SPP1 induces idiopathic pulmonary fibrosis and NSCLC progression via the PI3K/Akt/mTOR pathway.

BACKGROUND: The prevalence of non-small cell lung cancer (NSCLC) is notably elevated in individuals diagnosed with idiopathic pulmonary fibrosis (IPF). Secreted phosphoprotein 1 (SPP1), known for its involvement in diverse physiological processes, including oncogenesis and organ fibrosis, has an ambiguous role at the intersection of IPF and NSCLC. Our study sought to elucidate the function of SPP1 within the pathogenesis of IPF and its subsequent impact on NSCLC progression. METHODS: Four GEO datasets was analyzed for common differential genes and TCGA database was used to analyze the prognosis. The immune infiltration was analyzed by TIMER database. SPP1 expression was examined in human lung tissues, the IPF fibroblasts and the BLM-induced mouse lung fibrosis model. Combined with SPP1 gene gain- and loss-of-function, qRT-PCR, Western blot, EdU and CCK-8 experiments were performed to evaluate the effects and mechanisms of SPP1 in IPF progression. Effect of SPP1 on NSCLC was detected by co-cultured IPF fibroblasts and NSCLC cells. RESULTS: Through bioinformatics analysis, we observed a significant overexpression of SPP1 in both IPF and NSCLC patient datasets, correlating with enhanced immune infiltration of cancer-associated fibroblasts in NSCLC. Elevated levels of SPP1 were detected in lung tissue samples from IPF patients and bleomycin-induced mouse models, with partial colocalization observed with α-smooth muscle actin. Knockdown of SPP1 inhibits TGF-ß1-induced differentiation of fibroblasts to myofibroblasts and the proliferation of IPF fibroblasts. Conversely, SPP1 overexpression promoted IPF fibroblast proliferation via PI3K/Akt/mTOR pathway. Furthermore, IPF fibroblasts promoted NSCLC cell proliferation and activated the PI3K/Akt/mTOR pathway; these effects were attenuated by SPP1 knockdown in IPF fibroblasts. CONCLUSIONS: Our findings suggest that SPP1 functions as a molecule promoting both fibrosis and tumorigenesis, positioning it as a prospective therapeutic target for managing the co-occurrence of IPF and NSCLC.

Immunophenotype of lymphocytes and real-world outcome of COVID-19 infection in children with hematology and oncology.

BACKGROUND: Patients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear. METHODS: In this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China. RESULTS: A total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P < 0.0001), long duration of symptom (P < 0.0001), low lymphocytes count (P = 0.095), low CD3 + and CD8 + T cell count (P = 0.013, P = 0.022), high percentage of CD4 + TCM (P = 0.016), and low percentage of transitional B cells (P = 0.045) were high risk factors for severe COVID-19 infection. Cox regression model showed that the absolute lymphocytes count (P = 0.027) and long duration of symptom (P = 0.002) were the independent factors for severity. Patients with CD8 + dominant and B cell depletion subtype wasn't related with severity, but had higher percentage of CD8 + effector memory T cells (TEM) and terminally differentiated effector memory T cells (TEMRA) (P < 0.001, P < 0.001), and a longer COVID-19 duration (P = 0.045). CONCLUSION: The severity was relatively mild in children with immunodeficiencies in the third year of COVID-19 pandemic. Low lymphocyte count and long duration of symptom were the independent risk factors with COVID-19 severity. Delays in cancer care remain a major concern and the long outcome is pending.

[Prognostic analysis of childhood T-lymphoblastic lymphoma treated with leukemia regimen]. / 儿童Tæ·‹å·´æ¯ç»†èƒžæ·‹å·´ç˜¤é‡‡ç”¨ç™½è¡€ç— æ–¹æ¡ˆæ²»ç–—çš„é¢„åŽåˆ†æž.

OBJECTIVES: To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors. METHODS: A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen (ALL-2009 or CCCG-ALL-2015 regimen) from May 2010 to May 2022. RESULTS: The 29 children with T-LBL had a 5-year overall survival (OS) rate of 84%±7% and an event-free survival (EFS) rate of 81%±8%. The children with B systemic symptoms (unexplained fever >38°C for more than 3 days; night sweats; weight loss >10% within 6 months) at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms (P<0.05). The children with platelet count >400×109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates (P<0.05). There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen (P>0.05). Compared with the ALL-2009 regimen, the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections (P<0.05). CONCLUSIONS: The ALL regimen is safe and effective in children with T-LBL. Children with B systemic symptoms, platelet count >400×109/L, and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis. Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections, but it does not affect prognosis.

