Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension.

AIMS: Nuclear protein 1 (Nupr1) is a multifunctional stress-induced protein involved in the regulation of tumorigenesis, apoptosis, and autophagy. However, its role in pulmonary hypertension (PH) after METH exposure remains unexplored. In this study, we aimed to investigate whether METH can induce PH and describe the role and mechanism of Nupr1 in the development of PH. METHODS AND RESULTS: Mice were made to induce pulmonary hypertension (PH) upon chronic intermittent treatment with METH. Their right ventricular systolic pressure (RVSP) was measured to assess pulmonary artery pressure. Pulmonary artery morphometry was determined by H&E staining and Masson staining. Nupr1 expression and function were detected in human lungs, mice lungs exposed to METH, and cultured pulmonary arterial smooth muscle cells (PASMCs) with METH treatment. Our results showed that chronic intermittent METH treatment successfully induced PH in mice. Nupr1 expression was increased in the cultured PASMCs, pulmonary arterial media from METH-exposed mice, and METH-ingested human specimens compared with control. Elevated Nupr1 expression promoted PASMC phenotype change from contractile to synthetic, which triggered pulmonary artery remodeling and resulted in PH formation. Mechanistically, Nupr1 mediated the opening of store-operated calcium entry (SOCE) by activating the expression of STIM1, thereby promoting Ca2+ influx and inducing phenotypic conversion of PASMCs. CONCLUSIONS: Nupr1 activation could promote Ca2+ influx through STIM1-mediated SOCE opening, which promoted METH-induced pulmonary artery remodeling and led to PH formation. These results suggested that Nupr1 played an important role in METH-induced PH and might be a potential target for METH-related PH therapy.

Sedation efficacy of different dose of remimazolam with sufentanil for nerve block in young and elderly patients: a randomized, controlled study.

PURPOSE: Anxiety and pain commonly occur during nerve block, we aimed to investigate the sedation efficacy of different doses of remimazolam with sufentanil in young and elderly patients. METHODS: In this randomized trial, patients aged 18-85 years who underwent nerve block was enrolled. All patients received sufentanil 0.08 µg/kg for analgesia. Young patients (age < 65 years) were randomized into the control group (Group C, 0.9% saline), medium-dose remimazolam (Group M, 0.06 mg/kg) and high-dose remimazolam group (Group H, 0.08 mg/kg). Elderly patients (age ≥ 65 years) were randomized into the Group C, low-dose remimazolam group (Group L, 0.04 mg/kg) and Group M. Primary outcome was the success rate of procedure sedation. Respiratory depression and hypoxia were the interested safety outcomes. RESULTS: Ninety young and 114 elderly patients were enrolled, respectively. In comparison with Groups C and M, young patients in Group H had the highest success rate of procedure sedation (80.0 vs. 73.3 vs. 43.3%, P = 0.006). Elderly patients in Groups M and L had similar success rates of procedure sedation, which were significantly higher than that in Group C (78.9 vs. 78.9 vs. 50.0%, P = 0.007). In elderly patients, the incidence of respiratory depression and hypoxia tended to be higher in Group M than those in Groups L and C (both P < 0.001). CONCLUSION: Remimazolam 0.08 mg/kg provided the best sedation efficacy in young patients while remimazolam 0.04 mg/kg with the trend of less respiratory adverse events was more optimal for elderly patients. TRIAL REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=122016 .

Epidural Anesthesia-Analgesia and Recurrence-free Survival after Lung Cancer Surgery: A Randomized Trial.

