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Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits., (© 2024. The Author(s).)

Rationale: Intracranial atherosclerotic stenosis (ICAS) represents a prevalent global cause of stroke, posing a notably higher risk of stroke recurrence than other stroke etiologies. Herein, we report a case of a 39-year-old male patient diagnosed with ICAS, treated through an integrated approach incorporating Chinese and Western medicine with significant efficacy and satisfied clinical safety., Patient Concerns: This patient presented with 1 transient ischemic attack and prolonged headache, dizziness and poor sleep quality. In addition, the patient refused to undergo surgery due to the high cost and postoperative risks., Diagnoses: Diagnostic methods used to identify ICAS include conventional cerebral angiography, magnetic resonance angiography (MRA), CT angiography (CTA), transcranial Doppler ultrasound (TCD), and High-Resolution Magnetic resonance imaging. Considering the cost and risks associated with conventional angiography, noninvasive imaging has emerged as the method of choice for diagnosing ICAS. After a series of noninvasive examinations (CTA, TCD, and HR-MRI), the patient was diagnosed with ICAS., Interventions: The western medical regimen includes antiplatelet coagulation, blood pressure control, lipid regulation, plaque stabilization, and lifestyle modifications such as exercise, weight loss, and adherence to low-salt, low-fat diets. Complementing this, traditional Chinese medicine (TCM) treatment was guided by the principle of strengthening the spleen, resolving dampness, nourishing blood and harmonizing ying, resolving blood stasis and clearing collaterals. This involved the administration oral Chinese medicine such as modified Shenling Baizhu powder and modified Si Wu decoction., Outcomes: The efficacy of the treatment was assessed by evaluating the degree of luminal stenosis and peak systolic blood flow velocity in the M1 segment of the left middle cerebral artery (MCA) before and after the intervention. Encouragingly, posttreatment results demonstrated the disappearance of the plaque in the left MCA-M1 segment, with no significant lumen stenosis observed. Moreover, a notable and smooth reduction in blood flow velocity was achieved in the left MCA, indicating positive outcomes from the integrated traditional Chinese and Western medicine approach., Conclusion: This case report shows that a combination of traditional Chinese and Western medicine is safe and effective in the treatment of ICAS and is worthy of promotion in the clinic., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC., Methods: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m 2 intravenous infusion, day 1; capecitabine 1000 mg/m 2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14-15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed., Discussion: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer., Trial Registration: This study was registered at www., Clinicaltrials: gov ., Trial Registration Number: NCT05972655. Date of registration: 31 July 2023., (© 2024. The Author(s).)

Background: With the release of the coronavirus disease 2019 (COVID-19) pandemic in late 2022 in China, the number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) roared, including neonatal cases. However, there were few studies on neonatal COVID-19, especially multi-center case reports. This study aimed to explore clinical characteristics and short-term outcomes of neonatal COVID-19 in China., Methods: We reviewed 187 cases of neonatal COVID-19 between December 11, 2022, and January 12, 2023. The diagnosis was assessed by symptoms, laboratory tests, X-ray manifestations, and diagnosis code. Clinical characteristics and outcomes were evaluated., Results: In 187 neonatal cases with COVID-19, 84 (44.9%) had severe SARS-CoV-2 infection. Most patients had confirmed exposure to SARS-CoV-2. Fever and respiratory symptoms were common (75.4% and 71.7%, respectively). Severe patients were more likely to have high alanine transaminase (ALT) (> 40U/L) (11.9% vs. 3.9%) and high N-terminal pro-brain natriuretic peptide (NT-proBNP) (> 2000pg/mL) (38.0% vs. 19.6%), compared with nonsevere ones (P < 0.05). None of the patients received COVID-19-specific medical interventions. A few severe patients received corticosteroids (1.1%), and immunoglobulin (0.5%), respectively. All patients were discharged home after the medical care with a median length of stay (LOS) of four days and none of them met the criteria of multisystem inflammatory syndrome in neonates (MIS-N)., Conclusions: After the release of the epidemic situation of COVID-19 in late 2022 in China, more neonatal cases with severe COVID-19 had high ALT and NT-proBNP level. Few specific medical interventions were given, and the outcome was satisfying., (© 2024. The Author(s).)

Background: To evaluate the impact of implementation of 2019 European respiratory distress syndrome (RDS) guidelines on the incidence of bronchopulmonary dysplasia (BPD)., Method: We retrospectively collected the clinical data of very preterm infants (VPIs) born before 32 gestational weeks from January 1st 2018 to December 31st 2021. VPIs were divided into group A and group B according to their birth date which was before or at/after January 1st 2020, when the 2019 European RDS guidelines were introduced. BPD is considered as primary outcome. We statistically analyzed all the data, and we compared the general characteristics, ventilation support, medication, nutrition and the outcomes between the two groups., Results: A total of 593 VPIs were enrolled, including 380 cases in group A and 213 cases in group B. There were no statistic differences regarding to gender ratio, gestational age, birth weight and delivery mode between the two groups. Compared with group A, group B showed higher rate of antenatal corticosteroid therapy (75.1% vs. 65.5%). The improvement of ventilation management in these latter patients included lower rate of invasive ventilation (40.4% vs. 50.0%), higher rate of volume guarantee (69.8% vs. 15.3%), higher positive end expiratory pressure (PEEP) [6 (5, 6) vs. 5 (5, 5) cmH 2 O] and higher rate of synchronized nasal intermittent positive pressure ventilation (sNIPPV) (36.2% vs. 5.6%). Compared with group A, group B received higher initial dose of pulmonary surfactant [200 (160, 200) vs. 170 (130, 200) mg/Kg], shorter antibiotic exposure time [13 (7, 23) vs. 17 (9, 33) days], more breast milk (86.4% vs. 70.3%) and earlier medication for hemodynamically significant patent ductus arteriosus (hsPDA) treatment [3 (3, 4) vs. 8 (4, 11) days] (p < 0.05). As the primary outcome, the incidence of BPD was significantly decreased (16.9% vs. 24.2%) (p < 0.05), along with lower extrauterine growth retardation (EUGR) rate (39.0% vs. 59.7%), while there were no statistic differences regarding to other secondary outcomes, including mortality, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of preterm (ROP) and necrotizing enterocolitis (NEC). However, in the subgroups of infants less than 28 gestational weeks or infants less than 1,000 g, the incidence of BPD was not significantly decreased (p > 0.05)., Conclusions: After implementation of 2019 European RDS guidelines, the overall incidence of BPD was significantly decreased in VPIs. Continuous quality improvement is still needed in order to decrease the incidence of BPD in smaller infants who are less than 28 gestational weeks or less than 1,000 g., (© 2024. The Author(s).)

