One-shot screening: Utilization of a two-dimensional convolutional neural network for automatic detection of left ventricular hypertrophy using electrocardiograms.

BACKGROUND AND OBJECTIVE: Left ventricular hypertrophy (LVH) can impair ejection function and elevate the risk of heart failure. Therefore, early detection through screening is crucial. This study aimed to propose a novel method to enhance LVH detection using 12-lead electrocardiogram (ECG) waveforms with a two-dimensional (2D) convolutional neural network (CNN). METHODS: Utilizing 42,127 pairs of ECG-transthoracic echocardiogram data, we pre-processed raw data into single-shot images derived from each ECG lead and conducted lead selection to optimize LVH diagnosis. Our proposed one-shot screening method, implemented during pre-processing, enables the superimposition of waveform source data of any length onto a single-frame image, thereby addressing the limitations of the one-dimensional (1D) approach. We developed a deep learning model with a 2D-CNN structure and machine learning models for LVH detection. To assess our method, we also compared our results with conventional ECG criteria and those of a prior study that used a 1D-CNN approach, utilizing the same dataset from the University of Tokyo Hospital for LVH diagnosis. RESULTS: For LVH detection, the average area under the receiver operating characteristic curve (AUROC) was 0.916 for the 2D-CNN model, which was significantly higher than that obtained using logistic regression and random forest methods, as well as the two conventional ECG criteria (AUROC of 0.766, 0.790, 0.599, and 0.622, respectively). Incorporating additional metadata, such as ECG measurement data, further improved the average AUROC to 0.921. The model's performance remained stable across two different annotation criteria and demonstrated significant superiority over the performance of the 1D-CNN model used in a previous study (AUROC of 0.807). CONCLUSIONS: This study introduces a robust and computationally efficient method that outperforms 1D-CNN models utilized in previous studies for LVH detection. Our method can transform waveforms of any length into fixed-size images and leverage the selected lead of the ECG, ensuring adaptability in environments with limited computational resources. The proposed method holds promise for integration into clinical practice as a tool for early diagnosis, potentially enhancing patient outcomes by facilitating earlier treatment and management.

Coptisine protects against transient focal cerebral ischaemic injury by regulation of arachidonic acid metabolism.

OBJECTIVES: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear. METHODS: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated. RESULTS: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment. CONCLUSION: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.

The underlying molecular mechanism of ciliated epithelium dysfunction and TGF-ß signaling in children with congenital pulmonary airway malformations.

The aim of this study was to investigate the variation in gene expression in the complete transcripts of Congenitalpulmonary airwaymalformation (CPAM) of the lung using Next Generation Sequencing (NGS) technology. There were 20 cases involving children with CPAM were used for selection of study sample. NGS was used to establish RNA-Seq libraries for the two groups of samples separately, and both groups were conducted to differential expression analysis and Gene Ontology (GO) functional enrichment analysis. The pathways of the differential genes were analyzed to find the enriched target pathways. A total of 592 genes were expressed with significant differences (CPAM vs. normal tissue, P < 0.05). GO functional analysis of DEGs indicated that abnormal ciliary function played a role in the development of CPAM. Subsequently, analysis of these genes pathways showed the TGF-ß signaling pathway was significantly enriched. Finally, the results of immunohistochemical analysis of some DEGs showed that a significant reduction in the expression of SMAD6, a gene related to the TGF-ß signaling pathway, led to abnormal activation of the pathway. TGF-ß signaling pathway involved in the evolution of the disease obtained by DEGs enrichment pathway analysis. SMAD6, a gene involved in this pathway, might be a potential biomarker for the diagnosis and treatment of CPAM.

Gas Chromatography-Mass Spectrometry-Based Cerebrospinal Fluid Metabolomics to Reveal the Protection of Coptisine against Transient Focal Cerebral Ischemia-Reperfusion Injury via Anti-Inflammation and Antioxidant.

