The value of 18 F-FDG PET/CT quantitative indexes in the diagnosis of nondestructive posttransplant lymphoproliferative disorders after pediatric liver transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication after pediatric liver transplantation (pLT), which may lead to death. 18 F-FDG PET/CT is rarely considered in PTLD after pLT and lacks clear diagnostic guidelines, especially in the differential diagnosis of nondestructive PTLD. The aim of this study was to find a quantifiable 18 F-FDG PET/CT index to identify nondestructive PTLD after pLT. METHODS: This retrospective study collected the data of patients who underwent pLT, postoperative lymph node biopsy, and 18 F-FDG PET/CT at Tianjin First Central Hospital from January 2014 to December 2021. Quantitative indexes were established using lymph node morphology and the maximum standardized uptake value (SUVmax). RESULTS: A total of 83 patients met the inclusion criteria and were included in this retrospective study. To distinguish between PTLD-negative cases and nondestructive PTLD cases, according to the receiver operating characteristic curve, (the shortest diameter of the lymph node at the biopsy site [SDL]/the longest diameter of the lymph node at the biopsy site [LDL])*(SUVmax at the biopsy site [SUVmaxBio]/SUVmax of the tonsils [SUVmaxTon]) had the maximum area under the curve (0.923; 95% confidence interval: 0.834-1.000), and the cutoff value was 0.264 according to the maximum value of Youden's index. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93.6%, 94.7%, 97.8%, 85.7%, and 93.9%, respectively. CONCLUSIONS: (SDL/LDL)*(SUVmaxBio/SUVmaxTon) has good sensitivity, specificity, positive predictive and negative predictive values, and accuracy, and can be used as a good quantitative index for the diagnosis of nondestructive PTLD.

Linc-RAM is a metabolic regulator maintaining whole-body energy homeostasis in mice.

Long noncoding RNAs (lncRNAs) are known to have profound functions in regulating cell fate specification, cell differentiation, organogenesis, and disease, but their physiological roles in controlling cellular metabolism and whole-body metabolic homeostasis are less well understood. We previously identified a skeletal muscle-specific long intergenic noncoding RNA (linc-RNA) activator of myogenesis, Linc-RAM, which enhances muscle cell differentiation during development and regeneration. Here, we report that Linc-RAM exerts a physiological function in regulating skeletal muscle metabolism and the basal metabolic rate to maintain whole-body metabolic homeostasis. We first demonstrate that Linc-RAM is preferentially expressed in type-II enriched glycolytic myofibers, in which its level is more than 60-fold higher compared to that in differentiated myotubes. Consistently, genetic deletion of the Linc-RAM gene in mice increases the expression levels of genes encoding oxidative fiber versions of myosin heavy chains and decreases those of genes encoding rate-limiting enzymes for glycolytic metabolism. Physiologically, Linc-RAM-knockout mice exhibit a higher basal metabolic rate, elevated insulin sensitivity and reduced fat deposition compared to their wild-type littermates. Together, our findings indicate that Linc-RAM is a metabolic regulator of skeletal muscle metabolism and may represent a potential pharmaceutical target for preventing and/or treating metabolic diseases, including obesity.

Enzyme production and oil palm empty fruit bunch bioconversion to ethanol using a hybrid yeast strain.

Oil palm empty fruit bunch (OPEFB) is a lignocellulosic biomass generated in palm oil mills. It is a sustainable resource for fuels and chemicals. In this study, OPEFB was converted to ethanol by an integrative OPEFB conversion process including dilute alkaline pretreatment, cellulolytic enzyme production, separate OPEFB hydrolysis, and cofermentation using a hybrid xylose-fermenting yeast. OPEFB was pretreated using 1% (w/v) NaOH solution followed by 1% (v/v) H2 O2 . Further, cellulolytic enzymes were produced by submerged fermentation using Trichoderma reesei Rut C30 and used for OPEFB hydrolysis. The filter paper cellulase activity of the crude cellulolytic enzymes was 15.1 IU/mL, which was higher than those obtained by reported Trichoderma strains under laboratory conditions. Glucose and xylose yields reached 66.9% and 74.2%, respectively, at 30 filter paper unit (FPU)/g-biomass enzyme dosage and 10% (w/v) biomass loading. The hybrid yeast strain ScF2 was previously constructed through recursive genome shuffling of Pichia stipitis and Saccharomyces cerevisiae and was used in OPEFB hydrolysate fermentation. About 16.9 g/L ethanol was produced with an ethanol yield of 0.34 g/g sugars, which was 67% of theoretical ethanol yield.

