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Focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening is crucial for enhancing glioblastoma (GBM) therapies. However, an in vivo imaging approach with a high spatial-temporal resolution to monitor the BBB opening process in situ and synchronously is still lacking. Herein, we report the use of indocyanine green (ICG)-dopped microbubbles (MBs-ICG) for visualizing the FUS-induced BBB opening and enhancing the photothermal therapy (PTT) against GBM. The MBs-ICG show bright fluorescence in the second near-infrared window (NIR-II), ultrasound contrast, and ultrasound-induced size transformation properties. By virtue of complementary contrast properties, MBs-ICG can be successfully applied for cerebral vascular imaging with NIR-II fluorescence resolution of ∼168.9 μm and ultrasound penetration depth of ∼7 mm. We further demonstrate that MBs-ICG can be combined with FUS for in situ and synchronous visualization of the BBB opening with a NIR-II fluorescence signal-to-background ratio of 6.2 ± 1.2. Finally, our data show that the MBs-ICG transform into lipid-ICG nanoparticles under FUS irradiation, which then rapidly penetrate the tumor tissues within 10 min and enhance PTT in orthotopic GBM-bearing mice. The multifunctional MBs-ICG approach provides a novel paradigm for monitoring BBB opening and enhancing GBM therapy.

The application of an exogenous polymer matrix to construct aggregation-induced emission (AIE) nanoprobes promotes the utility of AIE luminogens (AIEgens) in diagnosing brain diseases. However, the limited fluorescence (FL) and low active-targeting abilities of AIE-based nanoprobes impede their imaging application. Here, we employed endogenous albumin as an effective matrix to encapsulate AIEgens to enhance FL quantum yield (QY) and active-targeting ability. The albumin-consolidated strategy effectively inhibited the intramolecular vibration of AIEgens and enhanced endocytosis mediated by the gp60 receptor. The QYs of three kinds of albumin-based AIE nanoprobes with FL emissions ranging from the visible (400-650 nm) to the second near-infrared (NIR-II, 1000-1700 nm) region was at least 10% higher, and the tumor-targeting efficiency was ∼25% higher, compared with those of nanoprobes constructed by the exogenous polymer. Albumin-based AIE nanoprobes have achieved active-targeting NIR-II imaging of brain tumors and cerebrovascular imaging with a high signal-to-background ratio (SBR, ∼90) and high resolution (∼70 μm) in mouse models. Therefore, the albumin-based AIE nanoprobes will enable FL imaging-guided surgery of brain tumors and cerebral ischemia, which will improve surgical efficacy to prevent recurrence and side effects.

To investigate the risk factor associated with central nervous system infection, a rare and dire complication after spinal surgery.Univariate and multivariate logistic regression analyses were performed to screen for the independent risk factors. According to the different administration methods of antibiotics, patients were divided into intravenous and intrathecal groups. The differences in time needed for body temperature, white blood cells (WBC), and C-reactive protein (CRP) to return to normal and the time of antibiotic application were compared between the 2 groups. In addition, the differences in WBC, neutrophil ratio, CRP, procalcitonin in blood, and WBC in cerebrospinal fluid were compared before intrathecal injection, after the first one, and the last one. The incidence of complications in the 2 groups was observed.Dural tears, laminectomy, and operation time3 hours were identified as independent risk factors. The time needed for body temperature, WBC, and CRP to return to normal and the antibiotic application time were significantly different between the 2 groups (all P0.05). Before and after the first intrathecal injection and after the last intrathecal injection, the differences in WBCs, neutrophil ratios, CRP, procalcitonin in blood, and cerebrospinal fluid-WBC were statistically significant in overall and pairwise comparisons (P0.05). Complications occurred in 2 and 14 cases, respectively.The independent risk factors for central nervous system infection after spinal surgery were a dural tear, laminectomy, and operation time3 hours. Combined intravenous and intrathecal injections of antibiotics led to a better effect than intravenous injection alone; however, this approach was associated with more complications.