Coptisine (Cop) exerts a neuroprotective effect on central nervous system disease, particularly ischemic stroke. However, its protective mechanism is still unclear. This study aimed to investigate the protective effect of Cop on cerebral ischemia-reperfusion (IR) rats with a middle cerebral artery occlusion model by integrating a gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach with biochemical assessment. Our results showed that Cop could improve neurobehavioral function and decrease the ischemia size in IR rats. In addition, Cop was found to decrease inflammatory mediators (e.g., prostaglandin D2 (PGD2) and tumor necrosis factor-α (TNF-α) and attenuate oxidative stress response (e.g., increase the superoxide dismutase (SOD) expression and decrease 8-iso-PGF2α level). Furthermore, the GC-MS-based cerebrospinal fluid (CSF) metabolomics analysis indicated that Cop influenced the level of glycine, 2,3,4-trihydroxybutyric acid, oleic acid, glycerol, and ribose during IR injury. Cop exhibited a good neuroprotective effect against cerebral IR injury and metabolic alterations, which might be mediated through its antioxidant and anti-inflammatory properties.

Endogenous hydrogen sulfide inhibition suppresses tumor growth by promoting apoptosis and pyroptosis in esophageal cancer cells.

BACKGROUND: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. METHODS: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-ß-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. RESULTS: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. CONCLUSION: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Inhibition of endogenous hydrogen sulfide production suppresses the growth of nasopharyngeal carcinoma cells.

Hydrogen sulfide (H2 S) has been widely recognized as one of gasotransmitters. Endogenous H2 S plays a crucial role in the progression of cancer. However, the effect of endogenous H2 S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine-ß-synthase), dl-propargylglycine (PAG, an inhibitor of cystathionine-γ-lyase), and l-aspartic acid (l-Asp, an inhibitor of 3-mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2 S in NPC growth. The results indicated that the combine (PAG + AOAA + l-Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l-Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)-extracellular signal-regulated protein kinase but higher expressions of p-p38 and p-c-Jun N-terminal kinase than those in the AOAA, PAG, and l-Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2 S generation could dramatically inhibit NPC growth via the ROS/mitogen-activated protein kinase pathway. Endogenous H2 S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2 S-producing enzymes could be designed and developed for NPC treatment.

Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPK/YAP pathway.

Non-small cell lung cancer (NSCLC) is characterized by high incidence and mortality, severely threatening human health. The infinite growth and metastasis of NSCLC cells result in a poor prognosis. Therefore, our study was to investigate the mechanism of Sestrin2 on the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Human embryonic lung fibroblasts, NSCLC cell lines, and nude mice were experimental subjects in this study. qRT-PCR and western blot were performed to evaluate the mRNA and protein expression of genes. CCK-8 and EdU assay were conducted to detect cell proliferation. The scratch test and Transwell assay were applied to examine cell migration and invasion. The bioinformatics analysis and Co-IP assay were employed to predict and consolidate the interaction between YAP and TEAD. We found the expression of Sestrin2 was declined but the expression of YAP was elevated in NSCLC cells. Sestrin2 sufficiency or YAP silencing could effectively impair cell growth and metastasis. Mechanistically, YAP interacted with TEAD to enhance FOXM1 expression. Additionally, the elevation of FOXM1 abolished the inhibitory influences of Sestrin2 sufficiency on NSCLC cell growth, invasion, and EMT process. Eventually, Sestrin2 elevation attenuated tumor growth in mice via modulation of the AMPK/YAP/FOXM1 axis, which was reversed by FOXM1 overexpression. Our consequences suggested Sestrin2 could inhibit the activation of YAP via prompting AMPK phosphorylation and then suppress FOXM1 expression through the interplay between YAP and TEAD to impair the capacities of NSCLC cell proliferation, migration, invasion, and EMT. This study provided a novel mechanism of Sestrin2 in NSCLC.

[Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China]. / é«˜è¶ äºŒå€ä½“æ ¸åž‹å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— çš„ä¸´åºŠç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored. RESULTS: Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×109/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05). CONCLUSIONS: The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.

Role of hydrogen sulphide in physiological and pathological angiogenesis.

