The protocol of enhanced recovery after cardiac surgery in adult patients: A stepped wedge cluster randomized trial.

BACKGROUND: The enhanced recovery after cardiac surgery is a bundle of measurements from preoperative to postoperative phases to improve patients' recovery. METHODS: This study is a multicenter, stepwise design, cluster randomized controlled trial. About 3,600 patients presenting during control and intervention periods are eligible if they are aged from 18 to 80 years old awaiting elective cardiac surgery with cardiopulmonary bypass (CPB). About 5 centers are randomly assigned to staggered start dates for one-way crossover from the control phase to the intervention phase. In the intervention periods, patients will receive ERAS strategy including preoperative, intraoperative, and postoperative approaches. During the control phase, patients receive usual care. The primary outcome consists of major adverse cardiac and cerebrovascular events (MACCEs), postoperative pulmonary complications (PPCs), and acute kidney injury (AKI). DISCUSSION: This study aims to compare the application of ERAS management protocol and traditional management protocol in adult cardiac surgery under extracorporeal circulation.

Integrative proteomics and metabolomics data analysis exploring the mechanism of brain injury after cardiac surgery in chronic stress rats.

OBJECTIVE: Preoperative chronic stress (CS) is associated with postoperative brain injury in patients undergoing open heart cardiac surgery. This research is to explore the potential molecular biological mechanisms of brain damage following cardiac surgery in preoperative CS rats by the analyses combining proteomics and metabolomics. METHODS: We constructed the chronic unpredictable stress (CUS) and cardiac surgery models in adult rats. We proved the brain injury in CUS cardiac surgery rats by Hematoxylin-Eosin (H&E) staining, followed by separating the hippocampal tissue and investigating the potential mechanisms of brain injury by the methods of data-independent acquisition proteomics and untargeted metabolomics. RESULTS: The signaling pathways of glycoproteins and metabolism of amino acids were the main possible mechanisms of brain injury in CUS rats following cardiac surgery according to the proteomics and metabolomics. In addition, the pathways of animo acids metabolism such as the pathways of lysine degradation and ß-alanine metabolism may be the main mechanism of cardiac surgery related brain injury in preoperative CUS rats. CONCLUSIONS: The pathways of animo acids metabolism such as lysine degradation and ß-alanine metabolism may be the potential mechanisms of brain injury in CUS rats following cardiac surgery. We should focus on the varieties of bioproteins and metabolites in these pathways, and related changes in other signaling pathways induced by the two pathways.

The protocol of Enhanced Recovery After Cardiac Surgery (ERACS) in congenital heart disease: a stepped wedge cluster randomized trial.

BACKGROUND: The Enhanced Recovery After Cardiac Surgery (ERACS) programs are comprehensive multidisciplinary interventions to improve patients' recovery. The application of the ERAS principle in pediatric patients has not been identified completely. METHODS: This study is a multicenter, stepwise design, cluster randomized controlled trial. 3030 patients presenting during control and intervention periods are eligible if they are aged from 28 days to 6 years old and awaiting elective correction surgery of congenital heart disease with cardiopulmonary bypass. 5 centers are randomly assigned to staggered start dates for one-way crossover from the control phase to the intervention phase. In the intervention periods, patients will receive a bundle strategy including preoperative, intraoperative, and postoperative approaches. During the control phase, patients receive the usual care. The primary outcome consists of major adverse cardiac and cerebrovascular events (MACCEs), postoperative pulmonary complications (PPCs), and acute kidney injury (AKI). DISCUSSION: This study aims to explore whether the bundle of ERAS measurements could improve patients' recovery in congenital heart surgery. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov . (NCT05914103).

Nanoscale Janus Z-Scheme Heterojunction for Boosting Artificial Photosynthesis.