Purpose Identifying stroke patients at risk of postthrombolysis intracranial hemorrhage (ICH) in the clinical setting is essential. We aimed to develop and evaluate a nomogram for predicting the probability of ICH in acute ischemic stroke patients undergoing thrombolysis. Patients and methods A retrospective observational study was conducted using data from 345 patients at a single center. The patients were randomly dichotomized into training (2/3; n=233) and validation (1/3; n=112) sets. A prediction model was developed by using a multivariable logistic regression analysis. Results The nomogram comprised three variables: the presence of atrial fibrillation (odds ratio [OR]: 4.92, 95% confidence interval [CI]: 2.09-11.57), the National Institutes of Health Stroke Scale (NIHSS) score (OR: 1.11, 95% CI: 1.04-1.18) and the glucose level on admission (OR: 1.27, 95% CI: 1.08-1.50). The areas under the receiver operating characteristic curve of the nomogram for the training and validation sets were 0.828 (0.753-0.903) and 0.801 (0.690-0.911), respectively. The Hosmer-Lemeshow test revealed good calibration in both the training and validation sets (P = 0.509 and P = 0.342, respectively). The calibration plot also demonstrated good agreement. A decision curve analysis demonstrated that the nomogram was clinically useful. Conclusion We developed an easy-to-use nomogram model to predict ICH, and the nomogram may provide risk assessments for subsequent treatment in stroke patients undergoing thrombolysis.

Objectives: Although DNA (cytosine-5)-methyltransferase 3 alpha (DNMT3A) gene mutations have been widely reported in myelodysplastic syndromes (MDS), the prognostic significance of DNMT3A mutations...

Background: Chidamide, a novel benzamide-type histone deacetylase (HDAC) inhibitor, exerts antitumor effects on several types of cancer. However, the role of Chidamide in chronic myeloid leukemia (CML) remains elusive. Therefore, the present study aimed to investigate the effects of Chidamide on CML cell proliferation and explore its underlying mechanism. Methods: Cell proliferation was assessed by CCK-8 assay, cell cycle distribution and apoptosis were detected by flow cytometry and the expression of related proteins was evaluated by western blot analysis. The potential mechanisms were systematically explored by the network-based pharmacological methods, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Results: The results revealed that Chidamide inhibited the proliferation of K562 cells in a dose- and time-dependent manner. In addition, Chidamide blocked cells in the G0/G1 phase via downregulating cyclin-dependent kinase 4, and induced apoptosis via upregulating Bax and downregulating of Bcl-2. Additionally, using network- based pharmacological methods, we found that PI3K/AKT signaling pathway is involved and significantly related to cell proliferation in CML. Intriguingly, cell treatment with Chidamide suppressed the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway via decreasing the levels of phosphorylated (p)-PI3K and p-AKT. Moreover, insulin-like growth factor 1 (IGF-1), a PI3K/AKT activator, reversed the inhibitory effects of Chidamide on K562 cell proliferation. Conclusion: The study demonstrated that Chidamide may inhibit the proliferation of K562 cells by promoting cell cycle arrest and apoptosis via suppressing the PI3K/AKT pathway, suggesting that Chidamide could be a promising approach to the treatment of CML.

The spread of coronavirus disease 2019 (COVID-19) around the world has put a heavy burden on human society and is also a great challenge facing medical staff. This study aimed to assess the difficulties faced by health care personnel (HCP) in using personal protective equipment (PPE) in clinical practice during the COVID-19 outbreak in Wuhan, China. One hundred twenty medical staff from the First Affiliated Hospital of Chongqing Medical University presented to the Wuhan First Hospital to provide medical assistance, from whom 20 HCP volunteered to participate in a focus group discussion attended by infection control nurse leaders. Participants’ responses and discussions were recorded, and the content was analyzed for themes. Observed difficulties included inappropriate PPE sizes, the design of the PPE and its complexity of use, doubts related to the quality and effectiveness of PPE, potential risks during doffing, space layout between clean and contaminated area, and poor comfort with PPE use. Other factors, such as the support environment, management, processes, preparedness, HCP, and equipment can also have a positive or negative impact on the use of PPE. Future efforts to optimize PPE use should focus on strengthening training for HCP using real items for increasing compliance with standardized protocols, improving PPE design, and performing further research on the risks, benefits, and best practices of PPE use.

