Deep learning for precise diagnosis and subtype triage of drug-resistant tuberculosis on chest computed tomography.

Deep learning, transforming input data into target prediction through intricate network structures, has inspired novel exploration in automated diagnosis based on medical images. The distinct morphological characteristics of chest abnormalities between drug-resistant tuberculosis (DR-TB) and drug-sensitive tuberculosis (DS-TB) on chest computed tomography (CT) are of potential value in differential diagnosis, which is challenging in the clinic. Hence, based on 1176 chest CT volumes from the equal number of patients with tuberculosis (TB), we presented a Deep learning-based system for TB drug resistance identification and subtype classification (DeepTB), which could automatically diagnose DR-TB and classify crucial subtypes, including rifampicin-resistant tuberculosis, multidrug-resistant tuberculosis, and extensively drug-resistant tuberculosis. Moreover, chest lesions were manually annotated to endow the model with robust power to assist radiologists in image interpretation and the Circos revealed the relationship between chest abnormalities and specific types of DR-TB. Finally, DeepTB achieved an area under the curve (AUC) up to 0.930 for thoracic abnormality detection and 0.943 for DR-TB diagnosis. Notably, the system demonstrated instructive value in DR-TB subtype classification with AUCs ranging from 0.880 to 0.928. Meanwhile, class activation maps were generated to express a human-understandable visual concept. Together, showing a prominent performance, DeepTB would be impactful in clinical decision-making for DR-TB.

Microbial contribution to 14 biogenic amines accumulation in refrigerated raw and deep-fried hairtails (Trichiurus lepturus).

Biogenic amines (BAs) produced by microbial decarboxylation of amino acids are crucial toxic nitrogenous compounds in fish. An optimized ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with simple pretreatment was established to detect 14 BAs in both raw (control check, CK) and deep-fried (DF) hairtails. This method exhibited a good linear relationship with average recoveries of 73.3-120.0 % and relative standard deviations of 2.5-10.0 %, respectively. The total BAs in CK and DF hairtails decreased sharply to 338.2 and 25.3 mg/kg on the 9th day, respectively. Four BAs, including cadaverine (CAD), histamine (HIS), tyramine (TYR), and putrescine (PUT) accounted for 92.5-99.9 % of total BAs were selected as the dominant BAs. Bacterial analysis showed that the abundance of DF was relatively low. Further correlation analysis proved that Vibrio had a significant (p < 0.05) positive correlation with total BAs and could be the main BA-producing bacterium in DF hairtail. This work provides new evidence of the accumulation of BAs in refrigerated hairtail.

High-throughput detection and dietary exposure risk assessment of 44 mycotoxins in Mango, Litchi, Longan, and their products in South China.

Mycotoxins exposure from food can trigger serious health hazards. This study aimed to establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous detection of 44 mycotoxins in fruits and their products, followed by dietary exposure risk assessment. The optimized UPLC-MS/MS method exhibited a good linear relationship with correlation coefficients ≥ 0.99041. The limits of detection (LOD) and the limits of quantification (LOQ) were within the range of 0.003 âˆ¼ 0.700 µg/kg and 0.01 âˆ¼ 2.00 µg/kg, respectively. The three fruits and their corresponding value-added products, with a total sampling size of 42, were subjected to analysis and detected with mycotoxins. Further dietary exposure risk assessment revealed that the hazard quotient (HQ) and hazard index (HI) of mycotoxins were 1.213 âˆ¼ 60.032 % and 5.573 âˆ¼ 93.750 %, indicating a low risk for Chinese consumers. However, we still need be cautious about 15-acetyl-deoxynivalenol (15-ADON), as it had 78.6 % occurrence among all samples. This work provides an accurate analysis strategy for 44 mycotoxins and contributes to mycotoxins supervision.

CircularRNA Hsa_circ_0093335 promotes hepatocellular carcinoma progression via sponging miR-338-5p.