BACKGROUND: Regional anesthesia and analgesia reduce the stress response to surgery and decrease the need for volatile anesthesia and opioids, thereby preserving cancer-specific immune defenses. This study therefore tested the primary hypothesis that combining epidural anesthesia-analgesia with general anesthesia improves recurrence-free survival after lung cancer surgery. METHODS: Adults scheduled for video-assisted thoracoscopic lung cancer resections were randomized 1:1 to general anesthesia and intravenous opioid analgesia or combined epidural-general anesthesia and epidural analgesia. The primary outcome was recurrence-free survival (time from surgery to the earliest date of recurrence/metastasis or all-cause death). Secondary outcomes included overall survival (time from surgery to all-cause death) and cancer-specific survival (time from surgery to cancer-specific death). Long-term outcome assessors were blinded to treatment. RESULTS: Between May 2015 and November 2017, 400 patients were enrolled and randomized to general anesthesia alone (n = 200) or combined epidural-general anesthesia (n = 200). All were included in the analysis. The median follow-up duration was 32 months (interquartile range, 24 to 48). Recurrence-free survival was similar in each group, with 54 events (27%) with general anesthesia alone versus 48 events (24%) with combined epidural-general anesthesia (adjusted hazard ratio, 0.90; 95% CI, 0.60 to 1.35; P = 0.608). Overall survival was also similar with 25 events (13%) versus 31 (16%; adjusted hazard ratio, 1.12; 95% CI, 0.64 to 1.96; P = 0.697). There was also no significant difference in cancer-specific survival with 24 events (12%) versus 29 (15%; adjusted hazard ratio, 1.08; 95% CI, 0.61 to 1.91; P = 0.802). Patients assigned to combined epidural-general had more intraoperative hypotension: 94 patients (47%) versus 121 (61%; relative risk, 1.29; 95% CI, 1.07 to 1.55; P = 0.007). CONCLUSIONS: Epidural anesthesia-analgesia for major lung cancer surgery did not improve recurrence-free, overall, or cancer-specific survival compared with general anesthesia alone, although the CI included both substantial benefit and harm.

Impact of goal-directed hemodynamic management on the incidence of acute kidney injury in patients undergoing partial nephrectomy: a pilot randomized controlled trial.

BACKGROUND: The incidence of acute kidney injury (AKI) remains high after partial nephrectomy. Ischemia-reperfusion injury produced by renal hilum clamping during surgery might have contributed to the development of AKI. In this study we tested the hypothesis that goal-directed fluid and blood pressure management may reduce AKI in patients following partial nephrectomy. METHODS: This was a pilot randomized controlled trial. Adult patients who were scheduled to undergo partial nephrectomy were randomized into two groups. In the intervention group, goal-directed hemodynamic management was performed from renal hilum clamping until end of surgery; the target was to maintain stroke volume variation < 6%, cardiac index 3.0-4.0 L/min/m2 and mean arterial pressure > 95 mmHg with crystalloid fluids and infusion of dobutamine and/or norepinephrine. In the control group, hemodynamic management was performed according to routine practice. The primary outcome was the incidence of AKI within the first 3 postoperative days. RESULTS: From June 2016 to January 2017, 144 patients were enrolled and randomized (intervention group, n = 72; control group, n = 72). AKI developed in 12.5% of patients in the intervention group and in 20.8% of patients in the control group; the relative reduction of AKI was 39.9% in the intervention group but the difference was not statistically significant (relative risk 0.60, 95% confidence interval [CI] 0.28-1.28; P = 0.180). No significant differences were found regarding AKI classification, change of estimated glomerular filtration rate over time, incidence of postoperative 30-day complications, postoperative length of hospital stay, as well as 30-day and 6-month mortality between the two groups. CONCLUSION: For patients undergoing partial nephrectomy, goal-directed circulatory management during surgery reduced postoperative AKI by about 40%, although not significantly so. The trial was underpowered. Large sample size randomized trials are needed to confirm our results. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02803372 . Date of registration: June 6, 2016.

Analgesic efficacy of two approaches of ultrasound-guided quadratus lumborum block for laparoscopic renal surgery: A randomised controlled trial.

BACKGROUND: Moderate-to-severe pain exists in the early postoperative period after laparoscopic renal surgery. OBJECTIVE: We investigated the analgesic effect of quadratus lumborum block (QLB) via two approaches in patients undergoing laparoscopic renal nephrectomy. DESIGN: A randomised controlled trial. SETTING: An academic tertiary care hospital in Beijing, China. PARTICIPANTS: Ninety-six patients aged 18 to 70 years who were scheduled for elective laparoscopic radical or partial nephrectomy. INTERVENTIONS: Eligible patients were allocated randomly to a control group (no block), lateral QLB group or posterior QLB group. Ultrasound-guided QLB was performed via either the lateral or posterior approach with 30 ml of 0.4% ropivacaine before surgery. MAIN OUTCOME MEASURES: The primary outcome was sufentanil equivalent consumption within 24 h. Among secondary outcomes, somatic and visceral pain intensity at rest and on coughing were assessed with a numerical rating scale (where 0 = no pain and 10 = the worst pain) until 24 h postoperatively. RESULTS: Sufentanil equivalent consumption did not differ among the three groups (118 ±â€Š36 µg in the control group, 115 ±â€Š47 µg in the lateral QLB group and 119 ±â€Š40 µg in the posterior QLB group; P = 0.955). However, both somatic (lateral QLB vs. control, median difference -1, P < 0.001 at rest and -2 to -1, P < 0.001 on coughing; posterior QLB vs. control, -1, P < 0.001 at rest and -2 to -1, P < 0.001 on coughing) and visceral pain scores (lateral QLB vs. control, -1 to 0, P < 0.001 at rest and -1, P < 0.001 on coughing; posterior QLB vs. control, -1 to 0, P < 0.001 at rest and -2 to -1, P < 0.001 on coughing) were significantly lower in the two QLB groups than in the control group. CONCLUSION: For patients undergoing laparoscopic renal surgery, a pre-operative single-shot QLB via the lateral or posterior approach did not decrease opioid consumption, but improved analgesia for up to 24 h after surgery. TRIAL REGISTRATION: www.chictr.org.cn identifier: ChiCTR1800019883.

