Effect of Qingshen granules on miR-23b and PINKl/Parkin pathway in rat NRK-52E cell transdifferentiation model / 中国药理学通报

Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.

Effectiveness and Safety of Tigecycline Combined with Cefoperazone-sulbactam Sodium in the Treatment of Multi-/extensively-drug Resistant Acinetobacter baumannii-associated Central Nervous System Infection:A Meta-analysis / 医药导报

Objective To evaluate the efficacy and safety of tigecycline combined with cefoperazone-sulbactam sodium in the treatment of multi-/extensively-drug resistant Acinetobacter baumannii(MDRAB/XDRAB)associated central nervous system(CNS)infection,and to provide clinical evidence for antibiotic treatment of MDRAB/XDRAB-related intracranial disease.Methods The Wanfang Data Knowledge Service Platform,Chinese Biomedical Literature Database,VIP Chinese Science and Technology Journal Full-text Database,China National Knowledge Infrastructure(CNKI),Pubmed,Embase database,and Cochrane Library were searched to extract the literature of randomized controlled studies on tigecycline and cefoperazone sulbactam in the treatment of MDRAB/XDRAB CNS infection until September 1st,2022.The included studies were assessed for quality using the Cochrane Collaboration Risk of Bias assessment tool,and valid data were extracted and meta-analyzed using RevMan5.4 software.Results A total of 184 articles were screened and 4 Chinese RCTs were finally included,with a sample size of 267 cases.Meta-analysis showed that the overall efficacy of combination therapy for MDRAB/XDRAB CNS infection was better than monotherapy[OR = 4.30,95%CI =(1.93,9.58),P＜0.01].Combination therapy had a better bacterial clearance[OR=4.20,95%CI=(2.08,8.48),P＜0.01].And combination therapy resulted in a lower incidence of adverse effects[OR= 0.19,95%CI =(0.05,0.67),P＜0.05].There was no apparent difference in cure rate between combination therapy and monotherapy(P＞0.05).Conclusion Current evidence suggests that tigecycline combined with cefoperazone-sulbactam sodium may have better clinical efficacy and safety than monotherapy for MDRAB/XDRAB CNS infections.Limited by the number and quality of included studies,needs to be verified by more and higher-quality studies.

Virulence determinants and genetic diversity of foodborne Yersinia enterocolitica isolated from Wenzhou / 中国人兽共患病学报

The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.

Study on Mechanism of Xiaojin Pills in Treatment of Breast Cancer Based on Network Pharmacology and Experimental Verification / 中国中医药信息杂志

Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

Progress in Prevention and Treatment of Acute Bone Loss in Orthopedics.

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient's bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians' understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients.

Impaired Kidney Function Portended a Bleak Prognosis for Surgically Treated Hypertensive Intracerebral Hemorrhage Patients.

Purpose: Spontaneous intracerebral hemorrhage (ICH) cases caused by hypertension often have poor prognoses. The use of dehydrant agents, such as mannitol, is common to reduce intracranial pressure and alleviate cerebral edema, but they may also pose a risk of worsening kidney function. This study aimed to investigate the impact of impaired kidney function on the outcomes of surgically treated hypertensive ICH patients. Methods: We conducted a retrospective analysis of a consecutive cohort of patients who underwent surgical intervention due to hypertension-related ICH at our institute between December 1, 2017, and January 31, 2022. Demographic, clinical, radiological, and prognostic data were collected. Patients were categorized into two groups based on 90-day mortality: group A [overall survival (OS) ≤3 months] and group B (OS >3 months). Survival analysis was performed to identify factors associated with poor outcomes. Results: Among the 232 eligible patients, group A exhibited significantly impaired kidney function, as indicated by mean estimated glomerular filtration rate (eGFR) at admission, postoperative, 3-day postoperative, and 7-day postoperative time points (91.9, 82.5, 73.5, 75.2 ml/min/1.73 m²). In contrast, group B did not show significant changes in kidney function (mean eGFR for the corresponding time points: 108.1, 106.5, 111.5, 109.6 ml/min/1.73 m²). The 3-day postoperative eGFR showed the strongest predictive ability for assessing prognosis [areas under the curve (AUC): 0.617, 0.675, 0.737, 0.730]. Univariate and multivariate analyses identified low Glasgow Coma Scale (GCS) score (3-8), ventricle intrusion of hematomas, cardiac failure, larger hematoma volume, infection, and lower 3-day postoperative eGFR as adverse factors for survival. Conclusions: Preserving kidney function is crucial for achieving favorable outcomes in hypertensive ICH cases. Impaired 3-day postoperative eGFR emerged as an independent risk factor for overall survival. Patients with cardiac failure, infection, and larger hematoma volume should receive careful management to improve outcomes.