Circular RNAs play an important role in the development of various malignancies, including hepatocellular carcinoma (HCC). Nevertheless, the role of Hsa_circ_0093335 (circ0093335) in HCC has not yet been explored. To investigate the biological effects and molecular mechanisms of circ0093335 on HCC. Circ0093335 expression was detected in HCC cells and clinical specimens using qRT-PCR. The association between circ0093335 expression and HCC patients' clinical characteristics was determined using SPSS. The role of circ0093335 in HCC was estimated by overexpression and knockdown experiments in vitro and in vivo. qRT-PCR, nucleoplasma separation assay, FISH assay, RIP, dual luciferase reporter assay and rescue assay were used to validate the regulatory effect of circ0093335 on miR-338-5p. The study findings showed that circ0093335 was upregulated in HCC. High circ0093335 expression was linked with the tumour-node-metastasis stage and microvascular tumour invasion. circ0093335 is greatly involved in HCC cell proliferation, aggressive ability and mouse tumour growth, according to many in vitro and in vivo tests. Mechanistically, circ0093335 downregulated miR-338-5p expression by sponging, consequently promoting HCC progression. Our research indicated that circ0093335 might be a target for HCC therapy since it promotes tumour progression by acting as a miR-338-5p 'sponge'.

Cerebral venous sinus thrombosis in a patient with Klebsiella pneumoniae primary liver abscess: a case report.

BACKGROUND: Liver abscess is a common emergency in the emergency department. However, cerebral venous sinus thrombosis (CVST) is a rare and serious cerebrovascular disease. Cases of CVST in patients with Klebsiella pneumoniae primary liver abscess (KLA) have not been described in the literature. We report a case of CVST in patients with KLA. CASE PRESENTATION: A 54-year-old male patient came to our department with a fever for 2 days and altered mental status for 1 day. Abdominal computed tomography (CT) and liver magnetic resonance imaging (MRI) revealed multiple liver abscesses. The blood culture was identified as Klebsiella pneumoniae sepsis. Head contrast-enhanced MRI and magnetic resonance venography (MRV) imaging showed multiple thrombus formation in the right transverse sinus and sigmoid sinus. The patient's infection and thrombosis were controlled within one week of multidisciplinary comprehensive treatment such as antibiotic and antithrombotic therapy, and a good clinical recovery during the 1-month follow-up. CONCLUSION: CVST after liver abscess is rare, clinicians should be aware of this complication and vigilant for the possibility of bacterial meningitis. The underlying mechanisms need to be further studied.

Schnurri-2 Promotes the Expression of Excitatory Glutamate Receptors and Contributes to Neuropathic Pain.

Neuropathic pain is a type of chronic pain with complex mechanisms, and current treatments have shown limited success in treating patients suffering from chronic pain. Accumulating evidence has shown that the pathogenesis of neuropathic pain is mediated by the plasticity of excitatory neurons in the dorsal horn of the spinal cord, which provides insights into the treatment of hyperalgesia. In this study, we found that Schnurri-2 (Shn2) was significantly upregulated in the L4-L6 segments of the spinal cord of C57 mice with spared nerve injury, which was accompanied by an increase in GluN2D subunit and glutamate receptor subunit 1 (GluR1) levels. Knocking down the expression of Shn2 using a lentivirus in the spinal cord decreased the GluN2D subunit and GluR1 levels in spared nerve injury mice and eventually alleviated mechanical allodynia. In summary, Shn2 regulates neuropathic pain, promotes the upregulation of GluN2D in glutamatergic neurons and increases the accumulation of GluR1 in excitatory neurons. Taken together, our study provides a new underlying mechanism for the development of neuropathic pain.

Chlorogenic acid improves diabetic retinopathy by alleviating blood-retinal-barrier dysfunction via inducing Nrf2 activation.

As one of the major diabetic microvascular complications, diabetic retinopathy (DR) is mainly initiated by the blood-retinal barrier (BRB) dysfunction. Chlorogenic acid (CGA) is a natural polyphenolic compound in Lonicerae Japonicae Flos, which traditionally has the beneficial function for eyes and is commonly included in many anti-diabetic formulas. In this study, the potential protective mechanism of CGA against DR was investigated. Streptozotocin (STZ) was used to induce diabetes in mice. CGA attenuated BRB dysfunction and reversed endothelial-mesenchymal transition (EndoMT) and epithelial-mesenchymal transition (EMT) in retinas in vivo. CGA inhibited microglia activation and reduced tumor necrosis factor (TNF)α release both in vivo and in vitro. CGA promoted nuclear factor erythroid 2-related factor 2 (Nrf2) activation and prevented EndoMT/EMT in TNFα-treated human retinal endothelial cells (HRECs) or retinal pigment epithelial APRE19 cells. CGA alleviated endothelial/epithelial barrier oxidative injury in HRECs or APRE19 cells stimulated with TNFα, but this effect was disappeared in cells co-incubated with Nrf2 inhibitor. Additionally, the CGA-supplied alleviation on BRB damage and EndoMT/EMT was markedly weakened in retinas from STZ-treated Nrf2 knock-out mice. All results suggest that CGA improves DR through attenuating BRB injury by reducing microglia-initiated inflammation and preventing TNFα-induced EndoMT/EMT and oxidative injury via inducing Nrf2 activation.

