Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

Research on the signaling pathway and the related mechanism of traditional Chinese medicine intervention in chronic gastritis of the "inflammation-cancer transformation".

Objective: The aim of this study is to uncover the traditional Chinese medicine (TCM) treatments for chronic gastritis and their potential targets and pathways involved in the "inflammation-cancer" conversion in four stages. These findings can provide further support for future research into TCM and its active components. Materials and methods: The literature search encompassed PubMed, Web of Science, Google Scholar, CNKI, WanFang, and VIP, employing keywords such as "chronic gastritis", "gastric cancer", "traditional Chinese medicine", "medicinal herb", "Chinese herb", and "natural plant". Results: Herbal remedies may regulate the signaling pathways linked to the advancement of chronic gastritis. Under the multi-target and multi-pathway independent or combined reaction, the inflammatory microenvironment may be enhanced, leading to repair of damaged gastric mucosal cells, buffering the progress of mucosal atrophic degeneration via the decrease of inflammatory factor expression, inhibition of oxidative stress-induced damage, facilitation of microvascular neovascularization in the gastric mucosa and regulation of the processes of gastric mucosal cell differentiation and proliferation. Simultaneously, the decreased expression of inflammatory factors may impact the expression of associated oncogenes and regulate the malignant proliferation of cells, thereby achieving the treatment and prevention objectives of gastric cancer through the reduction of cell metastasis and apoptosis. Conclusion: Chinese medicine formulations and individual drugs can be utilised at various stages of the "inflammation-cancer" progression of chronic gastritis to prevent and treat gastric cancer in a multi-level, multi-targeted, and multi-directional fashion. This can provide guidance for the accurate application of medicines during different stages of "inflammation-cancer" transformation. New insights into the mechanism of inflammation-cancer transformation and the development of novel drugs for chronic gastritis can be gained through an extensive investigation of TCM treatment in this condition.

A privacy-preserving publicly verifiable quantum random number generator.

Verifying the quality of a random number generator involves performing computationally intensive statistical tests on large data sets commonly in the range of gigabytes. Limitations on computing power can restrict an end-user's ability to perform such verification. There are also random number-based applications where an honest user needs to publicly demonstrate that the random bits they are using pass the statistical tests without the bits being revealed. Here, we report the implementation of an entanglement-based protocol that allows a third party to publicly perform statistical tests without compromising the privacy of the random bits.

Uncovering Potentially Therapeutic Phytochemicals, In silico Analysis, and Biological Assessment of South-Chinese Red Dragon Fruit (Hylocereus polyrhizus).

Red dragon fruit is gaining popularity globally due to its nutritional value and bioactive components. The study aimed to assess the phytochemical, nutritional composition, antioxidant, antibacterial, and cytotoxic properties of extracts from the South Chinese red dragon fruit peel, flesh, and seeds. Extract fractions with increasing polarity (ethyl acetate

Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10-3 g·kg-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3（TGF-β1/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β1 proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism / 环境与职业医学

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

Exploring the mechanism of Xihuang Pill's anti-hyperplasia of mammary glands effect based on UPLC-Q-orbitrap-MS technology / 药学学报

Based on UPLC-Q-orbitrap-MS and biological network analysis tools, the mechanism of Xihuang Pill in improving hyperplasia of mammary glands was systematically analyzed. The rat model of hyperplasia of mammary glands was established by intramuscular injection of estradiol benzoate and progesterone. LC-MS tissue metabolomics was used to explore the key metabolites and metabolic pathways of Xihuang Pill in improving hyperplasia of mammary glands in rat. The network analysis of the key metabolites regulated by Xihuang Pill was carried out by integrating biological network analysis tools, focusing on the key metabolic pathways, and exploring the potential targets of Xihuang Pill to improve hyperplasia of mammary glands. Compared with the control group, there were significant differences in the content of 49 differential metabolites in the tissues of the model group (P < 0.05). Xihuang Pills could significantly call back 17 metabolites such as L-alanine, threonine, indole-3-carboxylic aldehyde, lysine, arginine, alanylleucine, glycyltyrosine, γ-glutamyl leucine, vitamin B3, serine leucine, threonine leucine, isoleucine glutamic acid, γ-glutamyl tyrosine, decanoyl-L-carnitine, uric acid, leucylleucine, S-adenosyl-methionine. Further network analysis and literature research on the key metabolites regulated by Xihuang Pills showed that the AGE-RAGE signaling pathway may be one of the important pathways for Xihuang Pills to improve hyperplasia of mammary glands. STAT3, MAPK1, EGFR, CASP3, CASP8, PRKCA and JUN in the AGE-RAGE signaling pathway may be potential targets for Xihuang Pills to improve hyperplasia of mammary glands. The animal experiment operations involved in this paper follow the provisions of the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine and pass the ethical review of animal experiments (approval number: 2022-705).