Background: Continuous renal replacement therapy (CRRT) is commonly used for the treatment of acute kidney injury (AKI) in critically ill neonates. This study investigated the effectiveness and feasibility of CRRT for AKI in neonates who weigh ≤3 kg., Methods: Data from 19 neonates with a weight ≤3 kg and AKI who underwent CRRT at two centres between January 2015 and October 2021 were collected retrospectively. Kidney function, circulatory function, complications and clinical outcomes were recorded. Repeated-measures analyses of variance, t-tests and non-parametric tests were conducted., Results: The median patient age at CRRT initiation was 3 days (IQR: 1-7 days). The median patient weight at CRRT initiation was 2.67 kg (IQR: 2.20-2.85 kg). The median CCRT duration was 46 hours (IQR: 32-72 hours). The serum creatinine and blood urea nitrogen levels decreased significantly, and the mean arterial pressure increased significantly after 12 hours of CRRT and at the end of CRRT. The urinary output was significantly increased at the end of CRRT. 11 patients had thrombocytopaenia, 6 had electrolyte disorders and 3 had blocked tubes. Five patients were discharged, six died after their parents chose to discontinue treatment and eight died after active treatment. Weight at CRRT initiation and urinary output at the end of CRRT were significantly lower among patients who died than among patients who survived., Conclusions: CRRT is feasible and effective for AKI in neonates who weigh ≤3 kg when accompanied by elaborate supportive care. Lower body weight and persistent oliguria may be correlated with an increased risk of poor clinical outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aims to investigate the effects of hyperoxia exposure on TGF-β1-induced endothelial-mesenchymal transition (EndoMT) and regulatory T cell (Treg)-mediated immunomodulation in human pulmonary microvascular endothelial cells (HPMECs), which could provide a theoretical basis for further studies of the pathogenesis of bronchopulmonary dysplasia (BPD)., Methods: A BPD cell model was established by exposing HPMECs to hyperoxia. Flow cytometry was used to isolate CD4 + CD3 + CD25 + CD127- Tregs from the peripheral blood samples of preterm infants. HPMECs were divided into four groups based on whether they were exposed to hyperoxia and/or co-cultured with Tregs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to test the expression levels of TGF-β1, α-SMA, Foxp3, IL-10, and reactive oxygen species (ROS)., Results: The results showed that the expression levels of TGF-β1 and α-SMA in HPMECs increased at 24 h, 48 h, and 72 h of hyperoxia exposure. In the co-culture group of HPMECs and Tregs, Foxp3 and IL-10 expressions decreased at 48 h and 72 h of hyperoxia exposure. ROS expression increased in the hyperoxia group of HPMECs at 24 h, 48 h, and 72 h of hyperoxia exposure, which were higher than those in the hyperoxia group of HPMECs and Tregs., Conclusion: These findings suggest that hyperoxia exposure promotes EndoMT in HMPECs and inhibits the immunosuppressive effect of Tregs. Despite this, Tregs still seem could protect HPMECs from oxidative stress injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Sun, Yan, Liu, Lin, Weng, Gong and Cai.)

Objectives: To investigate the role and mechanism of epithelial-mesenchymal transition (EMT) in a rat model of bronchopulmonary dysplasia (BPD)., Methods: The experiment consisted of two parts. (1) Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group, with 24 rats in each group. The hyperoxia group was exposed to 85% oxygen to establish a BPD model, while the normoxia group was kept in room air at normal pressure. Lung tissue samples were collected on days 1, 4, 7, and 14 of the experiment. (2) Rat type II alveolar epithelial cells (RLE-6TN) were randomly divided into a normoxia group (cultured in air) and a hyperoxia group (cultured in 95% oxygen), and cell samples were collected 12, 24, and 48 hours after hyperoxia exposure. Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs, and immunofluorescence was used to detect the co-localization of surfactant protein C (SPC) and α-smooth muscle actin (α-SMA) in preterm rat lung tissue and RLE-6TN cells. Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells., Results: (1) Compared with the normoxia group, the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure. Co-localization of SPC and α-SMA was observed in lung tissue, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group. In the hyperoxia group, the mRNA and protein levels of TGF-β1, α-SMA, and N-cadherin were increased, while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group ( P <0.05). (2) SPC and α-SMA was observed in RLE-6TN cells, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group. Compared to the normoxia group, the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased, while the mRNA and protein levels of TGF-β1, α-SMA, and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure ( P <0.05)., Conclusions: EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD, leading to simplified alveolar structure and abnormal development, and is involved in the development of BPD. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 765-773 .

Background: Female sex has long been recognized to present a higher risk of stroke and atrial fibrillation (AF) recurrence after circumferential pulmonary vein isolation (CPVI) than in males. However, the underlying mechanisms and benefits of additional low-voltage area (LVA) modification in women remain unknown., Objective: The purpose of this study was to investigate differences in atrial substrate and efficacy of additive LVA ablation between sex subgroups., Methods: Patients with paroxysmal atrial fibrillation (PAF) aged 65-80 years were randomly assigned to either CPVI plus LVA modification (STABLE-SR) group or CPVI alone group. The primary outcome was freedom from atrial arrhythmias after a single ablation procedure., Results: Of 414 patients included in STABLE-SR-III, 204 (49.3%) were women (mean age 70.5 ± 4.7 years). Women demonstrated significantly higher LVA prevalence (51.5% vs 32.9%; P <.001) and LVA burden (6.5% vs 2.9%; P <.001) than men. In the STABLE-SR group, additional LVA ablation was associated with a 63% reduction in recurrence for women compared with the CPVI alone group (10.8% vs 29.4%; adjusted hazard ratio 0.37; 95% confidence interval 0.18-0.75; P for interaction = .040). However, this finding was not observed in men (18.7% vs 18.5%). In the female subgroup, both group 1 (CPVI + LVA modification) and group 3 (CPVI alone in females without LVA) had similar clinical outcomes, which were much better than in Group 2 (CPVI alone in women with LVA) (90% vs 83.8% vs 63.6%; P = .003)., Conclusion: In older patients with PAF, women demonstrated more advanced atrial substrate, including higher prevalence and burden of LVA compared with men. Women may receive greater benefit from additional LVA modification than men., Competing Interests: Disclosures Dr Chen reports receiving lecture fee from Biosense Webster, St. Jude Medical, Medtronic, Bayer, and Boehringer Ingelheim. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate gestational age-specific hematological features in preterm infants with necrotizing enterocolitis (NEC) and identify predictive hematological biomarkers for surgical NEC., Methods: We conducted a retrospective study comparing gestational age (GA)-specific clinical data between medical NEC (m-NEC) and surgical NEC (s-NEC) subgroups, stratified by GA as <28 weeks, 28 ≤ GA < 32 weeks, and 32 ≤ GA < 37 weeks. Multivariate logistic analysis and receiver operating characteristic curve were used to identify the independent predictors of s-NEC., Results: In comparison to m-NEC at NEC onset, s-NEC infants exhibited the following findings: In GA < 28 weeks, s-NEC infants had lower platelet counts. In 28 ≤ GA < 32 weeks, lower absolute lymphocyte counts, and significant percent drop in platelets, lymphocytes, and monocytes were observed. In 32 ≤ GA < 37 weeks, lower absolute lymphocyte counts and significant percent drop in lymphocytes were found. Independent predictors were able to distinguish s-NEC from m-NEC. The area under the curve (AUC) for platelet counts in GA < 28 weeks was 0.880, while C-reactive protein in 28 ≤ GA < 32 weeks had an AUC of 0.889. The AUC for lymphocyte counts in 32 ≤ GA < 37 weeks was 0.892., Conclusion: This study identified hematological abnormalities in the development of NEC based on gestational age. Independent predictors may help clinicians distinguish surgical NEC from medical NEC., Impact: Necrotizing enterocolitis (NEC) patients with different gestational ages (GA) exhibit different hematological features and independent predictors of surgical NEC differ among different GAs. Our research made the current studies about peripheral hematological features with NEC more complete by analyzing peripheral data collected within 24 h of birth, at day 5-7, day 3-4, day 1-2 before NEC onset, at the time of NEC onset, day 1, day 2, day 3, day 4-5, day 6-7 after NEC onset. Our study is helpful to clinicians in developing a more detailed diagnostic strategy based on GA for the early identification of surgical NEC., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Decitabine (DAC), a DNA methyltransferase inhibitor, has shown efficacy combined with chemotherapy for relapsed or refractory (R/R) acute myeloid leukemia (AML) in adults, but less is known about its efficacy in children. Accordingly, we conducted a study which involved a priming regimen consisting of DAC with cladribine, cytarabine, and granulocyte-stimulating factor (DAC-CLAG) and compared the efficacy and safety of this regimen with CLAG alone., Methods: A total of 39 R/R AML children who received the CLAG or DAC-CLAG regimen in Shanghai Children's Hospital were retrospectively enrolled in this non-randomized study. These regimens were studied sequentially over time. Twenty-two patients received CLAG from 2015, while 17 patients were administered epigenetic priming with DAC before CLAG from 2020. Patients were subsequently bridged to stem cell transplantation (SCT) or consolidation chemotherapy. Complete remission (CR) and adverse effects were analyzed by Fisher's exact test, and survival was analyzed by the Kaplan-Meier method., Results: DAC-CLAG conferred a numerically higher CR compared to CLAG (70.59% vs 63.64%; P = 0.740). High CR rates occurred in patients with good cytogenetics (P = 0.029) and prior induction without cladribine (P = 0.099). The 1-year event-free survival (EFS) was 64.71% ± 11.59% and 63.31% ± 10.35% in the DAC-CLAG and CLAG group (P = 0.595), and 1-year overall survival (OS) was 81.45% ± 9.72% and 77.01% ± 9.04%, respectively (P = 0.265). The 1-year OS and EFS after SCT were higher in the DAC-CLAG than in the CLAG cohort (100% vs 92.31% ± 7.39%, P = 0.072; 92.31% ± 7.39% vs 85.71% ± 9.35%, P = 0.158). Univariate analysis revealed that a good prognosis included good cytogenetics (P = 0.002), non-complex karyotype (P = 0.056), CR on reinduction (P < 0.0001), and bridging to SCT (P = 0.0007). Use of a hypomethylating agent (P = 0.049) and bridging to SCT (P = 0.011) were independent prognostic factors. Grade 3/4 hematologic toxicity and infection were the main adverse events., Conclusions: DAC prior to the CLAG regimen improved remission in pediatric R/R AML, and was feasible and well tolerated. CLAG ± DAC as a salvage therapy prior to SCT induced improved survival., (© 2024. The Author(s).)