Platelets Express Activated P2Y12 Receptor in Patients With Diabetes Mellitus.

BACKGROUND: Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood. METHODS: We measured P2Y12 expression on platelets from patients with type 2 diabetes mellitus and on platelets from rats with diabetes mellitus. We also assayed platelet P2Y12 activation by measuring cAMP and VASP phosphorylation. The antiplatelet and antithrombotic effects of AR-C78511 and cangrelor were compared in rats. Finally, we explored the role of the nuclear factor-κB pathway in regulating P2Y12 receptor expression in megakaryocytes. RESULTS: Platelet P2Y12 levels are 4-fold higher in patients with type 2 diabetes mellitus compared with healthy subjects. P2Y12 expression correlates with ADP-induced platelet aggregation (r=0.89, P<0.01). P2Y12 in platelets from patients with diabetes mellitus is constitutively activated. Although both AR-C78511, a potent P2Y12 inverse agonist, and cangrelor have similar antiplatelet efficacy on platelets from healthy subjects, AR-C78511 exhibits more powerful antiplatelet effects on diabetic platelets than cangrelor (aggregation ratio 36±3% versus 49±5%, respectively, P<0.05). Using a FeCl3-injury mesenteric arteriole thrombosis model in rats and an arteriovenous shunt thrombosis model in rats, we found that the inverse agonist AR-C78511 has greater antithrombotic effects on GK rats with diabetes mellitus than cangrelor (thrombus weight 4.9±0.3 mg versus 8.3±0.4 mg, respectively, P<0.01). We also found that a pathway involving high glucose-reactive oxygen species-nuclear factor-κB increases platelet P2Y12 receptor expression in diabetes mellitus. CONCLUSIONS: Platelet P2Y12 receptor expression is significantly increased and the receptor is constitutively activated in patients with type 2 diabetes mellitus, which contributes to platelet hyperactivity and limits antiplatelet drug efficacy in type 2 diabetes mellitus.

Nucleotide-binding oligomerization domain 2 receptor is expressed in platelets and enhances platelet activation and thrombosis.

BACKGROUND: Pattern recognition receptor nucleotide-binding oligomerization domain 2 (NOD2) is well investigated in immunity, but its expression and function in platelets has never been explored. METHOD AND RESULTS: Using reverse transcription polymerase chain reaction and Western blot, we show that both human and mouse platelets express NOD2, and its agonist muramyl dipeptide induced NOD2 activation as evidenced by receptor dimerization. NOD2 activation potentiates platelet aggregation and secretion induced by low concentrations of thrombin or collagen, and clot retraction, as well. These potentiating effects of muramyl dipeptide were not seen in platelets from NOD2-deficient mice. Plasma from septic patients also potentiates platelet aggregation induced by thrombin or collagen NOD2 dependently. Using intravital microscopy, we found that muramyl dipeptide administration accelerated in vivo thrombosis in a FeCl3-injured mesenteric arteriole thrombosis mouse model. Platelet depletion and transfusion experiments confirmed that NOD2 from platelets contributes to the in vivo thrombosis in mice. NOD2 activation also accelerates platelet-dependent hemostasis. We further found that platelets express receptor-interacting protein 2, and provided evidence suggesting that mitogen activated-protein kinase and nitric oxide/soluble guanylyl cyclase/cGMP/protein kinase G pathways downstream of receptor-interacting protein mediate the role of NOD2 in platelets. Finally, muramyl dipeptide stimulates proinflammatory cytokine interleukin-1ß maturation and accumulation in human and mouse platelets NOD2 dependently. CONCLUSIONS: NOD2 is expressed in platelets and functions in platelet activation and arterial thrombosis, possibly during infection. To our knowledge, this is the first study on NOD-like receptors in platelets that link thrombotic events to inflammation.