Artificial photosynthesis for CO2 reduction coupled with water oxidation currently suffers from low efficiency due to inadequate interfacial charge separation of conventional Z-scheme heterojunctions. Herein, an unprecedented nanoscale Janus Z-scheme heterojunction of CsPbBr3 /TiOx is constructed for photocatalytic CO2 reduction. Benefitting from the short carrier transport distance and direct contact interface, CsPbBr3 /TiOx exhibits significantly accelerated interfacial charge transfer between CsPbBr3 and TiOx (8.90 × 108 s-1 ) compared with CsPbBr3 :TiOx counterpart (4.87 × 107 s-1 ) prepared by traditional electrostatic self-assembling. The electron consumption rate of cobalt doped CsPbBr3 /TiOx can reach as high as 405.2 ± 5.6 µmol g-1 h-1 for photocatalytic CO2 reduction to CO coupled with H2 O oxidation to O2 under AM1.5 sunlight (100 mW cm-2 ), over 11-fold higher than that of CsPbBr3 :TiOx , and surpassing the reported halide-perovskite-based photocatalysts under similar conditions. This work provides a novel strategy to boost charge transfer of photocatalysts for enhancing the performance of artificial photosynthesis.

Early Postoperative Acetaminophen Administration and Severe Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Oxidative stress may contribute to the development of acute kidney injury (AKI) after cardiac surgery. Acetaminophen can be considered an antioxidant because it inhibits hemoprotein-catalyzed lipid peroxidation. We hypothesized that perioperative acetaminophen administration is associated with reduced AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who had cardiac surgery were identified from 2 publicly available clinical registries: the Medical Information Mart for Intensive Care III (MIMIC-III) and the eICU Collaborative Research Database (eICU). EXPOSURE: Administration of acetaminophen in the first 48 hours after surgery. OUTCOME: Severe AKI in the first 7 days after surgery, defined as stage 2 or stage 3 AKI according to KDIGO criteria. ANALYTICAL APPROACH: Multivariable cause-specific hazards regression analysis. RESULTS: We identified 5,791 patients from the MIMIC-III and 3,840 patients from the eICU registries. The overall incidence of severe AKI was 58% (3,390 patients) in the MIMIC-III cohort and 37% (1,431 patients) in the eICU cohort. Acetaminophen was administered in the early postoperative period to 4,185 patients (72%) and 2,737 patients (71%) in these 2 cohorts, respectively. In multivariable regression models, early postoperative use of acetaminophen was associated with a lower risk of severe AKI in both the MIMIC-III (adjusted hazard ratio [AHR], 0.86 [95% CI, 0.79-0.94]) and eICU (AHR, 0.84 [95% CI, 0.72-0.97]) cohorts. The benefit was consistent across sensitivity and subgroup analyses. LIMITATIONS: No data on acetaminophen dose. CONCLUSIONS: Early postoperative acetaminophen administration was independently associated with a lower risk of severe AKI in adults recovering from cardiac surgery. Prospective trials are warranted to assess the extent to which the observed association is causal and estimate the extent to which acetaminophen administration might prevent or reduce the severity of AKI. PLAIN-LANGUAGE SUMMARY: There is uncertainty about whether antioxidant medications such as acetaminophen may protect against kidney injury. Therefore, we evaluated the associations between acetaminophen use and kidney outcomes in adults recovering from cardiac surgery in 2 large clinical registries. Acetaminophen treatment was significantly associated with a 14%-16% lower risk of severe and any-stage acute kidney injury but similar risks of kidney replacement therapy and in-hospital mortality. Our findings suggest that acetaminophen use may protect against kidney injury in adult patients recovering from cardiac surgery.

Effect of large volume red blood cell apheresis on cardiovascular functions in healthy donors.

BACKGROUND: Requirements of blood transfusions rise rapidly in China. Improving the efficiency of blood donation could help maintaining sufficient blood supplement. We conducted a pilot research to investigate the reliability and safety of collecting more units of red blood cell by apheresis. METHODS: Thirty-two healthy male volunteers were randomized into two groups: red blood cell apheresis (RA) (n = 16) and whole blood (WB) donation (n = 16). RA group donated individualized RBC volumes by apheresis according to the volunteers' basal total blood volumes and haematocrit levels, WB group donated 400 mL whole blood. All volunteers were scheduled seven visit times in 8 weeks' study period. The cardiovascular functions were assessed by laboratory examinations, echocardiography and cardiopulmonary functional tests. All results were compared between groups at the same visit time and compared between visit 1(before donation) and other visit times within the same group. RESULTS: The average donated RBC volume in RA group and in WB group was 627.25 ± 109.74 mL and 175.28 ± 8.85 mL, respectively(p < 0.05); the RBC, haemoglobin and haematocrit levels changed significantly between times and between groups (p < 0.05). Cardiac biomarker levels such as NT-proBNP, hs-TnT and CK-MB did not change significantly between times or between groups (p > 0.05). The echocardiographic and cardiopulmonary results did not change significantly between times or between groups during the whole study period(p > 0.05). CONCLUSIONS: We provided an efficient and secure method for RBC apheresis. By harvesting more RBC volumes at one single-time, the cardiovascular functions did not change significantly compared with traditional whole blood donation.

