Laboratory tests and analysis of drug resistance in non-tuberculous mycobacteria.

Background: This study analyzed the laboratory diagnosis results and drug resistance of patients infected with non-tuberculous mycobacterium (NTM). Methods: We collected information on patients with positive indicators of NTM infection at the Henan Provincial Chest Hospital from 2020 to 2022. Acid-fast smear, mycobacterium culture, QB-SPOT assay, GeneXpert MTB/RIF assay, immunoglobulin E test, tuberculosis antibody test, and microplate method for drug sensitivity test were analyzed using strain identification as the gold standard. Results: The 242 cases of NTM infection were predominantly detected with slow-growing mycobacteria (a detection rate of 87.19%), among which Mycobacterium intracellulare (66.53%), Mycobacterium avium (15.70%), and Mycobacterium chelonei/abscessus complex (11.16%) ranked the top three in terms of the isolation rate. Males patients accounted for a higher proportion (58.26%) than females (41.74%), and the majority of them were over 60 years (50.83%). Among laboratory tests for patients with NTM infection, mycobacterium culture showed a highest detected rate (87.20%) among laboratory tests. The results of the drug sensitivity test demonstrated that the resistance rate of NTM was generally high. Moreover, the Mycobacterium avium complex with the highest isolation rate showed 100% resistant to doxycycline and minocycline, but exhibited relatively high sensitivity to moxifloxacin (a resistance rate of 7.89%) and rifabutin (a resistance rate of 13.16%). The Mycobacterium chelonei/abscessus complex was 100% resistant to doxycycline and relatively sensitive to cefoxitin (29.17%) and clarithromycin (37.50%). Conclusion: The NTM species isolated by the Henan Provincial Chest Hospital is dominated by Mycobacterium intracellulare and the highest positive rate is detected by mycobacterium culture among laboratory tests. NTM infection generally exhibits a high rate of drug resistance. Accordingly, the accurate diagnosis of NTM diseases requires enhanced drug sensitivity testing to provide patients with targeted combination drug treatment.

Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial.

STUDY QUESTION: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION: This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11-12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): -2.6%; 95% CI: -9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: -6.4%; 95% CI: -12.6% to -0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION: The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS: Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE: May 2018. DATE OF FIRST PATIENT'S ENROLMENT: November 2018.

Simultaneous determination of four active compounds in Centella asiatica by supramolecular solvent-based extraction coupled with high performance liquid chromatography-tandem mass spectrometry.

In the present study, a new and rapid method for determining four bioactive compounds of Centella asiatica (C. asiatica) in herbs was developed based on high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Supramolecular solvent (SUPRAS), formed by n-hexanol, tetrahydrofuran (THF) and water, was used for extracting madecassoside (MS), asiaticoside (AS), asiatic acid (AA) and madecassic acid (MA) from herbs. The sample was extracted with 4 mL of SUPRAS for 5 min. Then centrifugation was performed for phase separation followed by direct analysis by HPLC-MS/MS. Driving forces for the extraction of herbs in the SUPRAS involved both dispersion and hydrogen bond interactions. The effect of the parameters, including compounds of supramolecular solvents, dosage and vortex time, on the extraction efficiency was investigated. The recoveries were carried out at three levels with spiked samples and in the range of 91.6%-99.9%, with relative standard deviations between 1.7%-7.9%. The novel SUPRAS method, coupled with HPLC-MS/MS, was proved to be efficiency, green, and sensitive. It was applied for determination of four target compounds in herbs.

Exploring the influencing factors of unmet palliative care needs in Chinese patients with end-stage renal disease undergoing maintenance hemodialysis: a cross-sectional study.