DL-3-n-butylphthalide inhibits platelet activation via inhibition of cPLA2-mediated TXA2 synthesis and phosphodiesterase.

Aberrant platelet activation plays a critical role in the pathogenesis of heart attack and stroke. DL-3-n-butylphthalide (NBP) has been approved in China to treat stroke with multiple mechanisms. The anti-stroke effects of NBP may be related to its antiplatelet effects reported in rats in addition to its antioxidative, antiapoptotic, and angiogenic effects. However, the effects and the underlying mechanisms of NBP on human platelets are not yet clear. In this study, we found that NBP concentration-dependently inhibited human platelet aggregation and ATP release induced by ADP, thrombin, U46619, arachidonic acid, or collagen. NBP also inhibited PAC-1 binding induced by ADP or thrombin and platelet spreading on immobilized fibrinogen. NBP reduced TXA2 synthesis induced by thrombin or collagen via inhibiting cPLA2 phosphorylation, concomitantly with a marked decrease in intracellular calcium mobilization. Moreover, NBP also inhibited human platelet phosphodiesterase (PDE) and elevated 3,5-cyclic adenosine monophosphate level in platelets. In conclusion, NBP significantly inhibits human platelet activation via inhibition of cPLA2-mediated TXA2 synthesis and PDE, and may be effective as an antiplatelet drug to treat other arterial thrombotic diseases.

Response of solar-induced chlorophyll fluorescence-based spatial and temporal evolution of vegetation in Xinjiang to multiscale drought.

Climate change and human activities have increased droughts, especially overgrazing and deforestation, which seriously threaten the balance of terrestrial ecosystems. The ecological carrying capacity and vegetation cover in the arid zone of Xinjiang, China, are generally low, necessitating research on vegetation response to drought in such arid regions. In this study, we analyzed the spatial and temporal characteristics of drought in Xinjiang from 2001 to 2020 and revealed the response mechanism of SIF to multi-timescale drought in different vegetation types using standardized precipitation evapotranspiration index (SPEI), solar-induced chlorophyll fluorescence (SIF), normalized difference vegetation index (NDVI), and enhanced vegetation index (EVI) data. We employed trend analysis, standardized anomaly index (SAI), Pearson correlation, and trend prediction techniques. Our investigation focused on the correlations between GOSIF (a new SIF product based on the Global Orbital Carbon Observatory-2), NDVI, and EVI with SPEI12 for different vegetation types over the past two decades. Additionally, we examined the sensitivities of vegetation GOSIF to various scales of SPEI in a typical drought year and predicted future drought trends in Xinjiang. The results revealed that the spatial distribution characteristics of GOSIF, normalized difference vegetation index (NDVI), and enhanced vegetation index (EVI) were consistent, with mean correlations with SPEI at 0.197, 0.156, and 0.128, respectively. GOSIF exhibited the strongest correlation with SPEI, reflecting the impact of drought stress on vegetation photosynthesis. Therefore, GOSIF proves advantageous for drought monitoring purposes. Most vegetation types showed a robust response of GOSIF to SPEI at a 9-month scale during a typical drought year, with grassland GOSIF being particularly sensitive to drought. Our trend predictions indicate a decreasing trend in GOSIF vegetation in Xinjiang, coupled with an increasing trend in drought. This study found that compared with that of the traditional greenness vegetation index, GOSIF has obvious advantages in monitoring drought in the arid zone of Xinjiang. Furthermore, it makes up for the lack of research on the mechanism of vegetation GOSIF response to drought on multiple timescales in the arid zone. These results provide strong theoretical support for investigating the monitoring, assessment, and prediction of vegetation response to drought in Xinjiang, which is vital for comprehending the mechanisms of carbon and water cycles in terrestrial ecosystems.