S-Ketamine Exerts Antidepressant Effects by Regulating Rac1 GTPase Mediated Synaptic Plasticity in the Hippocampus of Stressed Rats.

Clinical studies have found that ketamine has a rapid and lasting antidepressant effect, especially in the case of patients with major depressive disorder (MDD). The molecular mechanisms, however, remain unclear. In this study, we observe the effects of S-Ketamine on the expression of Rac1, neuronal morphology, and synaptic transmission function in the hippocampus of stressed rats. Chronic unpredictable mild stress (CUMS) was used to construct stressed rats. The rats were given a different regimen of ketamine (20 mg/kg, i.p.) and Rac1 inhibitor NSC23766 (50 µg, ICV) treatment. The depression-like behavior of rats was evaluated by sucrose preference test and open-field test. The protein expression of Rac1, GluA1, synapsin1, and PSD95 in the hippocampus was detected by Western blot. Pull-down analysis was used to examine the activity of Rac1. Golgi staining and electrophysiological study were used to observe the neuronal morphology and long-term potentiation (LTP). Our results showed that ketamine can up-regulate the expression and activity of Rac1; increase the spine density and the expression of synaptic-related proteins such as GluA1, Synapsin1, and PSD95 in the hippocampus of stressed rats; reduce the CUMS-induced LTP impairments; and consequently improve depression-like behavior. However, Rac1 inhibitor NSC23766 could have effectively reversed ketamine-mediated changes in the hippocampus of rats and counteracted its antidepressant effects. The specific mechanism of S-Ketamine's antidepressant effect may be related to the up-regulation of the expression and activity of Rac1 in the hippocampus of stressed rats, thus enhancing synaptic plasticity.

A simple-to-use nomogram for predicting prolonged mechanical ventilation for children after Ebstein anomaly corrective surgery: a retrospective cohort study.

BACKGROUND: Prolonged mechanical ventilation (PMV) after pediatric cardiac surgery imposes a great burden on patients in terms of morbidity, mortality as well as financial costs. Ebstein anomaly (EA) is a rare congenital heart disease, and few studies have been conducted about PMV in this condition. This study aimed to establish a simple-to-use nomogram to predict the risk of PMV for EA children. METHODS: The retrospective study included patients under 18 years who underwent corrective surgeries for EA from January 2009 to November 2021. PMV was defined as postoperative mechanical ventilation time longer than 24 hours. Through multivariable logistic regression, we identified and integrated the risk factors to develop a simple-to-use nomogram of PMV for EA children and internally validated it by bootstrapping. The calibration and discriminative ability of the nomogram were determined by calibration curve, Hosmer-Lemeshow goodness-of-fit test and receiver operating characteristic (ROC) curve. RESULTS: Two hundred seventeen children were included in our study of which 44 (20.3%) were in the PMV group. After multivariable regression, we obtained five risk factors of PMV. The odds ratios and 95% confidence intervals (CI) were as follows: preoperative blood oxygen saturation, 0.876(0.805,0.953); cardiothoracic ratio, 3.007(1.107,8.169); Carpentier type, 4.644(2.065,10.445); cardiopulmonary bypass time, 1.014(1.005,1.023) and postoperative central venous pressure, 1.166(1.016,1.339). We integrated the five risk factors into a nomogram to predict the risk of PMV. The area under ROC curve of nomogram was 0.805 (95% CI, 0.725,0.885) and it also provided a good discriminative information with the corresponding Hosmer-Lemeshow p values > 0.05. CONCLUSIONS: We developed a nomogram by integrating five independent risk factors. The nomogram is a practical tool to early identify children at high-risk for PMV after EA corrective surgery.