A preliminary study on the mechanism of VASH2 in childhood medulloblastoma.

To study the differences in VASH2 expression in pediatric medulloblastoma (MB) tumor tissues of different molecular subtypes, to analyze the correlation between VASH2 and the molecular subtypes of medulloblastoma, clinicopathological data, and prognosis, and to explore the specific mechanism of VASH2's role in SHH medulloblastoma cell lines DAOY. We analyzed 47 pediatric medulloblastoma cases admitted to the Department of Pediatric Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University from January 2011 to December 2019, and the expression levels of YAP1 and GAB1 in these tumor tissues were detected by immunohistochemistry (IHC) and molecularly typed (WNT-type, SHH-type, and non-WNT/SHH-type). The correlation between VASH2 and molecular typing of medulloblastoma was analyzed. We also analyzed the medulloblastoma dataset in the GEO database (GSE30074 and GSE202043) to explore the correlation between VASH2 and the prognosis of medulloblastoma patients, as well as performed a comprehensive GO enrichment analysis specifically for the VASH2 gene to reveal the underlying biological pathways of its complex molecular profile. We used vasopressin 2 (VASH2) as a research target and overexpressed and knocked down VASH2 in SHH medulloblastoma cell lines DAOY by lentiviral vectors in vitro, respectively, to investigate its role in SHH medulloblastoma cell lines DAOY cell proliferation, apoptosis, migration, invasion and biological roles in the cell cycle. (1) Among 47 pediatric medulloblastoma cases, 8 were WNT type, 29 were SHH type, and 10 were non-WNT/SHH type. the positive rate of VASH2 was highest in the SHH type with a 68.97% positive rate, followed by non-WNT/SHH and lowest in the WNT type. The results of the multifactorial analysis showed that positive expression of VASH2 was associated with medulloblastoma molecular subtype (SHH type), site of tumor development (four ventricles), and gender (male), P < 0.05. (2) The results of cellular experiments showed that overexpression of VASH2 increased the invasion and migration ability of medulloblast Daoy, while knockdown of VASH2 inhibited the invasion and Overexpression of VASH2 upregulated the expression of Smad2 + 3, Smad4, Mmp2 and the apoptotic indicators Bcl-2 and Caspase3, while knockdown of VASH2 suppressed the expression of Smad2 + 3 and Mmp2, and silenced the expression of Smad4 and the apoptotic indicators Bcl2, Caspase3 expression. Flow cytometric cycle analysis showed that VASH2 overexpression increased the S phase in the Daoy cell cycle, while VASH2 knockdown decreased the S phase in the SHH medulloblastoma cell lines DAOY cell cycle. Bioinformatics analysis showed that there was no statistically significant difference between the expression of VASH2 genes in the GSE30074 and GSE202043 datasets and the prognosis of the patients, but the results of this dataset analysis suggested that we need to continue to expand the sample size of the study in the future. The results of the GO enrichment analysis showed that the angiogenic pathway was the most significantly enriched, and the PPI interactions network of VASH2 was obtained from the STRING database. Using the STRING database, we obtained the PPI interaction network of VASH2, and the KEGG enrichment analysis of VASH2-related genes showed that VASH2-related genes were related to the apoptosis pathway, and therefore it was inferred that VASH2 also affects the development of tumors through apoptosis. We found for the first time that the positive expression rate of VASH2 was closely associated with SHH-type pediatric medulloblastoma and that VASH2 was involved in the invasion, migration, cell cycle, and apoptotic capacity of SHH medulloblastoma cell lines DAOY by affecting downstream indicators of the TGF-ß pathway. This suggests that it is involved in the progression of pediatric medulloblastoma, and VASH2 is expected to be a diagnostic and therapeutic target for SHH-type pediatric medulloblastoma.