Lung transplantation after paraquat poisoning in an adolescent: one case report and literature review / 器官移植

Objective To summarize the effect of the timing of lung transplantation and related treatment measures on clinical prognosis of patients with paraquat poisoning. Methods Clinical data of a patient with paraquat poisoning undergoing bilateral lung transplantation were retrospectively analyzed. Clinical manifestations, auxiliary examination, diagnosis and treatment of this patient were summarized and analyzed. Results A 17-year-old adolescent was admitted to hospital due to nausea, vomiting, cough and systemic fatigue after oral intake of 20-30 mL of 25% paraquat. After symptomatic support treatment, the oxygen saturation was not improved, and pulmonary fibrosis continued to progress. Therefore, sequential bilateral lung transplantation was performed under extracorporeal membrane oxygenation (ECMO). After postoperative rehabilitation and active prevention and treatment for postoperative complications, the patient was discharged at postoperative 50 d. Conclusions The timing of lung transplantation after paraquat poisoning may be selected when the liver and kidney function start to recover. Active and targeted prevention of potential pathogen infection in perioperative period and early rehabilitation training contribute to improving clinical prognosis of lung transplant recipients.

Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

A new method for evaluating lung volume: AI-3D reconstruction.

Objective: This study aims to explore the clinical application of an AI-3D reconstruction system in measuring lung volume and analyze its practical value in donor-recipient size matching in lung transplantation. Methods: The study retrospectively collected data from 75 subjects who underwent a plethysmography examination and lung CT at the First Hospital of Jilin University. General data and information related to lung function, and imaging results were collected. The correlation between actual total lung volume (aTLV), predicted total lung volume (pTLV), and artificial intelligence three-dimensional reconstruction CT lung volume (AI-3DCTVol) was analyzed for the overall, male, and female groups. The correlation coefficient and the absolute error percentage with pTLV and AI-3DCTVol were obtained. Results: In the overall, male, and female groups, there were statistical differences (p <0.05) between the pTLV formula and AI-3D reconstruction compared to the plethysmography examination value. The ICC between pTLV and aTLV for all study participants was 0.788 (95% CI: 0.515-0.893), p <0.001. Additionally, the ICC value between AI-3D reconstruction and aTLV was 0.792 (95% CI: 0.681-0.866), p <0.001. For male study participants, the ICC between pTLV and aTLV was 0.330 (95% CI: 0.032-0.617), p = 0.006. Similarly, the ICC value between AI-3D reconstruction and aTLV was 0.413 (95% CI: 0.089-0.662), p = 0.007. In the case of female research subjects, the ICC between pTLV and aTLV was 0.279 (95% CI: 0.001-0.523), p = 0.012. Further, the ICC value between AI-3D reconstruction and aTLV was 0.615 (95% CI: 0.561-0.870), p <0.001. Conclusion: The AI-3D reconstruction, as a convenient method, has significant potential for application in lung transplantation.

Analysis of drug resistance in pulmonary tuberculosis patients with positive sputum tuberculosis culture in Northeast China.

Objective: The objective of this study is to determine the drug resistance status of pulmonary tuberculosis patients in Jilin Province. Methods: A retrospective survey was conducted on 395 sputum culture TB-positive patients admitted to the tuberculosis hospital in Jilin Province in 2019. Sputum samples were cultured in acidic Roche medium. Drug sensitivity testing was conducted using the proportional method. Sensitivity was reported if the percentage of drug resistance was less than 1%, and resistance was reported if the percentage was ≥1%. Statistical analysis was performed using SPSS 22.0. Results: 395 tuberculosis patients with positive sputum tuberculosis culture were included in the study, with 102 being initially treated and 293 being retreated. The study population consisted of 283 males and 112 females. Sex, age, nationality, occupation, marital status, diabetes comorbidity, initial treatment, normal health status, BCG vaccine vaccination, smoking, and alcohol consumption were considered as factors that may affect the rate of multidrug resistance. And only the history of treatment (initial treatment) was associated with multidrug resistance (p = 0.032). This indicates that retreatment is the most significant risk factor for the occurrence of multidrug resistance in tuberculosis. The multidrug resistance rate in retreated patients is 3.764 times higher than that in initially treated patients. Conclusion: The prevalence of multidrug-resistant is higher in retreated patients compared to initially treated patients in the study population. Multidrug resistance is only associated with the treatment history (initial retreatment) and not with other factors.