General Approach for Constructing Mechanoresponsive and Redox-Active Metal-Organic and Covalent Organic Frameworks by Solid-Liquid Reaction: Ferrocene as the Versatile Function Unit.

We report for the first time the construction of mechanoresponsive and redox-active metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) by anchoring ferrocene (Fc) pendants as mechanophores in the pore wall. This work outlines a simple, general, and low-cost route to tailor MOFs and COFs by a Fc unit for mechanoresponsive nature, the release of Fe ions, redox behavior, and modulation of the skeleton charge together.

Ultralow-Content Iron-Decorated Ni-MOF-74 Fabricated by a Metal-Organic Framework Surface Reaction for Efficient Electrocatalytic Water Oxidation.

Transition-metal-organic frameworks (MOFs) have been regarded as one of the most intriguing electrocatalysts because of its low cost and diversity in functional organic groups and metal centers. Different from the common strategies of tuning the ratio of metal centers in multivariate MOFs, here, ultralow-content Fe2O3 is decorated on the surface of monometallic Ni-MOF-74 based on the fast "phenol-iron (Fe)" surface reaction between Fe2+ and the surface hydroxyl group in Ni-MOF-74. Benefiting from this flexible method, the Fe loading can be finely modulated and thus a series of Fe-decorated Ni-MOF-74 with different Fe contents are prepared. The optimized 0.6 wt % Fe2O3@Ni-MOF-74 with the Fe loading of 0.6 wt % only needs the overpotential of 264 mV to deliver 10 mA cm-2, which obviously outperforms Fe-free Ni-MOF-74 (323 mV) and other Fe2O3@Ni-MOF-74 and is even superior to the commercial IrO2 benchmark (300 mV). X-ray photoelectron spectroscopy results disclose that Fe decoration can obviously modulate the electronic structure of Ni center in Ni-MOF-74, thereby resulting in enhanced oxygen evolution reaction activity. This work opens up a new avenue to fabricate excellent MOF-based electrocatalysts for direct utilization in an electrocatalytic process.

Mesorhizobium carbonis sp. nov., isolated from coal bed water.

A Gram-stain negative, aerobic, motile, short rod-shaped bacterium, designated as B2.3T, was isolated from coal bed water collected from Jincheng, Shanxi Province, China. The strain was able to grow at 10-40 °C (optimum 28-30 °C), pH 4.0-10.0 (optimum 7.0), and in the presence of 0-5.0% NaCl (optimum 3.0%, w/v). Phylogenetic analysis based on the 16S rRNA and concatenated housekeeping gene recA, atpD and glnA sequences showed strain B2.3T belongs to the genus Mesorhizobium, with Mesorhizobium oceanicum B7T as the closely related type strain. Strain B2.3T exhibited ANI value of 77.5% and GGDC value of 21.5% to M. oceanicum B7T. The major fatty acids were identified as summed feature 8 (C18:1ω7c and/or C18:1ω6c) and 11-methyl C18:1ω7c. The major polar lipids were found to consist of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as Quinone 10. Phenotypic and biochemical analysis results indicated that strain B2.3T can be distinguished from closely related type strains. On the basis of phenotypic, genotypic and chemotaxonomic characteristics, strain B2.3T is concluded to represent a novel species in the genus Mesorhizobium, for which the name Mesorhizobium carbonis sp. nov. is proposed. The type strain is B2.3T (=CGMCC 1.15730T = KCTC 52461T).