Effect of hemoglobin and oxygen saturation on adverse outcomes in children with tetralogy of fallot: a retrospective observational study.

BACKGROUND: Tetralogy of Fallot (TOF) is a common cyanotic congenital heart malformation that carries a high risk of right-to-left shunting. Anemia is characterized by decreased hemoglobin (Hb) levels that can affect tissue oxygen delivery and impact postoperative recovery in patients. Chronic hypoxia caused by right-to-left shunting of TOF could lead to compensatory increases in Hb to maintain systemic oxygen balance. This study aims to investigate whether preoperative Hb and blood oxygen saturation (SpO2) can predict adverse outcomes in children undergoing corrective surgery for TOF. METHODS: This retrospective study included patients under 18 years of age who underwent corrective surgery for TOF at Fuwai Hospital between January 2016 and December 2018. Adverse outcomes, including in-hospital death, extracorporeal membrane oxygenation implantation, ICU stay > 30 days, and severe complications, were considered as the primary outcome. Univariable and multivariable logistic analyses were performed to identify independent risk factors for adverse outcomes. Propensity score-matched (PSM) analysis was also conducted to minimize the confounding factors. RESULTS: A total of 596 children were included in the study, of which 64 (10.7%) experienced adverse outcomes. Hb*SpO2 < aaHb was identified as an independent risk factor for adverse outcomes (OR = 2.241, 95% CI = 1.276-3.934, P = 0.005) after univariable and multivariable logistic analyses. PSM analysis further confirmed the association between Hb*SpO2 < aaHb and adverse outcomes. Patients with Hb*SpO2 < aaHb had a significantly higher incidence of postoperative adverse outcomes, longer time of mechanical ventilation, and hospital stay, as well as higher in-hospital costs. CONCLUSIONS: Hb*SpO2 < aaHb is significantly associated with adverse outcomes in children undergoing corrective surgery for TOF. Clinicians can use this parameter to early identify high-risk children and optimize their postoperative management.

Effect of Dexmedetomidine on Maintaining Perioperative Hemodynamic Stability in Elderly Patients: A Systematic Review and Meta-analysis.

Objective Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist with sedative and analgesic properties but without respiratory depression effect and has been widely used in perioperative anesthesia. Here we performed a systematic review and meta-analysis to evaluate the effect of dexmedetomidine on maintaining perioperative hemodynamic stability in elderly patients.Methods PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched for randomized-controlled trials (RCTs) on the application of dexmedetomidine in maintaining perioperative hemodynamic stability in elderly patients from their inception to September, 2021. The standardized mean differences (SMD) with 95% confidence interval (CI) were employed to analyze the data. The random-effect model was used for the potential clinical inconsistency.Results A total of 12 RCTs with 833 elderly patients (dexmedetomidine group, 546 patients; control group, 287 patients) were included. There was no significant increase in perioperative heart rate (HR), mean arterial pressure (MAP), and diastolic blood pressure (DBP) in the dexmedetomidine group before and during the operation. In addition, the variations of hemodynamic indexes including HR, MAP, SBP (systolic blood pressure), and DBP were significantly lower in the dexmedetomidine group compared with the control group (HR: SMD = -0.87, 95% CI: -1.13 to -0.62; MAP: SMD = -1.12, 95% CI: -1.60 to -0.63; SBP: SMD = -1.27, 95% CI: -2.26 to -0.27; DBP: SMD = -0.96, 95% CI: -1.33 to -0.59). Subgroup analysis found that with the prolongation of 1.0 µg/kg dexmedetomidine infusion, the patient's heart rate declined in a time-dependent way.Conclusion Dexmedetomidine provides more stable hemodynamics during perioperative period in elderly patients. However, further well-conducted trials are required to assess the effective and safer doses of dexmedetomidine in elderly patients.