Background: Acupuncture may be an effective complementary treatment for Alzheimer's disease (AD). The aim of this study was to summarize the evidence provided by systematic reviews (SRs)/meta-analyses (MAs) on the effect of acupuncture on AD.Methods: Eight electronic databases were searched from their inception until October 19, 2020. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Moreover, the evidence quality of the outcome measures was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).Results: Eleven SRs/MAs met all inclusion criteria. According to the results of the AMSTAR-2, all included reviews were rated critically as being of low quality. With PRISMA, the reporting checklist was relatively complete, but some reporting weaknesses remained in the topics of the protocol and registration, search strategy, risk of bias, additional analyses, and funding. Based on the ROBIS tool, only two SRs/MAs had a low risk of bias. With the GRADE system, no high-quality evidence was found, and only seven outcomes provided moderate-quality evidence. Among the downgraded factors, the risk of bias within the original trials was ranked first, followed by inconsistency, imprecision, and publication bias.Conclusions: Acupuncture is a promising complementary treatment for AD. However, due to the low quality of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.

Objectives. Acupuncture has increasingly been used for insomnia relief after stroke. We aimed to evaluate the methodological quality and summarize the evidence regarding the effectiveness of acupuncture for poststroke insomnia (PSI) from systematic reviews/meta-analyses (SRs/MAs). Methods. Eight databases were searched from inception through August 23, 2020. SRs/MAs on acupuncture treatment for PSI were included. Methodological quality assessment was performed using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and evidence quality assessment was performed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results. Six SRs/MAs on acupuncture treatment for PSI were included. The AMSTAR-2 showed that the methodological quality of all included SRs/MAs was rated as critically low. According to the evaluation results of GRADE, 38.9% (7/18) of outcomes were rated as very low-quality evidence, 22.2% (4/18) were low-quality evidence, and 8.9% (7/18) were moderate-quality evidence. Descriptive analysis results showed that acupuncture was an effective treatment modality for PSI. Conclusions. All included reviews indicated that acupuncture was more effective than the control group for the treatment of PSI, but the credibility of the results is limited owing to the generally low methodological and evidence quality of the included SRs/MAs. More high-quality evidence is needed to determine whether acupuncture is more effective than other treatments.

Heparan sulfate proteoglycan 2 (HSPG2), also known as perlecan, is a large multi-domain extracellular matrix proteoglycan, which contributes to the invasion, metastasis and angiogenesis of solid tumor. However, very little is known about the effect of HSPG2 on acute myeloid leukemia (AML). This study aims to investigate the prognostic value of the HSPG2 gene in terms of overall survival and leukemia-free survival in patients with AML. Bone marrow mononuclear cells (BMMCs) from 4 AML patients and 3 healthy controls were processed for RNA-Sequencing (RNA-seq). The mRNA expression level of HSPG2 in BMMCs and CD34+ hematopoietic stem/progenitor cells (HSPC) obtained from enrolled participants and human leukemic cell lines was detected by RT-qPCR. Then the correlations between the expression of HSPG2 and a variety of important clinical parameters, such as median white blood cell (WBC) count and bone marrow (BM) blasts, were further analyzed. The expression level of HSPG2 was significantly upregulated in AML patients at the time of diagnosis, downregulated after complete remission and then elevated again at relapse. Moreover, HSPG2 expression was associated with median WBC count (P P = 0.02), median platelet count (P = 0.001), and BM blasts (P P = 0.001) and poorer leukemia-free survival (LFS) (P = 0.047). In the multivariate analysis model, HSPG2 was identified as an independent prognostic biomarker of AML. Taken together, these results indicate that HSPG2 overexpression was associated with poor prognosis in AML patients, and may be a prognostic biomarker and therapeutic target of AML.

