Echinacoside Prevents Sepsis-Induced Myocardial Damage via Targeting SOD2.

Echinacoside (ECH) is a prominent naturally occurring bioactive compound with effects of alleviating myocardial damage. We aimed to explore the beneficial effects of ECH against sepsis-induced myocardial damage and elucidate the potential mechanism. Echocardiography and Masson staining demonstrated that ECH alleviates cardiac function and fibrosis in the cecal ligation and puncture (CLP) model. Transcriptome profiling and network pharmacology analysis showed that there are 51 overlapping targets between sepsis-induced myocardial damage and ECH. Subsequently, chemical carcinogenesis-reactive oxygen species (ROS) were enriched in multiple targets. Wherein, SOD2 may be the potential target of ECH on sepsis-induced myocardial damage. Polymerase chain reaction results showed that ECH administration could markedly increase the expression of SOD2 and reduce the release of ROS. Combined with injecting the inhibitor of SOD2, the beneficial effect of ECH on mortality, cardiac function, and fibrosis was eliminated, and release of ROS was increased after inhibiting SOD2. ECH significantly alleviated myocardial damage in septic mice, and the therapeutic mechanism of ECH is achieved by upregulating SOD2 which decreased the release of ROS.

Hypoxemia in thoracoscopic lung resection surgery using a video double-lumen tube versus a conventional double-lumen tube: A propensity score-matched analysis.

Background: Malposition of the double-lumen tubes (DLTs) may lead to hypoxemia during one-lung ventilation (OLV). Video double-lumen tubes (VDLTs) enable continuous observation of DLT position and avoid displacement. We aimed to investigate whether VDLTs could reduce the incidence of hypoxemia during OLV compared with conventional double-lumen tubes (cDLT) in thoracoscopic lung resection surgery. Methods: This was a retrospective cohort study. Adult patients who underwent elective thoracoscopic lung resection surgery and required VDLTs or cDLTs for OLV at Shanghai Chest Hospital from January 2019 to May 2021 were included. The primary outcome was the incidence of hypoxemia during OLV between VDLT and cDLT. Secondary outcomes included bronchoscopy use, the degree of PaO2 decline, and arterial blood gas indices. Results: A total of 1,780 patients were finally analyzed in propensity score-matched cohorts (VDLT vs. cDLT 1:1 n = 890). The incidence of hypoxemia decreased from 6.5% (58/890) in cDLT group to 3.6% (32/890) in VDLT group (Relative Risk [RR]: 1.812, 95% CI: 1.19-2.76, p = 0.005). The use of bronchoscopy was reduced by 90% in VDLT group (VDLT 10.0% (89/890) vs. cDLT 100% (890/890), p < 0.001). PaO2 after OLV was 221 [136.0-325.0] mmHg in cDLT group compared to 234 [159.7-336.2] mmHg in VDLT group, p = 0.003. The percentage of PaO2 decline was 41.4 [15.4-61.9] % in cDLT group, while it was 37.7 [8.7-55.9] % in the VDLT group, p < 0.001. In patients who suffered from hypoxemia, there were no significant differences in arterial blood gas indices or the percentage of PaO2 decline. Conclusion: VDLTs reduce the incidence of hypoxemia and the use of bronchoscopy during OLV compared with cDLTs. VDLT may be a feasible option for thoracoscopic surgery.

A potential link between aberrant expression of ECRG4 and atrial fibrillation.

Esophageal cancer-related gene-4 (ECRG4), a 148-amino acid propertied and new tumor suppressor, is initially cloned from the normal esophageal epithelium. ECRG4 was found to be expressed not only in esophageal tissues but also in cardiomyocytes. Previous studies demonstrated that ECRG4 is constitutively expressed in esophageal epithelial cells, and its degree of downregulation is directly proportional to prognosis in patients with esophageal cancer. In the heart, ECRG4 shows greater expression in the atria than in the ventricles, which accounts for its heterogeneity. Downregulation of ECRG4 expression level correlates with esophageal cancer, as well as myocardial injuries and arrhythmias. As a result, this review summarizes the possible susceptibility gene, ECRG4 and its associated molecular mechanisms in cancer patients with atrial fibrillation and myocardial injury. The review begins by describing ECRG4's biological background, discusses its expression in the cardiovascular system, lists the clinical and animal research related to the downregulation of ECRG4 in atrial fibrillation, and focuses on its potential role in atrial fibrillation. Downregulation of ECRG4 may increase the risk of atrial fibrillation by affecting ion channels, MMPs expression and inflammatory response. We will then discuss how ECRG4 can be used in the treatment of tumors and arrhythmias, and provide a novel possible strategy to reduce the occurrence of perioperative cardiovascular adverse events in patients with tumors such as esophageal cancer and gastric cancer.