The role of hydrogen sulphide (H2 S) in angiogenesis has been widely demonstrated. Vascular endothelial growth factor (VEGF) plays an important role in H2 S-induced angiogenesis. H2 S promotes angiogenesis by upregulating VEGF via pro-angiogenic signal transduction. The involved signalling pathways include the mitogen-activated protein kinase pathway, phosphoinositide-3 kinase pathway, nitric oxide (NO) synthase/NO pathway, signal transducer and activator of transcription 3 (STAT3) pathway, and adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels. H2 S has been shown to contribute to tumour angiogenesis, diabetic wound healing, angiogenesis in cardiac and cerebral ischaemic tissues, and physiological angiogenesis during the menstrual cycle and pregnancy. Furthermore, H2 S can exert an anti-angiogenic effect by inactivating Wnt/ß-catenin signalling or blocking the STAT3 pathway in tumours. Therefore, H2 S plays a double-edged sword role in the process of angiogenesis. The regulation of H2 S production is a promising therapeutic approach for angiogenesis-associated diseases. Novel H2 S donors and/or inhibitors can be developed in the treatment of angiogenesis-dependent diseases.

Application of second-generation sequencing in congenital pulmonary airway malformations.

To investigate the differential expression of genes in whole transcripts of congenital pulmonary airway malformation (CPAM) using second-generation sequencing (also known as next-generation sequencing, NGS) technology. Children with CPAM were strictly screened after setting the criteria, and grouped by taking CPAM parietal tissue and CPAM lesion tissue respectively, and RNA-Seq libraries were established separately using second-generation sequencing technology, followed by differential expression analysis and GO (gene ontology) functional enrichment analysis, KEGG (Kyoto encyclopedia of genes and genomes, a database) pathway analysis and GSEA (Gene Set Enrichment Analysis) analysis. Five cases were screened from 36 children with CPAM, and high-throughput sequencing was performed to obtain 10 whole transcripts of samples with acceptable sequence quality and balanced gene coverage. One aberrantly expressed sample (3b) was found by analysis of principal components, which was excluded and then subjected to differential expression analysis, and 860 up-regulated genes and 203 down-regulated genes. GO functional enrichment analysis of differentially expressed genes demonstrates the functional class and cellular localization of target genes. The whole transcript of CPAM shows obvious gene up and down-regulation, differentially expressed genes are located in specific cells and belong to different functional categories, and NGS can provide an effective means to study the transcriptional regulation of CPAM from the overall transcriptional level.

Clinical Image Feature Analysis and Diagnostic Efficacy Evaluation of Pulmonary Ultrasound in the Diagnosis of Congenital Pulmonary Airway Malformations in Children: Based on a Single Center, Retrospective Cohort Study.

Objective: A single center, retrospective cohort study was conducted to analyze the clinical image features and diagnostic efficiency of pulmonary ultrasound in the diagnosis of congenital pulmonary airway malformations (CPAMs) in children. Methods: The starting and ending time of this study is from May 2019 to December 2021. This study included 200 children with CPAM diagnosed by prenatal ultrasound and postpartum CT imaging (aged from 1 hour to 3 years), including 103 males and 97 females. All of them were diagnosed by fetal ultrasound and were examined by chest X-ray (CXR), chest CT, and lung ultrasound (LUS). The clinical image characteristics and diagnostic efficiency of CXR, chest CT, and LUS in the diagnosis of CPAM in children were analyzed. Results: 200 lesions were limited to single lung, and the most common were right lower lobe, right lower lobe in 80 cases (40.0%), left lower lobe in 60 cases (30.0%), right upper lobe in 30 cases (15.0%), left upper lobe in 20 cases (10.0%), and right middle lobe in 10 cases (5.0%). Among the 200 cases of preoperative CT examination, 196 cases (98.00%) showed lesions and confirmed diagnosis, and 4 cases were missed. Chest X-ray showed multiple focal circular low-density shadow in the right lung, and the heart shadow and mediastinum moved slightly to the left. CXR showed multiple cystic transparent shadows in the left lower lung and slightly to the right of the mediastinum and heart. CXR showed multiple balloon cavities of different sizes in the right lung field, and the mediastinum and heart shadow shifted to the left. The direct signs of LUS (including single or multiple cystic lesions) were not significantly different from those of CXR, but the indirect signs were significantly higher than those of CXR. Conclusion: The most common CT findings of CPAM in children are cystic lesions, especially polycystic lesions, while LUS images of CPAM in children are various. LUS is a noninvasive and nonradiological examination method, which is easy to operate and repeat. LUS can be used for preliminary qualitative screening of CPAM in children, and the diagnostic value of indirect signs of LUS is better than that of CXR.