The clinical application of cytogenetic analysis and molecular-targeted drugs has dramatically improved the prognosis for many patients with hematologic malignancy, especially for those with chronic myeloid leukemia (CML) and acute promyelocytic leukemia (APL). Nevertheless, the treatment of hematologic malignancies is still faced with problems, such as disease recurrence and drug resistance, so further exploring the underlying molecular mechanism is urgent. With the discovery of different RNA species, the mechanism of RNA-RNA interaction has caught more and more attention. "Competing endogenous RNA (ceRNA) hypothesis" is one of the fascinating products of recent researches. CeRNAs are endogenous RNA transcripts that share mutual microRNA response elements (MREs) and regulate expression of each other by competing for the same microRNAs pools. The hypothesis links different RNA species together and enriches our understanding of the human genome. Here, we introduce the hypothesis critically, summary the research progress in the field of hematologic malignancies and the current investigation methods, and address its promising clinical value in offering new predictive, prognostic biomarkers and therapeutic targets.

Introduction: Identification of stroke patients at risk of postthrombolysis intracranial hemorrhage (ICH) in the clinical setting is essential. We aimed to develop and evaluate a nomogram for predicting the probability of intracranial hemorrhage (ICH) in acute ischemic stroke patients undergoing thrombolysis. Methods: A retrospective observational study was conducted with 287 participants from a single center (67.2% males, median age 65 years). The patients were randomly divided into a training set (160) and a validation set (127). Univariate and multivariate logistic regression analyses of clinical variables were performed to screen for significant prognostic factors. Nomograph that included significant prognostic variables was formulated to predict ICH. Areas under curve (AUC) of receiver operating characteristic (ROC) and calibration plots were formulated to evaluate the predictive accuracy of the nomograph. Results: A total of 41(14.3%) ICH events occurred. A nomogram was developed to predict ICH based on three variables in the training set: the presence of atrial fibrillation (OR: 4.01, P =0.009), the National Institutes of Health Stroke Scale (NIHSS) score (OR: 1.16, P =0.001) and glucose (OR: 1.37, P =0.006) on admission. The AUC-ROC for the training set was 0.817 (0.730-0.925), and for the validation set was 0.809 (0.710-0.904). Calibration plots showed good consistency between the two sets. Conclusion: We developed an easy-to-use nomogram model based on 3 independently clinical factors to predict ICH. The nomogram could be useful for individualized prediction of ICH in intravenous thrombolysis-treated stroke patients..

Factors such as environmental change during space flight have the widespread influences on physical and mental health, causing aerospace medical problems like cardiovascular dysfunction. One of its manifestations of cardiovascular disorders is orthostatic intolerance. At present, these measures to protect against the physiological effects of weightlessness provide a protective effect, but still cannot completely eliminate the adverse effects of weightlessness on cardiovascular system. Therefore, it is very necessary to find a convenient and effective protective countermeasures. Clinical practice and modern experimental research have revealed that acupuncture and moxibustion has very good regulating effect on cardiovascular system. However, until now, there is no unified stimulus standard (such as stimulus frequency, time etc), which seriously affects the repeatability of operation and the efficacy of acupuncture. Therefore it's very important to set a repeatable standard