MV-CVIB: a microbiome-based multi-view convolutional variational information bottleneck for predicting metastatic colorectal cancer.

Introduction: Imbalances in gut microbes have been implied in many human diseases, including colorectal cancer (CRC), inflammatory bowel disease, type 2 diabetes, obesity, autism, and Alzheimer's disease. Compared with other human diseases, CRC is a gastrointestinal malignancy with high mortality and a high probability of metastasis. However, current studies mainly focus on the prediction of colorectal cancer while neglecting the more serious malignancy of metastatic colorectal cancer (mCRC). In addition, high dimensionality and small samples lead to the complexity of gut microbial data, which increases the difficulty of traditional machine learning models. Methods: To address these challenges, we collected and processed 16S rRNA data and calculated abundance data from patients with non-metastatic colorectal cancer (non-mCRC) and mCRC. Different from the traditional health-disease classification strategy, we adopted a novel disease-disease classification strategy and proposed a microbiome-based multi-view convolutional variational information bottleneck (MV-CVIB). Results: The experimental results show that MV-CVIB can effectively predict mCRC. This model can achieve AUC values above 0.9 compared to other state-of-the-art models. Not only that, MV-CVIB also achieved satisfactory predictive performance on multiple published CRC gut microbiome datasets. Discussion: Finally, multiple gut microbiota analyses were used to elucidate communities and differences between mCRC and non-mCRC, and the metastatic properties of CRC were assessed by patient age and microbiota expression.

Integrated machine learning survival framework develops a prognostic model based on inter-crosstalk definition of mitochondrial function and cell death patterns in a large multicenter cohort for lower-grade glioma.

BACKGROUND: Lower-grade glioma (LGG) is a highly heterogeneous disease that presents challenges in accurately predicting patient prognosis. Mitochondria play a central role in the energy metabolism of eukaryotic cells and can influence cell death mechanisms, which are critical in tumorigenesis and progression. However, the prognostic significance of the interplay between mitochondrial function and cell death in LGG requires further investigation. METHODS: We employed a robust computational framework to investigate the relationship between mitochondrial function and 18 cell death patterns in a cohort of 1467 LGG patients from six multicenter cohorts worldwide. A total of 10 commonly used machine learning algorithms were collected and subsequently combined into 101 unique combinations. Ultimately, we devised the mitochondria-associated programmed cell death index (mtPCDI) using machine learning models that exhibited optimal performance. RESULTS: The mtPCDI, generated by combining 18 highly influential genes, demonstrated strong predictive performance for prognosis in LGG patients. Biologically, mtPCDI exhibited a significant correlation with immune and metabolic signatures. The high mtPCDI group exhibited enriched metabolic pathways and a heightened immune activity profile. Of particular importance, our mtPCDI maintains its status as the most potent prognostic indicator even following adjustment for potential confounding factors, surpassing established clinical models in predictive strength. CONCLUSION: Our utilization of a robust machine learning framework highlights the significant potential of mtPCDI in providing personalized risk assessment and tailored recommendations for metabolic and immunotherapy interventions for individuals diagnosed with LGG. Of particular significance, the signature features highly influential genes that present further prospects for future investigations into the role of PCD within mitochondrial function.

DeepTPpred: A Deep Learning Approach With Matrix Factorization for Predicting Therapeutic Peptides by Integrating Length Information.

The abuse of traditional antibiotics has led to increased resistance of bacteria and viruses. Efficient therapeutic peptide prediction is critical for peptide drug discovery. However, most of the existing methods only make effective predictions for one class of therapeutic peptides. It is worth noting that currently no predictive method considers sequence length information as a distinct feature of therapeutic peptides. In this article, a novel deep learning approach with matrix factorization for predicting therapeutic peptides (DeepTPpred) by integrating length information are proposed. The matrix factorization layer can learn the potential features of the encoded sequence through the mechanism of first compression and then restoration. And the length features of the sequence of therapeutic peptides are embedded with encoded amino acid sequences. To automatically learn therapeutic peptide predictions, these latent features are input into the neural networks with self-attention mechanism. On eight therapeutic peptide datasets, DeepTPpred achieved excellent prediction results. Based on these datasets, we first integrated eight datasets to obtain a full therapeutic peptide integration dataset. Then, we obtained two functional integration datasets based on the functional similarity of the peptides. Finally, we also conduct experiments on the latest versions of the ACP and CPP datasets. Overall, the experimental results show that our work is effective for the identification of therapeutic peptides.