Inhibition of RhoA/ROCK signalling pathway activity improves neural damage and cognitive deficits in the fluorosis model.

Excessive fluoride intake poses health risks to humans and animals. Many studies have indicated that fluoride exposure can damage the cytoskeleton and synapses, which has negative effects on the intellectual development of humans and animals. Our previous study suggested that the RhoA/ROCK signalling pathway is activated by NaF exposure in HT-22 cells and plays a vital role in cytoskeletal assembly and synaptogenesis. However, the mechanism underlying RhoA/ROCK-mediated cytoskeletal injury induced by fluoride remains unclear. In this study, Neuro-2A cells and ICR mice were used to investigate the effects of RhoA/ROCK activation inhibition on NaF-induced synaptic dysfunction and cognitive impairment. We detected the expression of GAP, RhoA, ROCK1/2, and (p)-MLC in vivo and in vitro model. The results showed that NaF exposure activated the RhoA/ROCK/MLC signalling pathway. We measured the effects of RhoA/ROCK inhibition on synaptic injury and intellectual impairment induced by NaF exposure. In vitro, Y-27632 suppressed activated RhoA/ROCK, attenuated morphological and ultrastructural damage, and decreased the survival rate and synapse-functional protein expression caused by NaF. In vivo, the results showed that the RhoA/ROCK/MLC pathway was inhibited by fasudil and improved pathological damage in the hippocampus, cognitive impairment, and decreased expression of neurofunctional proteins induced by NaF. Overall, these results suggest that fasudil and Y-27632 can reverse neurotoxicity caused by fluoride exposure. Furthermore, inhibition of RhoA/ROCK may be a future treatment for CNS injury, and more detailed studies on other neurodegenerative disease models are required to confirm its effectiveness.

Clinical application of liquid biopsy based on circulating tumor DNA in non-small cell lung cancer.

Lung cancer is a widely occurring and deadly malignancy, with high prevalence rates in China and across the globe. Specifically, non-small cell lung cancer (NSCLC) represents about 85% of all lung cancer cases. The 5-year disease-free survival rate after surgery for stage IB-IIIB NSCLC patients (disease-free survival, DFS) has notably declined from 73% to 13%. Early detection of abnormal cancer molecules and subsequent personalized treatment plans are the most effective ways to address this problem. Liquid biopsy, surprisingly, enables safe, accurate, non-invasive, and dynamic tracking of disease progression. Among the various modalities, circulating tumor DNA (ctDNA) is the most commonly used liquid biopsy modality. ctDNA serves as a credible "liquid biopsy" diagnostic tool that, to a certain extent, overcomes tumor heterogeneity and harbors genetic mutations in malignancies, thereby providing early information on tumor genetic alterations. Despite considerable academic interest in the clinical significance of ctDNA, consensus on its utility remains lacking. In this review, we assess the role of ctDNA testing in the diagnosis and management of NSCLC as a reference for clinical intervention in this disease. Lastly, we examine future directions to optimize ctDNA for personalized therapy.

Comprehensive analysis of lncRNA-mRNA co-expression networks in HPV-driven cervical cancer reveals the pivotal function of LINC00511-PGK1 in tumorigenesis.

