Ligand-Bound CO2 as a Nonclassical Route toward Efficient Photocatalytic CO2 Reduction with a Ni N-Confused Porphyrin.

Implementing the synergistic effects between the metal and the ligand has successfully streamlined the energetics for CO2 activation and gained high catalytic activities, establishing the important breakthroughs in photocatalytic CO2 reduction. Herein, we describe a Ni(II) N-confused porphyrin complex (NiNCP) featuring an acidic N-H group. It is readily deprotonated and exists in an anion form during catalysis. Owing to this functional site, NiNCP gave rise to an outstanding turnover number (TON) as high as 217,000 with a 98% selectivity for CO2 reduction to CO, while the parent Ni(II) porphyrin (NiTPP) was found to be nearly inactive. Our mechanistic analysis revealed a nonclassical reaction pattern where CO2 was effectively activated via the attack of the Lewis-basic ligand. The resulting ligand-bound CO2 adduct could be further reduced to produce CO. This new metal-ligand synergistic effect is anticipated to inspire the design of highly active catalysts for small molecule activations.

Accelerating Charge Kinetics in Photocatalytic CO2 Reduction by Modulating the Cobalt Coordination in Heterostructures of Cadmium Sulfide/Metal-Organic Layer.

Artificial photocatalytic CO2 reduction (CO2 R) holds great promise to directly store solar energy into chemical bonds. The slow charge and mass transfer kinetics at the triphasic solid-liquid-gas interface calls for the rational design of heterogeneous photocatalysts concertedly boosting interfacial charge transfer, local CO2 concentration, and exposure of active sites. To meet these requirements, in this study heterostructures of CdS/MOL (MOL = metal-organic layer) furnishing different redox Co sites are fabricated for CO2 R photocatalysts. It is found that the coordination environment of Co is key to photocatalytic activity. The best catalyst ensemble comprising ligand-chelated Co2+ with the bipyridine electron mediator demonstrates a high CO yield rate of 1523 µmol h-1 gcat -1 , selectivity of 95.8% and TON of 1462.4, which are ranked among the best seen in literature. Comprehensive photochemical and electroanalytical characterizations attribute the high CO2 R performance to the improved photocarrier separation and charge kinetics originated from the proper energy band alignment and coordination chemistry. This work highlights the construction of 2D heterostructures and modulation of transition metal coordination to expedite the charge kinetics in photocatalytic CO2 reduction.

TNF and IFNγ-induced cell death requires IRF1 and ELAVL1 to promote CASP8 expression.

TNFα and IFNγ (TNF/IFNγ) synergistically induce caspase-8 activation and cancer cell death. However, the mechanism of IFNγ in promoting TNF-initiated caspase-8 activation in cancer cells is poorly understood. Here, we found that in addition to CASP8, CYLD is transcriptionally upregulated by IFNγ-induced transcription factor IRF1. IRF1-mediated CASP8 and CYLD upregulation additively mediates TNF/IFNγ-induced cancer cell death. Clinically, the expression levels of TNF, IFNγ, CYLD, and CASP8 in melanoma tumors are increased in patients responsive to immune checkpoint blockade (ICB) therapy after anti-PD-1 treatment. Accordingly, our genetic screen revealed that ELAVL1 (HuR) is required for TNF/IFNγ-induced caspase-8 activation. Mechanistically, ELAVL1 binds CASP8 mRNA and extends its stability to sustain caspase-8 expression both in IFNγ-stimulated and in basal conditions. Consequently, ELAVL1 determines death receptors-initiated caspase-8-dependent cell death triggered from stimuli including TNF and TRAIL by regulating basal/stimulated caspase-8 levels. As caspase-8 is a master regulator in cell death and inflammation, these results provide valuable clues for tumor immunotherapy and inflammatory diseases.

Pulse Electrolysis Turns on CO2 Methanation through N-Confused Cupric Porphyrin.