Cytopenia: a report of haplo-cord transplantation in twin brothers caused by a novel germline GATA1 mutation and family survey.

Cytopenia due to the abnormal regulation of GATA1 could manifest as varying degrees of thrombocytopenia and/or anemia and more severely in male children than in female children. Here, we describe the case of pancytopenic and transfusion-dependent twin brothers at our center whose bone marrow puncture revealed low bone marrow hyperplasia. Whole-exome sequencing revealed that the twins had a new germline GATA1 mutation (nm_002049: exon 3:c.515 T >C:p.F172S), which confirmed the diagnosis of GATA1 mutation-related pancytopenia. The mutation was inherited from their mother, who was heterozygous for the mutation. Sanger sequencing verified the pathogenicity of the mutation. Further family morbidity survey confirmed that GATA1 mutation-related pancytopenia is an X-linked recessive genetic disorder. We developed haploid hematopoietic stem cell transplantation programs for twins, with the father as the only donor, and finally, the hematopoietic reconstruction was successful. Although they experienced acute graft-versus-host disease, hemorrhagic cystitis, and a viral infection in the early stage, no abnormal manifestations or transplant-related complications were observed 3 months after transplantation. Through hematopoietic stem cell transplantation technology for one donor and two receptors, we eventually cured the twins. The p.F172S variant in the new germline GATA1 mutation may play an essential role in the pathogenesis of GATA1 mutation-related cytopenia.

Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

[Effectiveness of autologous hematopoietic stem cell transplantation in the treatment of high-risk neuroblastoma in children: a single-center clinical study]. / å•ä¸­å¿ƒå„¿ç«¥é«˜å±ç¥žç»æ¯ç»†èƒžç˜¤è‡ªä½“é€ è¡€å¹²ç»†èƒžç§»æ¤çš„ç–—æ•ˆåˆ†æž.

OBJECTIVES: To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB). METHODS: A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed. RESULTS: Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05). CONCLUSIONS: Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.

Sequential infection of Epstein-Barr virus and cryptococcal encephalitis after umbilical cord blood transplantation in a child with X-linked adrenoleukodystrophy.

Dual infection with two pathogens can be found in few cases of encephalitis. Cases of sequential infection with EBV and cryptococcal encephalitis in post-transplant patients are rare. We describe a 5-year-old boy with X-linked adrenoleukodystrophy who presented sequential infection with EBV and cryptococcal encephalitis after umbilical cord blood transplant. The patient showed fever, vomiting and emotional agitation with EBV DNA detected in CSF on day 100. The child underwent 3 doses of intravenous rituximab with a good response. However, the child presented with right facial paralysis, headache, and fever on day 130 after 2 weeks of clinical stability. Brain MRI demonstrated chronic granuloma formed with ring enhancement. FilmArray ME PCR confirmed the existence of Cryptococcus neoformans/gattii in the CSF. The child underwent sequential treatment with amphotericin liposome B and flucytosine. Maintenance treatment with fluconazole was administered for 1 year. Facial paralysis was on longer present on day 260. Cryptococcus neoformans/gattii was not detected on day 310. The biochemistry and cell count of the CSF were completely normal on day 520. Follow-up 2.5 years after presentation, brain MRI changes showed near complete resolution of the lesions. The child survived for 3 years to the last following-up. Invasive cryptococcal encephalitis is rare and life-threatening complication of transplantation. It is important to recognize dual infections, and perform treatment quickly to improve the prognosis of encephalitis after transplantation.

Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer.

BACKGROUND: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). METHODS: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. RESULTS: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells. CONCLUSIONS: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

Anti-Inflammatory and Antioxidant Effects of Acetyl-L-Carnitine on Atherosclerotic Rats.