BACKGROUND: The role of palliative care for end-stage renal disease (ESRD) patients have been proven in some developed countries, but it is still unclear in the mainland of China. In fact, patients with ESRD experience many unmet palliative care needs, such as physical, psychological, social and spiritual needs, but the factors influencing these needs have not investigated. METHODS: A cross-sectional study was conducted at two hemodialysis centers in the mainland of China from January to September 2022. Convenience sampling was used to collect data on the participants' socio-demographics, clinical characteristics, the Palliative Care Outcome Scale (POS), the Dialysis Symptom Index (DSI), the Karnofsky Performance Status Scale (KPS), the Patient Health Questionnaire-9 item (PHQ-9), and the Social Support Rate Scale (SSRS). Data were analyzed using latent profile analysis, Kruskal-Wallis test, one-way analysis of variance (ANOVA), the chi-square test and multinomial logistic regression analysis. RESULTS: Three hundred five participants were included in this study, and divided palliative care needs into three categories: Class 1, mild palliative care needs (n = 154, 50.5%); Class 2, moderate palliative care needs (n = 89, 29.2%); Class 3, severe palliative care needs (n = 62, 20.3%). Based on the analysis of three profiles, the influencing factors of unmet needs were further analyzed. Compared with Class 3, senior high school education, the household per capita monthly income < 2,000, low KPS scores, high PHQ-9 scores, and low SSRS scores were less likely to be in Class 1 (OR = 0.03, P = 0.012; OR = 0.003, P < 0.001; OR = 1.15, P < 0.001; OR = 0.55, P < 0.001; OR = 1.35, P = 0.002; respectively) and Class 2 (OR = 0.03, P = 0.007; OR = 0.05, P = 0.011; OR = 1.10, P = 0.001; OR = 0.60, P = 0.001; OR = 1.32, P = 0.003; respectively), and high symptom severity were less likely to be in Class 1 (OR = 0.82, P = 0.001). Moreover, compared with Class 1, the household per capita monthly income < 2,000 (OR = 16.41, P < 0.001), high symptom severity scores (OR = 1.12, P = 0.002) and low KPS scores (OR = 0.95, P = 0.002) were more likely to be in Class 2. CONCLUSIONS: This study showed that almost half of ESRD patients receiving MHD presented moderate to severe palliative care needs, and the unmet needs were mainly affected by education level, financial pressure, functional status, symptom burden and social support. In the future, it is important to identify the populations with the greatest need for palliative care and consider the influencing factors of unmet needs from a comprehensive perspective, so as to help them improve health-related quality of life.

Separation and identification of degradation impurities of esomeprazole sodium.

Drug impurities are important factors that affect drug safety and efficacy. The aim of this study is to separate and confirm the structure of two degradation impurities of esomeprazole sodium, designated X and Y. The impurities X and Y were successfully isolated using preparative HPLC by developing separation methods with the help of ACD/Labs AutoChrom software. There was a steady increase in X and Y impurities in forced esomeprazole sodium degradation. Impurity X was confirmed as 6-methoxy-1h-benzo[d]imidazole-2-yl-4-amino-3,5-dimethylpyridinecarboxylate and impurity Y as 6-methoxy-1h-benzo[d]imidazole-2-yl-4-hydroxy-3,5-dimethylpyridinecarboxylate using nuclear magnetic resonance spectrometry, infrared spectroscopy, and high-resolution mass spectrometry. These findings provide a comprehensive understanding of the impurity profile of esomeprazole sodium because these impurities are reported for the first time. Based on our results, active pharmaceutical ingredient manufacturers can further control process parameters to reduce impurity generation, and drug production manufacturers can optimize the packaging and storage conditions of esomeprazole sodium.

Flexible Wearable Sensors in Medical Monitoring.

The popularity of health concepts and the wave of digitalization have driven the innovation of sensors in the medical field. Such continual development has made sensors progress in the direction of safety, flexibility, and intelligence for continuous monitoring of vital signs, which holds considerable promise for changing the way humans live and even treat diseases. To this end, flexible wearable devices with high performance, such as high sensitivity, high stability, and excellent biodegradability, have attracted strong interest from scientists. Herein, a review of flexible wearable sensors for temperature, heart rate, human motion, respiratory rate, glucose, and pH is highlighted. In addition, engineering issues are also presented, focusing on material selection, sensor fabrication, and power supply. Finally, potential challenges facing current technology and future directions of wearable sensors are also discussed.

The value of Xpert MTB/RIF assay of urine samples in the early diagnosis of smear-negative urinary tuberculosis.

