Immune response to Aeromonas hydrophila and molecular characterization of polymeric immunoglobulin receptor in juvenile Megalobrama amblycephala.

Polymeric immunoglobulin receptor (pIgR) is an important immune factor in the mucosal immune system of fish, which plays a key role in mediating the secretion and transport of immunoglobulin into mucus. In this study, the full-length cDNA sequence of Megalobrama amblycephala pIgR gene was firstly cloned and the immune response to Aeromonas hydrophila was detected. After being challenged by Aeromonas hydrophila at 3 d, significantly pathological features were observed in intestine, head kidney, spleen, liver and gill of Megalobrama amblycephala. The content of lysozyme (Lys) and the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) increased significantly at 1 d and reached the peak at 3 d, and the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in serum reached the peak at 5 d and 7 d after infection, respectively. The expression level of IL-1ß gene reached the peak at 3 d in intestine, 5 d in gill and spleen, 7 d in head kidney and liver of Megalobrama amblycephala after infected by Aeromonas hydrophila, respectively. The TNF-α gene expression reached the peak at 3 d in intestine and gill, 5 d in head kidney and spleen, 7 d in liver after infection, respectively. The experimental results showed that the infection of Aeromonas hydrophila caused the pathological changes of immune-related tissues and triggered the inflammation responses. The full-length cDNA sequence of Megalobrama amblycephala pIgR was 1828 bp, and its open reading frame (ORF) was 1023 bp, encoding 340 amino acids. The pIgR of Megalobrama amblycephala has a signal peptide sequence, followed by extracellular region, transmembrane region and intracellular region. The extracellular region includes two Ig-like domains (ILDs), and its tertiary structure is twisted "L". The phylogenetic tree was constructed using the adjacency method, and the pIgR genes of Megalobrama amblycephala and cyprinidae fish were clustered into a single branch. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pIgR gene in different tissues of Megalobrama amblycephala. The expression level of pIgR gene was the highest in liver, followed by intestine, head kidney, skin, middle kidney and spleen, lower in heart, gill and brain, and the lowest in muscle. After being infected by Aeromonas hydrophila, the expression level of Megalobrama amblycephala pIgR gene in intestine, head kidney, spleen, liver and gill showed a trend of increasing first and then decreasing within 28 d. The pIgR gene expression reached the peak in mucosal immune-related tissues (gill and intestine) was earlier than that in systemic immune-related tissues (head kidney and spleen), and the relative expression level of pIgR gene at peak in intestine (12.3 fold) was higher than that in head kidney (3.73 fold) and spleen (7.84 fold). These results suggested that Megalobrama amblycephala pIgR might play an important role in the mucosal immune system to against Aeromonas hydrophila infection.

Application of Repetitive Sequences in Fish Cell Depletion as a Target for the CRISPR/Cas9 System.

Specific cell depletion is a common means to study the physiological function of cell lineages and tissue regeneration. However, 100% depletion is difficult to achieve with existing cell depletion strategies. With the increasing maturity of CRISPR/Cas9 technology, it is increasingly used for the depletion of various cells. However, even with this technology, it is difficult to complete the depletion of specific gene knockout cells. For this reason, cell depletion with the use of repetitive sequences as the target of CRISPR/Cas9 was explored using zebrafish. All cells were used as the target cells for the first set of experiments. The results showed that injection of a mixture of DANA-gRNA and Cas9 mRNA into zygotes resulted in substantial cell apoptosis. Cells are almost invisible in the embryonic animal pole during the dome stage. The activities of the caspase-3 and caspase-9 proteins and the mRNA level of the P53 gene were significantly increased. Then, primordial germ cells (PGCs) in embryos were used as the target cells in subsequent experiments. To specifically knock out PGCs, we injected the mix of DANA-gRNA, pkop: Cas9 plasmid (the kop promotor allows Cas9 expression only in PGCs), and eGFP-nos3'UTR mRNA into zebrafish fertilized eggs. The results revealed that the activity of the caspase-3 protein was significantly increased, and the mRNA levels of P53, ku70, and ku80 were significantly upregulated, while the number of PGCs decreased gradually. Few PGCs labeled with GFP could be seen 20 h post-fertilization (hpf), and no PGCs could be seen at the germinal ridge 24 hpf. Therefore, the combination of CRISPR/Cas9 technology and repetitive sequences can achieve efficient cell depletion regardless of whether there is generalized expression or expression in specific cells. These results indicate that it is feasible to eliminate cells by using repeat sequences as CRISPR/Cas9 system target sites.