BACKGROUND The purpose of the present study was to evaluate the regulatory effects of acetyl-L-carnitine (ALCAR) on atherosclerosis in Wister rats and to explore its anti-atherosclerotic mechanism. MATERIAL AND METHODS We randomly divided 32 Wister rats into 4 groups: a normal diet group (control group, n=8), a normal diet+ALCAR group (ALCAR group, n=8), an atherosclerosis group (AS group, n=8), and an atherosclerosis+ALCAR group (AS+ALCAR group, n=8). The serum lipid distribution, oxidative stress, inflammatory factors and adiponectin (APN) in the blood, and heart and aortic tissues were determined using the standard assay kits, xanthine oxidase method, and ELISA, respectively. HE staining was performed to observe aortic pathology structure change, and the level of angiotensin II (AngII) in the aorta was assessed using radioimmunoassay. In addition, real-time quantitative PCR and Western blot analysis were applied to detect the expression of iNOS, IL-1ß, TNF-alpha, and CRP in the aortic and heart tissues. RESULTS Compared with the AS group, the levels of serum TC, TG, LDL, and VLDL in rats decreased significantly, while HDL level significantly increased in the AS+ALCAR group. ALCAR administration enhanced the SOD and GSH-Px activities and decreased MDA activity. APN level was significantly elevated in the AS group, but ALCAR had no significant effect on APN. Further, ALCAR reduced the expressions of inflammation factors TNF-alpha, IL-1ß, iNOS, and CRP, and the concentration of AngII in serum, aortic, and heart tissues. CONCLUSIONS ALCAR can inhibit the expressions of inflammatory factors and antioxidation to suppress the development of atherosclerosis by adjusting blood lipid in the myocardium of AS rats.

Preventive Effects of Different Drugs on Asymptomatic Lower Extremities Deep Venous Thrombosis After Artificial Joint Replacement: A Mixed Treatment Comparison.

This network meta-analysis aims to compare the preventive effects of 8 drugs (edoxaban, dabigatran, apixaban, rivaroxaban, warfarin, bemiparin, ximelagatran, and enoxaparin) on asymptomatic deep venous thrombosis (DVT) of lower extremities after artificial joint replacement. PubMed, Cochrane Library, and Embase were searched from their inception through October 2015 for randomized controlled trials comparing 8 drugs for the prevention of asymptomatic DVT of lower extremities after artificial joint replacement. Network meta-analysis combined the direct and indirect evidence to evaluate odd ratios (ORs) and surface under the cumulative ranking curves values. A total of 15 randomized controlled trials satisfying the inclusion criteria were enrolled. Edoxaban, apixaban, and rivaroxaban had poorer preventive effects on asymptomatic DVT of lower extremities after undergoing artificial joint replacement when compared with warfarin [OR = 0.16, 95% confidence interval (CI), 0.04-0.60; OR = 0.22, 95% CI, 0.07-0.64; OR = 0.16, 95% CI, 0.05-0.49, respectively]. When compared with enoxaparin, the preventive effects of edoxaban and rivaroxaban were poorer (OR = 0.37, 95% CI, 0.15-0.85; OR = 0.37, 95% CI, 0.21-0.59, respectively). The preventive effects of edoxaban and rivaroxaban were poorer than dabigatran (OR = 0.38, 95% CI, 0.14-0.99; OR = 0.38, 95% CI, 0.18-0.73, respectively). The surface under the cumulative ranking curves values showed that warfarin had better preventive effects on asymptomatic DVT of lower extremities after undergoing artificial joint replacement. Among the 8 drugs (edoxaban, dabigatran, apixaban, rivaroxaban, warfarin, bemiparin, ximelagatran, and enoxaparin), warfarin had better preventive effects on asymptomatic DVT of lower extremities after undergoing artificial joint replacement.

Hypoxia-inducible factor 1α in combination with vascular endothelial growth factor could predict the prognosis of postoperative patients with oesophageal squamous cell cancer.