Activation of the STING pathway induces peripheral sensitization via neuroinflammation in a rat model of bone cancer pain.

BACKGROUND: Neuroinflammation in the peripheral nervous system has been linked to cancer metastasis-induced bone pain. The stimulator of interferon genes (STING), an innate immune sensor for cytosolic DNA, plays an important role in inflammation and cancer metastasis and is reported to be a critical regulator of nociception. Here, we examined the role of STING in primary nociceptive neurons and chronic pain to determine if it could be a new target for treating bone cancer pain (BCP). METHODS: Walker 256 cancer cells were injected intratibially to induce bone cancer pain in rats. STING and its downstream inflammatory factors in dorsal root ganglia (DRG) were detected using western blotting and immunofluorescent staining. Transmission electron microscopy and the BCL2-associated X (Bax) expression were used to detect the mitochondrial stress in DRG neurons. C-176, a specific inhibitor of STING, was used to block STING activation and to test the pain behavior. RESULTS: Mechanical hyperalgesia and spontaneous pain were observed in BCP rats, accompanied by the upregulation of the STING expression in the ipsilateral L4-5 DRG neurons which showed significant mitochondrion stress. The STING/TANK-binding kinase 1 (TBK1)/nuclear factor-kappa B (NF-κB) pathway activation was observed in the DRGs of BCP rats as well as increased IL-1ß, IL-6, and TNF-α expression. C-176 alleviated bone cancer pain and reduced the STING and its downstream inflammatory pathway. CONCLUSION: We provide evidence that STING pathway activation leads to neuroinflammation and peripheral sensitization. Pharmacological blockade of STING may be a promising novel strategy for preventing BCP.

Two different troponin isoforms for detecting early myocardial injury after curative resection of oesophageal cancer.

BACKGROUND: The objective of this study was to explore the consistency and correlation of two troponin (cTn) subtypes, troponin I (cTnI) and high-sensitivity troponin T (hs-cTnT), which can be used to judge early myocardial injury after curative resection of oesophageal cancer. METHODS: This study is a secondary analysis of data obtained from a previous randomized controlled trial on postoperative myocardial injury in 70 patients undergoing elective curative resection of oesophageal cancer who were randomly assigned to undergo aggressive body temperature management (nasopharyngeal temperature 36.61 ± 0.18 °C) or standard body temperature management (35.80 ± 0.18 °C, n = 35 in each arm). The serum cTnI and hs-cTnT levels were measured in each patient at the 4 time points: before the operation and 6 h ~ 12 h, 24 h and 48 h after the operation. The diagnostic criteria of myocardial injury followed the third edition ESC/ACCF definition of myocardial infarction. The primary outcomes included the following: (1) the incidence of myocardial injury and the relationship between hs-cTnT and cTn and (2) the consistency and correlation of the two cTn subtypes. RESULTS: A total of 280 pairs of cTn samples were tested. The incidence of postoperative day 2 myocardial injury was 8.6% (3/35) among patients receiving aggressive body temperature management and 31.4% (11/35) among patients receiving standard body temperature management (P < 0.05). Among 3 patients who experienced myocardial injury in the aggressive body temperature management group, 2 met the diagnostic criteria for cTnI and hs-cTnT and only 1 met the diagnostic criteria for hs-cTnT. Among the 11 patients who experienced myocardial injury in the standard body temperature management group, 7 met the diagnostic criteria for cTnI and hs-cTnT and only 3 met the diagnostic criteria for hs-cTnT; only 1 met the diagnostic criteria for cTnI. The bias of cTnI and hs-cTnT was - 8.82 ± 31.91 ng/L. The consistency limit was - 71.37 ~ 53.73 ng/L. The proportion within the scope of the consistency of its corresponding boundary was 98.57%. The correlation coefficient of cTnI and hs-cTnT was 0.845 (P < 0.05). CONCLUSIONS: In the evaluation of postoperative myocardial injury in patients undergoing curative resection of oesophageal cancer, cTnI and hs-cTnT exhibit high consistency and a good correlation. The combination of cTnI and hs-cTnT can improve the detection rate of myocardial injury, thus providing a better reference than a single measure alone for reducing the risk of perioperative myocardial injury in patients. TRIAL REGISTRATION: ChiCTR-INR-17011621 . Registered June 10, 2017.