LncRNA ZFAS1 promotes invasion of medullary thyroid carcinoma by enhancing EPAS1 expression via miR-214-3p/UCHL1 axis.

lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual-fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR-214-3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR-214-3p/UCHL1 axis.

Clinical evaluation of a real-time PCR assay for diagnosis of Helicobacter pylori infection and antibiotic resistance.

OBJECTIVES: Helicobacter pylori (H. pylori) is a globally prevalent bacterium that increases the risk of developing various gastrointestinal diseases, including gastric adenocarcinoma. This study aimed to evaluate the performances of real-time PCR assay in detecting H. pylori infection, as well as clarithromycin and levofloxacin resistance, in both stool and gastric biopsy specimens. METHODS: Stool and gastric biopsy specimens were collected from patients within one to three days post-hospitalization. All patients were analyzed for H. pylori infection and resistance to clarithromycin and levofloxacin using a real-time PCR based molecular assay. RESULTS: 169 patients (83 males) with a mean age of 43.6±13.1 years were included in the study. The prevalence of H. pylori was 89.9% (152/169) in stool and 90.5% (153/169) in gastric biopsy samples. The molecular diagnostics employed in this study exhibited a sensitivity of 99.3% and a specificity of 100%, resulting in a diagnostic accuracy rate of 99.6%. Resistance to clarithromycin was 36.1% (61/169) in stool and 44.4% (75/169) in gastric biopsy samples. The molecular tests for clarithromycin resistance demonstrated a sensitivity of 96.8% and a specificity of 86.8%, with an overall diagnostic accuracy of 90.5%. Furthermore, resistance to levofloxacin was 22.5% (38/169) and 26.6% (45/169) in stool and gastric biopsy samples, respectively. The molecular test demonstrated a sensitivity of 80.9% and a specificity of 94.3%, resulting in a diagnostic accuracy of 90.5%. CONCLUSION: The implementation of real-time PCR-based screening for H. pylori infection and resistance to clarithromycin and levofloxacin in the stool may enhance the success rate of eradication therapy.

Optogenetic Stimulation of mPFC Alleviates White Matter Injury-Related Cognitive Decline after Chronic Ischemia through Adaptive Myelination.

White matter injury (WMI), which reflects myelin loss, contributes to cognitive decline or dementia caused by cerebral vascular diseases. However, because pharmacological agents specifically for WMI are lacking, novel therapeutic strategies need to be explored. It is recently found that adaptive myelination is required for homeostatic control of brain functions. In this study, adaptive myelination-related strategies are applied to explore the treatment for ischemic WMI-related cognitive dysfunction. Here, bilateral carotid artery stenosis (BCAS) is used to model ischemic WMI-related cognitive impairment and uncover that optogenetic and chemogenetic activation of glutamatergic neurons in the medial prefrontal cortex (mPFC) promote the differentiation of oligodendrocyte precursor cells (OPCs) in the corpus callosum, leading to improvements in myelin repair and working memory. Mechanistically, these neuromodulatory techniques exert a therapeutic effect by inducing the secretion of Wnt2 from activated neuronal axons, which acts on oligodendrocyte precursor cells and drives oligodendrogenesis and myelination. Thus, this study suggests that neuromodulation is a promising strategy for directing myelin repair and cognitive recovery through adaptive myelination in the context of ischemic WMI.

Efficacy and safety of high-dose ilaprazole-amoxicillin dual therapy for Helicobacter pylori eradication: a prospective, single-center, randomized trial.