Study on the relationship between genetic polymorphism of reductive folic acid carrier and the risk of neural tube defects.

BACKGROUND: To investigate the association of folate metabolism gene polymorphism with neural tube defects (NTDs) in Chinese population. METHODS: The subjects were divided into two groups, 495 children with NTDs (NTD group) and 255 healthy children (control group). RESULTS: The levels of folic acid, s-adenosine methionine (SAM), and Sam/s-adenosine homocysteine (SAH) in NTD group were lower than those in control group. There were significant differences in hey, SAH, and Sam levels between two groups, but there was no significant difference in folic acid content. High fever in early pregnancy, taking antiepileptic drugs, father's exposure to organic solvents, folic acid deficiency, and mother's diabetes were the important risk factors in NTDs. MTHFR 677C > T gene was a risk factor for NTD in children, while 1298A > C gene was a protective factor. CONCLUSION: Folic acid metabolism markers were different in NTD children and their mothers, and the overall trend showed that folate, SAM, and SAM/SAH levels were decreased, while Hcy and SAH levels were increased; MTHFR 677C > T gene of SNPs was a risk factor for the occurrence of NTDs, and MTHFR 1298A > C gene was a protective factor, and the environmental risk factor had a synergistic effect on occurrence of NTDs.

Determination of Anti-Mesenchymal Stem Cell Antibody in Cynomolgus Monkey Serum by Flow Cytometry and Its Application / 医药导报

Objective To develop an accurate,rapid and sensitive flow cytometry method for the determination of anti-mesenchymal stem cell antibody in cynomolgus monkey serum.Methods After the solutions of mesenchymal stem cell were centrifuged and washed,and the suspension was taken,positive controls or actual samples were added and incubated with mesenchymal stem cell,then were incubated with protein L-PE solution.After the removal of the free protein L-PE,the mean fluorescence intensity of the PE was detected by flow cytometry.Results The method sensitivity is 115.54 ng·mL-1,far higher than the non-clinical research recommended sensitivity of 250-500 ng·mL-1.The precision of intra-assay and inter-assay were less than 20%.Assay cut points,low positive control concentration determination,sensitivity,precision and stability were validated in this study.Conclusion The method is proved to be sensitive,specific,rapid and suitable for the determination of anti-mesenchymal stem cell antibody in monkey serum and immunogenicity study.

Identification of VASH1 as a Potential Prognostic Biomarker of Lower-Grade Glioma by Quantitative Proteomics and Experimental Verification.

Background: VASH1 is a novel angiogenic regulatory factor, that participates in the process of carcinogenesis and the development of diverse tumors. Our study aimed to investigate the expression and prognostic value of the VASH1 in Lower-Grade Glioma (LGG), to explore its functional network in LGG and its effects on biological behaviors. Methods: LGG transcriptome data, somatic mutation profiles and clinical features analyzed in the present study were obtained from the TCGA, GTEx, CCLE, CGGA, UALCAN, and GEPIA2 databases, as well as clinical data and tissue sections of 83 LGG patients in our hospital. The expression characteristics of VASH1 in LGG were investigated by univariate, multivariate, immunohistochemistry, qRT-PCR, and western-blot. Subsequently, we analyzed the prognostic significance of VASH1 in LGG patients by survival analysis, subject operation characteristic curve, correlation analysis, external validation, independent prognostic significance analysis, and clinical stratification, and confirmed its biological effect on glioma cell lines in vitro. Finally, we performed GO, KEGG, and GSEA to clarify biological functions and related pathways. CIBERSORT and ESTIMATE algorithms were used to calculate the proportion of immune cells and immune microenvironment fraction in LGG. Result: We found that VASH1 is highly expressed in LGG tissues and is associated with poor prognosis, WHO grade, IDH1 wild-type, and progressive disease (P < 0.05). Multivariate and the Nomogram model showed that high VASH1 expression was an independent risk factor for glioma prognosis and had better prognostic prediction efficacy in different LGG Patient cohorts (HR = 4.753 and P=0.002). In vitro experiments showed that knockdown of VASH1 expression in glioma cell lines caused increased glioma cell proliferation, invasion, and migration capacity. The mechanism may be related to VASH1 promoting microtubule formation and remodeling of immune microenvironment. Conclusion: Our study firstly found that high VASH1 expression was associated with poor prognosis. In addition, We identified the possible mechanism by which VASH1 functioned in LGG. VASH1 inhibits the invasion and migration of tumor cells by affecting microtubule formation and immune infiltration in the tumor microenvironment. May be an important endogenous anti-tumor factor for LGG and provide a potential biomarker for individualized treatment of LGG.