BACKGROUND: According to reports, between 30 and 40 percent of extrapulmonary tuberculosis (EPTB) cases are caused by urinary tract tuberculosis (UTB). It is critical to identify UTB quickly since it frequently precedes delayed medical attention, which can have detrimental effects. This study examined the use of Xpert MTB/RIF, a PCR test that can detect MTB as well as resistance to an important drug, rifampicin (RIF), in UTB particularly, for the early identification of UTB. METHODS: 180 participants with clinically presumptive UTB whose urine samples were chosen for urine sediment smear, culture, Xpert MTB/RIF, and TB-DNA testing at Henan Chest Hospital between January 2019 and July 2022. Evaluation of test performance using Composite Reference Standards (CRSs). We studied and compared the positivity rate for various tests using the t-test. The effectiveness of smear, culture, Xpert MTB/RIF, and TB-DNA was assessed using McNemar test. RESULTS: In this subject, a total of 108 participants were diagnosed with UTB, and the positivity rate was 67.1%. Compared with CRS, the positivity rate of Xpert MTB/RIF, smear, culture, and TB-DNA was 29.69% (19/64, P < 0.001), 7.56% (9/119, P < 0.1), 12.12% (4/33, P > 0.05), and 18.75% (6/32, P < 0.1), respectively. The sensitivity of Xpert MTB/RIF assay was significantly better than that of smear and culture tests (78.9% vs. 77.8%, P < 0.05; 78.9% vs. 75%, P < 0.05). Under CRS, the positivity rate for Xpert, culture, and TB-DNA was 31.6% (6/19, P < 0.1), 6.2% (1/16, P > 0.05), and 26.7% (4/15, P > 0.05) for TB-DNA, respectively, compared to smear negative. Xpert MTB/RIF assay specificity was significant for culture and TB-DNA (53.6% vs. 25%, P < 0.01; 53.6% vs. 38.9%, P < 0.05), and Xpert MTB/RIF assay FPV was significant for culture and TB-DNA (53.6% vs. 0%, P < 0.001; 53.6% vs. 0%, P < 0.001). CONCLUSION: Xpert MTB/RIF outperforms smear, cultures, and TB-DNA in detecting UTB, plus Xpert MTB/RIF is better suited for early diagnosis in smear-negative UTB.

Tumor Necrosis Factor Alpha Level in the Uterine Fluid of Patients with Polycystic Ovary Syndrome and Its Correlation with Clinical Parameters.

Objective: This study aimed to analyze tumor necrosis factor alpha (TNF-α) level in the uterine fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with the clinical parameters of PCOS. Methods: A total of 162 patients treated in the Reproductive Medicine Center of the General Hospital of Ningxia Medical University between December 2019 and November 2021 were enrolled as research subjects, including 80 patients with PCOS and 82 patients with other gynecological disease, who were used as the controls. The patients' general data, along with blood glucose, blood lipid, insulin, and sex hormone levels and other data, were collected. The TNF-α levels in the patients' serum and uterine fluid were detected using enzyme-linked immunosorbent assay. Results: Compared with the patients in the control group, the body mass index (BMI), anti-Müllerian hormone, luteinizing hormone, testosterone (T), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), and low-density lipoprotein (LDL) of patients with PCOS were higher, and high-density lipoprotein was lower (P < 0.05). The TNF-α levels in the serum and uterine fluid of patients with PCOS were higher than those in the control group (P < 0.01), and the TNF-α levels in the uterine fluid of these patients was significantly correlated with BMI, T, FINS, HOMA-IR, serum TNF-α, TG, and LDL (P < 0.05). Conclusion: There is local inflammation in the uterine cavity of patients with PCOS, and the detection of cytokines in uterine secretions may be a simple and feasible method of understanding the uterine microenvironment of patients with PCOS.

Palliative care needs and symptom burden in younger and older patients with end-stage renal disease undergoing maintenance hemodialysis: A cross-sectional study.