The purpose of the study is to investigate the clinicopathological and prognostic features of dual hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor (VEGF) expression in oesophageal squamous cell carcinoma (OSCC) patients. A total of 73 patients were enrolled in this study. The positive expression of HIF-1a was identified in 69.9% of the cases. Hypoxia-inducible factor 1a expression was correlative with pT (p = 0.008) and pTNM stage (p = 0.002). The positive expression of VEGF was identified in 63.0% of the cases. Vascular endothelial growth factor expression was correlative with pT (p = 0.005), pN (p = 0.045), and pTNM stage (p < 0.05). HIF-1a and VEGF expressions had a significantly positive correlation (p = 0.010). Dual positive expression of HIF-1a and VEGF was identified in 50.7% (37/73) of the cases, and it was significantly correlative with pT (p = 0.025), pN (p = 0.008), and pTNM stage (p = 0.014). The OSCC patients' 5-year survival rate was correlative with pT (p < 0.05), pN (p < 0.01), pTNM stage (p < 0.01), VEGF expression (p < 0.01), and dual expressions of HIF-1a and VEGF (p < 0.01). Cox regression analysis showed that pN and dual HIF-1a and VEGF expression were independent prognostic factors for the 5-year survival rate of the patients. In conclusion, HIF-1a combined with VEGF could enable us to more accurately predict the prognosis of OSCC patients.

Real-time polymerase chain reaction for diagnosing infectious mononucleosis in pediatric patients: A systematic review and meta-analysis.

In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis.

Plumbagin Mediates Cardioprotection Against Myocardial Ischemia/Reperfusion Injury Through Nrf-2 Signaling.

BACKGROUND Plumbagin is a potent antioxidant with anti-inflammatory and anti-carcinogenic action. Myocardial ischemia/reperfusion injury results in organ damage through oxidative stress and inflammatory mechanisms. In this study, we analyzed the potential role of plumbagin against myocardial I/R injury in Wistar rats. MATERIAL AND METHODS Oxidative stress was measured through ROS, lipid peroxide content, and antioxidant enzyme activities. The expression of redox signaling and inflammatory proteins was analyzed through Western blotting. Inflammatory cytokine expressions were determined through ELISA. RESULTS Oxidative stress status was reduced by plumbagin by decreasing ROS and lipid peroxide levels in rats with myocardial I/R (MI/R) injury. Plumbagin regulated redox imbalance induced by I/R injury by modulating the transcription factors NF-κB and Nrf-2. Further, downstream targets of NF-κB (COX-2, iNOS) and Nrf-2 (HO-1, NQO1 and GST) expression were significantly downregulated by plumbagin treatment. Pro-inflammatory cytokine expressions were significantly abrogated by plumbagin treatment. CONCLUSIONS This study shows the protective role of plumbagin against myocardial I/R injury by regulating antioxidant and inflammatory mechanisms.

Green industrial policy and green development of agriculture-Quasi-natural experiment based on the Yangtze River Economic Belt in China.

Based on the panel data of 30 provinces, municipalities, and autonomous regions in China from 2012 to 2022, from the perspective of harmony between man and nature, this paper selects 20 indicators to measure the level of agricultural green development from five dimensions such as ecological conservation and resource conservation by entropy weight method. On this basis, taking the implementation of green industrial policy in the Yangtze River Economic Belt as a quasi-natural experiment, the policy effect of green industrial policy on agricultural green development was analyzed by using the difference-in-difference method. The study found that: (1) the green development of agriculture is basically increasing year by year in each province, but there are some differences in the green development of agriculture among provinces; (2) Compared with the non-implementation areas of policies, the green development of agriculture in the implementation areas of policies has been significantly improved, and has passed a series of robustness tests; (3) The mechanism analysis shows that the green industrial policy has a crowding-out effect on industrial development, but significantly enhances the ecological construction and protection, thus promoting the green development of agriculture; (4) Heterogeneity analysis shows that the policy has a significant positive incentive effect on the upper and lower reaches of the Yangtze River Economic Belt, and the incentive effect on the middle reaches is not significant; (5) The impact of technological level on agricultural green development shows a positive U-shaped relationship. The improvement of education and information development levels also effectively promotes the green development of agriculture. This paper provides important empirical evidence and factual references for further promoting the green development of agriculture and the improvement of green industrial policies.

Dynamic evolution and spatial spillover effect of agricultural green development on eight economic regions in China.