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brain metastases. This process can be plausibly explained by the "seed and soil" hypothesis, which essentially states that tumor cells can interact with various components of the central nervous system microenvironment to produce adaptive changes; it is this interaction that determines the development of brain metastases. As a novel form of intercellular communication, exosomes play a key role in the brain metastasis microenvironment and carry various bioactive molecules that regulate receptor cell activity. In this paper, we review the roles and prospects of brain metastatic tumor cells, the brain metastatic tumor microenvironment, and exosomes in the development and clinical management of brain metastases.

The RPL4P4 Pseudogene Is a Prognostic Biomarker and Is Associated with Immune Infiltration in Glioma.

Objective: Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in gliomas. However, its biological function in gliomas remains unclear. Methods: In this study, we analyzed clinical data on patients with glioma obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx), and the GEPIA2 databases. We used the R language for the main analysis. Correlations among RPL4P4 expression, pathological characteristics, clinical outcome, and biological function were evaluated. In addition, the correlations of RPL4P4 expression with immune cell infiltration and glioma progression were analyzed. Finally, wound healing, Transwell, and CCK-8 assays were performed to analyze the function of RPL4P4 in glioma cells. Result: We found that RPL4P4 is highly expressed in glioma tissues and is associated with poor prognosis, IDH1 wild type, codeletion of 1p19q, and age. Multivariate analysis and the nomogram model showed that high RPL4P4 expression was an independent risk factor for glioma prognosis and had better prognostic prediction power. Moreover, high RPL4P4 expression correlated with immune cell infiltration, which showed a significant positive association with M2-type macrophages. Finally, RPL4P4 knockdown in glioma cell lines caused decreased glioma cell proliferation, invasion, and migration capacity. Conclusion: Our data suggest that RPL4P4 can function as an independent prognostic predictor of glioma. It also shows that RPL4P4 expression correlates with immune cell infiltration and that targeting RPL4P4 may be a new strategy for the treatment of glioma patients.

Effect of enhanced UV-B radiation on growth and photosynthetic physiology of Iris tectorum maxim.

Iris tectorum Maxim. is an important plant that plays a very crucial role in the ecological welfare of wetlands. In this study, the effects of different intensities of UV-B radiation on the growth, photosynthetic pigment content, chlorophyll fluorescence characteristics, chloroplast ultrastructure, and gas exchange parameters of Iris tectorum Maxim. were studied. The results showed that enhanced UV-B radiation had a significant influence on the above-mentioned parameters of iris. Compared with the control, enhanced UV-B radiation caused certain damage to the leaf appearance. With the increasing intensity of radiation, the apparent damage degree became more serious. Enhanced UV-B radiation significantly decreased leaf chlorophyll contents, and the effect accumulated with the exposure time. Enhanced UV-B radiation increased Fo, significantly increased the non-photochemical quenching coefficient NPQ, reduced PSII and Qp, and significantly decreased the Fm, Fv/Fm, and Fv/Fo in leaves. The effect of UV-B radiation on PSII destruction of Iris tectorum Maxim. increased as the radiation intensity increased and the exposure time prolonged. The chloroplast structure was damaged under the enhanced UV-B radiation. More specifically, thylakoid lamellae were distorted, swelling and even blurred, and a large number of starch granules appeared. The effect of the high intensity of radiation on chloroplast ultrastructure was greater than that of lower intensity. Enhanced UV-B radiation reduced significantly the net photosynthetic rate, stomatal conductance, and transpiration rate, and the degree of degradation increased with the increasing irradiation intensity. However, the intercellular CO2 content increased, which suggests that the main reason for the decrease of photosynthetic rate was the non-stomatal factors.