Background: Identification of stroke patients at risk of postthrombolysis intracranial hemorrhage (ICH) in the clinical setting is essential. However, studies in this area spare.We aimed to develop a nomogram by adding atrial fibrillation to the Multicenter Stroke Survey (MSS) score to predict the probability of ICH in acute ischemic stroke patients undergoing thrombolysis. Methods: A retrospective observational study was conducted with 287 participants from a single center (67.2% males, median age 65 years). Head computed tomography scan was performed after 24 hour to evaluate ICH occurrence, and a computed tomography scan was done immediately in case of clinical worsening. The risk factors associated with ICH were analysed. Based on multivariate logistic model, a nomogram was generated for ICH on the basis of atrial fibrillation and the MSS score. We assessed the discriminative performance by using the area under curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using calibration plot. Results: A total of 41(14.3%) ICH events occurred.The MSS score and atrial fibrillation were independent predictors of ICH in multivariate logistic regression analysis. Discrimination of the nomogram was superior to the MSS score alone (0.794 vs 0.741; P=0.034). The model was internally validated by using bootstrap (1000 samples) with AUC-ROC of 0.795. The calibration plot showed good agreement. Conclusion: We developed and internally validated a new nomogram using the MSS score and atrial fibrillation as predictors.The nomogram is a simple and accurate tool for predicting ICH in acute ischemic stroke patients undergoing thrombolysis. Further studies are warranted to validate our findings.

Metformin, a widely used antidiabetic drug, has previously been demonstrated to exert anti-cancer effects in certain hematological malignancies, but its effects on the transformation of myelodysplastic syndromes to acute myeloid leukemia (AML-MDS) remain unclear. The present study aimed to investigate the effects of metformin on SKM-1 cells (an AML-MDS cell line) and its underlying mechanisms. SKM-1 cells were treated with different concentrations of metformin. Cell proliferation was assayed by CCK-8. Apoptosis and cell cycle phases were detected by flow cytometry, while cell cycle related proteins and AMPK were tested by Western blot. SKM-1 cells were transfected with LV-AMPKα1-RNAi to reduce the expression of AMPK. Metformin inhibited cell proliferation in a dose and time dependent manner by inducing G0/G1 phase arrest rather than apoptosis induction. Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1. AMPK knockdown attenuated the effects of metformin on SKM-1 cells. These findings suggested that metformin inhibited proliferation of SKM-1 cells, potentially through an AMPK-mediated cell cycle arrest. Keywords: SKM-1 cells, Metformin, AMPK, Cell cycle

Due to the backwardness of domestic enterprise informatization, accounting computerization is often just input vouchers into the computer, and the system automatically sets out the table, which reduces only a part of the accounting work, and most accountants are still busy doing accounts. Passively address risks only when they arise. The core of good financial management is two aspects, on the one hand to ensure good cash flow, and do cash flow appreciation, on the other hand to do risk prevention and control. The specific approach is to effectively manage financial management and investment in the short term, control income and expenditure in the medium and long term, ensure the continuous cash flow at each time point, and at the same time take a step forward in risk prevention and control, and anticipate risks in advance and avoid them through a large number of tools. As a powerful tool, the computer is undoubtedly a very good choice. Based on this, this paper discusses the application of computer technology in enterprise financial management.

Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.

Ischemia-reperfusion injury (IRI) was one of the main causes of acute kidney injury. Mir-26a has been reported to play functions in cellular differentiation, cell growth, cell apoptosis and metastasis. Furthermore, the renal vein levels of Mir-26a were demonstrated to be lower in the poststenotic kidney. However, the effect of Mir-26a on the renal IRI has never been investigated. In our current study, Mir-26a overexpression results in attenuated renal IRI and promoted tregs expansion. The promoted renal function after IRI induced by Mir-26a overexpression was abrogated by depletion of tregs with anti-CD25 antibodies. Mir-26a also significantly suppressed IL-6 expression. And IL-6 overexpression led to significant suppression of the Mir-26a-induced upregulation of Foxp3. Next, we performed additional experiments to determine the therapeutic potential of Mir-26a during the recovery phase after renal IRI. Results showed that Mir-26a treatment after IRI also induced significant expansion of Foxp3(+)CD4(+) Tregs in both spleen and renal on day 10 after IRI. Taken together, our data indicate an important role for Mir-26a in promoting tregs expansion in renal IRI that involving repression of IL-6 expression.

Background Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. Results The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E–binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats. Conclusions The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.