Clinical risk score for early prediction of recurring SARS-CoV-2 positivity in non-critical patients.

Introduction: Recurrent positive results in quantitative reverse transcriptase-PCR (qRT-PCR) tests have been commonly observed in COVID-19 patients. We aimed to construct and validate a reliable risk stratification tool for early predictions of non-critical COVID-19 survivors' risk of getting tested re-positive within 30 days. Methods: We enrolled and retrospectively analyzed the demographic data and clinical characters of 23,145 laboratory-confirmed cases with non-critical COVID-19. Participants were followed for 30 days and randomly allocated to either a training (60%) or a validation (40%) cohort. Multivariate logistic regression models were employed to identify possible risk factors with the SARS-CoV-2 recurrent positivity and then incorporated into the nomogram. Results: The study showed that the overall proportion of re-positive cases within 30 days of the last negative test was 24.1%. In the training cohort, significantly contributing variables associated with the 30-day re-positivity were clinical type, COVID-19 vaccination status, myalgia, headache, admission time, and first negative conversion, which were integrated to build a nomogram and subsequently translate these scores into an online publicly available risk calculator (https://anananan1.shinyapps.io/DynNomapp2/). The AUC in the training cohort was 0.719 [95% confidence interval (CI), 0.712-0.727] with a sensitivity of 66.52% (95% CI, 65.73-67.30) and a specificity of 67.74% (95% CI, 66.97-68.52). A significant AUC of 0.716 (95% CI, 0.706-0.725) was obtained for the validation cohort with a sensitivity of 62.29% (95% CI, 61.30-63.28) and a specificity of 71.26% (95% CI, 70.34-72.18). The calibration curve exhibited a good coherence between the actual observation and predicted outcomes. Conclusion: The risk model can help identify and take proper management in high-risk individuals toward the containment of the pandemic in the community.

Mechanical Performance of a Ballastless Track System for the Railway Bridges of High-Speed Lines: Experimental and Numerical Study under Thermal Loading.

The mechanical performance of China Railway Track System type II (CRTS II) ballastless track suitable for High-Speed Railway (HSR) bridges is investigated in this project by testing a one-quarter-scaled three-span specimen under thermal loading. Stress analysis was performed both experimentally and numerically, via finite-element modeling in the latter case. The results showed that strains in the track slab, in the cement-emulsified asphalt (CA) mortar and in the track bed, increased nonlinearly with the temperature increase. In the longitudinal direction, the zero-displacement section between the track slab and the track bed was close to the 1/8L section of the beam, while the zero-displacement section between the track slab and the box girder bridge was close to the 3/8L section. The maximum values of the relative vertical displacement between the track bed and the bridge structure occurred in the section at three-quarters of the span. Numerical analysis showed that the lower the temperature, the larger the tensile stresses occurring in the different layers of the track structure, whereas the higher the temperature, the higher the relative displacement between the track system and the box girder bridge. Consequently, quantifying the stresses in the various components of the track structure resulting from sudden temperature drops and evaluating the relative displacements between the rails and the track bed resulting from high-temperature are helpful in the design of ballastless track structures for high-speed railway lines.

Expression Profiles of Long Noncoding RNAs in Mice with High-Altitude Hypoxia-Induced Brain Injury Treated with Gymnadenia conopsea (L.) R. Br.

BACKGROUND: The unique geographical environment at high altitudes may cause a series of diseases, such as acute altitude reaction, cerebral edema, and pulmonary edema. Gymnadenia conopsea (L.) R. Br. has been reported to have an effect on high-altitude hypoxia. However, the molecular mechanism, especially the expression of long noncoding RNAs (lncRNAs), is not yet clear. METHODS: The expression profiles of lncRNAs in high-altitude hypoxia-induced brain injury mice treated with Gymnadenia conopsea (L.) R. Br. by using a microarray method. RESULTS: A total of 226 differentially expressed lncRNAs, 126 significantly dysregulated mRNAs and 23 differentially expressed circRNAs were detected (>2.0-fold, p<0.05). The expression of selected lncRNAs, mRNAs and circRNAs was validated by qRT-PCR. KEGG analysis showed that the mRNAs coexpressed with lncRNAs were involved in inflammation and hypoxia pathways, including the HIF-1, PI3K-Akt, and NF-kappa B signaling pathways. The lncRNA-TF network analysis results indicated that the lncRNAs were regulated mostly by HMGA2, SRY, GATA4, SOX5, and ZBTB16. CONCLUSION: This study is the first to report the expression profiles of lncRNAs, mRNAs and circRNAs in mice with high-altitude hypoxia-induced brain injury treated with Gymnadenia conopsea (L.) R. Br. and may improve the understanding of the molecular mechanism of Gymnadenia conopsea (L.) R. Br. in treating high altitude hypoxia-induced brain injury.