Repair of Cranial Defects in Rabbits with 3D-Printed Hydroxyapatite/Polylactic Acid Composites.

Objective: The safety and efficacy of three-dimensional- (3D-) printed hydroxyapatite/polylactic acid (HA-PLA) composites in repairing cranial defects were evaluated in a rabbit experimental model. Methods: Twelve New Zealand rabbits were selected as experimental subjects. Two holes (A and B), each with a diameter of approximately 1 cm, were made in the cranium of each rabbit. Hole A served as the experimental manipulation, and hole B served as the control manipulation. A 3D-printed HA-PLA composite was used for placement onto hole A, whereas autologous bone powder was used for placement onto hole B. Samples from the experimental holes and the control holes were collected at 30 and 90 days after surgery. The obtained materials were examined in terms of their morphologies and histopathologies and were also subjected to simultaneous hardness tests. Results: Both the 3D-printed HA-PLA composite and autologous bone powder were able to repair and fill the cranial defects at 30 days and 90 days after surgery. At 30 days after surgery, the microhardness of the area repaired by the HA-PLA composite was lower than that of the area repaired by autogenous bone powder (p < 0.01), but neither of these treatments reached the hardness of normal bone at this time (p < 0.01). At 90 days after surgery, there was no statistically significant difference in the microhardness of the repaired area from the 3D-printed HA-PLA composite compared with that of the repaired area from autologous bone powder (p > 0.05), and there was no statistically significant difference in the hardness of the two repaired areas compared with that of the normal bone (p > 0.05). Hematoxylin-eosin staining showed that bone cells in the HA-PLA material in the experimental group grew and were arranged in an orderly manner. Bone trabeculae and marrow cavities were formed on the pore surface and inside of the HA-PLA scaffold, and the arrangement of bone trabeculae was regular. Conclusion: 3D-printed HA-PLA composites can induce bone regeneration, are biocompatible, have the same strength as autologous bone powder, are able to degrade, and are ultimately safe and effective for repairing cranial defects in rabbits. However, further research is needed to determine the feasibility of 3D-printed HA-PLA composites in human cranioplasty.

RMSCNN: A Random Multi-Scale Convolutional Neural Network for Marine Microbial Bacteriocins Identification.

The abuse of traditional antibiotics has led to an increase in the resistance of bacteria and viruses. Similar to the function of antibacterial peptides, bacteriocins are more common as a kind of peptides produced by bacteria that have bactericidal or bacterial effects. More importantly, the marine environment is one of the most abundant resources for extracting marine microbial bacteriocins (MMBs). Identifying bacteriocins from marine microorganisms is a common goal for the development of new drugs. Effective use of MMBs will greatly alleviate the current antibiotic abuse problem. In this work, deep learning is used to identify meaningful MMBs. We propose a random multi-scale convolutional neural network method. In the scale setting, we set a random model to update the scale value randomly. The scale selection method can reduce the contingency caused by artificial setting under certain conditions, thereby making the method more extensive. The results show that the classification performance of the proposed method is better than the state-of-the-art classification methods. In addition, some potential MMBs are predicted, and some different sequence analyses are performed on these candidates. It is worth mentioning that after sequence analysis, the HNH endonucleases of different marine bacteria are considered as potential bacteriocins.

Effect of obesity on in-hospital prognosis of patients with mechanical ventilation in PICU / 中国小儿急救医学

Objective:To evaluate the effect of obesity on in-hospital prognosis of patients with mechanical ventilation in PICU.Methods:We enrolled 301 patients who received mechanical ventilation treatment in PICU at Chongqing Medical University Affiliated Children′s Hospital, between June 2015 and June 2020, and stratified them into obese group(49 cases), overweight group(96 cases)and normal weight group(156 cases). Obesity was determined by reference to the growth and development standards published by the World Health Organization.Indicators included PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital and the rates of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers were observed.The influence of obesity on hospitalized prognosis of children in PICU was analyzed.Results:In obesity group, overweight group and normal weight group, PICU hospital mortality(2.0%, 10.4%, 12.2%), the rate of tracheal reintubation(14.3%, 5.2%, 9.0%), the rate of tracheotomy (2.0%, 1.0%, 2.6%), the rate of deep venous thrombosis(8.2%, 3.1%, 5.8%), and the rate of pressure ulcers(4.1%, 7.3%, 1.9%) did not have significant difference(all P>0.05). No ventilator-associated pneumonia and central venous catheter infection occurred in three groups.There were no significant differences in the PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital among the three groups(all P>0.05). Obesity was not an independent risk factor for in-hospital death in PICU patients on mechanical ventilation( B=1.975, SE=1.038, OR=7.206, 95% CI 0.942~55.127, P=0.057). Conclusion:Obesity does not prolong the duration of mechanical ventilation, length of stay in PICU and total length of stay in hospital, as well as not increase the rate of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers.Obesity is not an independent influencing factor for in-hospital death in patients with mechanical ventilation in PICU.