Efficacy and safety of DOACs in patients with peripheral arterial disease: A systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in patients with peripheral arterial disease are not completely understood. Therefore, we conducted a meta-analysis to explore the effects of DOACs in this population. METHODS: We systematically searched the PubMed, Cochrane Library, and Web of Science till April 2020 for relevant randomized controlled trials and observational studies, with no linguistic restrictions. The efficacy outcomes were cardiovascular death, stroke, myocardial infraction, major adverse cardiovascular events (MACE), acute limb ischemia, amputation, and target lesion revascularization. The safety outcome was major bleeding events. Random effects risk ratios with 95% confidence intervals were calculated. RESULTS: A total four randomized controlled trials were included in this meta-analysis. Among peripheral arterial disease patients, DOACs did not reduce the risk of cardiovascular death (RR = 1.02 95%CI 0.75-1.37, P = 0.92), stroke (RR = 0.73 95%CI 0.46-1.14, P = 0.16), myocardial infraction (RR = 0.85 95%CI 0.70-1.03, P = 0.10), MACE (RR = 0.73 95%CI 0.46-1.14, P = 0.16), or amputation (RR = 0.73 95%CI 0.46-1.14, P = 0.16) compared with control. However, DOACs were associated with reduction in acute limb ischemia (RR = 0.67 95%CI 0.55-0.80, P < 0.01) and target lesion revascularization (RR = 0.89 95%CI 0.81-0.99, P = 0.02) at the expense of major bleeding events (RR = 1.43 95%CI 1.16-1.77, P < 0.01) compared with control. CONCLUSIONS: Based on current evidence, no significant difference in cardiovascular death, stroke, myocardial infraction, MACE, and amputation was found when DOACs were compared to antiplatelet monotherapy. The benefits of preventing target lesion revascularization and acute limb ischemia were balanced by amplified risk of major bleeding. Larger randomized controlled trials are needed to figure out the uncertainty around efficacy and safety of medications for peripheral arterial disease.

Intraoperative Transesophageal Echocardiography During Cardiovascular Surgery in China.

OBJECTIVE: To perform a comprehensive nationwide survey of more than 90% of all cardiovascular hospitals in China to assess the current 2018 status of transesophageal echocardiography (TEE) equipment, operating physicians, education, impact on surgery, and reimbursement. DESIGN: In this nationwide survey, 716 cardiovascular hospitals in mainland China were included. A 15-question electronic survey was sent to these hospitals and the data were received directly from the questionnaire website for analysis. SETTING: Cardiovascular hospitals in mainland China. PARTICIPANTS: Departments of anesthesiology in cardiovascular hospitals in mainland China. INTERVENTIONS: Answer a 15-question survey. MEASUREMENTS AND MAIN RESULTS: About 90% of hospitals have acquired machines to perform TEEs with most of the machines controlled by the ultrasound department. Anesthesiologists performed intraoperative TEEs in 45% of the hospitals, but only 15% of the hospitals have anesthesiologists who have met the basic TEE training requirements. Most anesthesiologists (68%) believed TEE significantly contributed to patient care during cardiovascular surgeries. The overwhelming majority of surveyed hospital staff (93%) stated that they were planning to continue or start intraoperative TEE examinations in the future. CONCLUSION: Many hospitals in China have acquired equipment to perform intraoperative TEE examinations during cardiovascular surgeries. However, the number of anesthesiologists who can perform TEEs independently still is not adequate. Standardized trainings, a formal certification process, and governmental payment model changes must be provided to ensure high-quality TEE services and better surgical outcomes in China.

Diffusion-weighted imaging and diffusion kurtosis imaging for early evaluation of the response to docetaxel in rat epithelial ovarian cancer.