Breaking the D4h symmetry in the square-planar M-N4 configuration of macrocycle molecular catalysts has witnessed enhanced electrocatalytic activity, but at the expense of electrochemical stability. Herein, we hypothesize that the lability of the active Cu-N3 motifs in the N-confused copper (II) tetraphenylporphyrin (CuNCP) could be overcome by applying pulsed potential electrolysis (PPE) during electrocatalytic carbon dioxide reduction. We find that applying PPE can indeed enhance the CH4 selectivity on CuNCP by 3 folds to reach the partial current density of 170 mA cm-2 at >60 % Faradaic efficiency (FE) in flow cell. However, combined ex situ X-ray diffraction (XRD), transmission electron microscope (TEM), and in situ X-ray absorption spectroscopy (XAS), infrared (IR), Raman, scanning electrochemical microscopy (SECM) characterizations reveal that, in a prolonged time scale, the decomplexation of CuNCP is unavoidable, and the promoted water dissociation under high anodic bias with lowered pH and enriched protons facilitates successive hydrogenation of *CO on the irreversibly reduced Cu nanoparticles, leading to the improved CH4 selectivity. As a key note, this study signifies the adaption of electrolytic protocol to the catalyst structure for tailoring local chemical environment towards efficient CO2 reduction.

DLGAP5 triggers proliferation and metastasis of bladder cancer by stabilizing E2F1 via USP11.

Bladder cancer (BLCA) is one of the most widespread malignancies worldwide, and displays significant tumor heterogeneity. Understanding the molecular mechanisms exploitable for treating aggressive BLCA represents a crucial objective. Despite the involvement of DLGAP5 in tumors, its precise molecular role in BLCA remains unclear. BLCA tissues exhibit a substantial increase in DLGAP5 expression compared with normal bladder tissues. This heightened DLGAP5 expression positively correlated with the tumor's clinical stage and significantly affected prognosis negatively. Additionally, experiments conducted in vitro and in vivo revealed that alterations in DLGAP5 expression notably influence cell proliferation and migration. Mechanistically, the findings demonstrated that DLGAP5 was a direct binding partner of E2F1 and that DLGAP5 stabilized E2F1 by preventing the ubiquitination of E2F1 through USP11. Furthermore, as a pivotal transcription factor, E2F1 fosters the transcription of DLGAP5, establishing a positive feedback loop between DLGAP5 and E2F1 that accelerates BLCA development. In summary, this study identified DLGAP5 as an oncogene in BLCA. Our research unveils a novel oncogenic mechanism in BLCA and offers a potential target for both diagnosing and treating BLCA.

Oxygen-Free Csp3-H Oxidation of Pyridin-2-yl-methanes to Pyridin-2-yl-methanones with Water by Copper Catalysis.

Aromatic ketones are important pharmaceutical intermediates, especially the pyridin-2-yl-methanone motifs. Thus, synthetic methods for these compounds have gained extensive attention in the last few years. Transition metals catalyze the oxidation of Csp3-H for the synthesis of aromatic ketones, which is arresting. Here, we describe an efficient copper-catalyzed synthesis of pyridin-2-yl-methanones from pyridin-2-yl-methanes through a direct Csp3-H oxidation approach with water under mild conditions. Pyridin-2-yl-methanes with aromatic rings, such as substituted benzene, thiophene, thiazole, pyridine, and triazine, undergo the reaction well to obtain the corresponding products in moderate to good yields. Several controlled experiments are operated for the mechanism exploration, indicating that water participates in the oxidation process, and it is the single oxygen source in this transformation. The current work provides new insights for water-involving oxidation reactions.

Efficacy and safety of endoscopic retrograde cholangiopancreatography in recurrent pancreatitis of pediatric asparaginase-associated pancreatitis.

BACKGROUND: Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective. AIM: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP. METHODS: From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared. RESULTS: The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication. CONCLUSION: ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

A "Trinity" Design of Li-O2 Battery Engaging the Slow-Release Capsule of Redox Mediators.

Nonaqueous Li-O2 battery (LOB) represents one of the promising next-gen energy storage solutions owing to its ultrahigh energy density but suffers from problems such as high charging overpotential, slow redox kinetics, Li anode corrosion, etc., calling for a systemic optimization of the battery configuration and structural components. Herein, an ingenious "trinity" design of LOB is initiated by implementing a hollowed cobalt metal organic framework (MOF) impregnating iodized polypyrrole simultaneously as the cathode catalyst, anode protection layer, and slow-release capsule of redox mediators, so as to systemically address issues of impeded mass transport and redox kinetics on the cathode, dendrite growth, and surface corrosion on the anode, as well as limited intermediate solubility in the low donor-number (DN) solvent. As a result of the systemic effort, the LOB constructed demonstrates an ultralow discharge/charge polarization of 0.2 V, prolonged cycle life of 1244 h and total discharge capacity of 28.41 mAh cm-2 . Mechanistic investigations attribute the superb LOB performance to the redox-mediated solution growth mechanism of crystalline Li2 O2 with both enhanced reaction kinetics and reversibility. This study offers a paradigm in designing smart materials to raise the performance bar of Li-O2 battery toward realistic applications.