Cystathionine ß-Synthase Regulates the Proliferation, Migration, and Invasion of Thyroid Carcinoma Cells.

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine ß-synthase (CBS) plays a crucial role in the occurrence of several types of malignancies. And yet, the mechanism of action of CBS in the growth of thyroid carcinoma cells is still unrevealed. We found that CBS level in thyroid carcinoma tissue was higher than that in adjacent normal tissue. The overexpression of CBS enhanced the proliferation, migration, and invasion of thyroid cancer cells, while the downregulation of CBS exerted reverse effects. CBS overexpression reduced the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase in thyroid cancer cells, whereas CBS knockdown showed reverse trends. CBS overexpression decreased reactive oxygen species (ROS) levels but increased the levels of Wnt3a and phosphorylations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR), ß-catenin, and glycogen synthase kinase-3 beta, while CBS knockdown exerted opposite effects. In addition, CBS overexpression promoted the growth of xenografted thyroid carcinoma, whereas CBS knockdown decreased the tumor growth by modulating angiogenesis, cell cycle, and apoptosis. Furthermore, aminooxyacetic acid (an inhibitor of CBS) dose-dependently inhibited thyroid carcinoma cell growth. CBS can regulate the proliferation, migration, and invasion of human thyroid cancer cells via ROS-mediated PI3K/AKT/mTOR and Wnt/ß-catenin pathways. CBS can be a potential biomarker for diagnosing or prognosing thyroid carcinoma. Novel donors that inhibit the expression of CBS can be developed in the treatment of thyroid carcinoma.

Immune characteristics of children with autoimmune encephalitis and the correlation with a short-term prognosis.

BACKGROUND: Autoimmune encephalitis (AE) is a type of encephalopathy mediated by an antigenic immune response in the central nervous system. Most research related to autoimmune encephalitis (AE) is focused on early diagnosis, treatment and prognosis analysis; there has been little research conducted on the characteristics of immune function, and the relationship between immune function and prognoses of patients with autoimmune encephalitis needs to be studied further. METHODS: A total of 33 children with autoimmune encephalitis were identified through the clinic database and inpatient consults at Tianjin Children's Hospital from January 2013 to January 2021. Based on the one-year follow-up and the modified Rankin Scale (mRS) prognosis score, they were divided into a good prognosis group and a poor prognosis group. The immune function characteristics of the two groups of children with autoimmune encephalitis (AE) were compared using Spearman correlation to analyse the mRS score and immune function indicators (IgA, IgG, IgM, CD4, CD8, CD4/CD8), and binary logistic regression was used to analyse the independent risk factors of the prognoses in patients with autoimmune encephalitis (AE). RESULTS: The differences in abnormal mental disorders and limb dyskinesia, cognitive impairment, onset types, modified Rankin Scale (mRS) scores at admission, and immune function status during remission between the two groups were statistically significant (p < 0.05). CONCLUSION: There is a close correlation between modified Rankin Scale (mRS) scores and the immune function index CD4/CD8 in children with autoimmune encephalitis (AE) when they are admitted to the hospital. A young age, disturbance of consciousness, limb dyskinesia, abnormal immune function in remission and anti-NMDAR encephalitis are risk factors for poor prognoses in children with autoimmune encephalitis (AE). Clinical treatment requires more attention.