BACKGROUND: Mounting evidence suggests that noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in HPV-driven cervical cancer (CC) has not been extensively studied. Considering that HR-HPV infections contribute to cervical carcinogenesis by regulating the expression of lncRNAs, miRNAs and mRNAs, we aim to systematically analyze lncRNAs and mRNAs expression profile to identify novel lncRNAs-mRNAs co-expression networks and explore their potential impact on tumorigenesis in HPV-driven CC. METHODS: LncRNA/mRNA microarray technology was utilized to identify the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in HPV-16 and HPV-18 cervical carcinogenesis compared to normal cervical tissues. Venn diagram and weighted gene co-expression network analysis (WGCNA) were used to identify the hub DElncRNAs/DEmRNAs that were both significantly correlated with HPV-16 and HPV-18 CC patients. LncRNA-mRNA correlation analysis and functional enrichment pathway analysis were performed on these key DElncRNAs/DEmRNAs in HPV-16 and HPV-18 CC patients to explore their mutual mechanism in HPV-driven CC. A lncRNA-mRNA co-expression score (CES) model was established and validated by using the Cox regression method. Afterward, the clinicopathological characteristics were analyzed between CES-high and CES-low groups. In vitro, functional experiments were performed to evaluate the role of LINC00511 and PGK1 in cell proliferation, migration and invasion in CC cells. To understand whether LINC00511 play as an oncogenic role partially via modulating the expression of PGK1, rescue assays were used. RESULTS: We identified 81 lncRNAs and 211 mRNAs that were commonly differentially expressed in HPV-16 and HPV-18 CC tissues compared to normal tissues. The results of lncRNA-mRNA correlation analysis and functional enrichment pathway analysis showed that the LINC00511-PGK1 co-expression network may make an important contribution to HPV-mediated tumorigenesis and be closely associated with metabolism-related mechanisms. Combined with clinical survival data, the prognostic lncRNA-mRNA co-expression score (CES) model based on LINC00511 and PGK1 could precisely predict patients' overall survival (OS). CES-high patients had a worse prognosis than CES-low patients and the enriched pathways and potential targets of applicable drugs were explored in CES-high patients. In vitro experiments confirmed the oncogenic functions of LINC00511 and PGK1 in the progression of CC, and revealed that LINC00511 functions in an oncogenic role in CC cells partially via modulating the expression of PGK1. CONCLUSIONS: Together, these data identify co-expression modules that provide valuable information to understand the pathogenesis of HPV-mediated tumorigenesis, which highlights the pivotal function of the LINC00511-PGK1 co-expression network in cervical carcinogenesis. Furthermore, our CES model has a reliable predicting ability that could stratify CC patients into low- and high-risk groups of poor survival. This study provides a bioinformatics method to screen prognostic biomarkers which leads to lncRNA-mRNA co-expression network identification and construction for patients' survival prediction and potential drug applications in other cancers.

Efficacy of luteolin on the human gastric cancer cell line MKN45 and underlying mechanism.

OBJECTIVE: To investigate the antitumour efficacy of luteolin on gastric cancer (GC) and study the mechanism underpinning the action. METHODS: Effects of luteolin on cell growth inhibition, apoptosis, and cell cycle arrest in MKN45 cells were investigated using the cell counting kit-8 assay. Changes in the mitochondrial membrane potential after luteolin treatment were assessed using 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanineiodi-de (JC-1) staining. To investigate whether apoptotic effect by luteolin is related to the phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) pathway, cells were additionally treated with LY294002, a PI3K/Akt pathway inhibitor. Moreover, the expressions of apoptosis-related proteins, namely B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein (Bax), Akt, p-Akt, caspase-3, and cytochrome C, were detected after luteolin treatment. RESULTS: The study revealed that in MKN45 cells, luteolin could inhibit the cell proliferation in a time- and dose-dependent manner; block the cell cycle in the S-phase; induce apoptosis; reduce the mitochondrial membrane potential; increase the expression of Bax, caspase-3, and cytochrome C; and decrease the expression of Bcl-2 and p-Akt. Luteolin might be involved in the PI3K/Akt signalling pathway, indicating that this pathway could be a therapeutic target for GC treatment. CONCLUSION: Luteolin could inhibit the proliferation of GC cells and block the cell cycle in the S-phase. The mechanism of inducing apoptosis in these cells was related to the PI3K/Akt signalling pathway.

Effects of Catheter Tracking Management on Urinary Tract Function and Infection Rates in Patients With Spinal Cord Injury.