The Quality Evaluation of Highland Barley and Its Suitability for Chinese Traditional Tsampa Processing.

The physicochemical traits of highland barley prominently affect the quality of Tsampa. To find out the relevance between the physicochemical properties of raw material and the texture parameters of processed products, twenty-five physicochemical traits and ten quality parameters for seventy-six varieties of highland barley were measured and analyzed. The results showed that there was a significant difference between the physicochemical indexes for highland barleys of various colors. The dark highland barley generally has more fat, protein, total dietary fiber, phenolic, Mg, K, Ca, and Zn and less amylose, Fe, Cu, and Mo than light colored barley. Then, these highland barleys were made into Tsampa. A comprehensive quality evaluation model based on the color and texture parameters of Tsampa was established through principal component analysis. Then, cluster analysis was used to classify the tested samples into three edible quality grades predicated on the above evaluation model. At last, the regression analysis was applied to establish a Tsampa quality predictive model according to the physicochemical traits of the raw material. The results showed that amylose, protein, ß-Glucan, and a* and b* could be used to predict the comprehensive quality of Tsampa. The predicted results indicated that 11 of 14 validated samples were consistent with the actual quality, and the accuracy was above 78.57%. Our study built the approach of the appropriate processing varieties evaluation. It may provide reference for processing specific highland barley.

Blockchain-secure patient Digital Twin in healthcare using smart contracts.

Modern healthcare has a sharp focus on data aggregation and processing technologies. Consequently, from a data perspective, a patient may be regarded as a timestamped list of medical conditions and their corresponding corrective interventions. Technologies to securely aggregate and access data for individual patients in the quest for precision medicine have led to the adoption of Digital Twins in healthcare. Digital Twins are used in manufacturing and engineering to produce digital models of physical objects that capture the essence of device operation to enable and drive optimization. Thus, a patient's Digital Twin can significantly improve health data sharing. However, creating the Digital Twin from multiple data sources, such as the patient's electronic medical records (EMR) and personal health records (PHR) from wearable devices, presents some risks to the security of the model and the patient. The constituent data for the Digital Twin should be accessible only with permission from relevant entities and thus requires authentication, privacy, and provable provenance. This paper proposes a blockchain-secure patient Digital Twin that relies on smart contracts to automate the updating and communication processes that maintain the Digital Twin. The smart contracts govern the response the Digital Twin provides when queried, based on policies created for each patient. We highlight four research points: access control, interaction, privacy, and security of the Digital Twin and we evaluate the Digital Twin in terms of latency in the network, smart contract execution times, and data storage costs.

Mechanism of ferroptosis induced by endoplasmic reticulum stress in sepsis related lung injury / 安徽医科大学学报