Objectives: To investigate the current situation of palliative care needs and the symptom burden in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD), and to explore whether there are differences between younger and older patients. Methods: This cross-sectional study was conducted in the hemodialysis centers of two tertiary hospitals from November 2021 to June 2022. Participants were selected by convenience sampling. Socio-demographics, clinical characteristics, the Palliative Care Outcome Scale (POS), the Dialysis Symptom Index (DSI), and health-related quality of life (EQ-5D-3L) were used for evaluation. Descriptive statistics, between-group comparisons, and correlation analysis were used to analyze the data. Results: A total of 236 patients were enrolled, including 118 younger and 118 older patients. The total median (P 25, P 75) POS score was 16.0 (12.0, 23.0), and the score was higher in older patients (P < 0.01). The mean total number of symptoms in MHD patients was 15.04 ± 5.06, and the overall median symptom severity score was 59.0 (52.0, 71.0); these scores were higher in the older group (P < 0.01). The most common symptom was dry mouth (91.5%), followed by itching (83.1%), and dry skin (82.2%). Additionally, palliative care needs were significantly associated with symptom burden and health-related quality of life (HRQOL). Conclusions: The results showed that patients with ESRD undergoing MHD have a significant symptom burden and moderate palliative care needs, which are more severe in older patients. Therefore, interdisciplinary teams should be formed to actively manage patients' symptoms and meet the physical, psychological, social, and spiritual needs related to palliative care to improve patients' HRQOL.

Clinical Value of Contrast-Enhanced Ultrasound in Breast Cancer Diagnosis.

Breast cancer (BC) ranks first in morbidity and mortality among female malignant tumors worldwide. This study is aimed at clarifying clinical value of contrast-enhanced ultrasound (CEUS) in the diagnosis and differentiation of BC. A total of 108 BC patients admitted to our hospital from January 2019 to December 2021 were enrolled. All patients underwent conventional color Doppler ultrasound and CEUS imaging examination. All ultrasound images were analyzed by a senior (5+ years) sonographer. The lesion location, echo, size, and color Doppler flow imaging (CDFI) blood flow distribution of benign and malignant BC were assessed. The transverse and longitudinal diameters of malignant BC presented significant elevation compared with the control group (P < 0.05). CEUS is more reliable than conventional ultrasound in the differentiation of benign and malignant breast lesions, and CEUS has the best reliability. The comparison of CEUS observation indicators between benign and malignant groups demonstrated that CEUS enhancement patterns (time and intensity) and morphological features (lesion boundary, shape, range, homogeneity, and filling defect) presented statistical significance (P < 0.01). Irregular shape and range expansion were high-specificity indicators (all >90.00%); fast-forward, high enhancement, clear boundary, and range expansion were high-sensitivity (all >90.00%); and fast-forward, high enhancement, and clear boundary were low-specificity indicators (all <50.00%); moderate sensitivity is as follows: homogeneous enhancement and range expansion (all >80.00%). The area under curve of CEUS (0.735 ± 0.053) presented elevation relative to conventional ultrasound (0.901 ± 0.024), with statistical significance (Z1 = 2.462, P < 0.05). Relative to conventional ultrasound, the specificity and positive predictive value of CEUS presented elevation (P < 0.05). In conclusion, in the differentiation of benign and malignant breast lesions, CEUS has better diagnostic accuracy and reliability than conventional ultrasound. The diagnostic advantages of CEUS are to elevate the diagnostic specificity and positive predictive value and reduce the misdiagnosis rate.

Corrigendum: Artesunate Suppresses Choroidal Melanoma Vasculogenic Mimicry Formation and Angiogenesis via the Wnt/CaMKII Signaling Axis.

[This corrects the article DOI: 10.3389/fonc.2021.714646.].

Evolution of the earthworm (Eisenia fetida) microbial community in vitro and in vivo under tetracycline stress.

Bioremediation of contaminated soil has received increasing attention, and the effects of antibiotic residues on the soil ecological environment are a current research hotspot. Earthworms are the first choice of soil organisms to indicate the degree of soil pollution, and their detoxification mechanism after antibiotic stress must be further explored. Taking Eisenia fetida as the research object, an antibiotic (tetracycline) stress test was carried out in sterile artificial soil. The stress concentrations were set at 0, 0.3, 3, 30, 300 and 600 mg/kg. The ECO method was used to cultivate microbes in earthworms and soil. The carbon source utilization intensity algorithm developed by our team was used for data statistics, and a factor analysis model was constructed to explore the succession process of microbes of earthworms in vivo and in vitro under tetracycline stress. The results showed that there were four processes in the evolution of microbes under short-term tetracycline stress: at 1-3 days, the microbes in worms played a leading role; at 4-5 days, the microbes in the worms and the soil microbes jointly resisted TET stress; after 6-8 days of stress, the microbes in worms still played the main role, but their role was weakened; and after 9-10 days, soil microbes played a leading role, and tolerant microbes appeared. Under long-term stress, the microbes of earthworms in vivo and in vitro were obvious different, and there may be no regulatory relationship. And the factor analysis model is suitable for the analyse of the changes in microbial communities in vivo and in vitro under TET stress. The research results provide a reference method and model basis for the bioremediation of antibiotic-contaminated soil and the study of earthworm detoxification mechanisms, and help agricultural development.