Objective: High mortality and extrauterine growth retardation (EUGR) remain serious problems in preterm infants after necrotizing enterocolitis (NEC) surgery. This study investigated the risk factors for mortality and EUGR in preterm infants after NEC surgery., Study Design: The risk factors were analyzed retrospectively by univariate analysis and multivariate logistic regression analysis in 52 preterm infants, who underwent NEC surgery and were hospitalized in neonatology department of Shanghai Children's Hospital between May 2014 and December 2021. Patients were divided into survival and death groups. Survivors were divided into two groups according to whether EUGR occurred when they achieved full enteral feeding after surgery., Results: The mortality of preterm infants after NEC surgery was 26.9% (14/52). About 55.3% (21/38) of survivors developed postoperative EUGR. (1) Age at surgery, proportion of shock, and intestinal perforation differed significantly between the survival and death groups ( p  = 0.001, 0.005, and 0.02, respectively). Shock ( p  = 0.02, odds ratio [OR] = 8.86, 95% confidence interval [CI]: 1.43-55.10) and intestinal perforation ( p  = 0.03, OR = 6.12, 95% CI: 1.16-32.41) were significant risk factors for death. (2) Compared with the non-EUGR group, proportion of preoperative EUGR, postoperative 1-week calories, and parenteral nutrition time differed significantly in EUGR group ( p  = 0.001, 0.01, and 0.04, respectively). Preoperative EUGR ( p  = 0.02, OR = 18.63, 95%CI: 1.77-196.42) was a significant risk factor for postoperative EUGR., Conclusion: Shock and intestinal perforation are significant risk factors for death in preterm infants after NEC surgery. Survivors are prone to EUGR, and preoperative EUGR is a significant risk factor. In addition, adequate caloric intake and achievement of full enteral feeding as soon as possible may be beneficial to improve EUGR of preterm infants after NEC surgery., Key Points: · Shock and intestinal perforation are risk factors for death in preterm infants after NEC surgery.. · Preoperative EUGR is a risk factor for postoperative EUGR in preterm infants after NEC surgery.. · Active correction of shock and avoiding intestinal perforation may help improve the outcomes.., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Au nanotube-based composite membrane served as surface-enhanced Raman scattering (SERS) substrate with an ultralarge aspect ratio possesses an excellent flexibility and widely tunable surface plasmon resonance, and by introducing graphene oxide (GO) as a spacer layer, the SERS enhancement of the composite membrane is obviously better than those from the individual blocks of the Au nanotubes (AuNTS) membrane and the Au nanoparticle/graphene oxide (AuNP/GO) membrane. Such a "sandwich" (AuNP/GO/AuNT) structured membrane has a high SERS sensitivity and a wide tunability by controlling the size of Au nanoparticles and the thickness of graphene oxide, and the detection limits of the AuNP/GO/AuNT substrate for R6G and NBA are as low as 10 -12 and 10 -7 M, respectively; the large enhancement is attributed to the adsorption and chemical mechanism of graphene oxide and the physical mechanism of the Au nanoparticles and nanotubes (the electromagnetic field coupling between them).

Competing Interests: The authors have no conflicts to disclose.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus . Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro , the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Transition metal dichalcogenide (TMD) heterobilayers have emerged as a promising platform for exploring solid-state quantum simulators and many-body quantum phenomena. Their type II band alignment, combined with the moiré superlattice, inevitably leads to nontrivial exciton interactions and dynamics. Here, we unveil the distinct Auger annihilation processes for delocalized interlayer excitons in WS 2 /WSe 2 moiré heterobilayers. By fitting the characteristic efficiency droop and bimolecular recombination rate, we quantitatively determine an ultralow Auger coefficient of 1.3 × 10 -5 cm 2 s -1 , which is >100-fold smaller than that of excitons in TMD monolayers. In addition, we reveal selective exciton upconversion into the WSe 2 layer, which highlights the significance of intralayer electron Coulomb interactions in dictating the microscopic scattering pathways. The distinct Auger processes arising from spatial electron-hole separation have important implications for TMD heterobilayers while endowing interlayer excitons and their strongly correlated states with unique layer degrees of freedom.

To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). This retrospective study was conducted at two tertiary care children's hospitals between January 2015 and May 2022. A total of 26 neonates with septic shock and AKI were included in this study, with a mortality rate of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, and 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indices before CBP, urine output increased 12 h after CBP initiation (P = 0.003) and serum creatinine decreased (P = 0.019). After 24 h of CBP, blood urea nitrogen had decreased (P = 0.006) and mean arterial pressure had increased (P = 0.007). At the end of CBP, the vasoactive-inotropic score and blood lactate were decreased (P = 0.035 and 0.038, respectively) and PH was increased (P = 0.015). Thrombocytopenia was the most common complication of CBP.  Conclusion: CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality rate remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear. What is Known: • Over 50% of children with septic shock have severe AKI, of which 21.6% required CBP. • The clinical application of CBP in septic shock has attracted increasing attention. What is New: • CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. • The mortality rate in neonates with septic shock and AKI receiving CBP remains high., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina., Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study., Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk., Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants., Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda . This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Ma, Long, Yan, Peng, Cai, Zhong, Huang, Qiao, Zhou, Cai, Cheng, Zhou, Han, Liu, Zhang, Tang, Meng and Luo.)

Competing Interests: Competing interests: None declared.

Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) is clinically and genetically heterogeneous, with concurrent RB1/TP53 mutations, indicating an increased risk of transformation into small cell lung cancer (SCLC). When tumor cells convert into a different histological subtype, they lose their dependence on the original oncogenic driver, resulting in therapeutic resistance. However, the molecular details associated with this transformation remain unclear. It has been difficult to define molecular mechanisms of neuroendocrine (NE) transformation in lung cancer due to a lack of pre- and post-transformation clinical samples. In this study, we established a NSCLC cell line with concurrent RB1/TP53 mutations and built corresponding patient-derived xenograft (PDX) models to investigate the mechanisms underlying transformation to SCLC. Studying these PDX models, we demonstrate that EGFR loss facilitates lineage plasticity of lung adenocarcinoma initiated by biallelic mutations of TP53 and RB1. Gene expression analysis of these EGFR knockout tumors revealed altered expression of neuroendocrine synapse-associated lineage genes. There is an increased expression of epigenetic reprogramming factors like Sox2 and gene associated with neural development like NTRK in these EGFR knockout tumors. These findings uncovered the role of EGFR in the acquisition of plasticity, which is the ability of a cell to substantially modify its identity and take on a new phenotype, and defined a novel landscape of potential drivers of NE transformation in lung cancer., Competing Interests: Declaration of competing interest The authors of the above-mentioned paper have no affiliations or associations with any organization/entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In recent years, numerous guidelines and expert consensuses have recommended that digital technologies and products, such as digital therapeutics (DTx), be incorporated into cardiac rehabilitation (CR)., Objective: The study aims to compare the cost-effectiveness of DTx for home-based CR (HBCR) with that of the conventional HBCR for patients with atrial fibrillation (AF) after catheter ablation in a real-world clinical setting., Methods: Based on a single-center, prospective, blinded, randomized, parallel controlled trial of DTx-based HBCR for AF patients after catheter ablation, 100 AF patients undergoing catheter ablation were selected and randomized at a 1:1 ratio into a UC group (conventional HBCR) and DT group (DTx-based HBCR). The intervention lasted for 12 weeks. Medical cost data and clinical efficacy data (VO 2 max) were acquired from trial data. Effect data (QALYs, anxiety and depression status, health beliefs related to cardiovascular disease, and exercise self-efficacy) were obtained from a patient questionnaire. The cost-effectiveness analysis was conducted to assess the economic benefits of DTx-based HBCR versus conventional HBCR, and the robustness of the results was verified by sensitivity analysis., Results: In the DT group (n = 49), the mean QALYs increased 0.119 ± 0.09, VO 2 max increased 9.3 ± 8.0 mL/(min*kg), anxiety, depression, health belief, and exercise self-efficacy had improved, and the total medical cost was 75,080.55 ± 19,746.62 CNY. In the UC group (n = 48), the mean QALYs increased 0.077 ± 0.06, VO 2 max increased 4.9 ± 6.6 mL/(min*kg), anxiety, depression, health belief, and exercise self-efficacy had improved, and the total medical cost was 73,972.66 ± 16,582.04 CNY. The difference in the medical cost was 1107.89 CNY, and the incremental cost-effectiveness ratio was 33,572.42 CNY/QALY, which was lower than the willingness-to-pay threshold of 85,698 CNY (China's per capita GDP in 2022)., Conclusion: DTx-based HBCR is more effective and cost-effective than conventional HBCR., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background and Aim: Our previous study has revealed that OEA promotes motor function recovery in the chronic stage of ischemic stroke. However, the neuroprotective mechanism of OEA on motor function recovery after stroke still is unexplored. Therefore, the aim of this study was to explore the effects of OEA treatment on angiogenesis, neurogenesis, and white matter repair in the peri-infarct region after cerebral ischemia., Experimental Procedure: The adult male rats were subjected to 2 h of middle cerebral artery occlusion. The rats were treated with 10 and 30 mg/kg OEA or vehicle daily starting from day 2 after ischemia induction until they were sacrificed., Key Results and Conclusions: The results revealed that OEA increased cortical angiogenesis, neural progenitor cells (NPCs) proliferation, migration, and differentiation. OEA treatment enhanced the survival of newborn neurons and oligodendrogenesis, which eventually repaired the cortical neuronal injury and improved motor function after ischemic stroke. Meanwhile, OEA treatment promoted the differentiation of oligodendrocyte progenitor cells (OPCs) and oligodendrogenesis by activating the PPARα signaling pathway. Our results showed that OEA restores motor function by facilitating cortical angiogenesis, neurogenesis, and white matter repair in rats after ischemic stroke. Therefore, we demonstrate that OEA facilitates functional recovery after ischemic stroke and propose the hypothesis that the long-term application of OEA mitigates the disability after stroke., (© 2023 John Wiley & Sons Ltd.)

Background: The autonomic nervous system can be responsible for the initiation and maintenance of arrhythmias. Low-level tragus stimulation (LLTS), a noninvasive form of autonomic neuromodulation, has been shown to be effective in treating atrial fibrillation. We intended to treat frequent premature ventricular complexes (PVCs) with LLTS., Methods and Design: The present study will be a prospective multicenter, double-blind, randomized, controlled trial to assess the antiarrhythmic effects of LLTS on frequent PVCs in patients without structured heart disease (SHD). A total of 100 patients with PVC burden > 10% will be randomly assigned to the active or sham LLTS in 1:1 fashion and receive the proposed intervention for 6 months. The primary outcome is PVC burden at 6 months as assessed by 10 days of continuous ambulatory electrocardiographic monitoring. Secondary outcomes include heart rate variability (HRV), quality of life, skin sympathetic nerve activity, and inflammatory markers. Adverse events will also be recorded., Discussion: The present trial will be the first to evaluate the effect of LLTS on frequent PVCs on patients without SHD. LLTS may serve as a low-cost, minimal-risk, and non-invasive alternative to conventional antiarrhythmic therapy., Trial Registration: ClinicalTrial.gov NCT04909528. Registered on 17 June 2021. World health organization trial registration data set was shown in Supplementary Table 1., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Oxidative stress and inflammation have proven to be key factors contributing to the occurrence of BPD. Erythromycin has been shown to be effective in treating the redox imbalance seen in many non-bacterial infectious chronic inflammatory diseases. Methods: Ninety-six premature rats were randomly divided into air + saline chloride group, air + erythromycin group, hyperoxia + saline chloride group and hyperoxia + erythromycin group. Lung tissue specimens were collected from 8 premature rats in each group on days 1, 7 and 14, respectively. Results: Pulmonary pathological changes in premature rats after hyperoxia exposure were similar to those of BPD. Hyperoxia exposure induced high expression of GSH, TNF-α, and IL-1β. Erythromycin intervention caused a further increase in GSH expression and a decrease in TNF-α and IL-1β expression. Conclusion: GSH, TNF-α and IL-1β are all involved in the development of BPD. Erythromycin may alleviate BPD by enhancing the expression of GSH and inhibiting the release of inflammatory mediators.

