Effect of sarcopenia in predicting postoperative mortality in emergency laparotomy: a systematic review and meta-analysis.

BACKGROUND: While emergency laparotomy has been associated with high rates of postoperative mortality and adverse events, preoperative systematic evaluation of patients may improve perioperative outcomes. However, due to the critical condition of the patient and the limited operation time, it is challenging to conduct a comprehensive evaluation. In recent years, sarcopenia is considered a health problem associated with an increased incidence of poor prognosis. This study aimed to investigate the effect of sarcopenia on 30-day mortality and postoperative adverse events in patients undergoing emergency laparotomy. METHODS: We systematically searched databases including PubMed, Embase, and Cochrane for all studies comparing emergency laparotomy in patients with and without sarcopenia up to March 1, 2022. The primary outcome was of 30-day postoperative mortality. Secondary outcomes were the length of hospital stay, the incidence of adverse events, number of postoperative intensive care unit (ICU) admissions, and ICU length of stay. Study and outcome-specific risk of bias were assessed using the Quality in Prognosis Studies (QUIPS) tool. We rated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULT: A total of 11 eligible studies were included in this study. The results showed that patients with sarcopenia had a higher risk of death 30 days after surgery (OR = 2.42, 95% CI = 1.93-3.05, P < 0.00001). More patients were admitted to ICU after surgery (OR = 1.58, 95% CI = 1.11-2.25, P = 0.01). Both the ICU length of stay (MD = 0.55, 95% CI = 0.05-1.06, P = 0.03) and hospital length of stay (MD = 2.33, 95% CI = 1.33-3.32, P < 0.00001) were longer in the sarcopenia group. The incidence of postoperative complications was also significantly higher in patients with sarcopenia (OR = 1.78, 95% CI = 1.41-2.26, P < 0.00001). CONCLUSION: In emergency laparotomy, sarcopenia was associated with increased 30-day postoperative mortality. Both the lengths of stay in the ICU and the total length of hospital stay were significantly higher than those in non-sarcopenic patients. Therefore, we concluded that sarcopenia can be used as a tool to identify preoperative high-risk patients, which can be considered to develop new postoperative risk prediction models. Registration number Registered on Prospero with the registration number of CRD42022300132.

Corrigendum: Combined Scutellarin and C18H17NO6 Imperils the Survival of Glioma: Partly Associated With the Repression of PSEN1/PI3K-AKT Signaling Axis.

[This corrects the article DOI: 10.3389/fonc.2021.663262.].

Combined Scutellarin and C18H17NO6 Imperils the Survival of Glioma: Partly Associated With the Repression of PSEN1/PI3K-AKT Signaling Axis.

Glioma, the most common intracranial tumor, harbors great harm. Since the treatment for it has reached the bottleneck stage, the development of new drugs becomes a trend. Therefore, we focus on the effect of scutellarin (SCU) and its combination with C18H17NO6 (abbreviated as combination) on glioma and its possible mechanism in this study. Firstly, SCU and C18H17NO6 both suppressed the proliferation of U251 and LN229 cells in a dose-dependent manner, and C18H17NO6 augmented the inhibition effect of SCU on U251 and LN229 cells in vitro. Moreover, there was an interactive effect between them. Secondly, SCU and C18H17NO6 decreased U251 cells in G2 phase and LN229 cells in G2 and S phases but increased U251 cells in S phase, respectively. Meanwhile, the combination could further reduce U251 cells in G2 phase and LN229 cells in G2 and S phases. Thirdly, SCU and C18H17NO6 both induced the apoptosis of U251 and LN229. The combination further increased the apoptosis rate of both cells compared with the two drugs alone. Furthermore, SCU and C18H17NO6 both inhibited the lateral and vertical migration of both cells, which was further repressed by the combination. More importantly, the effect of SCU and the combination was better than positive control-temozolomide, and the toxicity was low. Additionally, SCU and C18H17NO6 could suppress the growth of glioma in vivo, and the effect of the combination was better. Finally, SCU and the combination upregulated the presenilin 1 (PSEN1) level but inactivated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling in vitro and in vivo. Accordingly, we concluded that scutellarin and its combination with C18H17NO6 suppressed the proliferation/growth and migration and induced the apoptosis of glioma, in which the mechanism might be associated with the repression of PSEN1/PI3K-AKT signaling axis.