Promoting the green development of agriculture is of great significance to realize agricultural and rural modernization in China. Based on the existing research, this paper innovatively explores the dynamic and spatial effects of agricultural green development in the eight newly zoned regions of China's economy. Based on the panel data of 30 provinces in China from 2013 to 2022, this paper selects 20 indicators to measure the level of agricultural green development from five dimensions such as ecological protection, resource conservation, environment-friendly, green supply and economic growth by entropy weight method and uses non-parametric estimation method to analyze the dynamic evolution trend of agricultural green development in the whole country and its eight economic regions. Then, a spatial econometric model is constructed to further explore the influence mechanism and spatial spillover effect of each influencing factor on agricultural green development. The findings demonstrate that the level of agricultural green development in 30 provinces of China continuously improved during the study period, but the dynamic evolution trend characteristics in the whole country and its eight economic regions are not the same. Specifically, the development differences between the whole country, the northeast region, the eastern coast, the southern coast and the northwest region increased, while that between the northern coast, the Yellow River basin and the middle reaches of the Yangtze River first increased and then decreased, and that in the southwestern region gradually narrowed. There is a significant spatial spillover effect on agricultural green development and its influencing factors. Moreover, there is heterogeneity in the influence characteristics and spatial spillover effects of various influencing factors on agricultural green development among the eight economic regions. Therefore, it is proposed that eight economic regions in China should formulate differentiated development strategies, focus on educational and technological innovation etc., and further promote agricultural green development.

ARC@DPBNPs suppress LPS-induced acute lung injury via inhibiting macrophage pyroptosis and M1 polarization by ERK pathway in mice.

AIM OF THE STUDY: Exploring the protective effect of ARC@DPBNP on lipopolysaccharides (LPS)-induced ALI and its underlying mechanism. MATERIALS AND METHODS: ALI model was established by intransally administrating LPS (4 mg/kg) into C57BL/6 mice. The suppression effects of ALI was first compared between ARC (intragastric administrated, with doses ranging from 10 to 80 mg/kg) and ARC@BPBNPs (intratracheally administrated, with doses ranging from 1 to 4 mg/kg). Changes in lung histology post intratracheal intervention of 3 mg/kg ARC@DPBNPs were detected. The expression of pyrotosis pathway-related proteins in lungs as well as in RAW264.7 cells was detected by western blotting. The ASC expression in lung macrophages was examined using immune-fluorescent staining. The polarization of RAW264.7 cells and lung macrophages were detected by flow cytometry. The network pharmacology was constructed by Cytoscape, and the molecular docking was perfomed by AutoDock Vina. RESULTS: Docking predicted the high affinity of ARC to MAPK1 (ERK2). HE staining showed that ARC@DPBNPs attenuated LPS-induced ALI at a remarkably lower dose than ARC. The improved histopathological changes, lung W/D weight ratio, and decreased of inflammatory factor levels in lung collectively demonstrated the alleviation effects of ARC@DPBNPs. Compared with the LPS group, ARC@DPBNPs down-regulated the ERK pathway, resulted in a suppression of the macrophage pyroptosis and M1 polarization. This suppression effects could be removed by the ERK activator Ro 67-7476. CONCLUSION: ARC@DPBNPs attenuated ALI by suppressing LPS-induced macrophage pyroptosis and polarization, probably through down-regulation of the ERK pathway.

Identification and validation of a novel five-gene signature in high-risk MYCN-not-amplified neuroblastoma.

OBJECTIVE: High-risk neuroblastoma patients often have poor outcomes despite multi-treatment options. The risk stratification of high-risk MYCN-not-amplified (HR-MYCN-NA) patients remains difficult. This study aims to identify a gene set signature that can help further stratify HR-MYCN-NA patients for a potential personalized therapeutic strategy. METHODS: Three microarrays and one single-cell RNA sequence dataset were acquired and analyzed. Firstly, the prognostic-related genes (PRGs) in HR-MYCN-NA tumor cells were identified using TARGET-NB and GSE137804 datasets. Then, the prognostic model was established by LASSO-Cox regression, and verified in external cohort (GSE49710, GSE45547). Moreover, a time-dependent receiver operating characteristic curve (ROC) and area under the ROC (AUC) was used to assess survival prediction. A nomogram was established to predict the 1-, 3- and 5-year overall survival (OS) of HR-MYCN-NA patients. RESULTS: In the training set, a five-PRGs signature, which include GAL, GFRA3, MARCKS, PSMD13, and ZNHIT3 genes, was identified and successfully stratified HR-MYCN-NA patients into ultra-high risk (UHR) and high-risk (HR) subtypes (HR = 4.29, P < 0.001). ROC curve analysis confirmed its predictive power (AUC = 0.74-0.82), suggesting a good predictive efficacy. Consistently, high-risk scores also predicted worse OS (HR = 2, P = 0.033) in the external validation dataset (AUC = 0.67-0.71). Moreover, the overall C-index of the nomogram was 0.75 (P < 0.001), which indicated good agreement between the observed and predicted survival rates. Further integrating the five PRGs signature with clinical factors, these 5 gene signature (HR = 4.45, P < 0.001) and tumor grade (HR = 4.15, P = 0.02) were found to be independent prognostic factors for HR-MYCN-NA patients. CONCLUSION: The novel five PRGs signature could well predict the survival of HR-MYCN-NA patients, which may provide constructive information for these subsets.