Immunotherapy combining tumor and endothelium cell lysis with immune enforcement by recombinant MIP-3α Newcastle disease virus in a vessel-targeting liposome enhances antitumor immunity.

BACKGROUND: Several agents for oncolytic immunotherapy have been approved for clinical use, but monotherapy is modest for most oncolytic agents. The combination of several therapeutic strategies through recombinant and nanotechnology to engineer multifunctional oncolytic viruses for oncolytic immunotherapy is a promising strategy. METHODS: An endothelium-targeting iRGD-liposome encapsulating a recombinant Newcastle disease virus (NDV), which expresses the dendritic cell (DC) chemokine MIP-3α (iNDV3α-LP), and three control liposomes were constructed. MIP-3α, HMGB1, IgG, and ATP were detected by western blotting or ELISA. The chemotaxis of DCs was examined by Transwell chambers. The phenotypes of the immune cells were analyzed by flow cytometry. The antitumor efficiency was investigated in B16 and 4T1 tumor-bearing mice. Immunofluorescence and immunohistochemistry were used to observe the localization of liposomes, molecular expression and angiogenesis. Synergistic index was calculated using the data of tumor volume, tumor angiogenesis and tumor-infiltrating lymphocytes. RESULTS: Compared with NDV-LP, treatment with iNDV3α-LP and NDV3α-LP induced stronger virus replication and cell lysis in B16 and 4T1 tumor cells and human umbilical vein endothelial cells (HUVECs) with the best response observed following iNDV3α-LP treatment. B16 and 4T1 cells treated with iNDV3α-LP produced more damage-associated molecular pattern molecules, including secreted HMGB1, ATP, and calreticulin. Moreover, iNDV3α-LP specifically bound to αvß3-expressing 4T1 cells and HUVECs and to tumor neovasculature. Tumor growth was significantly suppressed, and survival was longer in iNDV3α-LP-treated B16-bearing and 4T1-bearing mice. A mechanism study showed that iNDV3α-LP treatment initiated the strongest tumor-specific cellular and humoral immune response. Moreover, iNDV3α-LP treatment could significantly suppress tumor angiogenesis and reverse the tumor immune suppressive microenvironment in both B16-bearing and 4T1-bearing mice. CONCLUSIONS: In this study, iNDV3α-LP had several functions, such as tumor and vessel lysis, MIP-3α immunotherapy, and binding to αvß3-expressing tumor and its neovasculature. iNDV3α-LP treatment significantly suppressed tumor angiogenesis and reversed the tumor immunosuppressive microenvironment. These findings offer a strong rationale for further clinical investigation into a combination strategy for oncolytic immunotherapy, such as the formulation iNDV3α-LP in this study.

Chest tube drainage placement may not be a necessity in paediatric thoracoscopic surgery: a retrospective study.

OBJECTIVE: Chest tube drainage placement, a standard procedure in video-assisted thoracoscopic surgery, was reported to cause perioperative complications like pain and increased risk of infection. The present study was designed to evaluate the necessity of chest tube drainage inpaediatric thoracoscopic surgery. METHODS: Thirty children admitted to our hospital from April 2018 to April 2020 were included in the current study and were grouped as the tube group (children receiving video-assisted thoracoscopic surgery with chest tube drainage) and the non-tube group (children receiving video-assisted thoracoscopic surgery without chest tube drainage). Laboratory hemogram index, length of hospitalisation, post-operative performance of involved children, and psychological acceptance of indicated therapy by guardians of the involved children were investigated. RESULTS: Laboratory examination revealed that the mean corpuscular haemoglobin concentration in the non-tube group was significantly higher than that in the tube group on post-operative day 1 (p < 0.05). Children in the non-tube group had a shorter length of hospitalisation (7-9 days) than that of patients from the tube group. Additionally, the frequency of crying of children was decreased and psychological acceptance by patients' guardians was improved in the non-tube group when compared with the tube group. CONCLUSION: This study showed that chest tube drainage placement may not be necessary in several cases of paediatric video-assisted thoracoscopic surgery. Rapid recovery with decreased perioperative complications in children operated by video-assisted thoracoscopic surgery without tube placement could also reduce the burden of the family and society both economically and psychologically.

The Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio Predicts Disease-Free Survival in Resectable Esophageal Squamous Cell Carcinoma.

BACKGROUND: Recent studies have revealed that the presence of systemic inflammation is associated with poor survival for esophageal squamous cell carcinoma. We aimed to investigate prognostic values of preoperative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in resectable esophageal squamous cell carcinoma. METHODS: A cohort of 167 resectable ESCC patients was retrospectively reviewed between January 2017 and September 2020. The best cut-off value of NLR and PLR was selected by plotting the receiver operating characteristic curve. All reviewed patients were divided into high NLR/PLR or low NLR/PLR group to evaluate prognostic factors. RESULTS: Among the 167 patients, 34 (20.36%) were women and 133 (79.64%) were men. The mean age was 62.64 ±7.91 years, with an age range from 44 to 85 years. All patients were divided into low NLR (<2.20) or high NLR (≥2.20) group (AUC=62.5% with the sensitivity of 61.8% and specificity 60.9%, P=0.025), low PLR (<110) or high PLR (≥110) group (AUC=59.6% with the sensitivity of 82.4% and specificity 35.3%, P=0.083). High NLR and PLR were associated with a larger tumor diameter (P<0.05), while high NLR was also associated with poor tumor classification (P=0.022). There was a positive correlation between NLR and PLR (r = 0.614, P < 0.001). High NLR and PLR were significantly associated with poor disease-free survival. Multivariate analyses identified NLR as a prognostic factor in resectable ESCC. CONCLUSION: The NLR and PLR predict disease-free survival in resectable esophageal squamous cell carcinoma.

Shikonin attenuates H2O2-induced oxidative injury in HT29 cells via antioxidant activities and the inhibition of mitochondrial pathway-mediated apoptosis.

Shikonin, a natural naphthoquinone extracted from the roots of Lithospermumery throrhizon, possesses multiple pharmacological properties, including antioxidant, anti-inflammatory and antitumor effects. It has been hypothesized that the properties of shikonin are associated with its oxygen free radical scavenging abilities. However, the mechanism underlying the antioxidant activity of shikonin is not completely understood. The aim of the present study was to investigate the effect of shikonin against H2O2-induced oxidative injury in HT29 cells and to explore the underlying molecular mechanism. The concentration and duration of H2O2 treatment to cause maximal damage, and the effects of shikonin (2.5, 5 or 10 µg/ml) on the activity of H2O2-induced HT29 cells were determined by MTT assay. The apoptotic rate in HT29 cells was determined by annexin V/propidium iodide staining. HT29 cell cycle alteration was also analyzed by propidium iodide staining. Reactive oxygen species (ROS) production was assessed by monitoring 2',7'-dichlorofluorescin in diacetate fluorescence. Mitochondrial membrane potentials were determined by JC-1 staining. The activities of malondialdehyde, superoxide dismutase, caspase-9 and caspase-3 were measured using spectrophotometric assays. The expression levels of Bcl-2, Bax and cytochrome c were determined by western blotting. The results suggested that shikonin increased cell viability, reduced cell apoptosis and increased the proliferation index in H2O2-treated HT29 cells. Shikonin also significantly inhibited increases in intracellular reactive oxygen species (ROS), restored the mitochondrial membrane potential, prevented the release of lactic dehydrogenase and decreased the levels of superoxide dismutase and malondialdehyde in H2O2-induced HT29 cells. Furthermore, shikonin significantly decreased caspase-9 and caspase-3 activities, increased Bcl-2 expression and decreased Bax and cytochrome c expression levels in H2O2-induced HT29 cells. The results indicated that shikonin protected against H2O2-induced oxidative injury by removing ROS, ameliorating mitochondrial dysfunction, attenuating DNA oxidative damage and inhibiting mitochondrial pathway-mediated apoptosis.