Peroxisome proliferator-activated receptor alpha (PPARα) activation-induced hepatomegaly is accompanied by hepatocyte hypertrophy around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area. However, the molecular mechanisms underlying this spatial change of hepatocytes remains unclear. In this study, we examined the characteristics and possible reasons for the zonation distinction of hypertrophy and proliferation during PPARα activation-induced mouse liver enlargement. Mice were injected with corn oil or a typical mouse PPARα agonist WY-14643 (100 mg·kg -1 ·d -1 , i.p.) for 1, 2, 3, 5 or 10 days. At each time point, the mice were sacrificed after the final dose, and liver tissues and serum were harvested for analysis. We showed that PPARα activation induced zonal changes in hepatocyte hypertrophy and proliferation in the mice. In order to determine the zonal expression of proteins related to hepatocyte hypertrophy and proliferation in PPARα-induced liver enlargement, we performed digitonin liver perfusion to separately destroy the hepatocytes around the CV or PV areas, and found that PPARα activation-induced increase magnitude of its downstream targets such as cytochrome P450 (CYP) 4 A and acyl-coenzyme A oxidase 1 (ACOX1) levels around the CV area were higher compared with those around the PV area. Upregulation of proliferation-related proteins such as cell nuclear antigen (PCNA) and cyclin A1 (CCNA1) after WY-14643-induced PPARα activation mainly occurred around the PV area. This study reveals that the zonal expression of PPARα targets and proliferation-related proteins is responsible for the spatial change of hepatocyte hypertrophy and proliferation after PPARα activation. These findings provide a new insight into the understanding of PPARα activation-induced liver enlargement and regeneration., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Major depressive disorder (MDD) is a devastating psychiatric disease, and current therapies could not well meet the demand for MDD treatment. Exercise benefits mental illness, and notably, exercise has been recommended as an alternative option for MDD treatment in some countries. However, the paradigm and intensity of exercise for MDD treatment has yet to be determined. High-intensity interval training (HIIT) is a potent and time-efficient type of exercise training and has gained popularity in recent years. In this study, we exposed the mice to chronic unpredictable mild stress (CUMS) and found HIIT exerted substantial antidepressant effect. Moreover, HIIT further enhanced the antidepressant effect of fluoxetine, a classic antidepressant in the clinic, confirming the antidepressant role of HIIT. HIIT significantly reversed the CUMS-induced upregulations in HDAC2 mRNA and protein level in the ventral hippocampus. We also found HIIT rescued the CUMS-induced downregulation in the expression of brain-derived neurotrophic factor (BDNF) and HDAC2 overexpression counteracted the HIIT-induced increase in BDNF level. More importantly, both virus-mediated HDAC2 overexpression and microinfusion of TrkB-Fc, a BDNF scavenger, in the ventral hippocampus abolished the antidepressant effect of HIIT. Together, our results strongly demonstrate that HIIT attenuates depressive behaviors, probably via HDAC2-BDNF signaling pathway and reveal that HIIT may serve as an alternative option for MDD treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study., Methods: We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs . ≤3 days) from the intended date. Dose reduction (actual dose/standard dose * 100%) ≤85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m 2 ) regimen for all cycles. Relative dose intensity (RDI) ≤80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan-Meier and Cox proportional hazard models., Results: There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay ( p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and <0.001, respectively. Patients with high 5-FU RDI had better PFS than patients with low 5-FU RDI ( p < 0.001). While, there was no statistical difference in OS between the two groups. Then we stratified the analysis by age. In <65 years cohort, both PFS and OS were better in patients with high 5-Fu RDI than in those with low 5-Fu RDI ( p < 0.001, p = 0.005, respectively). But, in ≥65 years cohort, OS were better in patients with low 5-Fu RDI than in those with high 5-Fu RDI ( p = 0.025). Moreover, both dose reduction and RDI of irinotecan had no statistically significant difference in both PFS and OS., Conclusion: In the advanced colorectal cancer patients who received FOLFIRI based treatment as first-line regimen, chemotherapy dose delay and reduction dose of 5-Fu were associated with worse survival, especially among patients younger than 65 years., Competing Interests: The authors declare that they have no competing interests., (© 2023 Zhang et al.)

Background: The incidence of oropharyngeal squamous cell carcinomas (OPSCC) has increased in recent decades, and human papillomavirus (HPV) infection is the main cause of OPSCC. The data regarding causes of death (CODs) are vitally important in informing follow-up strategies and revising treatment strategies to deal with any possible preventable treatment-related COD. However, limited studies have assessed the competing COD by HPV status in patients with OPSCC., Objective: We aimed to analyze the distribution of the competing COD according to HPV status in OPSCC., Methods: We retrospectively included stage I-IVB patients with OPSCC from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The association between HPV status and head and neck cancer-specific mortality (HNCSM), second primary cancer mortality (SPCM), and noncancer-caused mortality (NCCM) were analyzed. The chi-square test, Kaplan-Meier analysis, and Fine and Gray model were used for statistical analysis., Results: We included 5852 patients in this study and 73.2% (n=4283) of them had HPV-related tumors. A total of 1537 (26.3%) patients died, including 789 (51.3%), 333 (21.7%), and 415 (27%) patients who died from head and neck cancer, second cancer, and noncancer causes, respectively. The 5-year HNCSM, SPCM, NCCM, and overall mortality were 14.7%, 6.5%, 7.7%, and 26.4%, respectively. Those with HPV-positive disease had a lower cumulative incidence of HNCSM (subdistribution hazard ratio [sHR] 0.362, 95% CI 0.315-0.417; P<.001), SPCM (sHR 0.400, 95% CI 0.321-0.496; P<.001), and NCCM (sHR 0.460, 95% CI 0.378-0.560; P<.001) than those with HPV-negative disease. The 5-year risk of HNCSM was 26.9% and 10.7% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of SPCM was 12.4% and 4.6% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of NCCM of death was 13.7% and 5.8% in those with HPV-negative and HPV-positive disease, respectively (P<.001). Using the Fine and Gray competing-risks model, our results show that those with HPV-negative tumors had a significantly higher risk of HNCSM (P<.001), SPCM (P<.001), and NCCM (P<.001) than those with HPV-negative tumors., Conclusions: HPV-positive OPSCC has a lower NCSM, SPCM, and NCCM as compared to those with HPV-negative OPSCC. HPV positivity is a favorable prognostic factor in the context of overcoming cancer as well as in terms of reducing the risk of other CODs in OPSCC. Our finding supports the need to tailor patient follow-up based on the HPV status of patients with OPSCC., (©Dong-Dong Zhang, Min Lei, Yue Wang, Pei-Ji Zeng, Yong-Jun Hong, Cheng-Fu Cai. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 29.08.2023.)

Light absorption and scattering exist in the underwater environment, which can lead to blurring, reduced brightness, and color distortion in underwater images. Polarized images have the advantages of eliminating underwater scattering interference, enhancing contrast, and detecting material information of the object in underwater detection. In this paper, from the perspective of polarization imaging, different concentrations (0.15 g/ml, 0.30 g/ml, and 0.50 g/ml), different wave bands (red, green, and blue), different materials (copper, wood, high-density PVC, aluminum, cloth, foam, cloth sheet, low-density PVC, rubber, and porcelain tile), and different depths (10 cm, 20 cm, 30 cm, and 40 cm) are set up in a chamber for the experimental environment. By combining the degradation mechanism of underwater images and the analysis of polarization detection results, it is proved that the degree of polarization images have greater advantages than degree of linear polarization images, degree of circular polarization images, S1, S2, and S3 images, and visible images underwater. Finally, a fusion algorithm of underwater visible images and polarization images based on compressed sensing is proposed to enhance underwater degraded images. To improve the quality of fused images, we introduce orthogonal matching pursuit (OMP) in the high-frequency part to improve image sparsity and consistency detection in the low-frequency part to improve the image mutation phenomenon. The fusion results show that the peak SNR values of the fusion result maps using OMP in this paper are improved by 32.19% and 22.14% on average over those using backpropagation and subspace pursuit methods. With different materials and concentrations, the underwater image enhancement algorithm proposed in this paper improves information entropy, average gradient, and standard deviation by 7.76%, 18.12%, and 40.8%, respectively, on average over previous algorithms. The image NIQE value shows that the image quality obtained by this paper's algorithm is improved by about 69.26% over the original S0 image.