Dual VEGF/PDGF knockdown suppresses vasculogenic mimicry formation in choroidal melanoma cells via the Wnt5a/ß-catenin/AKT signaling pathway.

OBJECTIVE: This study aimed to explore the effects of knocking down both vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) on vasculogenic mimicry (VM) formation in choroidal melanoma (CM) cells. METHODS: Cell counting Kit (CCK)-8, monoclonal formation, wound healing, transwell and flow cytometry assays were used to observe the cell effects in CM cell line, ocular choroidal melanoma-1 cells (OCM-1) with respect to proliferation, migration, invasion and apoptosis. Three-dimensional (3D) cultures were also used to characterize VM tube structural effects in OCM-1 cells and western blotting was used to characterize protein expression changes in VM-related markers. RESULTS: Dual VEGF/PDGF knockdown suppressed cell proliferation, migration and invasion, but promoted cell apoptosis. It also reduced VM tube structures in OCM-1 cells. VM associated markers including, VE-cadherin, EphA2 and MT1-MMP were also down-regulated in OCM-1 cells. Similarly, Wnt5a, ß-catenin and phosphorylated-AKT levels were also down-regulated. Western blotting and 3D cultures further demonstrated that combined Wnt5a silencing with dual VEGF/PDGF knockdown significantly decreased VE-cadherin and EphA2 levels and reduced VM tube structures in OCM-1 cells. CONCLUSIONS: Dual VEGF/PDGF knockdown suppressed cell growth and metastasis in OCM-1 cells, and blocked the Wnt5a/ß-catenin/AKT signaling pathway thereby inhibiting VM formation.

Constructing a Novel Signature Based on Immune-Related lncRNA to Improve Prognosis Prediction of Cervical Squamous Cell Carcinoma Patients.

We downloaded gene expression data, clinical data, and somatic mutation data of cervical squamous cell carcinoma (CSCC) patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Predictive lncRNAs were screened using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and risk scores were calculated for each patient according to the expression levels of lncRNAs and regression coefficients to establish a risk model that could be a novel signature. We assessed the correlation between immune infiltration status, chemotherapeutics sensitivity, immune checkpoint proteins (ICP), and the signature. Therefore, we selected 11 immune-related lncRNAs (WWC2,AS2, STXBP5.AS1, ERICH6.AS1, USP30.AS1, LINC02073, RBAKDN, IL21R.AS1, LINC02078, DLEU1, LINC00426, BOLA3.AS1) to construct the risk model. Patients who were in the high-risk group had a shorter survival time than those in the low-risk group (p < 0.001). Risk scores in the signature were negatively correlated with macrophage M1, macrophage M2, and T cell CD8 + ; what's more, T cell CD8 + was higher in the low-risk group. The expression levels of ICP such as PD-L1, PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 were substantially higher in the low-risk group. For chemotherapeutic agents, high-risk scores were associated with higher half-inhibitory concentrations (IC50) of cisplatin. These findings suggested that the risk model can be a novel signature for predicting CSCC patients' prognosis, and it also can be used to formulate clinical treatment plans for CSCC patients.

Association of lncRNA H19 polymorphisms with cancer susceptibility: An updated meta-analysis based on 53 studies.