Bone marrow relapse in stage 4 neuroblastoma of children in Shanghai.

OBJECTIVE: To characterize the epidemiological, clinical, and molecular features of bone marrow relapse in high-risk neuroblastoma (HR-NB) and to identify potential prognostic indicators and therapeutic approaches for this specific subset within the Shanghai pediatric oncology landscape. METHODS: A retrospective study was conducted on 256 patients diagnosed with stage 4 neuroblastoma at two major pediatric hospitals in Shanghai, China, between 2008 and 2018. Patient data was collected, including demographic information, treatment regimens, and outcomes. Kaplan-Meier method and log-rank test were used for overall survival (OS) and event-free survival (EFS) analysis. RESULTS: The study revealed that bone marrow relapse affected 50.78% of patients, making it the most frequent relapse site. Patients with bone marrow involvement at diagnosis face an increased risk of subsequent bone marrow relapse. Age over 18 months, multiple metastatic sites, and the absence of autologous stem cell transplantation (ASCT) were identified as significant risk factors for bone marrow relapse. The 3-year OS and EFS rates of patients with bone marrow relapse were 32.5% and 32.5%, respectively. Patients receiving ASCT demonstrated significantly higher survival rates. The lack of ASCT at diagnosis was significantly correlated with lower survival rates, particularly in patients experiencing bone marrow relapse. CONCLUSION: The study provides valuable insights into the challenges posed by bone marrow relapse in the setting of high-risk neuroblastoma. It emphasizes the need for tailored therapeutic approaches to improve outcomes, potentially involving novel targeted agents and immunotherapies. The study underscores the poor prognosis associated with bone marrow relapse in HR-NB and the urgent need for further research to optimize risk stratification and therapeutic strategies, including prospective investigation and the integration of advanced molecular profiling techniques.

Decitabine as epigenetic priming with CLAG induce improved outcome of relapsed or refractory acute myeloid leukemia in children.

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.

A novel rat lung transplantation model using venoarterial extracorporeal membrane oxygenation support.

Objectives: Extracorporeal membrane oxygenation (ECMO) has become an important life support technique during lung transplantation. We aimed to develop a rat model for lung transplantation using venoarterial (VA) ECMO support. Methods: Adult male Sprague-Dawley rats weighing 400 to 450 g were used in this study. ECMO circuits were created by obtaining venous access from the femoral vein with subsequent extracorporeal oxygen exchange, which was then returned to the circulatory system through the left carotid artery (ie, VA-ECMO). Simultaneously, the donor lungs were retrieved and immersed in cold, low-potassium dextran lung preservation solution. Orthotopic left lung transplantation supported by VA-ECMO was performed. Thereafter, a respiratory failure rat model was constructed using ventilation with a hypoxic and hypercapnic gas mixture, consisting of 6% oxygen, 8% carbon dioxide, and 86% nitrogen, before lung transplantation. Similarly, left lung transplantation supported by VA-ECMO was performed in rats with respiratory failure. Arterial blood gas levels were measured at designated time points throughout the experiment. Results: We found that VA-ECMO provided sufficient oxygenation and carbon dioxide removal to allow for smooth left lung transplantation in healthy rats and those with respiratory failure. Conclusions: We established a rat model for lung transplantation using VA-ECMO. Left lung transplantation using VA-ECMO support is also feasible and safe in rat models of respiratory failure. These models provide efficient and economical models for translational medicine for lung transplantation using ECMO. Moreover, it will be invaluable to evaluate the physiological and pathophysiological roles of ECMO during lung transplantation.