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients with extensive right ventricular free wall (RVFW) abnormal substrate, large-area homogenization with combined epicardial and endocardial approach is time consuming and often inadequate for modification., Objectives: This study aimed to explore the feasibility and efficacy of RVFW abnormal substrate isolation in such patients to control ventricular tachycardia (VT)., Methods: Eight consecutive ARVC patients with VT who had extensive abnormal RVFW substrate were included. VT induction was performed before substrate mapping and modification. Detailed voltage mapping was done during sinus rhythm. A circumferential linear lesion was deployed along the border zone of low-voltage area on the RVFW to achieve electrical isolation. Other small areas with fractionated or late potentials were further homogenized., Results: All 8 patients had RVFW endocardial low-voltage area. The entire RV low-voltage area was 113.8 ± 84.1 cm 2 (49.6% ± 29.8%) and the dense scar was 59.6 ± 39.8 cm 2 (25.0% ± 14.1%). Electrical isolation of abnormal substrate was achieved in 5 of 8 (62.5%) patients via endocardial approach alone and 3 of 8 (37.5%) patients via a combination of endocardial and epicardial approach. Electrical isolation was verified by slow automaticity (5 of 8, 62.5%) or RV noncapture (3 of 8, 37.5%) during high-output pacing inside the encircled area. VTs were induced in 6 patients before ablation, and all patients were rendered noninducible after ablation. During a median follow-up of 43 months (range: 24-53 months), 7 of 8 (87.5%) patients remained free of sustained VT., Conclusions: Electrical isolation of RVFW is feasible and can be the option in ARVC patients with extensive abnormal substrate., Competing Interests: Funding Support and Author Disclosures This trial was supported by National key research and development program of China (2017YFC1307800). Dr Chen has received lecture fees from Biosense Webster, St. Jude Medical, Medtronic, Bayer, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The basolateral amygdala (BLA) neurons are primarily glutamatergic and have been associated with emotion regulation. However, little is known about the roles of BLA neurons expressing neuronal nitric oxide synthase (nNOS, Nos1) in the regulation of emotional behaviors., Methods: Using Nos1 - cre mice and chemogenetic and optogenetic manipulations, we specifically silenced or activated Nos1 + or Nos1 - neurons in the BLA, or silenced their projections to the anterdorsal bed nucleus of the stria terminalis (adBNST) and ventral hippocampus (vHPC). We measured anxiety behaviors in elevated plus maze (EPM) and open-field test (OFT), and measured depression behaviors in forced swimming test (FST) and tail suspension test (TST)., Results: BLA Nos1 + neurons were predominantly glutamatergic, and glutamatergic but not GABAergic Nos1 + neurons were involved in controlling anxiety- and depression-related behaviors. Interestingly, by selectively manipulating the activities of BLA Nos1 + and Nos1 - excitatory neurons, we found that they had opposing effects on anxiety- and depression-related behaviors. BLA Nos1 + excitatory neurons projected to the adBNST, this BLA-adBNST circuit controlled the expression of anxiety- and depression-related behaviors, while BLA Nos1 - excitatory neurons projected to vHPC, this BLA-vHPC circuit contributed to the expression of anxiety- and depression-related behaviors. Moreover, excitatory vHPC-adBNST circuit antagonized the role of BLA-adBNST circuit in regulating anxiety- and depression-related behaviors., Conclusions: BLA Nos1 + and Nos1 - excitatory neuron subpopulations exert different effects on anxiety- and depression-related behaviors through distinct projection circuits, providing a new insight of BLA excitatory neurons in emotional regulation., Limitations: We did not perform retrograde labeling from adBNST and vHPC regions., Competing Interests: Conflict of interest All the authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Radiofrequency catheter ablation (RFCA) for patients with atrial fibrillation (AF) can generate considerable physical and psychological discomfort under conscious sedation. App-based mindfulness meditation combined with an electroencephalography (EEG)-based brain-computer interface (BCI) shows promise as effective and accessible adjuncts in medical practice., Objective: This study aimed to investigate the effectiveness of a BCI-based mindfulness meditation app in improving the experience of patients with AF during RFCA., Methods: This single-center pilot randomized controlled trial involved 84 eligible patients with AF scheduled for RFCA, who were randomized 1:1 to the intervention and control groups. Both groups received a standardized RFCA procedure and a conscious sedative regimen. Patients in the control group were administered conventional care, while those in the intervention group received BCI-based app-delivered mindfulness meditation from a research nurse. The primary outcomes were the changes in the numeric rating scale, State Anxiety Inventory, and Brief Fatigue Inventory scores. Secondary outcomes were the differences in hemodynamic parameters (heart rate, blood pressure, and peripheral oxygen saturation), adverse events, patient-reported pain, and the doses of sedative drugs used in ablation., Results: BCI-based app-delivered mindfulness meditation, compared to conventional care, resulted in a significantly lower mean numeric rating scale (mean 4.6, SD 1.7 [app-based mindfulness meditation] vs mean 5.7, SD 2.1 [conventional care]; P=.008), State Anxiety Inventory (mean 36.7, SD 5.5 vs mean 42.3, SD 7.2; P<.001), and Brief Fatigue Inventory (mean 3.4, SD 2.3 vs mean 4.7, SD 2.2; P=.01) scores. No significant differences were observed in hemodynamic parameters or the amounts of parecoxib and dexmedetomidine used in RFCA between the 2 groups. The intervention group exhibited a significant decrease in fentanyl use compared to the control group, with a mean dose of 3.96 (SD 1.37) mcg/kg versus 4.85 (SD 1.25) mcg/kg in the control group (P=.003).The incidence of adverse events was lower in the intervention group (5/40) than in the control group (10/40), though this difference was not significant (P=.15)., Conclusions: BCI-based app-delivered mindfulness meditation effectively relieved physical and psychological discomfort and may reduce the doses of sedative medication used in RFCA for patients with AF., Trial Registration: ClinicalTrials.gov NCT05306015; https://clinicaltrials.gov/ct2/show/NCT05306015., (©Ying He, Zhijie Tang, Guozhen Sun, Cheng Cai, Yao Wang, Gang Yang, ZhiPeng Bao. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 03.05.2023.)

Lignin, as a precious resource given to mankind by nature with abundant functional aromatic structures, has drawn much attention in the recent decade from academia to industry worldwide, aiming at harvesting aromatic compounds from this abundant and renewable natural polymer resource. How to efficiently depolymerize lignin to easy-to-handle aromatic monomers is the precondition of lignin utilization. Many strategies/methods have been developed to effectively degrade lignin into monomers, such as the traditional methods of pyrolysis, gasification, liquid-phase reforming, solvolysis, chemical oxidation, hydrogenation, reduction, acidolysis, alkaline hydrolysis, alcoholysis, as well as the newly developed redox-neutral process, biocatalysis, and combinatorial strategies. Therefore, there is a strong demand to systemically summarize these developed strategies and methods and reveal the internal transformation principles of the lignin. Focusing on the topic of lignin depolymerization to aromatic chemicals, this review reorganizes and categorizes the strategies/methods according to their mechanisms, orbiting the center of critical intermediates during the lignin linkage transformation, which includes the critical anionic intermediates, cationic intermediates, organometallic intermediates, organic molecular intermediates, aryl cation radical intermediates, and neutral radical intermediates. The corresponding introduction involves the generation and the transformation chemistry of the critical intermediates via the corresponding C-H/O-H/C-C/C-O chemical bond transformations, leading to the cleavage of the C-C/C-O linkage bonds. Accompanying the brief introduction of lignin chemistry and the final concluding remarks and perspectives on lignin depolymerization, this review aims to provide a current research process of lignin depolymerization, which may provide useful suggestions for this vigorous research field.

The catalytic carbon monoxide (CO) methanation is an ideal model reaction for the fundamental understanding of catalysis on the gas-solid interface and is crucial for various industrial processes. However, the harsh operating conditions make the reaction unsustainable, and the limitations set by the scaling relations between the dissociation energy barrier and dissociative binding energy of CO further increase the difficulty in designing high-performance methanation catalysts operating under milder conditions. Herein, we proposed a theoretical strategy to circumvent the limitations elegantly and achieve both facile CO dissociation and C/O hydrogenation on the catalyst containing a confined dual site. The DFT-based microkinetic modeling (MKM) reveals that the designed Co-Cr 2 /G dual-site catalyst could provide 4-6 orders of magnitude higher turnover frequency for CH 4 production than the cobalt step sites. We believe that the proposed strategy in the current work will provide essential guidance for designing state-of-the-art methanation catalysts under mild conditions.