Objective @#To explore the mechanism of ferroptosis induced by endoplasmic reticulum stress (ERs ) in acute respiratory distress syndrome (ARDS) .@*Methods @#In order to determine the effects of LPS on oxidative stress and Fe2 + level of mouse capillary alveolar epithelial cells (MLE12 cells ) , the cells were treated with LPS (0 , 1 , 2 , 5 μg/ml) for 24 h . To verify the role of ferroptosis in lipopolysaccharide ( LPS)-induced cell death , MLE12 cells were divided into control ( Con ) group , iron removal inhibitor ( Fer-1) group , LPS group and LPS + Fer-1 group . LPS + Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h , then the cells were exposed to 5 μg/ml LPS for 24 h . Con group was treated with solvent DMSO for 24 h . Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h , and then treated with DMSO for 24 h . The cells in LPS group were exposed to 5 μg/ml LPS for 24 h . The MLE12 cells were divided into three groups : Con + Vector group , Con + sequence similarity family 134 mem ber B ( FAM134B ) group , LPS + Vector group and LPS + FAM134B group . After transfected with vector or FAM134B overexpression plasmid for 48 h , the cells were exposed or not exposed to 5 μg/ml LPS for 24 h . Cell viability was measured by CCK-8 . The levels of malondialdehyde (MDA) , glutathione and iron , the protein levels of ferroptosis markers [ cyclooxygenase 2(PTGS2) , glutathione peroxidase 4(GPX4)] and ERs markers [glucose reg ulatory protein 78( GRP78) , activated transcription factor 4 ( ATF4) and C/EBP homologous protein ( CHOP)] were measured in different groups . In order to further confirm the results of in vitro cell experiments , 40 mice were randomly divided into Con + Vector group , Con + FAM134B group , LPS + Vector group and LPS + FAM134B group , with 10 mice in each group . LPS induced sepsis models were established in LPS + Vector group and LPS + FAM134B group , and the levels of GPX4 and ERs in lung tissue were evaluated by immunofluorescence staining and protein blot. @*Results @#LPS treatment increased the levels of PTGS2 and MDA , and decreased the levels of GPX4 and GSH in MLE12 cells in a dose dependent manner. Compared with LPS group , the cell viability , GPX4 and GSH levels in LPS + Fer-1 group increased significantly (P < 0.05) , while the PTGS2 protein level and MDA level decreased significantly (P < 0.05) . Compared with LPS + Vector group , LPS + FAM134B group significantly increased cell viability (P < 0.05) , decreased PTGS2 protein level (P < 0.05) and increased GPX4 level ( P < 0.05) . At the same time , the level of MDA in LPS + FAM134B group was lower than that in LPS + Vector group (P < 0.05) , and the level of GSH was higher than that in LPS + Vector group (P < 0.05) . In animal experiment , compared with LPS + Vector group , the expression levels of 4 HNE , ATF4 and CHOP in lung tissue of LPS + FAM134B group decreased significantly ( P < 0.05 ) , and the expression levels of GPX4 , FAM134B group in creased significantly (P < 0.05) .@*Conclusion @#LPS induces ferroptosis and ERs in MLE12 cells in a dose depend ent manner. Activating the endoplasmic reticulum autophagy associated FAM134B receptor helps to inhibit ERs and alleviate cell ferroptosis .

Investigation of a Novel Ultra-Low-Frequency Rotational Energy Harvester Based on a Double-Frequency Up-Conversion Mechanism.

Due to their lack of pollution and long replacement cycles, piezoelectric energy harvesters have gained increasing attention as emerging power generation devices. However, achieving effective energy harvesting in ultra-low-frequency (<1 Hz) rotational environments remains a challenge. Therefore, a novel rotational energy harvester (REH) with a double-frequency up-conversion mechanism was proposed in this study. It consisted of a hollow cylindrical shell with multiple piezoelectric beams and a ring-shaped slider with multiple paddles. During operation, the relative rotation between the slider and the shell induced the paddles on the slider to strike the piezoelectric beams inside the shell, thereby causing the piezoelectric beams to undergo self-excited oscillation and converting mechanical energy into electrical energy through the piezoelectric effect. Additionally, by adjusting the number of paddles and piezoelectric beams, the frequency of the piezoelectric beam struck by the paddles within one rotation cycle could be increased, further enhancing the output performance of the REH. To validate the output performance of the proposed REH, a prototype was fabricated, and the relationship between the device's output performance and parameters such as the number of paddles, system rotation speed, and device installation eccentricity was studied. The results showed that the designed REH achieved a single piezoelectric beam output power of up to 2.268 mW, while the REH with three piezoelectric beams reached an output power of 5.392 mW, with a high power density of 4.02 µW/(cm3 Hz) under a rotational excitation of 0.42 Hz, demonstrating excellent energy-harvesting characteristics.