Proton Shuttling by Polyaniline of High Brønsted Basicity for Improved Electrocatalytic Ethylene Production from CO2.

Hybrid organic/inorganic composites with the organic phase tailored to modulate local chemical environment at the Cu surface arise as an enchanting category of catalysts for electrocatalytic CO2 reduction reaction (CO2 RR). A fundamental understanding on how the organics of different functionality, polarity, and hydrophobicity affect the reaction path is, however, still lacking to guide rational catalyst design. Herein, polypyrrole (PPy) and polyaniline (PANI) manifesting different Brønsted basicity are compared for their regulatory roles on the CO2 RR pathways regarding *CO coverage, proton source and interfacial polarity. Concerted efforts from in situ IR, Raman and operando modelling unveil that at the PPy/Cu interface with limited *CO coverage, hydridic *H produced by the Volmer step favors the carbon hydrogenation of *CO to form *CHO through a Tafel process; Whereas at the PANI/Cu interface with concentrated CO2 and high *CO coverage, protonic H+ shuttled through the benzenoid -NH- protonates the oxygen of *CO, yielding *COH for asymmetric coupling with nearby *CO to form *OCCOH under favored energetics. As a result of the tailored chemical environment, the restructured PANI/Cu composite demonstrates a high partial current density of 0.41 A cm-2 at a maximal Faraday efficiency of 67.5 % for ethylene production, ranking among states of the art.

Electrolyte-Impregnated Mesoporous Hollow Microreactor to Supplement an Inner Reaction Pathway for Boosting the Cyclability of Li-CO2 Batteries.

Li-CO2 batteries that integrate energy storage with greenhouse gas fixation have received a great deal of attention in the pursuit of carbon neutrality. However, cyclic accumulation of the insulative and insoluble Li2CO3 on the cathode surface severely restrains the battery cyclability, especially under a high depth of discharge/charge. Herein, we design and fabricate a microreactor-type catalyst by embedding Ru nanoparticles into the shells of mesoporous hollow carbon spheres. We show that both the hollow cavity and mesoporous shell are indispensable for concertedly furnishing a high activity to catalyze reversible Li2CO3 formation/decomposition. This unique structure ensures that the Ru sites masked by exterior Li2CO3 deposits during charging can resume the redox process of discharge by working with the prestored electrolyte to establish an inner reaction path. The thus fabricated Li-CO2 batteries demonstrate remarkable cyclability of 1085 cycles under 0.5 Ah g-1 and 326 cycles under 2 Ah g-1 at 1 A g-1, outshining most of the literature reports. This study highlights a smart catalyst design to boost the reversibility and cyclability of Li-CO2 batteries through an "in & out" strategy.

Pectolinarigenin inhibits bladder urothelial carcinoma cell proliferation by regulating DNA damage/autophagy pathways.

Pectolinarigenin (PEC), an active compound isolated from traditional herbal medicine, has shown potential anti-tumor properties against various types of cancer cells. However, its mechanism of action in bladder cancer (BLCA), which is one of the fatal human carcinomas, remains unexplored. In this study, we first revealed that PEC, as a potential DNA topoisomerase II alpha (TOP2A) poison, can target TOP2A and cause significant DNA damage. PEC induced G2/M phase cell cycle arrest via p53 pathway. Simultaneously, PEC can perform its unique function by inhibiting the late autophagic flux. The blocking of autophagy caused proliferation inhibition of BLCA and further enhanced the DNA damage effect of PEC. In addition, we proved that PEC could intensify the cytotoxic effect of gemcitabine (GEM) on BLCA cells in vivo and in vitro. Summarily, we first systematically revealed that PEC had great potential as a novel TOP2A poison and an inhibitor of late autophagic flux in treating BLCA.

How can multiscenario flow paths of water supply services be simulated? A supply-flow-demand model of ecosystem services across a typical basin in China.