Development of a Respiratory Support Score as a Visualization Tool in Intensive Care.

BACKGROUND: In the modern era, many devices exist to support patients with respiratory insufficiency. There is currently no way to depict changes in the degree of support a patient is receiving over time. METHODS: We enrolled 4,889 subjects undergoing 5,732 cardiac surgical visits between 2011 and 2017 and extracted data elements related to respiratory support from the electronic medical record. We created an algorithm to use these data to categorize a subject's respiratory support type and to calculate an empirically derived respiratory support score (RSS) at each postoperative minute; the RSS is scored on a scale of 0 to 100. The RSS was then used to identify the timing and incidence of nonprocedural re-intubations, which were electronically verified against secondary verification fields (eg, nursing extubation note). Rates of nonprocedural re-intubations and noninvasive ventilation were compared between surgical mortality risk scores (STAT scores). RESULTS: Computerized assignment of RSS was performed for 3 million subject time points. Mechanical ventilation duration varied significantly by STAT score (P < .001). Nonprocedural re-intubations increased nonsignificantly with increasing STAT score (P = .059, overall 4.3%); time to nonprocedural re-intubation did not (P = .53). Noninvasive ventilation use was more common and was prolonged with increasing STAT score (P < .001). CONCLUSIONS: Elements of respiratory support can be automatically extracted and transformed into a numerical RSS for visualization of respiratory course. The RSS provides a clear visual depiction of respiratory care over time, particularly in subjects with a complex ICU course. The score also allows for the automated adjudication of meaningful end points, including timing of extubation and incidence of nonprocedural re-intubation.

Impact of the superior cavopulmonary anastomosis on cerebral oxygenation.

BACKGROUND: Patients with univentricular heart disease may undergo a superior cavopulmonary anastomosis, an operative intervention that raises cerebral venous pressure and impedance to cerebral venous return. The ability of infantile cerebral autoregulation to compensate for this is not well understood. MATERIALS AND METHODS: We identified all patients undergoing a superior cavopulmonary anastomosis (cases) and compared metrics of cerebral oxygenation upon admission to the ICU with patients following repair of tetralogy of Fallot or arterial switch operation (controls). The primary endpoint was cerebral venous oxyhaemoglobin saturation measured from an internal jugular venous catheter. Other predictor variables included case-control assignment, age, weight, sex, ischemic times, arterial oxyhaemoglobin saturation, mean arterial blood pressure, and superior caval pressure. RESULTS: A total of 151 cases and 350 controls were identified. The first post-operative cerebral venous oxyhaemoglobin saturation was significantly lower following superior cavopulmonary anastomosis than in controls (44 ± 12 versus 59 ± 15%, p < 0.001), as was arterial oxyhaemoglobin saturation (81 ± 9 versus 98 ± 5%, p < 0.001). Cerebral venous oxyhaemoglobin saturation correlated poorly with superior caval pressure in both groups. When estimated by linear mixed effects model, arterial oxyhaemoglobin saturation was the primary determinant of central venous oxyhaemoglobin saturation in both groups (ß = 0.79, p = 3 × 10-14); for every 1% point increase in arterial oxyhaemoglobin saturation, there was a 0.79% point increase in venous oxyhaemoglobin saturation. In this model, no other predictors were significant, including superior caval pressure and case-control assignment. CONCLUSION: Cerebral autoregulation appears to remain intact despite acute imposition of cerebral venous hypertension following superior cavopulmonary anastomosis. Following superior cavopulmonary anastomosis, cerebral venous oxyhaemoglobin saturation is primarily determined by arterial oxyhaemoglobin saturation.

Sensitivity of a Next-Generation NIRS Device to Detect Low Mixed Venous Oxyhemoglobin Saturations in the Single Ventricle Population.