The analgesic efficacy of ultrasound-guided transversus abdominis plane block for retroperitoneoscopic renal surgery: a randomized controlled study.

BACKGROUND: Ultrasound-guided lateral transversus abdominis plane (TAP) block can provide definite analgesia to the anterior abdominal wall. However, whether this method is useful in renal surgery through the lateral abdominal wall pathway remains unknown. The study aimed to evaluate the analgesic efficacy of lateral TAP block for retroperitoneoscopic partial or radical nephrectomy. METHOD: In this prospective, randomized, double-blind, placebo-controlled trial, eligible patients were randomized into two groups. After anaesthesia induction, ultrasound-guided lateral TAP block was performed with either 30 ml of 0.4% ropivacaine (Group T) or an equivalent volume of normal saline (Group C). The primary outcomes were opioid consumption during surgery and in the first 24 h after surgery. Secondary outcomes included postsurgical pain intensity immediately awakening from anaesthesia and at 0.5, 1, 2, 6, 12, and 24 h after surgery, as well as recovery variables including the incidence of postoperative nausea and vomiting (PONV), sleep quality, time to first ambulation, drainage and length of hospital stay. RESULTS: A total of 104 patients were enrolled and randomized (53 in Group T and 51 in Group C). Laparoscopic surgery was converted to open surgery in one patient of Group T; this patient was excluded from the outcome analysis. The opioid consumption during surgery (intravenous morphine equivalent dose: median 35.0 mg [interquartile range 18.0, 49.6] in Group C vs. 40.3 mg [20.9, 59.0] in Group T, P = 0.281) and in the first 24 h after surgery (10.8 mg [7.8, 21.7] in Group C vs. 13.2 mg [8.0, 26.6] in Group T, P = 0.311) did not differ significantly between groups. There were no significant differences between groups regarding the pain intensity at all time points after surgery and the recovery variables (all P > 0.05). CONCLUSIONS: Our results showed that, in patients undergoing retroperitoneoscopic renal surgery, preoperative lateral TAP did not decrease intra- and postoperative opioid consumption, nor did it relieve pain intensity or promote postoperative recovery in the first 24 h after surgery. However, the trial might be underpowered. TRIAL REGISTRATION: This study was registered on November 4, 2017, in the Chinese Clinical Trail Registry with the identification number ChiCTR-INR-17013244 .

Competition Between H2SO4(-)(CH3)3N and H2SO4-H2O Interactions: Theoretical Studies on the Clusters [(CH3)3N]·(H2SO4)·(H2O)(3-7).

The role of the nucleation of sulfuric acid with amines in aerosol formation and its implications for environment is one of the fundamental unsettled questions in atmospheric chemistry. We have investigated the cluster of [(CH3)3N]·(H2SO4)·(H2O)n (n = 3­7) by molecular dynamics to obtain configurational sampling combination with CAM-B3LYP/6-311G(d,p) level to locate the global and many local minima for each cluster size. According to the binding energies at the method of MP2/6-311++G(d,p), the total binding energies decrease with the increasing of the water molecules. For each global minimum, the average binding energies decrease from n = 3 to 4, then increase slowly. The protons of H2SO4 are preferred to transfer to the (CH3)3N to form ion-pair HSO4(­) and (CH3)3NH(+), and the (CH3)3NH(+) ions are coordinated at the first hydrated shell of HSO4(­) when n is between 3 and 5 and coordinated at the second or third hydrated shell when n is larger than 5.

Erector spinae plane block versus quadratus lumborum block for postoperative analgesia after laparoscopic nephrectomy: A randomized controlled trial.