Engineered porous/hollow Burkholderia pseudomallei loading tumor lysate as a vaccine.

Due to its size, shape, and inherent expression of pathogen-associated molecular patterns and invasion-assistant adhesion proteins, Burkholderia pseudomallei can easily attach to, and then be internalized by, dendritic cells (DCs), leading to more efficient antigen cross-presentation if modified as carrier. Herein, we engineered Burkholderia pseudomallei as a porous/hollow carrier (SB) for loading tumor lysates (L) and adjuvant CpG (C) to be used as a tumor vaccine (SB-LC). We found that the adhesion proteins of Burkholderia pseudomallei promote internalization of the SB-LC vaccine by DCs, and result in enhanced DC maturation and antigen cross-presentation. SB-LC induces robust cellular and humoral antitumor responses that synergistically inhibit tumor growth with minimal adverse side effects in several tumor models. Moreover, SB-LC vaccination reverses the immunosuppressive tumor microenvironment, apparently as a result of CD8+-induced tumor ferroptosis. Thus, SB-LC is a potential model tumor vaccine for translating into a clinically viable treatment option.

The feasibility of ultrasound Graf method in screening infants and young children with congenital hip dysplasia and follow-up of treatment effect.

BACKGROUND: Congenital hip dysplasia is a common limb deformity in infants and young children. This study aimed to clarify the feasibility of ultrasound Graf method in screening congenital hip dysplasia of infants and young children, and its application value in follow-up treatment. METHODS: A total of 1,313 infants and young children with clinically suspected congenital hip dysplasia in our hospital from December 2016 to January 2018 were selected as the participants and were examined by ultrasound Graf method. The acetabulum shape and the measured values of α and ß angles of the participants were observed. The development of the hip joint and distribution of congenital hip dysplasia were analyzed, and the treatment effect was followed up. RESULTS: Among 1,313 infants and young children with suspected congenital hip dysplasia, the positive rate of congenital hip dysplasia was 6.02% (79/1,313). The lesions were located on both sides in 14 cases, on the left side in 67 cases, and on the right side in 26 cases. The α angle of cases with congenital hip dysplasia was significantly lower than that of normal cases, and the ß angle was significantly higher than that of normal cases (P<0.05). Ultrasound follow-up results showed that out of 24 cases who underwent hip abduction exercises, 22 (91.67%) returned to normal, and the remaining 2 returned to normal after Pavlik sling treatment. Among 46 cases treated with Pavlik sling, 42 (91.30%) returned to normal, and the remaining 4 cases returned to normal after closed reduction and plaster fixation. A total of 9 participants underwent plaster fixation after closed reduction, all of which returned to normal. CONCLUSIONS: Ultrasound Graf method can be used as the first choice for screening infants and young children with congenital hip dysplasia. It can be followed up to observe the clinical treatment effect, and it has high clinical application value.

[Clinical Features and Prognosis of Acute Lymphoblastic Leukemia Children with P2RY8-CRLF2 Gene Rearrangement].

OBJECTIVE: To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement. METHODS: A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification. RESULTS: Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×109/L. These patients presented different immunophenotype, including 3 cases of common B-ALL and 2 cases of pre B-ALL. Four patients carried a normal karyotype and 1 patient carried 46, XY, der (20) [22]/46, XY[2]. For the children with P2RY8-CRLF2 gene rearrangement, 1 patient (20%) could not achieve complete remission (CR), and minimal residual disease (MRD) of 2 patients (40%) was higher than 1% on day 33 of induction chemotherapy; while in group without P2RY8-CRLF2 gene rearrangement, all the patient achieved CR, and MRD in 6 patients (5.8%) was higher than 1% on day 33 of induction chemotherapy. The 3 year event-free survival (EFS) of ALL children in group with P2RY8-CRLF2 gene rearrangement was significantly lower than that in group without P2RY8-CRLF2 gene rearrangement (60.0%±21.9% vs 85.9%±3.9%) (P<0.05). CONCLUSION: The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.