Context: Patients with bone-marrow injuries, such as spinal cord injuries (SCIs), usually have urinary dysfunction, changes to the urethra's anatomical structure, and pathophysiological changes of the urinary system, which can lead to urodynamic changes. If a patient receives improper treatment, repeated infections of the urinary system can easily occur, causing hydronephrosis and damage to renal function. Objective: The study intended to explore the effects of catheter follow-up management for patients with SCIs on the function of the bladder and the urinary tract and on urinary tract infections (UTIs), selecting antibiotics reasonably according to a bacterial culture and drug sensitivity test. Design: The research team designed a randomized controlled trial. Setting: The study took place at the Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine (TCM)-Western Medicine (WM) in Cangzhou City, Hebei Province, People's Republic of China. Participants: Participants were 92 patients with SCIs who were treated at the hospital between January 2020 and December 2021. Intervention: The research team randomly divided participants into an intervention group (n = 45) and a control group (n = 47). The control group received routine treatment, while the intervention group received catheter follow-up management. Outcome Measures: At baseline and postintervention after six weeks of treatment, the research team: (1) examined participants' bladder function, (2) examine urodynamic indexes including measurement of the maximum bladder volume, maximum urethral closure pressure, maximum urinary flow rate, and maximum detrusor pressure, and (3) assessed participants' QoL using the World Health Organization Quality of Life Questionnaire Abbreviated (WHOQOL-BREF). Results: Improvements in bladder function, urodynamic indexes, QoL, and UTIs occurred in both groups. The intervention group's: (1) total effective rate for bladder function was 91.11%, which was significantly higher than that of the control group (P = .022); (2) maximal bladder volume, urethral closure pressure, and urinary flow rate were 365.59 ± 54.43 ml, 81.19 ± 8.8 cmH2O, and 18.60 ± 2. 43 ml/s, respectively, and were significantly higher than those of the control group (all P = .000); (3) maximal detrusor pressure was 47.48 ± 5.64 cmH2O, which was significantly lower than that of the control group (p=0.000); (4) scores on the WHOQOL-BREF's subdimensions and total score were significantly higher than those in the control group: psychological, 17.92 ± 1.55; physiological, 30.30 ± 1.82; independence, 22.43 ± 1.40; social relations, 16.82 ± 1.32; environment, 21.19 ± 1.85; and total score, 110.02 ±16.64 (all P = .000); (5) incidence of urinary tract infection was 17.78 which was significantly lower than that of the control group (P = .003). The distribution of bacterial species in the UTIs of the intervention and control groups wasn't significantly different (P = .869). The two bacterial groups were Escherichia coli and Enterococcus. Drug sensitivity tests showed that the Escherichia coli were less susceptible to gentamicin, levofloxacin, and piperacillin than to ciprofloxacin, and the Enterococcus were less susceptible to gentamicin, ciprofloxacin, and levofloxacin than to piperacillin. Conclusions: For patients with SCIs, catheter follow-up management can be helpful in restoring the function of the bladder and urinary tract, can improve patients' QoL, and reduce their rate of UTIs. Clinically, medical practitioners should select antibiotics reasonably according to a bacterial culture and drug-sensitivity test.

Analysis of the influencing factors in the long-term survival of esophageal cancer.

Background: To analyze the prognosis and diagnostic value of relevant hematological indexes on the survival status of patients with esophageal squamous cell carcinoma after radical surgery. Methods: This study included 206 patients with esophageal cancer who underwent surgical R0 resection. The data, including the basic information, preoperative blood routine, albumin, fibrinogen, surgery-related information, postoperative pathology, and overall survival, of the patients were compared. Results: The survival and death groups showed a significant difference in overall survival (OS), the degree of differentiation, depth of infiltration, pathological stage, vascular infiltration, nerve infiltration, fibrinogen, white blood cell, neutrophils, platelet, and platelet hematocrit (P<0.05). Tumor located in the middle thorax, larger lesion length, deeper invasion, later pathological stage, vascular infiltration, nerve infiltration, lymph node metastasis, cardiovascular disease, and higher smoking grade were risk factors for poor prognosis of esophageal squamous cell carcinoma (ESCC) (P<0.05). Cardiovascular disease, lower differentiation, tumor located in the middle thorax, and nerve infiltration were independent risk factors for the reduction of survival time of patients with ESCC (P<0.05). Conclusions: History of cardiovascular disease, tumor located in the middle chest, poorly differentiated esophageal squamous cell carcinoma, visible nerve cancer invasion, hematocrit (HCT), mean erythrocyte hemoglobin concentration (MCHC), and hemoglobin (HB) are independent risk factors for the long-term survival of patients with ESCC.