Ecosystems provide many benefits to humans, and among them, water supply is crucial for human survival and development. This research focused on the Yangtze River Basin as the research area, quantitatively evaluated the temporal-spatial dynamic changes in the supply and demand of water supply services and determined the spatial relationship between the supply and demand regions of water supply services. We constructed the supply-flow-demand model of water supply service to quantify its flow. In our research, the Bayesian model was used to establish a multiscenario model of the water supply service flow path to simulate it and clarify its spatial flow path, flow direction and flow magnitude from the supply region to the demand region and determine its changing characteristics and driving factors in the basin. The results show that (1) In 2010, 2015 and 2020, the amount of water supply services showed a decreasing trend and was approximately 133.57 × 1012 m3, 129.97 × 1012 m3 and 120.82 × 1012 m3, respectively. (2) From 2010 to 2020, the trend of the cumulative flow of water supply service flow decreased each year and was 59.814 × 1012 m3, 56.930 × 1012 m3, 56.325 × 1012 m3 respectively. (3) Under the multiscenario simulation, the flow path of the water supply service was generally the same. The proportion of the water supply region was the highest under the green environmental protection scenario, at 73.8 %, and the proportion of the water demand region was the highest under the economic development and social progress scenario, at 27.3 %. (4) The provinces and municipalities in the basin were divided into three types of regions according to the matching relationship between supply and demand: catchment region, flow pass-through region and outflow region. The number of outflow regions was lowest, accounting for 23.53 %% of the regions, while the number of flow pass-through regions was the highest, accounting for 52.94 %.

The Myc Family and the Metastasis Suppressor NDRG1: Targeting Key Molecular Interactions with Innovative Therapeutics.

Cancer is a leading cause of death worldwide, resulting in ∼10 million deaths in 2020. Major oncogenic effectors are the Myc proto-oncogene family, which consists of three members including c-Myc, N-Myc, and L-Myc. As a pertinent example of the role of the Myc family in tumorigenesis, amplification of MYCN in childhood neuroblastoma strongly correlates with poor patient prognosis. Complexes between Myc oncoproteins and their partners such as hypoxia-inducible factor-1α and Myc-associated protein X (MAX) result in proliferation arrest and pro-proliferative effects, respectively. Interactions with other proteins are also important for N-Myc activity. For instance, the enhancer of zest homolog 2 (EZH2) binds directly to N-Myc to stabilize it by acting as a competitor against the ubiquitin ligase, SCFFBXW7, which prevents proteasomal degradation. Heat shock protein 90 may also be involved in N-Myc stabilization since it binds to EZH2 and prevents its degradation. N-Myc downstream-regulated gene 1 (NDRG1) is downregulated by N-Myc and participates in the regulation of cellular proliferation via associating with other proteins, such as glycogen synthase kinase-3ß and low-density lipoprotein receptor-related protein 6. These molecular interactions provide a better understanding of the biologic roles of N-Myc and NDRG1, which can be potentially used as therapeutic targets. In addition to directly targeting these proteins, disrupting their key interactions may also be a promising strategy for anti-cancer drug development. This review examines the interactions between the Myc proteins and other molecules, with a special focus on the relationship between N-Myc and NDRG1 and possible therapeutic interventions. SIGNIFICANCE STATEMENT: Neuroblastoma is one of the most common childhood solid tumors, with a dismal five-year survival rate. This problem makes it imperative to discover new and more effective therapeutics. The molecular interactions between major oncogenic drivers of the Myc family and other key proteins; for example, the metastasis suppressor, NDRG1, may potentially be used as targets for anti-neuroblastoma drug development. In addition to directly targeting these proteins, disrupting their key molecular interactions may also be promising for drug discovery.

Spatially Confined Silver Nanoparticles in Mercapto Metal-Organic Frameworks to Compartmentalize Li Deposition Toward Anode-Free Lithium Metal Batteries.