STUDY OBJECTIVE: We compared the analgesic effects of erector spinae plane block versus quadratus lumborum block following laparoscopic nephrectomy. DESIGN: A randomized controlled trial. SETTING: A tertiary hospital in Beijing, China. PATIENTS: Patients scheduled for elective laparoscopic nephrectomy. INTERVENTIONS: A total of 110 patients were enrolled and randomized to receive either erector spinae plane block (n = 55) or quadratus lumborum block (n = 55) under ultrasound guidance. Patient-controlled sufentanil analgesia was provided after surgery. MEASUREMENTS: Our primary outcome was cumulative opioid consumption within 24 h after surgery. Secondary outcomes included postoperative pain intensity, subjective sleep quality, and quality of recovery. MAIN RESULTS: All 110 patients (mean 53 years, 57.3% female) were included in the intention-to-treat analysis. Cumulative sufentanil equivalent within 24 h was lower in patients given erector spinae plane block (median 13 µg, interquartile range 4 to 33) than in those given quadratus lumborum block (median 25 µg, interquartile range 13 to 39; median difference - 8 µg, 95% CI -15 to 0, P = 0.041). Pain intensity (0-10 range where 0 = no pain and 10 = the worst pain) at 2, 6, 12, and 24 h after surgery was lower with erector spinae plane block (at rest: median differences -1 point, all P ≤ 0.009; with movement: median differences -2 to -1 points, all P < 0.001). Subjective sleep quality on the night of surgery (the Richards-Campbell Sleep Questionnaire: 0-100 range, higher score better; median difference 12, 95% CI 2 to 23, P = 0.018) and quality of recovery at 24 h (the Quality of Recovery-15: 0-150 range, higher score better; median difference 8, 95% CI 2 to 15, P = 0.012) were better with erector spinae plane block. No procedure-related adverse events occurred. CONCLUSIONS: Compared with quadratus lumborum block, erector spinae plane block provided better analgesia as manifested by lower opioid consumption and pain intensity for up to 24 h after laparoscopic nephrectomy.

Blocking Sigmar1 exacerbates methamphetamine-induced hypertension.

AIM: Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension. METHODS AND RESULTS: We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-ß/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells. CONCLUSION: Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-ß/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Comparison of two frailty indices in predicting life-threatening morbidity and mortality among older patients undergoing elective high-risk abdominal surgery.

Background: Frailty predicts an increased risk of postoperative morbidity and mortality. Comparison of the predictive performance between two deficit accumulation models of frailty, the modified frailty index (mFI) and the revised-Risk Analysis Index (RAI-rev), is poorly understood. This study compared the predictive abilities of the above two frailty indices in predicting life-threatening morbidity and mortality among older patients following elective high-risk abdominal surgery. Methods: This retrospective cohort study extracted perioperative data of older patients (age ≥65 years) undergoing elective high-risk abdominal surgery at a single institution between January 2018 and December 2020. Preoperative frailty was screened by mFI and RAI-rev scoring systems. The primary outcome was the composite of postoperative life-threatening morbidity and mortality during hospitalization. Multivariable logistic regression analyses were performed to investigate the association of the two frailty indices with the primary outcome. Receiver-operating characteristic (ROC) curve was employed to test the predictive performances of the two frailty instruments in predicting the composite primary outcome. The difference between the area under the curves (AUCs) was assessed by DeLong's test. Results: 1,132 older patients (mean age, 73.4 ± 6.2 years; 63.9% male) were included. Of these, 107 (9.5%) developed postoperative life-threatening morbidity and mortality. In multivariable logistic regression analyses, rising continuous frailty scores (mFI: adjusted OR 1.319 per 0.09-point increase in score, 95% CI 1.151-1.511, p < 0.001; RAI-rev: adjusted OR 1.052 per 1-point increase in score, 95% CI 1.018-1.087, p = 0.002) as well as dichotomized frailty measures (mFI ≥0.27: adjusted OR 2.059, 95% CI 1.328-3.193, p = 0.001; RAI-rev ≥45: adjusted OR 1.862, 95% CI 1.188-2.919, p = 0.007) were associated with increased odds of the primary outcome separately. ROC curve analysis showed that the discrimination of mFI and RAI-rev scores for the life-threatening morbidity and mortality was poor and comparable (AUC: 0.598 [95% CI 0.569-0.627] vs. 0.613 [95% CI 0.583-0.641]; DeLong's test: Z = 0.375, p = 0.7075). Conclusion: High mFI and RAI-rev scores were associated with an increased risk of life-threatening morbidity and mortality in older patients undergoing elective high-risk abdominal surgery. However, both frailty indices displayed poor discrimination for postoperative life-threatening morbidity and mortality.

Calpain: the regulatory point of myocardial ischemia-reperfusion injury.

Calpain is a conserved cysteine protease readily expressed in several mammalian tissues, which is usually activated by Ca2+ and with maximum activity at neutral pH. The activity of calpain is tightly regulated because its aberrant activation will nonspecifically cleave various proteins in cells. Abnormally elevation of Ca2+ promotes the abnormal activation of calpain during myocardial ischemia-reperfusion, resulting in myocardial injury and cardiac dysfunction. In this paper, we mainly reviewed the effects of calpain in various programmed cell death (such as apoptosis, mitochondrial-mediated necrosis, autophagy-dependent cell death, and parthanatos) in myocardial ischemia-reperfusion. In addition, we also discussed the abnormal activation of calpain during myocardial ischemia-reperfusion, the effect of calpain on myocardial repair, and the possible future research directions of calpain.