Optimal time point for neutrophil-to-lymphocyte ratio to predict stroke-associated pneumonia.

PURPOSE: This study aimed at the population receiving thrombolytic therapy and to explore the optimal time point for neutrophil-to-lymphocyte ratio (NLR) in predicting stroke-associated pneumonia (SAP). METHODS: We assessed patients undergoing intravenous thrombolysis (IVT) for acute ischemic stroke. Blood parameters were sampled before thrombolysis (within 30 min after admission) and within 24-36 h after thrombolysis, respectively. The primary outcome measure was the occurrence of SAP. Multivariate logistic regression analysis was performed to analyze the association between admission blood parameters and the event of SAP. We also used receiver operating characteristic (ROC) curve analysis to assess the discriminative ability of blood parameters measured at different times in predicting SAP. RESULTS: Among the 388 patients, SAP occurred in 60 (15%) patients. Multivariate logistic regression analysis showed that NLR was significantly associated with SAP (NLR before IVT: aOR = 1.288; 95%CI = 1.123-1.476; p < 0.001; NLR after IVT: (aOR = 1.127, 95%CI = 1.017-1.249; p = 0.023). The ROC curve showed that the predictive ability of NLR after IVT was better than NLR before IVT, not only in predicting the occurrence of SAP but also in predicting short-term and long-term functional outcomes, hemorrhagic transformation, and 1-year mortality. CONCLUSION: Increased NLR measured within 24-36 h after IVT has a significant predictive effect on the occurrence of SAP and can be used to predict short-term and long-term poor functional outcomes, hemorrhagic transformation, and 1-year mortality.

Application and evaluation of artificial intelligence TPS-assisted cytologic screening system in urine exfoliative cytology / 中华病理学杂志

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.

Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database / 中华心血管病杂志

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

Effect of endoscopic hemostasis combined with octreotide on hemodynamics and clinical outcome of patients with acute upper gastrointestinal bleeding / 中国现代医生

Objective To explore the effect of endoscopic hemostasis combined with octreotide on hemodynamics and clinical outcome of patients with acute upper gastrointestinal bleeding.Methods From January 2019 to June 2022,80 patients with acute upper gastrointestinal bleeding in Xinyu Yinhe Hospital of Jiangxi Province,and according to random number table method,40 cases each in the control group and 40 cases in the observation group.The control group was treated with conventional endoscopic,while the observation group was treated with octreotide on this basis.The clinical efficacy,high sensitivity C-reactive protein(hs-CRP),cortisol(Cor)levels and hemodynamic changes[cardiac output(CO),heart rate(HR),mean arterial pressure(MAP)]were compared between the two groups.Results The total effective rate of the observation group was significantly higher(P<0.05).After treatment,hs-CRP and Cor levels in 2 groups were lower than before,and hs-CRP and Cor levels in observation group were significantly lower(P<0.05).After treatment,the levels of CO,HR and MAP in the two groups were decreased,and the levels of CO,HR and MAP in the observation group were significantly lower(P<0.05).Conclusion Endoscopic hemostasis combined with octreotide can promote the hemodynamic indexes of patients with acute upper gastrointestinal bleeding to return to normal,improve the levels of hs-CRP and Cor,and improve clinical efficacy.

ChrII-Encoded DNA Helicase: A Preliminary Study.