As the promising next-generation energy storage solution, lithium metal battery (LMB) has gained great attention but still suffers from troubles associated with the highly active metallic lithium. Herein, it is aimed to develop an anode-free LMB engaging no Li disk or foil by modifying the Cu current collector with mercapto metal-organic frameworks (MOFs) impregnating Ag nanoparticles (NPs). While the polar mercapto groups facilitate and guide Li+ transport, the highly lithiophilic Ag NPs help to enhance the electric conductivity and lower the energy barrier of Li nucleation. Furthermore, the MOF pores allow compartmentalizing bulk Li into a 3D matrix Li storage so that not only the local current density is reduced, but also is the plating/stripping reversibility greatly enhanced. As a result, full cells pairing the prelithiated Ag@Zr-DMBD/Cu anodes with LiFePO4 cathodes demonstrate a high initial specific capacity of 159.8 mAh g-1 , first-cycle Coulombic efficiency of 96.6%, and long-term cycling stability over 1000 cycles with 99.3% capacity retention at 1 C. This study underlines the multi-aspect functionalization of MOFs to impart lithiophilicity, polarity, and porosity to achieve reversible Li plating/stripping and paves the way for realizing high-performance anode-free LMBs through exquisite modification of the Cu current collector.

Integrated analysis of the roles of oxidative stress related genes and prognostic value in clear cell renal cell carcinoma.

BACKGROUND: Patients with clear cell renal cell carcinoma (ccRCC), which is the most commonly diagnosed subtype of renal cell carcinoma, are at risk of tumor metastasis and recrudescence. Previous research has shown that oxidative stress can induce tumorigenesis in many cancers and can be a target of cancer treatment. Despite these findings, little progress has been made understanding in the association of oxidative stress-related genes (OSRGs) with ccRCC. METHODS: In vitro experiments were conducted with MTT survival assays, qRT‒PCR, apoptosis assays, cell cycle assays, ROS assays, and IHC staining. RESULTS: In our study, 12 differentially expressed oxidative stress-related genes (DEOSGs) and related transcription factors (TFs) that are relevant to overall survival (OS) were screened, and their mutual regulatory networks were constructed with data from the TCGA database. Moreover, we constructed a risk model of these OSRGs and performed clinical prognostic analysis and validation. Next, we performed protein-protein interaction (PPI) network analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of MELK, PYCR1, and PML. A tissue microarray also verified the high expression of MELK and PYCR1 in ccRCC. Finally, in vitro cellular experiments demonstrated that knockdown of MELK or PYCR1 significantly inhibited ccRCC cell proliferation by causing cell apoptosis and inducing cell cycle arrest in the G1 phase. Intracellular ROS levels were elevated after these two genes were knocked down. CONCLUSION: Our results revealed the potential DEORGs to be used in ccRCC prognostic prediction and identified two biomarkers, named PYCR1 and MELK, which regulated the proliferation of ccRCC cells by affecting ROS levels. Furthermore, PYCR1 and MELK could be promising targets for predicting the progression and prognosis of ccRCC, thereby serving as new targets for medical treatments.

Common and unique alterations of functional connectivity in major depressive disorder and bipolar disorder.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level. METHODS: In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied. RESULTS: Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD. CONCLUSIONS: Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders.

Covalently Grafting Graphene onto Si Photocathode to Expedite Aqueous Photoelectrochemical CO2 Reduction.

Silicon semiconductor functionalized with molecular catalysts emerges as a promising cathode for photoelectrochemical (PEC) CO2 reduction reaction (CO2 RR). However, the limited kinetics and stabilities remains a major hurdle for the development of such composites. We herein report an assembling strategy of silicon photocathodes via chemically grafting a conductive graphene layer onto the surface of n+ -p Si followed by catalyst immobilization. The covalently-linked graphene layer effectively enhances the photogenerated carriers transfer between the cathode and the reduction catalyst, and improves the operating stability of the electrode. Strikingly, we demonstrate that altering the stacking configuration of the immobilized cobalt tetraphenylporphyrin (CoTPP) catalyst through calcination can further enhance the electron transfer rate and the PEC performance. At the end, the graphene-coated Si cathode immobilized with CoTPP catalyst managed to sustain a stable 1-Sun photocurrent of -1.65 mA cm-2 over 16 h for CO production in water at a near neutral potential of -0.1 V vs. reversible hydrogen electrode. This represents a remarkable improvement of PEC CO2 RR performance in contrast to the reported photocathodes functionalized with molecular catalysts.

External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children: A multicenter randomized controlled trial.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children. AIM: To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children. METHODS: This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated. RESULTS: A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed. CONCLUSION: External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.