Long Noncoding RNA H19 Overexpression Protects against Hypoxic-Ischemic Brain Damage by Inhibiting miR-107 and Up-Regulating Vascular Endothelial Growth Factor.

Long noncoding RNAs play critical roles in cellular homeostasis, and long noncoding RNA H19 (H19) is implicated in several pathologic conditions. The putative role of H19 in the pathogenesis and progression of hypoxic-ischemic brain damage (HIBD) is not yet understood. Therefore, a series of in vivo and in vitro experiments were designed to investigate the potential roles of H19 in neuronal apoptosis and cognitive dysfunction in HIBD. H19 expression was decreased in HIBD rat models established by partial occlusion of carotid artery. H19 bound to and decreased the expression of miR-107, which also increased VEGF expression. H19 overexpression reduced neuronal apoptosis and alleviated cognitive dysfunction in HIBD rats. The up-regulation of miR-107 reversed the protective effects conferred by H19. In addition, the cell model of HIBD was established by oxygen-glucose deprivation in neuronal cells used. H19 overexpression in oxygen-glucose deprivation neurons increased B-cell lymphoma-2 and decreased B-cell lymphoma-2-associated X, total and cleaved caspase-3 expressions. Taken together, the results showed that H19 expresses at a low level in HIBD. H19 overexpression decreased miR-107 and increased VEGF expression, which resulted in repressed neuronal apoptosis and alleviated cognitive dysfunction. Thus, H19 may serve as a molecular target for translational research for HIBD therapy.

MicroRNA-22-3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5.

Cell death after spinal cord ischemia/reperfusion (I/R) can occur through necrosis, apoptosis, and autophagy, resulting in changes to the immune environment. However, the molecular mechanism of this immune regulation is not clear. Accumulating evidence indicates that microRNAs (miRs) play a crucial role in the pathogenesis of spinal cord I/R injury. Here, we hypothesized miR-22-3p may be involved in spinal cord I/R injury by interacting with interferon regulatory factor (IRF) 5. Rat models of spinal cord I/R injury were established by 12-min occlusion of the aortic arch followed by 48-hr reperfusion, with L4-6 segments of spinal cord tissues collected. MiR-22-3p agomir, a lentivirus-delivered siRNA specific for IRF5, or a lentivirus expressing wild-type IRF5 was injected intrathecally to rats with I/R injury to evaluate the effects of miR-22-3p and IRF5 on hindlimb motor function. Macrophages isolated from rats were treated with miR-22-3p mimic or siRNA specific for IRF5 to evaluate their effects on macrophage polarization. The levels of IL-1ß and TNF-α in spinal cord tissues were detected by ELISA. miR-22-3p was down-regulated, whereas IRF5 was up-regulated in rat spinal cord tissues following I/R. IRF5 was a target gene of miR-22-3p and could be negatively regulated by miR-22-3p. Silencing IRF5 or over-expressing miR-22-3p relieved inflammation, elevated Tarlov score, and reduced the degree of severity of spinal cord I/R injury. Increased miR-22-3p facilitated M2 polarization of macrophages and inhibited inflammation in tissues by inhibiting IRF5, thereby attenuating spinal cord I/R injury. Taken together, these results demonstrate that increased miR-22-3p can inhibit the progression of spinal cord I/R injury by repressing IRF5 in macrophages, highlighting the discovery of a promising new target for spinal cord I/R injury treatment.

Effect of ketamine combined with lidocaine in pediatric anesthesia.

BACKGROUND: We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine. METHODS: This case-control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High-performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated. RESULTS: Intra- and post-operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine-lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine-lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine-lidocaine complex, elimination half-life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone. CONCLUSIONS: Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half-life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions.