Sugammadex Reduced the Incidence of Postoperative Pulmonary Complications in Susceptible Patients Identified by ARISCAT Risk Index: Systematic Review and Meta-analysis.

INTRODUCTION: The efficacy of sugammadex on postoperative pulmonary complications (PPCs) in susceptible patients, compared with neostigmine, remains indeterminate. The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) Group Investigators proposed a risk index for the early identification of susceptible patients, with excellent externally validated discrimination ability. Meta-analytical techniques were applied to evaluate the efficacy of sugammadex on PPCs in patients with ARISCAT-defined risk factors. METHODS: The study is registered on PROSPERO, number CRD42021261156. We searched PubMed, Scopus, Embase, Cochrane library, GreyNet, and OpenGrey for eligible randomized controlled trials (RCTs) without restricting the language or year of publication. RESULTS: Twelve RCTs consisting of 1182 patients susceptible to PPCs were included. A robust reduction was observed on the incidence of PPCs in susceptible patients who received sugammadex [RR 0.66; 95% CI (0.54, 0.80), p < 0.01], with a low level of between-study heterogeneity (I2 = 45.98%; H2 = 1.85). Similar protective effects were also proved in avoiding residual neuromuscular block (NMB) [RR 0.25; 95% CI (0.11, 0.56); p < 0.01], atelectasis [RR 0.74; 95% CI (0.59, 0.95); p = 0.02], pneumonia [RR 0.49; 95% CI (0.28, 0.88); p = 0.02], and respiratory failure [RR 0.61; 95% CI (0.39, 0.96); p = 0.03]. No difference was observed regarding adverse events [RR 0.85; 95% CI (0.72, 1.01); p = 0.06]. CONCLUSION: Low to moderate quality of evidence demonstrated the edge of sugammadex over neostigmine for NMB reversal in reducing the likelihood of PPCs and residual NMB in patients with ARISCAT-defined risk factors. Clinicians may reassess the type of reversal agent when treating patients susceptible to PPCs.

Comparison of two preoperative positioning techniques and unpositioning methods in non-intubated video-assisted thoracoscopic surgery.

Background: Using the non-intubated video-assisted thoracoscopic surgery (VATS) approach for small pulmonary nodules (SPNs) can accelerate patients' postoperative recovery. However, locating the SPNs intraoperatively by palpation can be difficult for thoracic surgeons. The advantages of using different preoperative positioning materials are different, especially for pulmonary-nodule-location-needle (P-N-L-N) and the microcoil. This retrospective study analyzed the advantages of two preoperative positioning techniques for VATS under non-intubation anesthesia. Methods: The data were collected for a total of 150 patients with pulmonary nodules who underwent non-intubated VATS at the First People's Hospital of Yunnan Province from January 2018 to January 2021. The patients were divided into a preoperative positioning group (including a P-N-L-N group and microcoil group) and an unlocalized group. These included patients were all compliant with surgical guidelines and were suitable for preoperative localization. Their intraoperative and postoperative indicators were compared, and among these indicators, the operative time, number of postoperative drainage days, postoperative total drainage volume, postoperative discharge time was efficacy group and the intraoperative blood loss was safety group. Results: Preoperative localization helped surgeons to explore nodules faster intraoperatively and remove SPNs precisely under non-intubated VATS. But the advantages of using different preoperative positioning materials are different. Positioning with either microcoil or P-N-L-N resulted in less operation time (P-N-L-N group: 94.90±28.42 min, microcoil group: 112.80±28.6 min, P<0.05), less intraoperative blood loss (P-N-L-N group: 35.80±21.17 mL, microcoil group: 75.00±65.22 mL, P<0.001) and less postoperative thoracic drainage volume (P-N-L-N group: 64.90±181.96 mL, microcoil group: 648.52±708.81 mL, P<0.001). However, the postoperative discharge time (P-N-L-N group: 5.02±1.35 days, microcoil group: 5.40±2.79 days, P=0.38) and postoperative drainage time(P-N-L-N group: 2.58±1.70 days, microcoil group: 3.18±2.49 days, P=0.16) was not statistically significant. Positioning with P-N-L-N seemed to have a better auxiliary effect for non-intubated VATS, suggesting its use can assist surgeons to determine the location of the lesion more accuracy intraoperatively. There was no significant difference in the pathological results among the groups. Conclusions: Localization of SPNs is beneficial in non-intubated VATS, and the use of P-N-L-N was more effective than the microcoil in reducing operative time, intraoperative blood loss, postoperative total drainage volume, and postoperative discharge time.

