mouse heart and was also seen in a lipoploysaccharide (LPS) -induced cellular inflammation model. To explore this further both pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 levels were examined, also in both models, In addition inflammatory cytokine (IL-1ß, TNF-α, IL-8 and MCP-1) production and IκB-α protein level and p65 phosphorylation were examined in both septic mice and LPS-induced cells. Thus three parameters - cardiomyocyte apoptosis, inflammatory response and NF-κB pathway activation were evaluated under similar conditions. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in the myocardial cells. KLF13 was downregulated in both the septic mouse heart and the LPS-induced cellular inflammation model. Furthermore, both models showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-κB pathway (increased p65 phosphorylation and decreased IκB-α protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially NF-κB signalling) and cardiomyocyte apoptosis.

Risk factors of perioperative acute kidney injury in elderly patients: a single-center retrospective study.

PURPOSE: The elderly are vulnerable to perioperative acute kidney injury. The aim of this study was to determine the risk factors that associated with acute kidney injury among elderly patients. METHODS: Clinical data of elderly patients (> 65 years) who underwent noncardiac, nonrenal surgery between Dec 1 2009 and July 1 2016 were collected for this single-centered historical cohort study. Univariate and multivariate analyses were conducted to explore the risk factors that contribute to acute kidney injury, which was defined as a serum creatinine increase >0.3 mg/dL within 48 h or 1.5 times increase in serum creatinine within 7 days after surgery. RESULTS: 7775 patients were eligible for the final analysis, among which 511 (6.57%) patients developed acute kidney injury. We observed 21 risk factors being associated with perioperative acute kidney injury, with the most important disposing factors being history of kidney disease (adjusted OR = 2.94, 95% CI 2.25-3.84), operation time > 180 min (aOR = 2.93, 95% CI 2.04-4.24), preoperative eGFR [15, 30) (aOR = 2.43, 95% CI 1.29-4.45), and protective factor being intraoperative use of sufentanil (aOR = 0.35, 95% CI 0.23-0.54). CONCLUSION: This study determined risk factors for perioperative acute kidney injury among the elderly in the Second Xiangya Hospital and visualized the risk factors using nomogram and Excel calculator, which may provide some clues to further investigations. Overall, the prevalence of AKI among this large cohort is 6.57%. CLINICAL TRIALS REGISTRATION: http://www.chictr.org.cn ; ChiCTR1900027007; October 28, 2019.

A comparison between bronchial blockers and double-lumen tubes for patients undergoing lung resection: A propensity score-matched cohort study.

Objective: The aim of this study is to compare the effect of bronchial blockers (BB) and double-lumen tubes (DLT) on patients' postoperative recovery after lung resection. Method: 4,636 patients undergoing lung resection and receiving either BB or DLT intubation were reviewed and matched using the propensity score matching method. The primary outcome was the surgical duration. The secondary outcomes included diagnostic results of postoperative chest X-ray, postoperative oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, chest tube duration, incidence of ICU admission, length of hospital stay and incidence of the 30-day readmission. Results: After matching, 401 patients receiving BB were matched to 3,439 patients receiving DLT. There was no statistical difference on the surgical duration between the two groups (P>0.05). However, compared with the DLT group, patients in the BB group showed more infiltrate especially at the surgery side (14.96% versus 9.07%, P<0.001) based on the chest X-ray, together with higher incidence of ICU admission (5.23% versus 2.61%, P<0.05). Additionally, no statistical differences were found between the two groups about chest tube duration, oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, duration of surgery, hospital stays and 30-day readmission (P>0.05). Conclusions: Compared with the DLT, patients receiving BB technique tend to have increased pulmonary infiltrate (especially the surgery side) and higher incidence of ICU admission at the early post-operative stage, which may have an influence on the patients' recovery.

The Role of Bone Morphogenetic Protein 4 in Microglial Polarization in the Process of Neuropathic Pain.