Background: Until now, there have been no randomized controlled trials directly evaluating the efficacy of high-dose ilaprazole-amoxicillin dual therapy (HT) in comparison to other standard treatments for H. pylori (Helicobacter pylori) infection. This study aimed to compare the effectiveness and safety of HT with bismuth quadruple therapy (BQT) as an initial treatment for H. pylori. Methods: This single-center, prospective, randomized clinical controlled trial recruited 225 consecutive patients. They were assigned to either HT group (ilaprazole, 10 mg, twice daily; amoxicillin 1,000 mg, three times daily) or BQT group (compound bismuth aluminate granules, 2.6 g, three times daily; ilaprazole, 5 mg, twice daily; amoxicillin, 1,000 mg, twice daily; clarithromycin, 500 mg, twice daily) for 14 days. The 13C-urea breath test assessed eradication success 4 weeks after treatment. The primary outcome focused on the eradication rate, with secondary outcomes including safety and compliance. Results: From February 2023 to March 2023, 228 subjects were screened, and 225 were randomized. The HT and BQT groups showed eradication rates of 76.3% and 61.3% (p = 0.015) both by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. HT was associated with fewer adverse events than BQT (27.2% vs. 81.8%, p = 0.002). The most commonly reported adverse events was bitter taste of mouth (3.5% vs. 60.4%, p < 0.001). There was no significant difference in compliance between the two groups (89.5% vs. 92.8%, p = 0.264). Conclusion: The 14-day HT treatment demonstrates better efficacy in H. pylori eradication treatment and improved safety and compliance compared to BQT. The results provide supporting evidence for 14-day HT can be potentially considered as a first-line regimen for empirical treatment. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=186562, identifier ChiCTR2200066284.

Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast.

Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n = 22) and IDC-NSTs (n = 24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues.

Linc-RAM promotes muscle cell differentiation via regulating glycogen phosphorylase activity.

Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes, especially skeletal muscle cell differentiation. Most of the lncRNAs identified to date are localized in the nucleus and play regulatory roles in gene expression. The cytoplasmic lncRNAs are less well understood. We previously identified a long intergenic non-coding RNA (linc-RNA) activator of myogenesis (Linc-RAM) that directly binds MyoD in the nucleus to enhance muscle cell differentiation. Here, we report that a substantial fraction of Linc-RAM is localized in the cytoplasm of muscle cells. To explore the molecular functions of cytoplasmic Linc-RAM, we sought to identify Linc-RAM-binding proteins. We report here that Linc-RAM physically interacts with glycogen phosphorylase (PYGM) in the cytoplasm. Knockdown of PYGM significantly attenuates the function of Linc-RAM in promoting muscle cell differentiation. Loss-of-function and gain-of function assays demonstrated that PYGM enhances muscle cell differentiation in an enzymatic activity-dependent manner. Finally, we show that the interaction between Linc-RAM and PYGM positively regulates the enzymatic activity of PYGM in muscle cells. Collectively, our findings unveil a molecular mechanism through which cytoplasmic Linc-RAM contributes to muscle cell differentiation by regulating PYGM activity. Our findings establish that there is crosstalk between lncRNAs and cellular metabolism during myogenic cell differentiation.

Population Pharmacodynamic Analyses of Human Anti-Rabies Virus Monoclonal Antibody (Ormutivimab) in Healthy Adult Subjects.

Ormutivimab is the first recombinant human anti-rabies monoclonal antibody (rhRIG) approved for clinical application in China. In this study, a population pharmacodynamic (PPD) model was established to compare the neutralizing antibody activities of Ormutivimab and human rabies immunoglobulin (HRIG), alone or combined with human rabies vaccine (Vero), in a phase II clinical trial, and to recommend a target dose for the phase III trial. The model was verified to fit the PPD data well. The stability of the model was verified by the bootstrap method. The level of neutralizing antibodies in vivo increased rapidly after administration of Ormutivimab or HRIG. Neutralizing antibodies with a strong activity were produced at 7 days (Ormutivimab + vaccine) or 10 days (HRIG + vaccine) after induction by the vaccine in vivo. Compared to that induced by HRIG + vaccine, the level of the neutralizing antibodies induced by Ormutivimab + vaccine peaked higher and faster. The levels of neutralizing antibodies induced by Ormutivimab + vaccine and HRIG + vaccine were similar within 21 days after administration. According to these results and the safety data, 20 IU·kg-1 was recommended as the target dose in the confirmatory study of Ormutivimab. Registration: ClinicalTrials.gov #NCT02559921.

Efficacy of ormutivimab, a novel recombinant human anti-rabies monoclonal antibody, in post-exposure prophylaxis animal models.

