Integrative metagenomic and metabolomic analyses reveal the potential of gut microbiota to exacerbate acute pancreatitis.

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.

The role of proteomics in acute pancreatitis: new and old knowledge.

INTRODUCTION: Around 20% of individuals diagnosed with acute pancreatitis (AP) may develop severe acute pancreatitis (SAP), possibly resulting in a mortality rate ranging from 15% to 35%. There is an urgent need to thoroughly understand the molecular phenotypes of SAP resulting from diverse etiologies. The field of translational research on AP has seen the use of several innovative proteomic methodologies via the ongoing improvement of isolation, tagging, and quantification methods. AREAS COVERED: This paper provides a comprehensive overview of differentially abundant proteins (DAPs) identified in AP by searching the PubMed/MEDLINE database (2003-2023) and adds significantly to the current theoretical framework. EXPERT OPINION: DAPs for potentially diagnosing AP based on proteomic identification need to be confirmed by multi-center studies that include larger samples. The discovery of DAPs in various organs at different AP stages via proteomic technologies is essential better to understand the pathophysiology of AP-related multiple organ dysfunction syndrome. Regarding the translational research of AP, novel approaches like single-cell proteomics and imaging using mass spectrometry may be used as soon as they become available.

A Circulating Panel of circRNA Biomarkers for the Noninvasive and Early Detection of Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Delayed manifestation of symptoms and lack of specific diagnostic markers lead patients being diagnosed with PDAC at advanced stages. This study aimed to develop a circular RNA (circRNA)-based biomarker panel to facilitate noninvasive and early detection of PDAC. METHODS: A systematic genome-wide discovery of circRNAs overexpressed in patients with PDAC was conducted. Subsequently, validation of the candidate markers in the primary tumors from patients with PDAC was performed, followed by their translation into a plasma-based liquid biopsy assay by analyzing 2 independent clinical cohorts of patients with PDAC and nondisease controls. The performance of the circRNA panel was assessed in conjunction with the plasma levels of cancer antigen 19-9 for the early detection of PDAC. RESULTS: Initially, a panel of 10 circRNA candidates was identified during the discovery phase. Subsequently, the panel was reduced to 5 circRNAs in the liquid biopsy-based assay, which robustly identified patients with PDAC and distinguished between early-stage (stage I/II) and late-stage (stage III/IV) disease. The areas under the curve of this diagnostic panel for the detection of early-stage PDAC were 0.83 and 0.81 in the training and validation cohorts, respectively. Moreover, when this panel was combined with cancer antigen 19-9 levels, the diagnostic performance for identifying patients with PDAC improved remarkably (area under the curve, 0.94) for patients in the validation cohort. Furthermore, the circRNA panel could also efficiently identify patients with PDAC (area under the curve, 0.85) who were otherwise deemed clinically cancer antigen 19-9-negative (<37 U/mL). CONCLUSIONS: A circRNA-based biomarker panel with a robust noninvasive diagnostic potential for identifying patients with early-stage PDAC was developed.

Cardiac complications caused by biliary diseases: A review of clinical manifestations, pathogenesis and treatment strategies of cholecardia syndrome.

Gallbladder and biliary diseases (GBDs) are one of the most common digestive diseases. The connections between GBDs and several organs other than the liver have gradually surfaced accompanied by the changes in people's diet structure and the continuous improvement of medical diagnosis technology. Among them, cholecardia syndrome that takes the heart as the important target of GBDs complications has been paid close attention. However, there are still no systematic report about its corresponding clinical manifestations and pathogenesis. This review summarized recent reported types of cholecardia syndrome and found that arrhythmia, myocardial injury, acute coronary syndrome and heart failure are common in the general population. Besides, the clinical diagnosis rate of intrahepatic cholestasis of pregnancy (ICP) and Alagille syndrome associated with gene mutation is also increasing. Accordingly, the underlying pathogenesis including abnormal secretion of bile acid, gene mutation, translocation and deletion (JAG1, NOTCH2, ABCG5/8 and CYP7A1), nerve reflex and autonomic neuropathy were further revealed. Finally, the potential treatment measures and clinical medication represented by ursodeoxycholic acid were summarized to provide assistance for clinical diagnosis and treatment.

WGBS of embryonic gonads revealed that long non-coding RNAs in the MHM region might be involved in cell autonomous sex identity and female gonadal development in chickens.