Long non-coding RNA MALAT1 sponges microRNA-429 to regulate apoptosis of hippocampal neurons in hypoxic-ischemic brain damage by regulating WNT1.

Hypoxic-ischemic brain damage (HIBD) is a common neurological disorder. Emerging reports reveal that long non-coding RNAs and microRNAs (miRs) are implicated in the progress of HIBD. In this study we tried to ascertain whether lncRNA MALAT1, with the involvement of miR-429 and WNT1, affects HIBD. Initially, a HIBD mouse model was established. Then, we treated HIBD mice with dexmedetomidine (DEX) and then up- or down-regulated the expression of MALAT1, miR-429 and WNT1 in HIBD mice and neurons. Meanwhile, brain injury and hippocampal neuronal apoptosis were evaluated. Moreover, the interaction among MALAT1, miR-429 and WNT1 in HIBD was investigated. MALAT1 and WNT1 were high-expressed in brain tissues of HIBD mice while miR-429 was low-expressed in brain tissues from HIBD mice. Interestingly, MALAT1 silencing was observed to enhance the cerebral protection of DEX against HIBD. In addition, it was confirmed that MALAT1 sponged miR-429 downregulating expression of miR-429, thereby promoting apoptosis of hippocampal neurons. This effect was achieved through up-regulating the level of WNT1. Taken together, this study demonstrates that silencing of MALAT1 enhances the cerebral protection of DEX against HIBD by suppressing WNT1 expression through miR-429.

NF-κB signaling pathway inhibition suppresses hippocampal neuronal apoptosis and cognitive impairment via RCAN1 in neonatal rats with hypoxic-ischemic brain damage.

NF-κB is a core transcription factor, the activation of which can lead to hypoxic-ischemic brain damage (HIBD), while RCAN1 plays a protective role in HIBD. However, the relationship between NF-κB and RCAN1 in HIBD remains unclear. This study aimed to explore the mechanism of NF-κB signaling pathway in hippocampal neuron apoptosis and cognitive impairment of neonatal rats with HIBD in relation to RCAN1. Initially, microarray analysis was used to determine the differentially expressed genes related to HIBD. After the establishment of HIBD rat models, gain- or loss-of-function assay was performed to explore the functional role of NF-κB signaling pathway in HIBD. Then, the learning and memory ability of rats was evaluated. Expression of RCAN1, NF-κB signaling pathway-related genes and glial fibrillary acidic protein (GFAP), S-100ß and acetylcholine (Ach) level, and acetylcholinesterase (AchE) activity were determined with neuron apoptosis detected to further explore the function of NF-κB signaling pathway. RCAN1 could influence the development of HIBD. In the HIBD model, the expression of RCAN1 and NF-κB-related genes increased, and NF-κB p65 showed a significant nuclear shift. By activation of NF-κB or overexpression of RCAN1, the number of neuronal apoptosis, S-100ß protein level, and AchE level increased significantly, Ach activity decreased significantly, and GFAP positive cells increased. In addition, after the activation of NF-κB or overexpression of RCAN1, the learning and memory ability of HIBD rats was inhibited. All the results show that activation of NF-κB signaling pathway promotes RCAN1 expression, thus increasing neuronal apoptosis and aggravating cognitive impairment in HIBD rats.

microRNA-128 enhances neuroprotective effects of dexmedetomidine on neonatal mice with hypoxic-ischemic brain damage by targeting WNT1.