The association between polymorphisms in lncRNA H19 and cancer susceptibility remains to be inconsistent. This study aimed to provide a more precise estimation of the relationship between lncRNA H19 polymorphisms and the risk of cancer based on all available published studies. 53 studies encompassing 32,376 cases and 43,659 controls were included in our meta-analysis by searching the Pubmed, Embase, Web of Science, WanFang, and China National Knowledge Infrastructure databases. Pooled ORs and their 95% CIs were used to estimate the strength between the SNPs in H19 (rs217727, rs2839698, rs2107425, rs3024270, rs2735971, rs3741216, and rs3741219) and cancer susceptibility. The results showed that H19 rs2839698 polymorphism was associated with increased cancer risk in all participants under three genetic models. However, no significant association was identified between the other six SNPs as well as an overall cancer risk. Stratification by ethnicity showed that rs2839698 mutation indicated to be an important hazardous factor for the Asian population. While rs2107425 mutation had a protective effect on the Caucasian population. Stratification by cancer type identified that rs217727 mutation was linked to increased susceptibility to oral squamous cell carcinoma, lung cancer, and hepatocellular carcinoma; whereas rs2839698 mutation was associated with an elevated risk of hematological tumor and digestive system tumor (p < 0.05). Besides, the rs2735971 mutation was connected with the digestive system tumor. In summary, the rs217727, rs2839698, rs2107425 and rs2735971 polymorphisms in H19 have associations with cancer susceptibility.

Artesunate Suppresses Choroidal Melanoma Vasculogenic Mimicry Formation and Angiogenesis via the Wnt/CaMKII Signaling Axis.

Angiogenesis and vasculogenic mimicry (VM) are considered to be the main processes to ensure tumor blood supply during the proliferation and metastasis of choroidal melanoma (CM). The traditional antimalarial drug artesunate (ART) has some potential anti-CM effects; however, the underlying mechanisms remain unclarified. Recent studies have shown that the Wnt5a/calmodulin-dependent kinase II (CaMKII) signaling pathway has a close correlation with angiogenesis and VM formation. This study demonstrated that ART eliminated VM formation by inhibiting the aforementioned signaling pathway in CM cells. The microvessel sprouting of the mouse aortic rings and the microvessel density of chicken chorioallantoic membrane (CAM) decreased significantly after ART treatment. VM formation assay and periodic acid schiff (PAS) staining revealed that ART inhibited VM formation in CM. Moreover, ART downregulated the expression levels of the angiogenesis-related proteins vascular endothelial growth factor receptor (VEGFR) 2, platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor (VEGF) A, and VM-related proteins ephrin type-A receptor (EphA) 2 and vascular endothelial (VE)-cadherin. The expression of hypoxia-inducible factor (HIF)-1α, Wnt5a, and phosphorylated CaMKII was also downregulated after ART treatment. In addition, we further demonstrated that ART inhibited the proliferation, migration, and invasion of OCM-1 and C918 cells. Collectively, our results suggested that ART inhibited angiogenesis and VM formation of choroidal melanoma likely by regulating the Wnt5a/CaMKII signaling pathway. These findings further supported the feasibility of ART for cancer therapy.

Structural characteristics and proximity comparison of China's urban innovation cooperation network.

How to promote and improve the level of urban innovation cooperation is a major issue in China's current high-quality economic development. Thus, enhancing innovation ability is essential to achieving high-quality economic growth under the "new normal". Based on the data of Chinese invention patents from 1985 to 2017, this paper analyzes the characteristics of China's urban innovation cooperation network and the different roles of proximity by using social network analysis and exploratory spatial data analysis methods. The analysis results show that: (1) On the whole, the development of China's urban innovation cooperation network is characterized by stages (initial development stage, rapid development stage, and gradual decline stage); The urban innovation cooperation network has strong connectivity and centripetal concentration but its imbalance needs to be further improved; The degree of urban participation has gradually increased, consolidating the stability of the network structure. (2) The centrality of urban innovation cooperation network has obvious characteristics of administrative center orientation, coastal areas orientation, and 'strong east and weak west'; Beijing is the center and bridge of the network, and the network flattening characteristics are obvious; A hierarchical 'core-edge' structure is gradually formed for the urban innovation cooperation network, and the pyramid structure with Beijing standing at the top is being consolidated. (3) The geographical proximity presents a significant global spatial positive correlation, while the network proximity and pure network proximity have a more significant global spatial negative correlation; The local spatial autocorrelation of China's urban innovation cooperation system based on network proximity is more obvious and identifiable than that based on the geographical proximity, which better reflects the new development model of "relationship economy".