DNA methylation plays a key role in sex determination and differentiation in vertebrates. However, there are few studies on DNA methylation involved in chicken gonad development, and most focused on male hypermethylated regions (MHM). It is unclear whether there are specific differentially methylated regions (DMRs) in chicken embryonic gonads regulating sex determination and differentiation. Here, the DNA methylation maps showed that the difference of DNA methylation level between sexes was much higher at embryonic day 10 (E10) than that at embryonic day 6 (E6), and the significant differentially methylated regions at both stages were mainly distributed on the Z chromosome, including MHM1 and MHM2. The results of bisulphite sequencing PCR (BSP) and qRT-PCR showed hypomethylation of female MHM and upregulation of long non-coding RNAs (lncRNAs) whose promoter in the MHM region was consistent with the sequencing results, and similar results were in brain and muscle. In female sex-reversed gonads, the methylation pattern of MHM remained unchanged, and the expression levels of the three candidate lncRNAs were significantly decreased compared with those in females, but were significantly increased compared to males. The fluorescence in situ hybridization (FISH) results also showed that these lncRNAs were highly expressed in female embryonic gonads. The results of methyltransferase inhibitor and dual-luciferase reporter assay suggest that lncRNA expression may be regulated by DNA methylation within their promoters. Therefore, we speculated that MHM may be involved in cell-autonomous sex identity in chickens, and that lncRNAs regulated by MHM may be involved in female sexual differentiation.

Eliminating COVID-19 as the immediate culprit for igniting pancreatitis.

The impact of severe acute respiratory syndrome coronavirus 2 infection on the potential development of pancreatitis is a subject of ongoing debate within academic discourse. Establishing a causal link between COVID-19 and pancreatitis may not be fully supported by relying only on retrospective studies or case reports. This study examined the relationship between COVID-19 phenotypes and pancreatitis by Mendelian randomization (MR) method. The identification of instrumental variables (single nucleotide polymorphisms) that exhibit a robust association with the COVID-19 phenotypes was accomplished through a meticulous process of rigorous screening procedures. We included acute pancreatitis and chronic pancreatitis (CP) as the outcomes in the MR analysis, even though no definitive studies exist between COVID-19 and CP. A direct causal relationship between genetically predicted COVID-19 phenotypes and pancreatitis risk cannot be established. There is an ongoing debate over the designation of COVID-19 as a definitive cause of pancreatitis.

[Relationship Between Precipitation, River Water, and Groundwater Conversion in the Upper Reaches of Xilin River During the Rainy Season].

To deeply understand the hydrological cycle process and the transformation mechanism of different water bodies in the grassland inland river basin, the atmospheric precipitation, river water, and groundwater in the Xilin River Basin were taken as the research objects, the hydrogen and oxygen stable isotopes were analyzed, and the multi-scale spatio-temporal characteristics were analyzed to explore the quantitative transformation relationship between different water bodies in the basin. The results showed that:① the Xilin River Basin had an obvious inland semi-arid climate, the atmospheric precipitation was the main source of recharge for the river water and groundwater, and the groundwater and river water experienced different degrees of non-equilibrium evaporation at the same time. ② The isotopic composition of the river water showed the characteristics of depletion in spring and autumn and enrichment in summer and showed a trend of increasing from upstream to downstream in space. The variation in δ18O in shallow and deep groundwater during the growing season was basically the same, and the main difference between the two occurred at the end of the growing season, that is, the former tended to be stable, whereas the latter showed an upward trend, which reflected that the deep groundwater had a lagged response to the infiltration and recharge of atmospheric precipitation and surface water, and both of them were depleted gradually from southeast to northwest in space. ③ Based on the estimation results of the endmember mixing model, the average recharge ratio of atmospheric precipitation and shallow groundwater to river water in summer was 52.69% and 47.31%, respectively, indicating that shallow groundwater was an important recharge source of river water in the inland river basin even during the rainy season. The results of this study provide theoretical guidance for water resource regulation and ecological environment protection in a typical semi-arid grassland inland river basin.

Emodin Ameliorates Severe Acute Pancreatitis-Associated Acute Lung Injury in Rats by Modulating Exosome-Specific miRNA Expression Profiles.

Background: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear. Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO. Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats. Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO.

Glucocorticoid Treatment in Acute Respiratory Distress Syndrome: An Overview on Mechanistic Insights and Clinical Benefit.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP).

Polymer Dielectrics with Outstanding Dielectric Characteristics via Passivation with Oxygen Atoms through C-F Vacancy Carbonylation.