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

Disturbances in immune regulation, intestinal dysbiosis and inflammation characterize ankylosing spondylitis (AS), which is associated with RUNX3 loss-of-function variants. ZAP70 W163C mutant (SKG) mice have reduced ZAP70 signaling, spondyloarthritis and ileitis. In small intestine, Foxp3 + regulatory T cells (Treg) and CD4 + CD8αα + TCRαβ + intraepithelial lymphocytes (CD4-IEL) control inflammation. TGF-β and retinoic acid (RA)-producing dendritic cells and MHC-class II + intestinal epithelial cells (IEC) are required for Treg and CD4-IEL differentiation from CD4 + conventional or Treg precursors, with upregulation of Runx3 and suppression of ThPOK. We show in SKG mouse ileum, that ZAP70 W163C or ZAP70 inhibition prevented CD4-IEL but not Treg differentiation, dysregulating Runx3 and ThPOK. TGF-β/RA-mediated CD4-IEL development, T-cell IFN-γ production, MHC class-II + IEC, tissue-resident memory T-cell and Runx3-regulated genes were reduced. In AS intestine, CD4-IEL were decreased, while in AS blood CD4 + CD8 + T cells were reduced and Treg increased. Thus, genetically-encoded TCR signaling dysfunction links intestinal T-cell immunodeficiency in mouse and human spondyloarthropathy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest exists., (Copyright © 2022. Published by Elsevier Inc.)

Solving the problem of the low temperature and low salt resistances of conventional polyacrylamide and the high cost of functional monomers, and thus, introducing it to the interlayer space provided by a layered structure for polymer modification, is a promising option. In this study, montmorillonite was used as the inorganic clay mineral, and an intercalated polyacrylamide/clay nanocomposite was synthesized via in situ intercalation polymerization. The optimal synthesis conditions were a clay content of 10.7%, preparation temperature of 11 °C, initiator concentration of 2.5 × 10 -4 mol/L, and chain extender concentration of 5%. The IR results showed that the polymer was successfully introduced to the nanocomposite. The synthesized intercalated polyacrylamide/clay nanocomposite exhibited a better thickening effect, good viscoelasticity, and better salt resistance and thermal stability than polyacrylamide. In addition, the thickening capacity and thermal stability were superior to the salt-resistant polymer, with a 16.0% higher thickening viscosity and a 15.1% higher viscosity retention rate at 85 °C for 60 d. The intercalated polyacrylamide/clay nanocomposite further expanded the application of polyacrylamide in petroleum exploitation.

Background: Bronchopulmonary dysplasia (BPD) is a severe pulmonary complication causing morbidity and mortality in preterm infants. A key histopathological feature of BPD is late lung growth retardation, in which the process of alveolarization is hindered and the mechanism of which is unclear. Emerging evidence indicates that microRNAs (miRNAs) promote the development of BPD via the inhibition of their target genes. MiR-495 has been reported to be involved in various lung diseases. However, the physiological function of miR-495 in BPD has not yet been fully understood., Methods: Differentially expressed miRNAs in peripheral blood of patients with BPD were compared with those of normal controls. A dual-luciferase reporter assay was performed to identify the target genes of miR-495. A BPD neonatal rat model was established by injecting lipopolysaccharide (LPS) in the amniotic sac of pregnant rats. The morphology of the lungs was observed using hematoxylin and eosin (HE) staining. The expression of miR-495, neural precursor cell expressed developmentally down-regulated 4-like ( NEDD4L ), and epithelial Na + channel ( ENaC ) was tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot analysis, and immunofluorescent (IF) staining., Results: The expression of miR-495 was significantly increased in the peripheral blood samples of premature infants with BPD and verified using qRT-PCR. NEDD4L was proven to be the target gene of miR-495. Additionally, miR-495 expression was also increased in the lungs of rat pups with BPD at postnatal day (P) 3 compared with the control group. qRT-PCR and Western blot results showed that NEDD4L expression was decreased while ENaC expression was increased at the transcriptional and translational levels. IF staining results showed that NEDD4L level was decreased while ENaC level was increased in the LPS-induced BPD rat model, which was consistent with abnormal changes in alveolar structure., Conclusions: The aberrant overexpression of miR-495 may contribute to the development of BPD by targeting NEDD4L-ENaC pathway, implying an imbalance in lung fluid clearance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3293/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

In this study, we positioned three quaternary ammonium halide-containing cellulose derivatives (PQF, PQCl, PQBr) as interfacial modification layers between the nickel oxide (NiO x ) and methylammonium lead iodide (MAPbI 3 ) layers of inverted perovskite solar cells (PVSCs). Inserting PQCl between the NiO x and MAPbI 3 layers improved the interfacial contact, promoted the crystal growth, and passivated the interface and crystal defects, thereby resulting in MAPbI 3 layers having larger crystal grains, better crystal quality, and lower surface roughness. Accordingly, the photovoltaic (PV) properties of PVSCs fabricated with PQCl-modified NiO x layers were improved when compared with those of the pristine sample. Furthermore, the PV properties of the PQCl-based PVSCs were much better than those of their PQF- and PQBr-based counterparts. A PVSC fabricated with PQCl-modified NiO x (fluorine-doped tin oxide/NiO x /PQCl-0.05/MAPbI 3 /PC 61 BM/bathocuproine/Ag) exhibited the best PV performance, with a photoconversion efficiency (PCE) of 14.40%, an open-circuit voltage of 1.06 V, a short-circuit current density of 18.35 mA/cm 3 , and a fill factor of 74.0%. Moreover, the PV parameters of the PVSC incorporating the PQCl-modified NiO x were further enhanced when blending MAPbI 3 with PQCl. We obtained a PCE of 16.53% for this MAPbI 3 :PQCl-based PVSC. This PQCl-based PVSC retained 80% of its initial PCE after 900 h of storage under ambient conditions (30 °C; 60% relative humidity).

To investigate the risk factors for death in critically ill neonates receiving continuous renal replacement therapy (CRRT). This retrospective study analyzed the clinical data of critically ill neonates receiving CRRT at two tertiary hospitals from January 2015 to December 2021. A multi-factor logistic regression analysis was performed, and the predictive value of relevant risk factors on death was verified by receiver operating characteristic (ROC) curve. A total of 59 cases of critically ill neonates were included in this study, with a mortality of 37.3%. The most common primary disease in these cases was neonatal sepsis, followed by neonatal asphyxia, and inborn errors of metabolism (IEM). Univariate analysis showed that the risk factors related to death included primary diseases; the number of organs involved in multiple organ dysfunction syndrome (MODS), neonatal critical illness scores (NCIS), and indications of CRRT; the blood lactate, blood glucose, hemoglobin, and platelet before CRRT initiation; and the incidence of bleeding or thrombosis during CRRT. Multi-factor logistic regression analysis showed that risk factors for death in critically ill neonates receiving CRRT included the occurrence of neonatal sepsis, the number of organs involved in MODS, and the NCIS. ROC curve analysis showed that the number of organs involved in MODS and NCIS had a good predictive value for death in critically ill neonates receiving CRRT, with the areas under the curve (AUC) being 0.700 and 0.810, respectively., Conclusion: Neonatal sepsis, the number of organs involved in MODS, and NCIS were independent risk factors for death in critically ill neonates receiving CRRT. Moreover, the number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT., What Is Known: • The population to which CRRT is applicable is gradually expanding from critically ill children to critically ill neonates. • The mortality of critically ill neonates receiving CRRT remains high., What Is New: • The most common primary disease in critically ill neonates receiving CRRT was neonatal sepsis, followed by neonatal asphyxia and inborn errors of metabolism (IEM). • The number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Sabatier principle defines the essential criteria for being an ideal catalyst in heterogeneous catalysis, while approaching the Sabatier optimal is a major pursuit in catalyst design. The Haber-Bosch (H-B) process, converting nitrogen (N 2 ) and hydrogen (H 2 ) to ammonia (NH 3 ), is a holy grail reaction for humans and also a great model reaction for fundamental research, where the established volcano plot between ammonia synthesis activity and nitrogen binding energy among metals has successfully guided new catalyst design. However, reaching the top of the activity volcano is still very challenging. Herein, we identify an elegant strategy to promote the ferromagnetic (FM) catalysts to be the Sabatier optimal of ammonia synthesis via a second-order ferromagnetic-paramagnetic phase transition, which represents an ideal and novel interdisciplinary of the aforementioned century-old classic principle, reaction, and theory in chemistry, physics, and material science. The paramagnetic (PM) Co and Ni metals could have 2-4 orders of magnitude higher ammonia synthesis activity than their ferromagnetic counterparts, holding the potential to achieve a near-ambient H-B process. We believe that our discovery will open a novel avenue for revisiting the catalytic performances of paramagnetic phases of ferromagnetic materials in heterogeneous catalysis.