Background: Neuropathic pain (NP) is known to be highly correlated with microglial polarization, of which the regulatory mechanism remains to be elucidated. Here, the aim of this study is to further investigate the relationship between bone morphogenetic protein 4 (BMP4) and microglial polarization in the process of NP. Methods: Firstly, normal adult rats received intrathecal BMP4 administration to assess BMP4's effect on microglial polarization. Secondly, a BMP4 antagonist - Noggin - was applied to a rat NP model achieved by L5 spinal nerve ligation (SNL) to investigate whether antagonizing BMP4 signaling could alleviate allodynia by reversing the imbalance of the M1/M2 polarization ratio. In both experiments, Von-Frey filaments were used to test the changes in the paw withdrawal threshold (PWT), and Western blotting, immuno-fluorescence, PCR and flow cytometry were further performed to investigate microglial activity and the expression patterns of M1 and M2 markers, respectively. Results: Firstly, BMP4 administration induced a significant PWT decrease and microglial activation in normal rats; Western blotting, PCR and flow cytometry further revealed that M1 markers including CD16, MHCII, and TNF-α showed a marked elevation after BMP4 application; while M2 markers, such as Arg-1, CD204 and IL-4, peaked at an early stage (P1 or P4) and then fell to the Sham level on P7, leading to a persistent imbalance of the M1/M2 ratio throughout the 1st week. Secondly, Noggin treatment significantly relieved allodynia and microglial activation in SNL rats. Moreover, Noggin persistently downregulated the M1 marker levels and simultaneously induced a late-stage elevation of M2 markers expressions, thereby reversing the imbalance of the M1/M2 polarization ratio. Conclusion: Our results indicate that BMP4 has the ability to induce microglial polarization. Antagonizing BMP4 signaling can relieve pain behavior via mitigating microglial activation and reversing the imbalance of the M1/M2 polarization ratio in the process of NP.

Combined Programmed Intermittent Bolus Infusion With Continuous Infusion for the Thoracic Paravertebral Block in Patients Undergoing Thoracoscopic Surgery: A Prospective, Randomized, and Double-blinded Study.

BACKGROUND: Continuous thoracic paravertebral block (TPVB) connected with patient-controlled analgesia (PCA) pump is an effective modality to reduce postoperative pain following thoracic surgery. For the PCA settings, the programmed intermittent bolus infusion (PIBI) and continuous infusion (CI) are commonly practiced. However, the comparative effectiveness between the 2 approaches has been inconsistent. Thus, the aim of this study was to explore the optimal PCA settings to treat postthoracotomy pain by combing PIBI and CI together. METHODS: All enrolled patients undergoing thoracoscopic surgery accepted ultrasound-guided TPVB catheterization before the surgery and then were randomly allocated in to 3 groups depending on different settings of the PCA pump connecting to the TPVB catheter: the PIBI+CI, PIBI, and CI groups. Numerical Rating Scales were evaluated for each patient at T1 (1 h after extubation), T2 (12 h after the surgery), T3 (24 h after the surgery), T4 (36 h after the surgery), and T5 (48 h after the surgery). Besides, the consumptions of PCA ropivacaine, the number of blocked dermatomes at T3, and the requirement for extra dezocine for pain relief among the 3 groups were also compared. RESULTS: First, the Numerical Rating Scale scores in the PIBI+CI group were lower than the CI group at T2 and T3 (P<0.05) when patients were at rest and were also lower than the CI group at T2, T3, and T4 (P<0.01) and the PIBI group at T3 when patients were coughing (P<0.01). Second, the 2-day cumulative dosage of PCA in the PIBI+CI group was lower than both the CI and PIBI groups (P<0.01). Third, the number of blocked dermatomes in the PIBI and PIBI+CI groups were comparable and were both wider than the CI group at T3 (P<0.01). Finally, a smaller proportion (not statistically significant) of patients in the PIBI+CI group (5.26%, 2/38) had required dezocine for pain relief when compared with the PIBI group (19.44%, 7/36) and the CI group (15.79%, 6/38). CONCLUSIONS: The combination of PIBI and CI provides superior analgesic modality to either PIBI or CI alone in patients undergoing thoracoscopic surgery. Therefore, it should be advocated to improve the management of postoperative pain, clinical outcomes, and ultimately patient satisfaction.

A systematic review and meta-analysis of neostigmine for urinary retention after surgeries.

Background: The aim of this research is to analyze the efficacy of neostigmine in the treatment of postoperative urinary retention (POUR). Methods: In this research, we screened multiple databases including PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI). After a systematic search process, data extraction was conducted. Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. Results: After searching for articles, 20 eligible trials including 1,850 patients after surgery were extracted. Our results suggested that the neostigmine group had a higher effective rate for urinary retention than the Chinese traditional and physical therapy group (OR =7.47, 95% CI: 4.10-13.59, overall effect P<0.001). Further subgroup analysis showed that neostigmine acupoint injection was better than neostigmine intramuscular injection. Time to first voiding in the neostigmine acupoint injection group was shorter than that in the neostigmine intramuscular injection group (MD =-81.92, 95% CI: -130.13 to -33.70, overall P<0.001, I2=99% with random effects model). Furthermore, neostigmine acupoint injection improved urine excretion (MD =243.40, 95% CI: 201.62-285.18, overall P<0.0001) and reduced the residual urine volume (MD =-41.31, 95% CI: -58.05 to -24.58, overall P<0.001, I2=75% with random effects model). The results of the sensitivity analysis and publication bias showed that this research was robust and had little publication bias. Discussion: Our meta-analysis results suggest that neostigmine can effectively improve the symptoms of POUR and neostigmine acupoint injection may achieve a better therapeutic effect.