Postoperative Myocardial Injury in Middle-Aged and Elderly Patients Following Curative Resection of Esophageal Cancer With Aggressive or Standard Body Temperature Management: A Randomized Controlled Trial.

BACKGROUND: Risk of intraoperative hypothermia is relatively high in middle-aged and elderly patients undergoing curative resection of esophageal cancer, which may cause myocardial ischemia during the early postoperative period. The objective of this study was to compare aggressive or standard body temperature management for lowering the incidence of postoperative myocardial injury that was assessed by troponin levels collected at a priori defined set times in these patients. METHODS: Seventy patients undergoing elective curative resection of esophageal cancer were randomly assigned to undergo aggressive body temperature management (nasopharyngeal temperature ≥36°C) or standard body temperature management (n = 35 in each arm). The primary outcome was myocardial injury, defined as the occurrence of elevated troponin I (>0.06 µg/L) or elevated high-sensitivity troponin T (≥0.065, or 0.02 µg/L≤ high-sensitivity troponin T <0.065 µg/L, but with an absolute change of at least 0.005 µg/L) or both during 2 days after surgery. Secondary outcomes included (1) severe arrhythmia, including atrial fibrillation, supraventricular tachycardia, frequent premature ventricular contractions intraoperatively or during 3 days postoperatively; (2) hypoxemia or metabolic acidosis during the first 12 h postoperatively; and (3) deep vein thrombosis or pulmonary embolism during 3 days postoperatively. RESULTS: Incidence of postoperative 2-day myocardial injury was 8.6% (3/35) among patients receiving aggressive body temperature management and 31.4% (11/35) among patients receiving standard body temperature management (P = .017, χ). Relative risk of myocardial injury in the aggressive body temperature management group was 0.27 (95% CI, 0.08-0.89). Incidence of intra- and postoperative 3-day severe cardiac arrhythmia was 2.9% (1/35) among patients receiving aggressive body temperature management and 28.6% (10/35) among patients receiving standard body temperature management. Incidence of postoperative 12-h hypoxia was 17.1% (6/35) with aggressive body temperature management and 40.0% (14/35) with standard body temperature management. Incidence of postoperative 12-h metabolic acidosis was 20% (7/35) among patients receiving aggressive body temperature management and 48.6% (17/35) among patients receiving standard body temperature management. Incidence of postoperative 3-day deep vein thrombosis or pulmonary embolism was 0% (0/35) with aggressive body temperature management and 2.9% (1/35) with standard body temperature management. CONCLUSIONS: Aggressive body temperature management may be associated with a lower incidence of postoperative myocardial injury.

Influence of tidal volume and positive end-expiratory pressure on ventilation distribution and oxygenation during one-lung ventilation.

OBJECTIVE: The aim of the study was to explore the feasibility of titrating tidal volume (V T) and positive end-expiratory pressure (PEEP) during one-lung ventilation (OLV) based on ventilation distribution and oxygenation. APPROACH: Twenty-four consecutive patients requiring intubation with a double-lumen tube and subsequent OLV for thoracic surgical procedures were examined prospectively in lateral posture. Electrical impedance tomography (EIT), blood gases, respiratory mechanics were successfully measured in 21 patients at various combinations of V T (4 ml kg-1, 6 ml kg-1, 8 ml kg-1 body weight) and PEEP (0 cm H2O, 4 cm H2O, 8 cm H2O) during OLV. MAIN RESULTS: Low V T and low PEEP resulted in low global respiratory system compliance (C rs). Arterial partial pressure of O2 (PaO2) decreased with falling V T. Regional C rs measured with EIT showed high values at high V T and high PEEP in all but two patients. Regional C rs in mid and most dependent regions indicated tidal recruitment/derecruitment in eight patients at 8 ml kg-1 of V T and 4 cm H2O of PEEP; in four patients at 8 ml kg-1 and 0 cm H2O; in one patient at 6 ml kg-1 and 8 cm H2O. The changes in regional C rs induced by decreasing PEEP from 8 to 4 cm H2O were much smaller than those from 4 to 0 cm H2O. Ventilation distribution was most inhomogeneous with V T of 8 ml kg-1. All measures differed significantly among various V T and PEEP steps (p < 0.05). SIGNIFICANCE: By using EIT in combination with PaO2, it is feasible to titrate V T and PEEP at the bedside during OLV.