Protective Effect of Ginsenosides Rg1 and Rb1 Against Intestinal Epithelial Barrier Injury Induced by Lipopolysaccharide in Vitro / 中国实验方剂学杂志

ObjectiveTo investigate the effects of ginsenoside Rg1 and ginsenoside Rb1 on the release of inflammatory factors of human myeloid leukemia monocytes （THP-1） induced by lipopolysaccharide （LPS） and their protective effects on the inflammatory injury of intestinal epithelial cells （Caco-2） induced by THP-1 cell activation based on the co-culture system of THP-1 and Caco-2. MethodFirstly，the microfluidic chip of co-culture of THP-1 and Caco-2 cells was prepared. In the experiment， a blank group， an LPS group， and drug intervention groups were set up.The cells in the blank group were cultured conventionally. In the LPS group，LPS （1 mg·L-1） was added to the lower THP-1 cells after the upper Caco-2 cells formed a monolayer barrier. On the basis of the LPS group， 33 mg·L-1 ginsenoside Rg1 and 33 mg·L-1 ginsenoside Rb1 were added to THP-1 cells respectively. After the co-culture of THP-1 cells and Caco-2 cells for 24 hours， the fluorescein isothiocyanate （FITC）-Dextran fluorescence value in the lower chip channel was detected by FITC-Dextran tracer method. A blank group， an LPS group，and drug intervention groups were set up in the THP-1 cell experiment. THP-1 cells in the blank group were cultured conventionally. In the LPS group， LPS （1 mg·L-1） was added to THP-1 cells.Ginsenoside Rg1 and ginsenoside Rb1 of the corresponding doses （11，33，100 mg·L-1） were added to the drug intervention groups respectively on the basis of the LSP group. After 24 hours of cell culture， the activity of THP-1 cells was detected by cell counting kit-8 （CCK-8）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of inflammatory cytokines such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor （TNF）-α of THP-1 cells. A blank group， an LPS group， and drug intervention groups were set up in the Caco-2 cell experiment. Caco-2 cells in the blank group were cultured conventionally， and in other groups， the corresponding cell supernatant in the second part of the THP-1 cell experiment was employed in Caco-2 cells. After 24 hours of cell culture，the activity of Caco-2 cells was detected by CCK-8. Real-time PCR was used to detect the expression of IL-6，interleukin-8 （IL-8）， TNF-α， and Occludin of Caco-2 cells. The expression of tight junction protein Occludin in Caco-2 cells was detected by Western blot. ResultBoth ginsenoside Rg1 and ginsenoside Rb1 could effectively protect LPS-induced intestinal epithelial barrier permeability in the co-culture system of THP-1 and Caco-2 cells （P<0.01）. Ginsenosides Rg1 and Rb1 antagonized LPS-induced increased expression of IL-6，IL-1β， and TNF-α in THP-1 cells （P<0.05）. When the supernatant of THP-1 cells treated with ginsenosides Rg1 and Rb1 was co-cultured with Caco-2 cells， the expression of IL-6，IL-8， and TNF-α in Caco-2 cells was significantly reduced （P<0.01）， and the expression of tight junction protein Occludin was up-regulated. ConclusionIn the co-culture system of THP-1 and Caco-2 cells simulating the intestinal epithelial barrier function in vitro，ginsenosides Rg1 and Rb1 play a protective role against LPS-induced intestinal epithelial barrier injury by regulating the release of inflammatory cytokines by THP-1 cells， thereby regulating the inflammatory response and cell barrier integrity of Caco-2 cells.