Collaborative multicenter logistics delivery network optimization with resource sharing.

Collaboration among logistics facilities in a multicenter logistics delivery network can significantly improve the utilization of logistics resources through resource sharing including logistics facilities, vehicles, and customer services. This study proposes and tests different resource sharing schemes to solve the optimization problem of a collaborative multicenter logistics delivery network based on resource sharing (CMCLDN-RS). The CMCLDN-RS problem aims to establish a collaborative mechanism of allocating logistics resources in a manner that improves the operational efficiency of a logistics network. A bi-objective optimization model is proposed with consideration of various resource sharing schemes in multiple service periods to minimize the total cost and number of vehicles. An adaptive grid particle swarm optimization (AGPSO) algorithm based on customer clustering is devised to solve the CMCLDN-RS problem and find Pareto optimal solutions. An effective elite iteration and selective endowment mechanism is designed for the algorithm to combine global and local search to improve search capabilities. The solution of CMCLDN-RS guarantees that cost savings are fairly allocated to the collaborative participants through a suitable profit allocation model. Compared with the computation performance of the existing nondominated sorting genetic algorithm-II and multi-objective evolutionary algorithm, AGPSO is more computationally efficient. An empirical case study in Chengdu, China suggests that the proposed collaborative mechanism with resource sharing can effectively reduce total operational costs and number of vehicles, thereby enhancing the operational efficiency of the logistics network.

Integrated analysis of key microRNAs /TFs /mRNAs/ in HPV-positive cervical cancer based on microRNA sequencing and bioinformatics analysis.

BACKGROUND: Cervical squamous cell carcinoma (CESC) is one of the most common malignancies associated with mortality in females. Its onset and prognosis are primarily concerned with persistent infection with high-risk types of human papillomavirus (HPV). However, the molecular mechanisms of HPV-positive CESC remain unclear. METHODS: In this study, we conducted a high-throughput sequencing to identify differentially expressed miRNAs (DEMs). Besides, three series were selected from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Then the miRNA-TF-gene regulatory network was constructed using bioinformatic methods. Genes in the network were performed functional enrichment analysis and protein-protein interaction (PPI) network analysis. Ultimately, the expression levels of six key miRNAs, TFs, and mRNAs were validated by 20 HPV-positive CESC tissues and 15 normal cervical samples. RESULTS: A total of 52 DEMs and 300 DEGs differed between the HPV-positive CESC and normal cervical samples. Then the miRNA-TF-gene regulatory network was constructed consisting of 22 miRNAs, 6 TFs, and 76 corresponding genes, among which miR-149-5p, miRNA-1248 and E2F4 acted as key regulators. PPI network analysis showed that ten genes including TOP2A, AURKA, CHEK1, KIF11, MCM4, MKI67, DTL, FOXM1, SMC4, and FBXO5 were recognized as hub genes with the highest connectivity degrees. Besides, five key molecules miRNA-149-5p, E2F4, KIF11, DTL, and SMC4 were suggested to play crucial roles in the development of HPV-positive CESC. CONCLUSION: These results present a unique insight into the pathological mechanisms of HPV-positive CESC and possibly provides potential therapeutic targets.

The percentage of cells with 17p deletion and the size of 17p deletion subclones show prognostic significance in chronic lymphocytic leukemia.

TP53 disruption is considered to be the most important prognostic factor in chronic lymphocytic leukemia (CLL), but not all patients with TP53 disruption have similar dismal outcomes. We evaluated the prognostic value of TP53 disruption in CLL patients without treatment indications. Data of 305 CLL patients were analyzed. 41 of them (13%) had TP53 disruption. Patients with lower percentage of cells with del(17p) had significantly better survival. Patients with mutated IGHV, ß2-microglobulin ≤3.5 mg/L, wild-type TP53, age ≤65 years or without complex karyotype (CK) had relatively favorable outcomes in the del(17p) group. Furthermore, patients with del(17p) as a minor clone showed survival advantage compared with those with del(17p) as a major clone. These data suggest that the percentage of cells with del(17p), the size of the del(17p) subclone, CLL International Prognostic Index, and CK should be considered to build refined prognostication models for patients with TP53 disruption.