Human rabies is a serious public health problem that can't be ignored. Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP). However, current PEP relies on RIG purified from pooled human or equine plasma, which are either in chronic shortage or associated with safety concerns. Monoclonal antibodies have become widely accepted as safer and more cost-effective alternatives to RIG products in recent years. Here, we assessed the neutralization breadth of human monoclonal antibody ormutivimab and its protective efficacy in PEP models. Ormutivimab was able to neutralize a broad panel of Chinese prevalent street RABVs with neutralizing potency form 198-1487.6 IU/mL. Furthermore, ormutivimab offered comparable protection to that with HRIG both at standard doses (20 IU/kg) and higher doses (100 IU/kg and 200 IU/kg). The interference of ormutivimab on vaccine potency was also analyzed and found slightly reduced neutralizing antibody titers similar to HRIG. The broad-spectrum neutralization activities, highly protective potency, and rapid onset of action make ormutivimab an effective candidate for human rabies PEP.

Impact of big data analytics on sales performance in pharmaceutical organizations: The role of customer relationship management capabilities.

In this era of technology development, every business wants to equip its salesforce with a sustainable salesforce automation system to improve sales performance and customer relationship management (CRM) capabilities. This study investigates the impact of big data analytics (BDA) on CRM capabilities and the sales performance of pharmaceutical organizations. A research model was tested based on 416 valid responses collected from pharmaceutical companies through a structured questionnaire. Structural equation modeling (SEM) was employed using Smart-PLS3 to confirm the contribution of BDA to improving CRM capabilities and sales performance. The study finds that individual characteristics such as self-efficacy, playfulness, and social norms, along with organizational characteristics such as voluntariness, user involvement, user participation, and management support, are positive predictors of salesforce perception of BDA. This positive perception of BDA increased the person-technology fit in the salesforce, which ultimately increased the CRM capabilities and sales performance.

Overexpressed versican promoted cell multiplication, migration and invasion in gastric cancer.

Versican (VCAN) is verified to promote development among many cancers, whose function on gastric cancer (GC) is less studied. This work explored the effect of VCNA on GC. The differentially expressed VCAN between tumor and normal samples, among different cancer stages and the overall survival of GC patients with high and low VCAN levels were predicted through Gene Expression Profiling Interactive Analysis 2 (GEPIA2). The association between VCAN and clinicopathological parameters was analyzed by clinical investigation. AGS and NCI-N87 cells were transfected with VCAN short hairpin RNA (shVCAN) and VCAN overexpression plasmid. The VCNA, Cyclin D1, Cyclin E, E-Cadherin, N-Cadherin and Vimentin expression was detected through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Cell viability was assessed through MTT assay. Cell migration was measured by wound healing assay and cell invasion was evaluated through Transwell assay. Cell cycle was determined by flow cytometry assay. VCAN was upregulated in GC and its high expression related to advanced TNM stage, Lymph node metastasis, Depth of invasion and Grade. VCAN knockdown inhibited multiplication, migration, invasion, Cyclin D1, Cyclin E, N-Cadherin and Vimentin expression while induced cycle arrest and E-Cadherin level of GC cells, whereas overexpressed VCAN showed opposite results. VCAN had a potential to be a biomarker for GC and overexpressed VCAN promoted GC cell multiplication, migration and invasion.

The self-psychological safety maintenance and its influencing factors of community frontline staff during COVID-19 pandemic.