BACKGROUND: DNA helicases are unwinding enzymes that are essential for many cellular processes. Research has suggested that both the model microorganisms of a single chromosome and the model microorganisms of multiple chromosomes adopt DNA helicases encoded by chromosome I. Therefore, studying DNA helicases encoded by chromosome II may lay some foundation for understanding nucleic acid metabolism processes. OBJECTIVE: To prove the existence of DNA helicase encoded by chromosome II and to reveal its difference compared to DNA helicase encoded by chromosome I. METHODS: The DNA helicases of Pseudoalteromonas spongiae JCM 12884T and Pseudoalteromonas tunicata DSM 14096T were analyzed by sequence alignment and phylogenetic relationships with other known DNA helicases. Then, proteins of P. spongiae JCM 12884T and P. tunicata DSM 14096T were obtained by heterologous expression. N-terminal sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed to confirm the form of proteins. A fluorescence resonance energy transfer (FRET) assay was used to measure the activity of helicases. RESULTS: DnaB-pspo and DnaB-ptun belong to the same family, the PRK08840 superfamily, and form a branch with helicases encoded by chromosome I. YwqA-pspo and YwqA-ptun have similar domains and form another branch with helicases encoded by chromosome II. All four helicases have DNA unwinding activity. YwqA is more efficient than DnaB for DNA unwinding, especially YwqA-pspo, which is encoded by bidirectional replication chromosome II. CONCLUSION: This is the first study to show that the existence of a DNA helicase encoded by chromosome II, and DNA helicase encoded by chromosome II is more efficient than chromosome I for DNA unwinding.

The effect of ultrasound monitoring of inferior vena cava collapse index guiding fluid replacement on circulation in elderly patients during induction of general anesthesia / 中国医师杂志

Objective:To investigate the effect of ultrasound monitoring of inferior vena cava collapse index (IVC-CI) guiding fluid replacement on circulation in elderly patients during induction of general anesthesia.Methods:A total of 71 elderly patients who underwent elective surgery under general anesthesia and tracheal intubation at Hunan Provincial People′s Hospital from April 2021 to September 2022 were randomly divided into control group (35 cases) and observation group (36 cases) using a random number table method. Before anesthesia, both groups of patients underwent IVC ultrasound examination and calculated the IVC-CI value. For patients with IVC-CI≥40%, the observation group was given 8 ml/kg of crystal solution before anesthesia induction, while the control group was not treated. The incidence of hypotension, the use of vasoactive drugs, and the total infusion volume from anesthesia induction to skin incision were recorded in two groups. Mean arterial blood pressure (MBP), heart rate (HR), oxygen saturation (SpO 2), cardiac index (CI), and cardiac volume variability (SVV) before anesthesia (T 0), 5 min after induction (T 1), 1 min after tracheal intubation (T 2), 5 min after tracheal intubation (T 3), 10 min after tracheal intubation (T 4), and 1 min before skin incision (T 5) were recorded and compared between the two groups. Results:The incidence of hypotension (27.8% vs 60.0%) and utilization rate of vasoactive drugs (25.0% vs 48.6%) in the observation group were lower than those in the control group, and the total infusion volume during anesthesia induction was higher than that in the control group, with statistical significance (all P<0.05). SVV, CI and MBP at T 1, T 3, T 4 and T 5 were significantly different from those at T 0 in the control group ( F=3.85, 14.66, 3.96, all P<0.05). SVV, CI and MBP at T 1, T 3, T 4 and T 5 in the observation group were significantly different from those at T 0 ( F=3.51, 13.20, 4.35, all P<0.05). There was no significant difference in SVV, CI, MBP, HR and SpO 2 between 2 groups (all P>0.05). Conclusions:For the elderly patients with preoperative IVC-CI≥40%, pre-filling with 8ml/kg crystal solution before anesthesia induction can significantly reduce the incidence of hypotension and the utilization rate of vasoactive drugs in the elderly patients during anesthesia induction.

Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro.

Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment.

[Effects of bosutinib on the malignant behavior of thyroid papillary carcinoma B-CPAP cells and its mechanisms].