The development of advanced electrical equipment necessitates polymer dielectrics with a higher electric strength. Unfortunately, this bottleneck problem has yet to be solved because current material modification methods do not allow direct control of deep traps. Here, we propose a method for directly passivating deep traps. Measurements of nanoscale microregion charge characteristics and trap parameters reveal a significant reduction in the number of deep traps. The resulting polymer dielectric has an impressively high electrical strength, less surface charge accumulation, and a significantly increased flashover voltage and breakdown strength. In addition, the energy storage density is increased without sacrificing the charge-discharge efficiency. This reveals a new approach to increasing the energy storage density by reducing the trap energy levels at the electrode-dielectric interface. We further calculated and analyzed the microscopic physical mechanism of deep trap passivation based on density functional theory and characterized the contributions of orbital composition and orbital hybridization.

Procoagulant effect of extracellular vesicles in patients after transcatheter aortic valve replacement or transcatheter aortic valve replacement with percutaneous coronary intervention.

Patients with severe aortic stenosis (AS) after replacement of the transcatheter aortic valve (TAVR) are more likely to develop thrombotic complications such as cerebral embolism and artificial valve thrombosis. However, the mechanism is not yet well defined. We aimed to explore the plasma extracellular vesicles (EVs) levels and their role in the induction of procoagulant activity (PCA) in patients receiving TAVR alone or TAVR with percutaneous coronary intervention (PCI). EVs were analyzed with flow cytometer. Markers of platelet and endothelial cell activation were quantified using selective enzyme-linked immunosorbent assay (ELISA) kits. Procoagulant activity (PCA) was assessed by clotting time, purified clotting complex assays, and fibrin production assays. Our results confirmed that EVs with positive phosphatedylserin (PS+EV), platelet EVs (PEVs) and positive tissue factor EVs (TF+EVs) were higher in patients following TAVR than before TAVR, particularly in TAVR with PCI. Furthermore, endothelial-derived EVs (EEVs) were also higher in patients after TAVR with PCI than pre-TAVR, however, the EEVs levels in TAVR alone patients were gradually reduce than pre-TAVR. In addition, we further proved that total EVs contributed to dramatically shortened coagulation time, increased intrinsic/extrinsic factor Xa and thrombin generation in patients after TAVR, especially in TAVR with PCI. The PCA was markedly attenuated by approximately 80% with lactucin. Our study reveals a previously unrecognized link between plasma EV levels and hypercoagulability in patients after TAVR, especially TAVR with PCI. Blockade of PS+EVs may improve the hypercoagulable state and prognosis of patients.

Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway.

The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased Firmicutes/Bacteroidetes ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. IMPORTANCE Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.

Outcomes of allogeneic or autologous stem cell transplantation followed by maintenance chemotherapy in adult patient with B-ALL in CR1 with no detectable minimal residual disease.

Autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for B-cell acute lymphoblastic leukaemia (B-ALL) has been rigorously debated in recent years. We retrospectively analysed the outcomes of 355 adult patients with B-ALL in first complete remission who had received auto-HSCT or allogeneic HSCT (allo-HSCT) in our centre. The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after three chemotherapy cycles. Auto-HSCT demonstrated comparable 3-year overall survival (OS) (72.7% vs. 68.5%, p = 0.441) and leukaemia-free survival rates (62.8% vs. 56.1%, p = 0.383) compared to allo-HSCT for patients with negative MRD, while the advantage of lower non-relapse mortality (1.5% vs. 25.1%, p < 0.001) was offset by a higher cumulative incidence of relapse (CIR) rates (35.7% vs. 18.9%, p = 0.018), especially in high-risk patients. For patients at high risk and with positive MRD, there was a lower trend of 3-year OS (50.0% vs. 66.0%, p = 0.078) and significantly higher CIR rates (71.4% vs. 39.1%, p = 0.018) in auto-HSCT. However, no significant interaction was observed in the tests. In conclusion, auto-HSCT appears to be an attractive treatment for patients with negative MRD after three chemotherapy cycles. For MRD-positive patients, allo-HSCT may be a more effective treatment.

Soil cooling can improve maize root-shoot growth and grain yield in warm climate.