ABSTRACT: The present study was designed to determine the self-psychological safety maintenance and its influencing factors of community staff on the front-line during Coronavirus Disease 2019 (COVID-19) pandemic.A total of 126 frontline staff in community were involved in the current cross-section study. Online questionnaires including the anxiety sensitivity index-3 (ASI-3), patient health questionnaire (PHQ-9), simple coping style questionnaire (SCSQ) and general self-efficacy scale (GSES) were utilized to analyze psychological state, coping style and self-efficacy of the surveyed staff.The ASI-3 standard score of 126 community frontline staff was 10.01 ±â€Š2.82, of which 21 community frontline staff scored > 16, and the detection rate of anxiety was 16.67%. The anxiety state of doctors and nursing staff was significantly lower than that of administrative staff, logistics staff and other staff, and the rate of anxiety of having colleagues with suspected symptoms was significantly higher than that without colleagues with suspected symptoms (P < .05). The PHQ-9 standard score was 2.03 ±â€Š0.16, of which 19 frontline staff in the community scored more than 5, and the detection rate of depression was 15.08%. Among them, the depression state of those with bachelor degree or above was significantly lower than that of those with junior college education, and the rate of depressive symptoms of community frontline staff with colleagues harboring suspected symptoms were significantly higher than those without colleagues with suspected symptoms (P < .05). The aggregated results showed that most of the community frontline staff in anxiety state group and depression group adopted negative coping style while most of the community frontline staff in the non-anxiety group and the non-depression group adopted positive coping style (P < .05). Additionally, lower score of self-efficacy of the community frontline staff was observed in the anxiety state group and the depression state group (P < .05).During the outbreak of COVID-19, several community frontline staff showed negative psychology of anxiety and depression, which could affect their coping style and self-efficacy. Early and effective psychological safety maintenance was required to alleviate the negative psychology of community frontline staff.

Downregulation of lncRNA ZFAS1 inhibits the hallmarks of thyroid carcinoma via the regulation of miR­302­3p on cyclin D1.

At present, treatment options for thyroid carcinoma remain limited. The present study aimed to investigate the role of ZFAS1 in various major hallmarks of cancer and the underlying mechanisms in thyroid carcinoma cells. The interactions between long non­coding RNAs (lncRNAs), microRNAs (miRs) and target genes were predicted by bioinformatics and confirmed by performing dual­luciferase assays. The mRNA and protein expressions were determined by reverse transcription­quantitative PCR and western blotting. Cell invasion, migration, and viability were evaluated via Transwell, wound­healing and Cell Counting Kit­8 assays, respectively. The results demonstrated that lncRNA ZFAS1 expression was upregulated in thyroid carcinoma tissues, TT and SW579 cells, and was associated with the proliferation of these two cell lines. Notably, downregulation ZFAS1 reduced migration and invasion, and reversed the promotive effects of miR­302a­3p inhibitor on the proliferation, migration and invasion of TT and SW579 cells. Moreover, cyclin D1 (CCND1) is targeted by miR­302a­3p, and was regulated by ZFAS1. In addition, the downregulation of ZFAS1 not only reversed the promotive effects of miR­302a­3p inhibitor on CCND1 expression and the epithelial­mesenchymal transition (EMT) of TT and SW579 cells, but also targeted and increased the expression of miR­302a­3p, and further reduced the expression of CCND1, resulting in suppression of the proliferation, migration, invasion and EMT of thyroid carcinoma cells.

KIF11 Promotes Proliferation of Hepatocellular Carcinoma among Patients with Liver Cancers.

BACKGROUND: Hepatocellular carcinoma (HCC) lacks effective treatments and has a poor prognosis. Therefore it is needed to develop more effective drug targets. Kinesin family member 11 (KIF11) has been reported to affect the progression of several cancers, and its high expression associates with the prognosis of patients. However, the relevant mechanisms of KIF11 in HCC progression have not been studied. METHOD: Through the cancer genome atlas (TCGA) database and immunohistochemical (IHC) staining of patients' specimens, we determined that KIF11 was highly expressed in HCC tissues and associated with prognosis. We established a KIF11 stably depleted hepatoma cell line, through cell-cloning experiments and cell counting kit-8 (CCK-8) assays to detect the effects on proliferation in vitro. The role of KIF11 in promoting cell proliferation was verified in mice. RESULT: The expression of KIF11 was negatively correlated with the overall survival (OS) and disease-free survival (DFS) and positively correlated with tumor size of HCC patients. KIF11 depletion inhibits cell proliferation and tumor growth in vitro and in vivo. Conclusion. KIF11 can be used as a positive correlation marker for HCC prognosis and served as a potential therapeutic target.