Objective: To investigate the effects of bosutinib on the malignant behavior of thyroid papillary carcinoma B-CPAP cells and its possible mechanisms. Methods: Thyroid papillary carcinoma B-CPAP cells were cultured in vitro with a concentration gradient of(1、2、3、4 and 5 µmol/L)bosutinib intervened for 24 hours, DMSO was used as the control group. Five parallel compound holes were set in each group. Cell counting kit (CCK-8 method) method was used to detect cell proliferation. Transwell assay and cell wound healing assay were used to detect cell invasion and migration. TUNEL staining assay and flow cytometry were used to detect cell apoptosis. Western blot was used to detect the expressions of autophagic proteins (Beclin-1, LC3, p62) and signal pathway proteins (SIK2, p-mTOR, mTOR, p-ULK1, ULK1). Results: Compared with the control group, the cell proliferation activity, migration ability and invasion ability were decreased (P＜0.01), while the cell apoptosis rate was increased (P＜0.01) in the bosutinib concentration groups of 2, 3, 4 and 5 µmol/L . In the concentration groups of 4 and 5 µmol/L, the expression of Beclin-1 (P＜0.05), LC3- Ⅱ/LC3- Ⅰ (P＜0.05), SIK2 (P＜0.01) and p-ULK1 (P＜0.01) protein was decreased, while the expression of p62 (P＜ 0.05) and p-mTOR (P＜0.01) protein was increased. Conclusion: Bosutinib may inhibit the autophagy of thyroid papillary carcinoma cells through SIK2-mTOR-ULK1 signaling pathway to inhibit their proliferation, invasion and migration and promote apoptosis, thereby weakening their malignant behavior.

Effect of 6-Shogaol on invasion and migration of triple negative breast cancer cells via Hedgehog/Glil signaling pathway / 中国药理学通报

Aim To explore the effects of the expression of the transcription faetor Glil of Hedgehog ( Hh ) signaling pathway and the 6-Shogaol mediated Hedge- hog/Glil pathway on the proliferation, invasion and migration in MDA-MB-231 eells of triple negative breast eaneer.Methods MDA-MB-231 eells were transfected by lentiviral vectors to stably overexpressed Glil gene.The overexpression efficiency of Glil was verified by qRT-PCR and Western blot.CCK-8 and EdlJ assays were used to detect the effect of Glil expression and 6-Shogaol on cell viability.Cell scratch assay and Transwell assay were used to detect the ability of migration and invasion.Western blot was used to detect the proteins expression of Hedgehog signaling pathway and other related genes.Results MDA-MB- 231-Glil overexpression cell line was successfully established.When Gli 1 gene was overexpressed, the invasion and migration ability of cells was significantly improved, anrl the expression of Hh signaling pathway gene Glil , EMT marker gene Vimentin, Hippo signaling pathway genes YAP and TEAD4 inereased.When the expression of Glil was inhibited by the Hh/Gli pathway inhibitor Gant61 , the proliferation, invasion and migration abilities were suppressed.When the eells were treated with 6-Shogaol, the abilities of proliferation, invasion and migration were inhibited as well as the proteins expression of Glil , Vimentin, YAP and TEAD4 deereased.Conclusions Glil gene ean promote the invasion and migration of MDA-MB-231 eells.6-Shogaol ean inhibit proliferation, invasion and migration of breast eaneer eells through Hedgehog signaling pathway, suggesting that transcription factor Glil may be one of the targets of 6-Shogaol.

Characterization of the complete chloroplast genome of Hordeum vulgare L. var. trifurcatum with phylogenetic analysis.

In the present study, the complete chloroplast genome of Hordeum vulgare L. var. trifurcatum was sequenced, assembled and compared with closely related species. The chloroplast genome of Hordeum vulgare L. var. trifurcatum was composed of 84 protein-coding genes (PCG), 8 ribosomal RNA (rRNA) genes, and 38 transfer RNA (tRNA) genes. The Hordeum vulgare L. var. trifurcatum chloroplast genome is 136,485 bp in size, with the GC content of 38.32%. Phylogenetic analysis based on the combined chloroplast gene dataset indicated that the Hordeum vulgare L. var. trifurcatum exhibited a close relationship with Hordeum vulgare subsp. spontaneum and Hordeum vulgare subsp. vulgare.