Security analysis of sports competition under the influence of covid-19 / Análise de segurança da competição esportiva sob a influência da covid-19 / Análisis de seguridad de la competición deportiva bajo la influencia del covid-19

ABSTRACT Introduction The continuous growth of COVID-19 has harmed sports competitions. Although the existing method of non-opening to spectators is very effective for preventing and controlling COVID-19, it will also seriously blow the sports economy's development. Objective Explore the safety of sports competition under the influence of COVID-19 to realize sports practice in a safe and regulated condition. Methods Firstly, the current public's willingness to participate in the competition was analyzed by questionnaire survey. Then, using the literature search method, this paper discusses the safety needs of sports competitions under the normalization of the prevention and control of COVID-19 in the research area at the present stage. Results By completely controlling the crowd shift rule and skillfully controlling the crowd pace, the transmission risk in the competition process can be effectively reduced. Conclusion The relevant departments and stadium managers should fully analyze the current epidemic prevention and control needs and strengthen spectator safety management in the study area in combination with regional characteristics and the actual spectator situation. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O crescimento contínuo da COVID-19 tem tido um impacto negativo sobre as competições esportivas. Embora o método existente de não-abertura aos espectadores seja muito eficaz para a prevenção e controle da COVID-19, ele também trará um sério golpe ao desenvolvimento da economia esportiva. Objetivo Explorar a segurança da competição esportiva sob a influência da COVID-19, de forma a realizar a prática esportiva em uma condição segura e regulamentada. Métodos Primeiramente, a disposição do público atual para participar da competição foi analisada por meio de pesquisa por questionário. Em seguida, utilizando o método de pesquisa bibliográfica, este trabalho discute as necessidades de segurança das competições esportivas sob a normalização da prevenção e controle da COVID-19 na área de pesquisa na presente fase. Resultados Controlando completamente a regra do deslocamento da multidão e controlando habilmente o ritmo da multidão, o risco de transmissão no processo de competição pode ser efetivamente reduzido. Conclusão Os departamentos e gerentes de estádios pertinentes devem analisar plenamente as necessidades atuais de prevenção e controle de epidemias e fortalecer a gestão da segurança dos espectadores na área de estudo em combinação com as características regionais e a situação real dos espectadores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El continuo crecimiento del COVID-19 ha tenido un impacto negativo en las competiciones deportivas. Aunque el método actual de no abrir para los espectadores es muy eficaz para la prevención y el control del COVID-19, también supondrá un duro golpe para el desarrollo de la economía deportiva. Objetivo Explorar la seguridad de la competición deportiva bajo la influencia del COVID-19, para llevar a cabo la práctica deportiva en condiciones seguras y reguladas. Métodos En primer lugar, se analizó la disposición del público actual a participar en el concurso mediante una encuesta por cuestionario. A continuación, utilizando el método de búsqueda bibliográfica, este trabajo analiza las necesidades de seguridad de las competiciones deportivas en el marco de la normalización de la prevención y el control del COVID-19 en el ámbito de la investigación en la etapa actual. Resultados Si se controla completamente la regla de desplazamiento de la multitud y se controla hábilmente el ritmo de la multitud, se puede reducir eficazmente el riesgo de transmisión en el proceso de competición. Conclusión Los departamentos competentes y los gestores de los estadios deben analizar a fondo las necesidades actuales de prevención y control de epidemias y reforzar la gestión de la seguridad de los espectadores en la zona de estudio en combinación con las características regionales y la situación real de los espectadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Optimization of extraction technology for couplet medicinals of Astragalus membranaceus-Puerariae lobata by multi-index comprehensive scoring method combined with orthogonal experiment / 中国药房

OBJECTIVE To optimize extraction technology of couplet medicinals of Astragalus membranaceus-Puerariae lobatae. METHODS With contents of puerarin，daidzin，calycosin-7-O-β-D-glucopyranoside，daidzein，calycosin and formononetin and the yield of dry extract as index，the analytic hierarchy method was used to determine the weight coefficient of each index and calculate the comprehensive score. The effects of solid-liquid ratio， extraction times and extraction time on the comprehensive score were investigated by single factor test. The level of each factor was determined. By multi-index comprehensive scoring method， using comprehensive scores of above 7 indexes as indexes，the extraction technology of couplet medicinals of A. membranaceus-P. lobata was optimized by orthogonal experiment，and the validation tests were conducted. RESULTS The weight coefficient for the contents of puerarin，daidzin，calycosin-7-O-β-D-glucopyranoside，daidzein，calycosin and formononetin and the yield of dry extract were respectively 0.304 7，0.065 2，0.185 8，0.185 8，0.107 8，0.107 8 and 0.042 7. The optimal extraction technology was determined as follows： solid-liquid of 1∶8（g/mL），extracting 3 times and for 1 h each time. RSD of each evaluation index in the validation test results was lower than 3.00% （n＝3）. CONCLUSIONS The optimized extraction technology for A. membranaceus-P. lobata is stable and feasible.