BACKGROUND: To investigate diffusion-weighted magnetic imaging (DWI) and diffusion kurtosis magnetic imaging (DKI) for the early detection of the response to docetaxel (DTX) chemotherapy in rat epithelial ovarian cancer (EOC). METHODS: 7,12-Dimethylbenz[A]anthracene was applied to induce orthotopic EOC in Sprague-Dawley rats. Rats with EOC were treated with DTX on day 0 (treatment group) or were left untreated (control group). DWI and DKI were performed on days 0, 3, 7, 14 and 21 after treatment. On day 21, the tumors were categorized into the sensitive and insensitive groups according to the size change. The cutoff values of the DWI and DKI parameters for the early response were determined. The experiment was repeated, and the treatment group was divided into the sensitive and insensitive groups according to the initially obtained cutoff values. The DWI and DKI parameters were correlated with tumor size, proliferation, apoptosis and tumor necrosis. RESULTS: In the sensitive vs. insensitive or control group, significant differences were found in the Δ% of the DWI and DKI parameters (ADC, D and K) from day 3 and in tumor size from day 14. Early on day 7, the Δ% of K had an AUC of 1 and sensitivity and specificity values of 100% and 100%, respectively, to detect the response to DTX using a cutoff value of 19.03% reduction in K. From day 7, significant differences were found in the Δ% of Ki-67 and CA125 in the sensitive vs. control group and from day 14 in the sensitive vs. insensitive group. From day 14, there were significant differences in the Δ% of Bcl-2, apoptosis and tumor necrosis in the sensitive vs. control or insensitive group. The Δ% values of ADC and D were negatively correlated with the Δ% values of tumor size, Ki-67, CA125 and Bcl-2 and were positively correlated with the Δ% values of apoptosis and tumor necrosis. The Δ% of K was positively correlated with the Δ% values of tumor size, Ki-67, CA125 and Bcl-2 and was negatively correlated with the Δ% values of apoptosis and tumor necrosis. CONCLUSIONS: DWI and DKI parameters, especially K, are superior for imaging tumor size for the early detection of the response to DTX chemotherapy in induced rat EOC.

Therapeutic plasma exchange: A prospective randomized trial to evaluate 2 strategies in patients with liver failure.

OBJECTIVE: To compare two means of performing therapeutic plasma exchange (TPE) in patients with liver failure. METHOD: This open-label monocentric randomized trial, conducted in a single prestigious general healthcare facility, recruited liver failure patients with an indication to receive artificial liver support therapy for TPE. All patients underwent TPE procedures and were administered in a random sequence: heparin-free or systemic heparinization with unfractionated heparin. The primary endpoint was completion of TPE sessions, and the secondary endpoints included the safety and efficacy. RESULTS: In the period of the studying, there were 164 patients being recruited in and underwent total of 398 randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2 of them (0.87%) were switched from heparin-free to unfractionated heparin eventually. No significant differences were found between the two groups for either RRs or IRs (P > 0.05). CONCLUSION: Heparin-free regimen is feasible and safer than systemic heparinization with unfractionated heparin in the process of TPEs in patients with liver failure.

Levels of six antibiotics used in China estimated by means of wastewater-based epidemiology.

Due to lack of proper regulation, information about antibiotics consumption in many countries such as China is difficult to obtain. In this study, a simple method based on wastewater-based epidemiology was adopted to estimate their usage in four megacities of China. Six antibiotics (norfloxacin, ofloxacin, sulfamethoxazole, trimethoprim, erythromycin and roxithromycin), which are the most frequently consumed antibiotics in China, were selected as the targets. Based on our results, Chongqing had the largest total annual consumption of the selected six antibiotics among the four megacities, followed by Guangzhou, then Hong Kong, with Beijing having the least, with values of 4.4 g/y/P, 4.0 g/y/P, 1.6 g/y/P, and 1.3 g/y/P, respectively. Compared with the daily consumption per capita in Italy, the estimated consumption levels of the selected six antibiotics in four cities of China were 12-41 times those of Italy. Our results suggested that the consumption of antibiotics in China was excessive.

Gp120 in the pathogenesis of human immunodeficiency virus-associated pain.

OBJECTIVE: Chronic pain is a common neurological comorbidity of human immunodeficiency virus (HIV)-1 infection, but the etiological cause remains elusive. The objective of this study was to identify the HIV-1 causal factor that critically contributes to the pathogenesis of HIV-associated pain. METHODS: We first compared the levels of HIV-1 proteins in postmortem tissues of the spinal cord dorsal horn (SDH) from HIV-1/acquired immunodeficiency syndrome patients who developed chronic pain (pain-positive HIV-1 patients) and HIV-1 patients who did not develop chronic pain (pain-negative HIV-1 patients). Then we used the HIV-1 protein that was specifically increased in the pain-positive patients to generate mouse models. Finally, we performed comparative analyses on the pathological changes in the models and the HIV-1 patients. RESULTS: We found that HIV-1 gp120 was significantly higher in pain-positive HIV-1 patients (vs pain-negative HIV-1 patients). This finding suggested that gp120 was a potential causal factor of the HIV-associated pain. To test this hypothesis, we used a mouse model generated by intrathecal injection of gp120 and compared the pathologies of the model and the pain-positive human HIV-1 patients. The results showed that the mouse model and pain-positive human HIV-1 patients developed extensive similarities in their pathological phenotypes, including pain behaviors, peripheral neuropathy, glial reactivation, synapse degeneration, and aberrant activation of pain-related signaling pathways in the SDH. INTERPRETATION: Our findings suggest that gp120 may critically contribute to the pathogenesis of HIV-associated pain.