Clinical application of extracorporeal membrane oxygenation in 4 children with severe adenovirus pneumonia / 中华实用儿科临床杂志

Objective:To retrospectively analyze the clinical application of extracorporeal membrane oxygenation (ECMO) in severe adenovirus pneumonia, and to evaluate the application value of ECMO in children with severe adenovirus pneumonia.Methods:Children diagnosed with severe adenovirus pneumonia and intervened with ECMO in the Hunan Children′s Hospital from January 1, 2018 to December 31, 2019 were recruited in this study for analyzing.The gender, age, clinical manifestations, mechanical ventilation duration, ECMO duration, the length of hospital stay, complications and prognosis were collected and analyzed.Results:A total of 4 children were included in the study, involving 2 cases were successfully evacuated from ECMO.Finally, 3 children died, and 1 case survived.Three death cases had a longer than 18 days of duration from the onset to the start with ECMO.Their ventilator assist time before star-ting ECMO was 3-5 days, and ECMO intervention time was longer, with the maximum of 27.5 days.The survived case had an 11-day duration from the onset to the start with ECMO, and the ventilator assisted time and ECMO intervention time were 5 days, and less than 10 days, respectively.Conclusions:ECMO treatment for children with severe adenovirus pneumonia has a low success rate, but it is still the most important way to save children.Early application of ECMO can improve the prognosis of children with severe adenovirus pneumonia.

Prevention and treatment of cognitive dysfunction caused by radiotherapy to the brain / 国际肿瘤学杂志

Radiation-induced brain injury is a serious untoward effect of radiotherapy for malignant tumors. Patients received radiotherapy frequently occur cognitive dysfunction which seriously affects the quality of life. Although the exact mechanisms regarding radiation-induced cognitive dysfunction remain unclear, prevention strategies targeting cognitive dysfunction are increasingly applied to clinical intervention, including whole brain radiotherapy with hippocampus avoidance, stereotactic radiosurgery in patients with multiple brain metastases, and pretreatment with neuroprotective drugs such as memantine and donepezil. In addition, measures including appropriate radiotherapy management models, regular cognitive tests, and therapeutic measures at the appropriate time are critical to improve the quality of life for brain tumor patients.

Situation Comparison and Enlightenment of ADR Collection by Social Media between European and American Countries and China / 中国药房

OBJECTIVE：To c ompare the situation of adverse drug reaction （ADR） collection by social media between European and American countries and China ，so as to provide reference for the improvement of corresponding work in China. METHODS：By retrieving relevant literatures from CNKI ，Web of Science ，Elsevier ScienceDirect ，SpringerLink and so on ， referring to the official website of International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use （ICH），the current situation of ADR collection by social media in European and American countries（organizations）such as the United States ，the European Union ，the United Kingdom ，France was introduced ，and compared with the corresponding work in China. The advantages and possible problems of using social media to collect ADR were analyzed so as to put forward some suggestions on how to use social media to collect ADR in China. RESULTS & CONCLUSIONS：Since 2013，many countries in Europe and the United States have started to collect ADRs using social media （such as Twitter ，Facebook），such as the draft on drug safety issues on social media issued by the Pharmaceutical Research and Manufacturers of America （PhRMA），and the EU organization ’s Innovative Medicines Initiative （IMI）network to identify adverse drug reaction in web media （WEB-RADR）projects. Through this way ，it is more convenient for patients to report ADR ，and helpful for the pharmacovigilance department to collect ADR information in time ，and can be used as an important supplement to the traditional drug safety information report. However ，there are some advantages ，such as mismatch between the health vocabulary spontaneously reported by patients and medical professional vocabulary ，the challenges of balancing the relationship between public health maintenance and patient privacy protection ，and various deviations affecting the reporting rate and quality of ADR collected by social media. When using social media （such as Wechat ，microblog，QQ and other social media or tools ，as well as applications and small programs ）to collect ADR information in China ，it is suggested to ensure the ease of use and security of reporting ADR applications ，and improve the design of applications to comply with E 2B （R3） data elements and information specifications of ICH guidelines for the electronic transmission of individu al security reports. At the same time ，we should give full play to the supervisory role of regulatory department ，consider non-regulatory factors ，and take privacy protection measures to make it conform to ethics.