Background: The role of the Human Papillomavirus (HPV) status in patients with hypopharyngeal squamous cell carcinoma (HSCC) remains controversial., Objective: Our aim was to determine the prognostic and predictive effects of HPV status in patients with locally advanced HSCC (stage III-IVB) receiving primary radiotherapy., Methods: Patients diagnosed with stage III-IVB HSCC between 2010 and 2016 were identified. HPV status, demographics, clinicopathological characteristics, treatment, and survival data were captured. Kaplan-Meier analysis, multivariable Cox regression analysis, and propensity score matching analysis were performed., Results: We identified 531 patients in this study and 142 (26.7%) patients with HPV-positive diseases. No significant differences were observed between those with HPV-negative and HPV-positive diseases with regard to demographics, clinicopathological characteristics, and chemotherapy use. HPV-positive HSCC had better head and neck cancer-specific survival (HNCSS; P=.001) and overall survival (OS; P<.001) compared to those with HPV-negative tumors. Similar results were found using the multivariable Cox regression analysis. Sensitivity analyses showed that the receipt of chemotherapy was associated with significantly improving HNCSS (P<.001) and OS (P<.001) compared to not receiving chemotherapy in HPV-negative HSCC, whereas comparable HNCSS (P=.59) and OS (P=.12) were found between both treatment arms in HPV-positive HSCC. Similar results were found after propensity score matching., Conclusions: Approximately one-quarter of HSCC may be HPV-related, and HPV-positive HSCC is associated with improved survival outcomes. Furthermore, additional chemotherapy appears to be not related to a survival benefit in patients with HPV-positive tumors who received primary radiotherapy., (©Shi-Ping Yang, Xiang-Ying Lin, Min Hu, Cheng-Fu Cai. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 16.12.2022.)

Objectives: To evaluate the efficacy and safety of tacrolimus (TAC) for the treatment of primary Sjögren's syndrome (pSS) with refractory immune thrombocytopenia (RITP)., Methods: Twenty-three pSS patients with RITP treated with TAC from June 2018 to June 2021 at the First Affiliated Hospital of Soochow University were enrolled in this retrospective cohort study. Platelet response, clinical and immunological parameters, toxicity and safety were compared and analysed at baseline and different points after TAC treatment., Results: At 4 weeks after treatment, 2 patients (8.7%) attained a complete response (CR, platelet count ≥100×109/L and no bleeding), 15 patients (65.2%) achieved a partial response (PR, platelet count ≥ 30×109/L but <100×109/L and no bleeding or a platelet count at least twice that before treatment), and the other 6 patients (26.1%) did not respond to TAC treatment. At 8 weeks after treatment, a CR was seen in 4 patients (17.4%), and the percentage of patients with a PR increased to 78.3% (18 patients). The percentage of patients with a CR increased to 47.8% (11 patients), and 9 patients (39.1%) achieved a PR without relapse at 12 weeks after treatment. At 24 weeks after treatment, 14 patients (60.9%) achieved a CR, and 8 patients (34.8%) achieved a PR. Compared to before treatment, the level of IgG was decreased significantly at 24 weeks after treatment, whereas there was no significant difference in the levels of IgM or IgA between baseline and 24 weeks after treatment. Additionally, the absolute CD3+ T cell count, European SS Disease Activity Index (ESSDAI) score, and levels of IL-2 and INF-γ were significantly decreased at 24 weeks after treatment., Conclusions: TAC is effective and well tolerated by pSS patients with RITP, and the mechanism underlying the effect of TAC in these patients may be related to reduced Th1 cytokine expression.

Background: Pancreatic cancer (PC) is a highly lethal malignancy regarding digestive system, which is the fourth leading factor of cancer-related mortalities in the globe. Prognosis is poor due to diagnosis at advanced disease stage, low rates of surgical resection, and resistance to traditional radiotherapy and chemotherapy. In order to develop novel therapeutic strategies, further elucidation of the molecular mechanisms underlying PC chemoresistance is required. Ribosomal RNA biogenesis has been implicated in tumorigenesis. Small nucleolar RNAs (snoRNAs) is responsible for post-transcriptional modifications of ribosomal RNAs during biogenesis, which have been identified as potential markers of various cancers. Here, we investigate the U3 snoRNA-associated protein RRP9/U3-55 K along with its role in the development of PC and gemcitabine resistance., Methods: qRT-PCR, western blot and immunohistochemical staining assays were employed to detect RRP9 expression in human PC tissue samples and cell lines. RRP9-overexpression and siRNA-RRP9 plasmids were constructed to test the effects of RRP9 overexpression and knockdown on cell viability investigated by MTT assay, colony formation, and apoptosis measured by FACS and western blot assays. Immunoprecipitation and immunofluorescence staining were utilized to demonstrate a relationship between RRP9 and IGF2BP1. A subcutaneous xenograft tumor model was elucidated in BALB/c nude mice to examine the RRP9 role in PC in vivo., Results: Significantly elevated RRP9 expression was observed in PC tissues than normal tissues, which was negatively correlated with patient prognosis. We found that RRP9 promoted gemcitabine resistance in PC in vivo and in vitro. Mechanistically, RRP9 activated AKT signaling pathway through interacting with DNA binding region of IGF2BP1 in PC cells, thereby promoting PC progression, and inducing gemcitabine resistance through a reduction in DNA damage and inhibition of apoptosis. Treatment with a combination of the AKT inhibitor MK-2206 and gemcitabine significantly inhibited tumor proliferation induced by overexpression of RRP9 in vitro and in vivo., Conclusions: Our data reveal that RRP9 has a critical function to induce gemcitabine chemoresistance in PC through the IGF2BP1/AKT signaling pathway activation, which might be a candidate to sensitize PC cells to gemcitabine. Video abstract., (© 2022. The Author(s).)

To explore the optimal stage of initiating continuous renal replacement therapy (CRRT) in the treatment of neonatal acute kidney injury (AKI), a total of 25 AKI neonates treated with CRRT were hospitalized at the Department of Neonatology of Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University (Shanghai, China) from November 2016 to June 2021. According to the renal function, the AKI neonates prior to CRRT were divided into two groups as follows: AKI stage 0-1 and AKI stage 2-3. The changes noted in specific indicators including renal function, electrolyte concentration, and acid-base balance index were analyzed at 0, 12, 24 and 48 h, and at the end of the CRRT treatment. Among the 25 neonates with AKI, serum potassium, urea nitrogen and creatinine levels were significantly decreased following 12 h of CRRT treatment and reached the normal range following 24 h of CRRT treatment with a significant increase in the volume of urine. The serum creatinine levels of the neonates in the AKI stage 0-1 group were significantly decreased following 24 h of CRRT treatment and urine output was significantly increased. At 24 h and following CRRT treatment, the levels of serum creatinine of AKI stage 2-3 neonates were higher than those of AKI stage 0-1 neonates (F=3.013, 5.005; P<0.05), and at all time-points, the urine output of AKI stage 0-1 was higher than that of AKI stage 2-3 (F=13.785, 4.008, 0.965; P<0.05). A total of four cases of thrombocytopenia, two cases of obstruction, and two cases of hypotension were noted in the course of CRRT treatment (the occurrence rate was 8/25). Therefore, it was concluded that CRRT could be an effective measure for the treatment of AKI neonates. Thus, ideally CRRT treatment of AKI neonates should be initiated in cases characterized as AKI stages 0-1., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhang et al.)