Global warming causes topsoil temperatures to increase, which potentially leads to maize yield loss. We explored the effects of soil warming/cooling on root-shoot growth and maize grain yields by performing pot experiments with a heat-sensitive maize hybrid (HS208) and a normal maize hybrid (SD609) in warm temperate climate in 2019 and 2020. Our results reveal, for the first time, differences in root characteristics, leaf photosynthetic physiology, and yield responses to soil warming and cooling between normal and heat-sensitive maize varieties under a warm temperate climate. Soil warming (+2 and 4 °C) inhibited whole root growth by decreasing root length, volume, and dry mass weight, which indirectly reduced leaf photosynthetic capacity and decreased grain yield/plant by 15.10-24.10% versus control plants exposed to ambient temperature. Soil cooling (-2 °C) promoted root growth and leaf photosynthesis, and significantly increased grain yield of HS208 by 12.61%, although no significant change was found with SD609. It can be seen that under unfavorable conditions of global warming, selection of excellent stress-resistant hybrids plays an important role in alleviating the soil heat stress of maize in warm temperate climate regions.

Root zone temperature regulates potassium absorption and photosynthesis in maize (Zea mays).

Affected by climate warming, the impact of crop root zone warming (RZW) on maize seedling growth and nutrient uptake deserve attention. The characteristics of K uptake in maize under root zone warming and the combined impacts of potassium deficiency and RZW are still unclear. The present study aimed to investigate the effects of RZW on potassium absorption and photosynthesis of maize seedlings under the difference in potassium. The results showed that RZW and low potassium treatment significantly affected root shoot development and photosynthetic physiological characteristics of maize seedlings. Moreover, the interaction of RZW and potassium content had striking influence on maize seedlings. Under the normal potassium with root zone medium temperature treatment, the development of maize was the most vigorous. Under the dual stress of high root zone temperature and low potassium, the root absorption area, total potassium content and root activity were significantly reduced, which then influenced the light energy use efficiency and dry matter accumulation. Securing the supply of potassium fertilizer under high root zone temperature stress is useful to alleviate the impact of high temperature stress.

Exosome-derived CIRP: An amplifier of inflammatory diseases.

Cold-inducible RNA-binding protein (CIRP) is an intracellular stress-response protein and a type of damage-associated molecular pattern (DAMP) that responds to various stress stimulus by altering its expression and mRNA stability. Upon exposure to ultraviolet (UV) light or low temperature, CIRP get translocated from the nucleus to the cytoplasm through methylation modification and stored in stress granules (SG). During exosome biogenesis, which involves formation of endosomes from the cell membrane through endocytosis, CIRP also gets packaged within the endosomes along with DNA, and RNA and other proteins. Subsequently, intraluminal vesicles (ILVs) are formed following the inward budding of the endosomal membrane, turning the endosomes into multi-vesicle bodies (MVBs). Finally, the MVBs fuse with the cell membrane to form exosomes. As a result, CIRP can also be secreted out of cells through the lysosomal pathway as Extracellular CIRP (eCIRP). Extracellular CIRP (eCIRP) is implicated in various conditions, including sepsis, ischemia-reperfusion damage, lung injury, and neuroinflammation, through the release of exosomes. In addition, CIRP interacts with TLR4, TREM-1, and IL-6R, and therefore are involved in triggering immune and inflammatory responses. Accordingly, eCIRP has been studied as potential novel targets for disease therapy. C23 and M3, polypeptides that oppose eCIRP binding to its receptors, are beneficial in numerous inflammatory illnesses. Some natural molecules such as Luteolin and Emodin can also antagonize CIRP, which play roles similar to C23 in inflammatory responses and inhibit macrophage-mediated inflammation. This review aims to provide a better understanding on CIRP translocation and secretion from the nucleus to the extracellular space and the mechanisms and inhibitory roles of eCIRP in diverse inflammatory illnesses.

Retractions relevant to COVID-19: does the retraction rate jump during the pandemic?

INTRODUCTION: Since the outbreak of Coronavirus Disease 2019, the scientific community has acted promptly before many publications appeared in the scientific literature. It posed a question of whether the expedited research and publication process would impair the research integrity, further leading to the rise in retractions. Hence in this study, we aimed to examine the characteristics of retracted articles related to COVID-19 and provide some insight into the scientific publishing of COVID-19 literature. METHODS: In this study, by searching Retraction Watch on 10 March 2022, the largest database on retraction, we included 218 COVID-19-related retracted articles. RESULTS: We found that the retraction rate of COVID-19 research was 0.04%. Of the 218 papers, 32.6% were retracted or withdrawn with a retraction notice giving no indication of the reason, and 9.2% due to honest mistakes made by authors. Retractions owing to misbehavior by authors comprised 33% of those retractions. DISCUSSION: We came to the conclusion that the changed publication norms certainly led to a number of retractions that could have been circumvented, the post-publication review and scrutiny were also enhanced.

Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia.

This is a small phase I study examining the safety and efficacy of a cladribine (CLAD)-containing conditioning regimen prior to autologous hematopoietic stem cell transplantion (auto-HSCT) for patients with acute myeloid leukemia (AML). All patients, aged 15-54 years (median 32 years), had favorable/intermediate risk AML (n = 20) or acute promyelocytic leukemia (APL; n = 2) and no evidence of minimal residual disease (MRD) prior to transplantation. Fourteen of the 22 patients received the conditioning regimen as follows: busulfan (Bu) + cyclophosphamide (Cy) + CLAD + cytarabine (Ara-c) or idarubicin. The conditioning regimen of 8 patients was without Cy nor idarubicin to reducing adverse cardiac reaction: the regimen of Bu + CLAD+ Ara-c for 6 patients; and the regimen of Bu + melphalan + CLAD + Ara-c for the other 2 patients. All 22 AML patients received peripheral blood stem cell transplantation. The number of infused mononuclear cells and CD34+ cells was 10.00 (2.88-20.97) × 108/kg and 1.89 (1.52-10.44) × 106/kg, respectively. Hematopoietic reconstitution was achieved in all patients, with a median time of 13 (10-34) days for neutrophils and 28 (14-113) days for platelets. Two patients suffered from pulmonary infection, 4 patients suffered from septicemia during the neutropenic stage, and the others suffered from infection or gastrointestinal reaction without exceeding grade 3 after conditioning, which were all alleviated by anti-infection and other supportive treatment. None of the patients died of transplantation-related complications. At a median follow-up of 29.5 (ranging from 4.0 to 60.0) months, three patients relapsed after auto-HSCT at a median time of 6 (ranging from 0.5 to 10.0) months. One patient died due to relapse at 18 months after auto-HSCT. The remaining 21 patients were all alive, including 19 patients with negative MRD. The other 2 patients achieved negative MRD after allogeneic HSCT or chemotherapy. The estimated 2-year survival, relapse, and Leukemia-free survival rates were 94.1 ± 5.7%, 14.7 ± 7.9% and 85.3 ± 7.9%, respectively. A CLAD-combination conditioning regimen is efficient and safe for auto-HSCT, indicating an effective approach for AML treatment.

Ferroptosis in Rat Lung Tissue during Severe Acute Pancreatitis-Associated Acute Lung Injury: Protection of Qingyi Decoction.

Qingyi decoction (QYD) has anti-inflammatory pharmacological properties and substantial therapeutic benefits on severe acute pancreatitis (SAP) in clinical practice. However, its protective mechanism against SAP-associated acute lung injury (ALI) remains unclear. In this study, we screened the active ingredients of QYD from the perspective of network pharmacology to identify its core targets and signaling pathways against SAP-associated ALI. Rescue experiments were used to determine the relationship between QYD and ferroptosis. Then, metabolomics and 16s rDNA sequencing were used to identify differential metabolites and microbes in lung tissue. Correlation analysis was utilized to explore the relationship between core targets, signaling pathways, metabolic phenotypes, and microbial flora, sorting out the potential molecular network of QYD against SAP-associated lung ALI. Inflammatory damage was caused by SAP in the rat lung. QYD could effectively alleviate lung injury, improve respiratory function, and significantly reduce serum inflammatory factor levels in SAP rats. Network pharmacology and molecular docking identified three key targets: ALDH2, AnxA1, and ICAM-1. Mechanistically, QYD may inhibit ferroptosis by promoting the ALDH2 expression and suppress neutrophil infiltration by blocking the cleavage of intact AnxA1 and downregulating ICAM-1 expression. Ferroptosis activator counteracts the pulmonary protective effect of QYD in SAP rats. In addition, seven significant differential metabolites were identified in lung tissues. QYD relatively improved the lung microbiome's abundance in SAP rats. Further correlation analysis determined the correlation between ferroptosis, differential metabolites, and differential microbes. In this work, the network pharmacology, metabolomics, and 16s rDNA sequencing were integrated to uncover the mechanism of QYD against SAP-associated ALI. This novel integrated method may play an important role in future research on traditional Chinese medicine.