Association between inflammatory bowel diseases and Parkinson's disease: systematic review and meta-analysis.

Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease (IBD) and Parkinson's disease (PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched PubMed, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle-Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population (adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15-1.34, P < 0.001). A meta-analysis of the temporal relationship revealed that the incidence of IBD was significantly increased before (adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18-1.35, P < 0.001) and after (adjusted RR = 1.40, 95% CI: 1.20-1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis (adjusted HR = 1.25, 95% CI: 1.13-1.38, P < 0.001) or Crohn's disease (adjusted HR = 1.33, 95% CI: 1.21-1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men (adjusted HR = 1.23, 95% CI: 1.10-1.39) and women (adjusted HR = 1.26, 95% CI: 1.10-1.43); however, older (> 65 years old) IBD patients (adjusted HR = 1.32, 95% CI: 1.17-1.48) may have a higher risk than younger (≤ 65 years old) patients (adjusted HR = 1.24, 95% CI: 1.08-1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk (adjusted HR = 1.6, 95% CI: 1.2-2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.

Methamphetamine induces thoracic aortic aneurysm/dissection through C/EBPß.

AIMS: Thoracic aortic aneurysm/dissection (TAAD) is a life-threatening disease with diverse clinical manifestations. Although the association between methamphetamine (METH) and TAAD is frequently observed, the causal relationship between METH abuse and aortic aneurysm/dissection has not been established. This study was designed to determine if METH causes aortic aneurysm/dissection and delineate the underlying mechanism. METHODS AND RESULTS: A new TAAD model was developed by exposing METH to SD rats pre-treated with lysyl oxidase inhibitor ß-aminopropionitrile (BAPN). Combination of METH and BAPN caused thoracic aortic aneurysm/dissection in 60% of rats. BAPN+METH significantly increased the expression and activities of both matrix metalloproteinase MMP2 and MMP9, consistent with the severe elastin breakage and dissection. Mechanistically, METH increased CCAAT-enhancer binding protein ß (C/EBPß) expression by enhancing mothers against decapentaplegic homolog 3 (Smad3) and extracellular regulated protein kinase (ERK1/2) signaling. METH also promoted C/EBPß binding to MMP2 and MMP9 promoters. Blocking C/EBPß significantly attenuated METH+BAPN-induced TAAD and MMP2/MMP9 expression. Moreover, BAPN+METH promoted aortic medial smooth muscle cell (SMC) apoptosis through C/EBPß-mediated IGFBP5/p53/PUMA signaling pathways. More importantly, the expression of C/EBPß, MMP2/MMP9, and apoptosis-promoting proteins was increased in the aorta of human patients with thoracic aortic dissection, suggesting that the mechanisms identified in animal study could be relevant to human disease. CONCLUSIONS: Our study demonstrated that METH exposure has a casual effect on TAAD. C/EBPß mediates METH-introduced TAAD formation by causing elastin breakage, medial cell loss and degeneration. Therefore, C/EBPß may be a potential factor for TAAD clinical diagnosis or treatment.

The Fra-1: Novel role in regulating extensive immune cell states and affecting inflammatory diseases.

Fra-1(Fos-related antigen1), a member of transcription factor activator protein (AP-1), plays an important role in cell proliferation, apoptosis, differentiation, inflammation, oncogenesis and tumor metastasis. Accumulating evidence suggest that the malignancy and invasive ability of tumors can be significantly changed by directly targeting Fra-1. Besides, the effects of Fra-1 are gradually revealed in immune and inflammatory settings, such as arthritis, pneumonia, psoriasis and cardiovascular disease. These regulatory mechanisms that orchestrate immune and non-immune cells underlie Fra-1 as a potential therapeutic target for a variety of human diseases. In this review, we focus on the current knowledge of Fra-1 in immune system, highlighting its unique importance in regulating tissue homeostasis. In addition, we also discuss the possible critical intervention strategy in diseases, which also outline future research and development avenues.