Regional cerebral oxygenation index (rSO2) based on near-infrared spectroscopy (NIRS) is frequently used to detect low venous oxyhemoglobin saturation (ScvO2). We compared the performance of 2 generations of NIRS devices. Clinically obtained, time-matched cerebral rSO2 and ScvO2 values were compared in infants monitored with the FORE-SIGHT (n = 73) or FORE-SIGHT ELITE (n = 47) by linear regression and Bland-Altman analyses. In both devices, cerebral rSO2 correlated poorly with measured ScvO2 (FORE-SIGHT partial correlation 0.50 [95% confidence interval {CI}, 0.40-0.58]; FORE-SIGHT ELITE partial correlation 0.47 [0.39-0.55]) and mean bias was +8 (standard deviation [SD] 13.2) for FORE-SIGHT and +14 (SD 12.5) for FORE-SIGHT ELITE. When ScvO2 was <30%, rSO2 was <40 in 8% of FORE-SIGHT ELITE readings. Future NIRS should be validated in more hypoxic cohorts.

Screening and Identification of the Main Metabolites of Schisantherin a In Vivo and In Vitro by Using UHPLC-Q-TOF-MS/MS.

Schisantherin A is an active ingredient originating from Schisandra chinensis (Turcz.) which has hepatoprotective and anti-oxidation activities. In this study, in vitro metabolisms investigated on rat liver microsomes (RLMs) and in vivo metabolisms explored on male Sprague Dawley rats of Schisantherin A were tested, respectively. The metabolites of Schisantherin A were identified using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Based on the method, 60 metabolites were successfully identified and structurally characterized including 48 phase-I and 12 phase-II metabolites. Among the metabolites, 45 metabolites were reported for the first time. Moreover, 56 and eight metabolites were detected in urine and bile and 19 metabolites were identified in rats' plasma. It demonstrated that hepatic and extra-hepatic metabolic pathways were both involved in Schisantherin A biotransformation in rats. Five in vitro metabolites were structurally characterized for the first time. The results indicated that the metabolic pathways mainly include oxidation, reduction, methylation, and conjugation with glucuronide, taurine, glucose, and glutathione groups. This study provides a practical strategy for rapidly screening and identifying metabolites, and the results provide basic data for future pharmacological and toxicology studies of Schisantherin A and other lignin ingredients.

Circ-Foxo3 is positively associated with the Foxo3 gene and leads to better prognosis of acute myeloid leukemia patients.

BACKGROUND: The Foxo3 gene, belonging to the forkhead family, is one of the classes of transcription factors characterized by a forkhead DNA-binding domain, which usually considered being a cancer suppressor gene. Circ-Foxo3 is a circular structure which connects the 3'end to the 5'end. Scholars detected that circ-Foxo3 could compete with Foxo3 for binding to some miRNAs. METHODS: In this study, we will test the expression of Foxo3 and circ-Foxo3 in de novo acute myeloid leukemia (AML) patients to explore the relationship between Foxo3 gene and circ-Foxo3. All the de novo AML samples and normal control samples was measured by real-time quantitative PCR. A receiver operating characteristic curve was conducted to differentiate AML patients from control people. Association of Foxo3 expression and overall survival was conducted by Kaplan-Meier survival analysis. RESULTS: We found that the expression of Foxo3 gene in de novo patients was significantly lower than control samples (P = 0.009). Meanwhile, circ-Foxo3 also expressed lower in de novo AML patients than in control samples (P = 0.040). In different classifications, this trend could be observed more remarkably. In non-M3 patients, the Foxo3 high patients' survival time was longer than Foxo3 low patients (P = 0.002). Besides, in non-favorable risk groups, patients with low expression of Foxo3 had longer survival time than Foxo3 high patients (P = 0.004). Furthermore, in normal Karyotypic patients, the overall survival time of patients with high-expressed Foxo3 was significantly longer than those with low expression (P = 0.034). Besides, Pearson analysis was also conducted between these two genes in AML patients. Results revealed that they were positively correlated (R = 0.63, P < 0.001). CONCLUSION: In conclusion, we found that low expression of circ-Foxo3 and Foxo3 were frequent in AML patients, and patients with high expression of Foxo3 often had a trend of better prognosis.

Low Expression of Pseudogene POU5F1B Affects Diagnosis and Prognosis in Acute Myeloid Leukemia (AML).

BACKGROUND The transcription factor Oct-4 is necessary for maintaining pluripotency and self-renewal of embryonic stem cells, and POU5F1B is a processed pseudogene of Oct-4 with coding capacity. The purpose of this study is to evaluate the expression and clinical implication of POU5F1B in AML. MATERIAL AND METHODS The expression of the POU5F1B transcript was evaluated in 175 newly diagnosed AML patients and 39 healthy controls by use of real-time quantitative PCR (RQ-PCR). RESULTS POU5F1B was underexpressed in AML compared with controls (P<0.001). The receiver operating characteristic (ROC) curve revealed that the POU5F1B transcript level was able to differentiate AML patients from healthy individuals (AUC=0.682). In non-APL AML patients, the POU5F1Blow group had significantly higher WBC than the POU5F1Bhigh group (20.2×109 vs. 4.6×109 L⁻¹, P=0.021). Among whole-cohort AML, non-APL AML, and intermediate-risk AML, POU5F1Bhigh patients had obviously higher complete remission (CR) rates than POU5F1Blow patients (P=0.012, P=0.012 and P=0.027). In addition, Kaplan-Meier analysis demonstrated better overall survival (OS, P=0.019, P=0.007 and P=0.046, respectively) in POU5F1Bhigh patients compared with POU5F1Blow patients. Furthermore, in multivariate survival analysis, POU5F1B was independently associated with OS in non-APL AML patients and intermediate-risk AML as a favorable prognostic factor. CONCLUSIONS POU5F1B was frequently underexpressed in AML, and might contribute to the diagnosis and prognosis of AML.

Structural studies of the binding of an antagonistic cyclic peptide to the VEGFR1 domain 2.

Physiological and pathological angiogenesis is mainly regulated by the binding of the vascular endothelial growth factor (VEGF) to its receptors (VEGFRs). Antagonists of VEGFR are very attractive for the treatment of diseases related to excessive angiogenesis. Our previously designed C-terminal alkylated cyclic peptides [YKDEGLEE]-NHR (R = alkyl, arylalkyl) disrupt the interaction between VEGF and VEGFRs in biological assays. In this paper, we described the structural studies of the binding of one of these cyclic peptides named Peptide 3 to the VEGFR1 domain 2 (VEGFR1-D2). The molecular docking and NMR mapping identified the binding site on VEGFR1-D2. The anti-angiogenic effect of our peptide was evaluated by an experiment of VEGF-induced tube formation in two cell lines, retinal cell type RF6/A and vascular endothelial cell type HUVEC. Some new peptides were also synthesized and compared by an ELISA-based assay, in order to verify their ability to disrupt the formation of the complex VEGF-A/VEGFR1. In conclusion, the structural studies of Peptide 3 with VEGFR1-D2 will help the design of more efficient VEGFR antagonists. Moreover, Peptide 3, with improved receptor binding affinity, could be more suitable for VEGFR targeting bioimaging studies once labeled.

Novel Cucurbitane Triterpenes from the Tubers of Hemsleya amabilis with Their Cytotoxic Acitivity.

Chemical research of the medicinal plant Hemsleya amabilis (Cucurbitaceae) yielded five new cucurbitane-type triterpenes hemslelis A⁻E (1⁻5) by silica gel column, ODS column, and semi-HPLC techniques. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Compounds 1⁻5 were evaluated for their cytotoxic activities against three human tumor cell lines, Hela, HCT-8, and HepG-2, with the IC50 ranging from 5.9 to 33.9 µM compared to Cisplatin.

Low Expression of FUS1 Is Negatively Correlated with miR-378 and May Predict Adverse Prognoses in Acute Myeloid Leukemia.

FUS1 is a tumor suppressor gene that has been found to be frequently lost in a variety of solid tumors. In this study, we aimed to investigate the expression status of the FUS1 gene in acute myeloid leukemia (AML), as well as its clinical significance. We further explored the correlation between the expression of FUS1 and miR-378 in AML. We detected expression of the FUS1 transcript in bone marrow mononuclear cells from 23 controls and 158 newly diagnosed AML patients by real-time quantitative polymerase chain reaction. Downregulated FUS1 expression was found in 139 out of 158 (87.97%) AML cases; this rate was significantly lower than that in all 23 controls (p = 0.012). Receiver operating characteristic curve analysis revealed that the FUS1 transcript level could discriminate AML patients from controls effectively (area under the ROC curve = 0.663). Kaplan-Meier analysis demonstrated that non-M3-AML patients with a low FUS1 expression had a shorter overall survival (p = 0.049) and leukemia-free survival (p = 0.051) than those with a high FUS1 expression. Furthermore, we studied the correlation between the expression of FUS1 and miR-378 in 53 newly diagnosed AML patients. We found that the correlation coefficient was -0.346, which showed that FUS1 and miR-378 were negatively correlated in AML patients (p = 0.011). These results indicate that the low expression of FUS1 is a common molecular event in AML.