OBJECTIVE: Hypoxic-ischemic brain damage (HIBD) is a major cause of acute mortality and chronic neurological morbidity in infants and children. Dexmedetomidine (DEX) is an effective choice in HIBD treatment. Recent findings have revealed that microRNA-128 (miR-128) is implicated in cerebral ischemia reperfusion. Hence, this study aimed to investigate the role of miR-128 in HIBD. METHODS: HIBD models of neonatal mice were established. HIBD mice were treated with DEX, and injected with agomir (ago)-miR-128 or antagomir (anti)-miR-128 into the lateral ventricles to explore the influence of miR-128 on the neuroprotective effects of DEX on HIBD. Subsequently, the mice body weight, left/right (L/R) brain weight ratio, left-brain water content as well as learning and memory abilities were measured. Furthermore, the pathological changes of brain tissues and apoptosis rate of nerve cells were determined. The potential relationship between miR-128 and WNT1 was analyzed. RESULTS: Over-expression of miR-128 caused an increase in mouse body weight, L/R brain weight ratio, and learning and memory abilities, while led to a decline in left-brain water content, brain tissue injury and apoptosis rate of nerve cells in DEX-treated HIBD mice. WNT1 was targeted and negatively regulated by miR-128. Silencing of WNT1 exerted the same effect as miR-128 on enhancing the neuroprotective effect of DEX on HIBD mice. CONCLUSION: Collectively, miR-128 enhanced neuroprotective effect of DEX on HIBD neonatal mice by inhibiting WNT1.

[Influence of capsaicin sensitive C fibers denervation on lung ischemia-reperfusion injury].

OBJECTIVE: To investigate the role of Capsaicin sensitive C fibers (CapsCF) denervation in lung ischemia-reperfusion (IR) injury and the possible mechanism related to oxidative stress. METHODS: Thirty two male New Zealand rabbits were randomized into four groups: IR group (IR), sham group (S), capsaicin pretreated IR group (CIR), and capsaicin pretreated sham group (CS). The rabbits in CIR and CS groups were pretreated with capsaicin (100 mg/kg) to induce functional ablation of CapsCF, and then subjected to lung ischemia and reperfusion. The rabbits in IR group were not treated with capsaicin before lung ischemia and reperfusion. Thereafter, blood samples and lung tissue samples were obtained for blood gas and biochemical analyses, including the measurements of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT). The lung wet/dry weight ratio and histopathological changes were also assessed. RESULTS: Compared to S and CS group, partial pressure of oxygen (PO2) values in IR and CIR groups significantly decreased (P < 0.05). In contrast, the alveolar-arterial oxygen gradient (A-aDO2), lung wet/dry weight ratio increased in IR and CIR groups (P < 0.05). Capsaicin pretreatment in CIR group increased lung wet/dry weight ratio and lung pathologic lesions, along with higher level of MDA and lower activity of SOD and CAT (P < 0.05, vs. IR). CONCLUSION: Denervation of CapsCF aggravated lung ischemia-reperfusion injury of rabbits, which seems to be closely related to the excerbation of oxidative stress.

Effects of propofol on the minimum alveolar concentration of sevoflurane for immobility at skin incision in adult patients.

STUDY OBJECTIVE: To determine the effect of propofol on skin incision at target plasma concentrations of one to 6 µg/mL on the minimum alveolar concentration (MAC) of sevoflurane. DESIGN: Prospective, randomized, single-blinded study. SETTING: Operating room of a university hospital. PATIENTS: 122 adult, ASA physical status I and II patients with cholecystitis and gastric cancer, presenting for elective abdominal surgery. INTERVENTIONS: Each group received propofol at different target-controlled plasma concentrations of 0, 1, 2, 3, 4, 5 and 6 µg/mL, respectively. The end-tidal concentration of sevoflurane was stable at a predetermined value for at least 15 minutes. Skin incision was performed after return of neuromuscular function. MEASUREMENTS: Patients were observed for gross purposeful movement for one minute after skin incision. Heart rate and mean arterial pressure were recorded before induction of anesthesia, before incision, and after incision. MAIN RESULTS: The MAC of sevoflurane when used alone was 2.2% ± 0.11%. Propofol decreased the MAC of sevoflurane by 12.3% at one µg/mL, 30.5% at two µg/mL, 35% at three µg/mL, 46.8% at 4 µg/mL, 57.7% at 5 µg/mL, and 72.7% at 6 µg/mL. The linear regression equation of the interaction between sevoflurane and propofol was Y = 2.1679 - 0.256 X, R(2) = 0.9407, where X = plasma propofol concentration, Y = sevoflurane concentration, and R(2) = correlation coefficient. CONCLUSIONS: Propofol decreases the MAC of sevoflurane in a concentration-dependent manner in adult patients.