Plant antifungal proteins and their applications in agriculture.

Fungi are far more complex organisms than viruses or bacteria and can develop numerous diseases in plants that cause loss of a substantial portion of the crop every year. Plants have developed various mechanisms to defend themselves against these fungi which include the production of low-molecular-weight secondary metabolites and proteins and peptides with antifungal activity. In this review, families of plant antifungal proteins (AFPs) including defensins, lectins, and several others will be summarized. Moreover, the application of AFPs in agriculture will also be analyzed.

Oxidation- and CaMKII-mediated sarcoplasmic reticulum Ca(2+) leak triggers atrial fibrillation in aging.

BACKGROUND: Advanced age is a well-recognized predisposition to atrial fibrillation (AF). However, the cellular electrophysiological changes that underlie the heightened susceptibility to AF in aged individuals remain poorly understood. Sarcoplasmic reticulum (SR) Ca(2+) leak that results from posttranslational modification of type 2 ryanodine receptor channels (RyR2) has been implicated in arrhythmogenesis. We hypothesize that aging alters atrial myocytes Ca(2+) homeostasis and RyR2 function, which create a substrate for AF initiation. METHODS AND RESULTS: We examined the susceptibility to AF in aged (24 months) and young adult (4-5 months) mice using an intraesophageal atrial electrical stimulation protocol. Aged mice showed significant higher AF induction rate (43.3%, n = 30) than young adults (8.8%, n = 34, P < 0.01). In accordance with these in vivo findings, significantly increased diastolic SR Ca(2+) leak and arrhythmogenic Ca(2+) activities with reduced SR Ca(2+) content were observed in aged atrial myocytes. Western blot showed RyR2 oxidation and phosphorylation at Ser2814 (Ca(2+) /calmodulin-dependent protein kinase II [CaMKII] site), but not phosphorylation at Ser2808 (protein kinase A [PKA] and CaMKII site), were increased in aged atrial myocytes. The selective CaMKII inhibitor (KN-93), as well as the antioxidant reagent (DTT) reversed the diastolic Ca(2+) leak and the frequency of spontaneous Ca(2+) transients in aged atrial myocytes, whereas PKA inhibition with H-89 was ineffective. CONCLUSIONS: Aging increases both the oxidation and CaMKII-phosphorylation of RyR2, which result in diastolic SR Ca(2+) leak and facilitate AF initiation. These results contribute to the electrophysiological remodeling of aged atria and suggest a therapeutic strategy for AF treatment in aging.

Advances in Research on Protein Arginine Methyltransferase 2: Functions and Diseases.

Protein arginine methylation stands as a prevalent post-translational modification process, exerting vital roles in cellular signal transduction, gene expression, and cell cycle regulation. Amidst the protein arginine methyltransferase (PRMT) family, PRMT2 stands as a less explored constituent. Nonetheless, its regulatory roles in transcriptional regulation, post-transcriptional modification, methylation activity regulation, immunoregulation, and developmental regulation have garnered attention. These capabilities enable PRMT2 to exert pivotal regulatory functions in certain malignancies, metabolic disorders, inflammatory diseases, and atherosclerosis. In this review, we highlight the structure and functions of PRMT2, emphasizing its association with diseases. We also discuss PRMT2 inhibitors and explore the potential for therapeutic targeting.

Integration of network pharmacology and serum medicinal chemistry to investigate the pharmacological mechanisms of QiZhuYangGan Decoction in the treatment of hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown. AIM OF THE STUDY: By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action. MATERIALS AND METHODS: The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl4 in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis. RESULT: Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization. CONCLUSIONS: QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD.