Role of prostaglandin E2 and its receptors in chronic liver disease.

Chronic liver disease (CLD) is a major global health burden in terms of growing morbidity and mortality. Although many conditions can cause CLD, leading to cirrhosis and hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most common culprits. Prostaglandin E2 (PGE2), produced in the liver, is an important lipid mediator derived from the ω-6 polyunsaturated fatty acid, arachidonic acid, and plays a critical role in hepatic homeostasis. The physiological effects of PGE2 are mediated through four classes of E-type prostaglandin (EP) receptors, namely EP1, EP2, EP3 and EP4. In recent years, an increasing number of studies has been done to clarify the effects of PGE2 and EP receptors in regulating liver function and the pathogenesis of CLD to create a new potential clinical impact. In this review, we overview the biosynthesis and regulation of PGE2 and discuss the role of its synthesizing enzymes and receptors in the maintenance of normal liver function and the development and progress of CLD. We also discuss the potential of the PGE2-EP receptors system in treating CLD with various etiologies.

Extranodal Extension at Pretreatment MRI and the Prognostic Value for Patients with Rectal Cancer.

Background Detection of extranodal extension (ENE) at pathology is a poor prognostic indicator for rectal cancer, but whether ENE can be identified at pretreatment MRI is, to the knowledge of the authors, unknown. Purpose To evaluate the performance of pretreatment MRI in detecting ENE using a matched pathologic reference standard and to assess its prognostic value in patients with rectal cancer. Materials and Methods This single-center study included a prospective development data set consisting of participants with rectal adenocarcinoma who underwent pretreatment MRI and radical surgery (December 2021 to January 2023). MRI characteristics were identified by their association with ENE-positive nodes (χ2 test and multivariable logistic regression) and the performance of these MRI features was assessed (area under the receiver operating characteristic curve [AUC]). Interobserver agreement was assessed by Cohen κ coefficient. The prognostic value of ENE detected with MRI for predicting 3-year disease-free survival was assessed by Cox regression analysis in a retrospective independent validation cohort of patients with locally advanced rectal cancer (December 2019 to July 2020). Results The development data set included 147 participants (mean age, 62 years ± 11 [SD]; 87 male participants). The retrospective cohort included 110 patients (mean age, 60 years ± 9; 79 male participants). Presence of vessel interruption and fusion (both P < .001), heterogeneous internal structure, and the broken-ring and tail signs (odds ratio range, 4.10-23.20; P value range, <.001 to .002) were predictors of ENE at MRI, and together achieved an AUC of 0.91 (95% CI: 0.88, 0.93) in detecting ENE. Interobserver agreement was moderate for the presence of vessel interruption and fusion (κ = 0.46 for both) and substantial for others (κ = 0.61-0.67). The presence of ENE at pretreatment MRI was independently associated with worse 3-year disease-free survival (hazard ratio, 3.00; P = .02). Conclusion ENE can be detected at pretreatment MRI, and its presence was associated with worse prognosis for patients with rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Eberhardt in this issue.

Fully semantic segmentation for rectal cancer based on post-nCRT MRl modality and deep learning framework.

PURPOSE: Rectal tumor segmentation on post neoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) has great significance for tumor measurement, radiomics analysis, treatment planning, and operative strategy. In this study, we developed and evaluated segmentation potential exclusively on post-chemoradiation T2-weighted MRI using convolutional neural networks, with the aim of reducing the detection workload for radiologists and clinicians. METHODS: A total of 372 consecutive patients with LARC were retrospectively enrolled from October 2015 to December 2017. The standard-of-care neoadjuvant process included 22-fraction intensity-modulated radiation therapy and oral capecitabine. Further, 243 patients (3061 slices) were grouped into training and validation datasets with a random 80:20 split, and 41 patients (408 slices) were used as the test dataset. A symmetric eight-layer deep network was developed using the nnU-Net Framework, which outputs the segmentation result with the same size. The trained deep learning (DL) network was examined using fivefold cross-validation and tumor lesions with different TRGs. RESULTS: At the stage of testing, the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD) were applied to quantitatively evaluate the performance of generalization. Considering the test dataset (41 patients, 408 slices), the average DSC, HD95, and MSD were 0.700 (95% CI: 0.680-0.720), 17.73 mm (95% CI: 16.08-19.39), and 3.11 mm (95% CI: 2.67-3.56), respectively. Eighty-two percent of the MSD values were less than 5 mm, and fifty-five percent were less than 2 mm (median 1.62 mm, minimum 0.07 mm). CONCLUSIONS: The experimental results indicated that the constructed pipeline could achieve relatively high accuracy. Future work will focus on assessing the performances with multicentre external validation.

PET/CT Examination of Teratomas after Stem Cell Transplantation for a Spinal Cord Injury: A Case Report.

BACKGROUND: In clinical practice, stem cell transplantation has become an effective method for treating spinal cord nerve injury. Up to now, there has been no report on teratoma caused by transplanted stem cell's abnormal differentiation in the clinic, especially in the analysis of imaging manifestations. Therefore, this article aims to analyze the PET/CT imaging manifestations of teratoma caused by stem cell transplantation to improve the imaging diagnosing capability. CASE PRESENTATION: A patient with a spinal cord injury who had received a stem cell transplant was examined by PET/CT on September 10th, 2020. The PET/CT images of the lesion showed irregular mixed low density on the right side of the erector spinae muscle area at the level of the cervical 3-5 vertebral body, with a maximum cross-section of 9.1×3.9 cm. The 18F-FDG metabolism of the lesion was increased, and the maximum standard uptake value (SUVmax) was 10.7. The boundary was unclear with the third cervical vertebra and cervical 3 and 4-level vertebral plates. Based on the patient's medical history, the lesion was diagnosed as an abnormal proliferative tumor, which was consistent with the pathological examination results. CONCLUSION: To date, there have been no clinical reports on teratomas caused by stem cell transplantation for spinal cord injury at home or abroad. This case report enhances the knowledge of the diagnosis and treatment methods of this type of disease and confirms the diagnostic value of PET/CT examination.

Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients.

BACKGROUND: About 10%-31% of colorectal liver metastases (CRLM) patients would concomitantly show hepatic lymph node metastases (LNM), which was considered as sign of poor biological behavior and a relative contraindication for liver resection. Up to now, there's still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM, except for pathology examination of lymph node after resection. AIM: To compare the ability of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery. METHODS: In this retrospective study, 97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging, including DWI with ten b values before and after chemotherapy. Various parameters, such as the apparent diffusion coefficient from the mono-exponential model, and the true diffusion coefficient, the pseudo-diffusion coefficient, and the perfusion fraction derived from the intravoxel incoherent motion model, along with distributed diffusion coefficient (DDC) and α from the stretched-exponential model (SEM), were measured. The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups. A nomogram was constructed to predict the hepatic lymph node status. The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient. RESULTS: Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes. A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients, with an area under the curve of 0.873. Furthermore, parameters from SEM showed substantial repeatability. CONCLUSION: The developed nomogram, incorporating the pre-treatment DDC and the short axis of the largest lymph node, can be used to predict the presence of hepatic LNM in CRLM patients undergoing chemotherapy before surgery. This nomogram was proven to be more valuable, exhibiting superior diagnostic performance compared to quantitative parameters derived from multiple b values of DWI. The nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.

Network pharmacology-based approach to understand the effect and mechanism of chrysophanol against cognitive impairment in Wilson disease.

Wilson disease (WD) is a rare hereditary copper metabolism disorder, wherein cognitive impairment is a common clinical symptom. Chrysophanol (CHR) is an active compound with neuroprotective effects. The study aims to investigate the neuroprotective effect of CHR in WD and attempted to understand the potential mechanisms. Network pharmacology analysis was applied to predict the core target genes of CHR against cognitive impairment in WD. The rats fed with copper-laden diet for 12 weeks, and the effect of CHR on the copper content in liver and 24-h urine, the learning and memory ability, the morphological changes and the apoptosis level of neurons in hippocampal CA1 region, the expression level of Bax, Bcl-2, Cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT proteins were detected. Network pharmacology analysis showed that cell apoptosis and PI3K-AKT signaling pathway might be the main participants in CHR against cognitive impairment in WD. The experiments showed that CHR could reduce the copper content in liver, increase the copper content in 24-h urine, improve the ability of the learning and memory, alleviate the damage and apoptosis level of hippocampal neurons, down-regulate the expression of Bax, Cleaved Caspase-3, and up-regulate the expressions of Bcl-2, p-PI3K/PI3K, p-AKT/AKT. These results suggested that CHR could alleviate cognitive impairment in WD by inhibiting cell apoptosis and triggering the PI3K-AKT signaling pathway.

Radiomics analysis from magnetic resonance imaging in predicting the grade of nonfunctioning pancreatic neuroendocrine tumors: a multicenter study.

OBJECTIVES: To explore the potential of radiomics features to predict the histologic grade of nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) patients using non-contrast sequence based on MRI. METHODS: Two hundred twenty-eight patients with NF-PNETs undergoing MRI at 5 centers were retrospectively analyzed. Data from center 1 (n = 115) constituted the training cohort, and data from centers 2-5 (n = 113) constituted the testing cohort. Radiomics features were extracted from T2-weighted images and the apparent diffusion coefficient. The least absolute shrinkage and selection operator was applied to select the most important features and to develop radiomics signatures. The area under receiver operating characteristic curve (AUC) was performed to assess models. RESULTS: Tumor boundary, enhancement homogeneity, and vascular invasion were used to construct the radiological model to stratify NF-PNET patients into grade 1 and 2/3 groups, which yielded AUC of 0.884 and 0.684 in the training and testing groups. A radiomics model including 4 features was constructed, with an AUC of 0.941 and 0.871 in the training and testing cohorts. The fusion model combining the radiomics signature and radiological characteristics showed good performance in the training set (AUC = 0.956) and in the testing set (AUC = 0.864), respectively. CONCLUSION: The developed model that integrates radiomics features with radiological characteristics could be used as a non-invasive, dependable, and accurate tool for the preoperative prediction of grade in NF-PNETs. CLINICAL RELEVANCE STATEMENT: Our study revealed that the fusion model based on a non-contrast MR sequence can be used to predict the histologic grade before operation. The radiomics model may be a new and effective biological marker in NF-PNETs. KEY POINTS: The diagnostic performance of the radiomics model and fusion model was better than that of the model based on clinical information and radiological features in predicting grade 1 and 2/3 of nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Good performance of the model in the four external testing cohorts indicated that the radiomics model and fusion model for predicting the grades of NF-PNETs were robust and reliable, indicating the two models could be used in the clinical setting and facilitate the surgeons' decision on risk stratification. The radiomics features were selected from non-contrast T2-weighted images (T2WI) and diffusion-weighted imaging (DWI) sequence, which means that the administration of contrast agent was not needed in grading the NF-PNETs.

Small arteriole sign: an imaging feature for staging T4a colon cancer.

OBJECTIVES: By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance. METHODS: Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test. RESULTS: In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001). CONCLUSION: Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer. CLINICAL RELEVANCE STATEMENT: Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer. KEY POINTS: • The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. • Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. • SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.

Establishment of a digital electrocardiogram telemonitoring system and remote consultation service.

BACKGROUND: The use of telemonitoring electrocardiogram (ECG) improves the detection rate of various arrhythmias as it offers an extended recording time and does not impose activity restrictions. However, many community hospitals lack the resources to conduct this test due to a lack of cardiac function specialists and antiquated screening equipment. OBJECTIVE: To establish a digital ECG telemonitoring system and remote consultation service between tertiary hospitals and community medical service stations to improve diagnosis and treatment effectiveness. METHODS: We used the PI ECG telemonitoring data acquisition system, with a personal digital assistant (PDA) or computer serving as the platform for ECG acquisition, storage, display, printing, and transmission. We introduced this system to standardize the storage and transmission of ECG telemonitoring data, and ensure accurate transmission, reproducibility, and preservation of data. RESULTS: The implementation of the PI ECG telemonitoring data acquisition system enabled the sharing of remote ambulatory electrocardiography data between Beijing Shijitan Hospital and its affiliated community hospitals. This has resulted in reduced waiting times for patients to receive reports (from 0.3 to 1 hour, to 0.1 or less), shortened consultation times (from 2 hours to 0.1 hour), and improved patient satisfaction with consultations (> 20% of the patients reported they were highly satisfied). The system successfully combined the goals of intelligence, real-time synchronization, and efficiency, revolutionizing ECG telemonitoring diagnosis in the network era. CONCLUSION: Sharing digital telematics information between tertiary and community hospitals enables a tiered approach to diagnosis and treatment and allows for more efficient, accurate, and convenient remote diagnostics.

The psoas muscle density as a predictor of postoperative complications in elderly patients undergoing rectal cancer resection.

Background: Muscle depletion that impairs normal physiological function in elderly patients leads to poor prognosis. This study aimed to evaluate the association between total abdominal muscle area (TAMA), total psoas area (TPA), psoas muscle density (PMD), and short-term postoperative complications in elderly patients with rectal cancer. Methods: All elderly patients underwent rectal cancer resection with perioperative abdominal computed tomography (CT). Complications were assessed according to the Clavien-Dindo classification. Severe complications were defined as grade III-V following the Clavien-Dindo classification. Univariate and multivariate analyses were performed to evaluate risk factors of short-term severe postoperative complications. Results: The cohort consisted of 191 patients with a mean age of 73.60 ± 8.81 years. Among them, 138 (72.25%) patients had Clavien-Dindo 0- II, 53 (27.75%) patients had severe postoperative complications (Clavien-Dindo III-V), and 1(0.52%) patient died within 30 days of surgery. PMD was significantly higher in the Clavien-Dindo 0-II cohort compared to the Clavien-Dindo III-V cohort (p=0.004). Nevertheless, TAMA and TPA failed to exhibit significant differences. Moreover, the multivariate regression analysis implied that advanced age [OR 1.07 95%CI (1.02-1.13) p=0.013], male [OR 5.03 95%CI (1.76-14.41) p=0.003], high charlson comorbidity index (CCI) score [OR 3.60 95%CI (1.44-9.00) p=0.006], and low PMD [OR 0.94 95%CI (0.88-0.99) p=0.04] were independent risk factors of Clavien-Dindo III-V. Conclusion: Preoperative assessment of the PMD on CT can be a simple and practical method for identifying elderly patients with rectal cancer at risk for severe postoperative complications.

Molecular characterization of Clostridium perfringens isolates from a tertiary children's hospital in Guangzhou, China, establishing an association between bacterial colonization and food allergies in infants.

BACKGROUND: Cow's milk protein allergy (CMPA) is one of the most common types of food allergy in infants. Faecal pathogen cultures showed that the positive rate of Clostridium perfringens was more than 30%, which was significantly higher than that for other bacteria. Therefore, it is speculated that Clostridium perfringens colonization may be one of the pathogenetic factors for CMPA in infants. We conducted a real-world evidence study. Infants aged 0-6 months with diarrhoea and mucoid and/or bloody stools were recruited from a large tertiary hospital in China. Faecal pathogen cultures for the detection of Clostridium perfringens were confirmed by flight mass spectrometry, and potential toxin genes were identified using PCR. After 12 months of follow-up, the diagnoses of CMPA and food allergy were recorded. The correlation was assessed by Pearson correlation analysis. RESULTS: In this study, 358 infants aged 0-6 months with gastrointestinal symptoms and faecal pathogen cultures were recruited. A total of 270 (44.07% girls; mean age, 2.78 ± 2.84 months) infants were followed up for 12 months. Overall, the rate of positivity for Clostridium perfringens in faecal pathogen cultures was 35.75% (128/358) in infants aged ≤ 6 months. The earliest Clostridium perfringens colonization was detected within 2 days after birth. The majority of Clostridium perfringens isolates were classified as type C in 85 stool samples. In the Clostridium perfringens-positive group, 48.21% (54/112) of infants were clinically diagnosed with food allergies after 12 months, including 37.5% (42/112) with CMPA, which was significantly higher than that of the negative group, with 7.59% (12/158) exhibiting food allergies and 5.06% (8/158) presenting CMPA (P < 0.0001). Faecal Clostridium perfringens positivity was significantly correlated with CMPA, food allergy, faecal occult blood, faecal white blood cells, antibiotic use, increased peripheral blood platelet counts, and decreased haemoglobin levels (P < 0.0001). CONCLUSIONS: This study demonstrates that intestinal colonization by Clostridium perfringens is common in infants. The majority of Clostridium perfringens isolates are classified as type C. Colonization of the intestine by Clostridium perfringens is associated with the development of CMPA and food allergy in infants.

Complete chloroplast genome of Adonis pseudoamurensis W.T.Wang (Ranunculaceae).

Adonis pseudoamurensis W.T. Wang 1980 is an important traditional medicinal plant used for the treatment of cardiac diseases. The complete chloroplast (cp) genome of Adonis pseudoamurensis is reported for the first time in this study. The circular cp genome is 156,917 bp in length, consisting of a large single-copy region (86,262 bp), a small single-copy region (18,067 bp), and two inverted repeat regions (26,294 bp). The genome encodes 129 genes, comprising 84 protein-coding genes, 37 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis showed that A. pseudoamurensis is closely related to A. amurensis.

STAT3-EphA7 axis contributes to the progression of esophageal squamous cell carcinoma.

BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.

Supportive care needs of patients who had a stroke: a scoping review protocol.

INTRODUCTION: Incidences of stroke are on the rise and approximately 80 million stroke survivors worldwide live with disabilities. Supportive care needs of stroke survivors are not adequately defined, and the assessment tools to help care service providers identify these needs are unclear. The overall aim of this scoping review will be to map the supportive care needs of stroke survivors against the Supportive Care Needs Framework. METHODS AND ANALYSIS: This scoping review will be conducted following Arksey and O'Malley's methodological framework and Joanna Briggs Institute (JBI) updated methodological guidance for scoping review. This review will mainly use Arksey and O'Malley's methodological framework as the basic framework. The review will also follow JBI's updated methodological guidance for scoping reviews to optimise the review. For the search strategy, the three-step method recommended by the JBI will be used in the study. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Six English databases, including PubMed, CINAHL, Web of Science, Embase, Cochrane Library and PsycInfo, and four Chinese databases, including CNKI, Wanfang, VIP and China Biomedical Literature Database will be systematically searched from inception to the present. Studies published in English and Chinese will be included. ETHICS AND DISSEMINATION: Ethical approval is not required as this scoping review does not involve human participants. The findings shall be disseminated at scientific conferences and published in a peer-reviewed journal.

Effectiveness of acceptance and commitment therapy in patients who had a stroke: a systematic review protocol.

INTRODUCTION: Stroke is a common chronic disease with high rates of morbidity and disability and a great burden on patients. As a result, it affects daily activities of patients and causes negative emotions, which seriously affect their quality of life. As a new type of cognitive-behavioural therapy, acceptance and commitment therapy (ACT) may be useful to improve the mental health of patients who had a stroke. This study aimed to systematically evaluate the intervention effect of ACT in patients who had a stroke, which may provide further clinical evidence. METHODS AND ANALYSIS: A systematic search of databases, including CNKI, WanFang Data, VIP, CBM, PubMed, Embase, Cochrane Library, CINAHL and APA PsycArticles, will be conducted from their inception to 31 October 2022. All randomised controlled trials, quasi-experiments and case studies relevant to ACT will be included in English and Chinese. Two independent reviewers will conduct the review, with data extraction and quality evaluation. Review Manager V.5.4 will be used to assess the risk of bias and meta-analysis. ETHICS AND DISSEMINATION: This systematic review does not require formal ethical approval, because all data will be analysed anonymously. The results will provide an overall review and evidence of the efficacy of ACT in patients who had a stroke. These findings will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42022355629.

[Effect of Inhibiting SIX1 Expression on Drug-resistance of Acute Myeloid Leukemia Cell Line HL-60/ADR Cells].

OBJECTIVE: To establish HL-60 cells and adriamycin resistant HL-60 cells (H-60/ADR) in which the expression of homologous box gene 1 (SIX1) was inhibited, and investigate the effect of inhibiting the expression of SIX1 on the drug resistance. METHODS: Lentivirus was used to transfect HL-60 and HL-60/ADR cells, and the cell lines stably inhibiting the expression of SIX1 were screened by puromycin. CCK-8 assay was used to detect the proliferation ability of cells in each group, apoptosis kit was used to detect the cell apoptosis, and real-time quantitative PCR was used to detect the expression level of drug-resistant related genes. RESULTS: HL-60 and HL-60/ADR stably transfected cell lines with down-regulation of SIX1 expression were successfully constructed. Compared with control group, the inhibition of SIX1 expression significantly inhibited the proliferation of HL-60 and HL-60/ADR cells (P <0.05), increased the apoptosis rate (P <0.05), and the sensitivity of cells to adriamycin increased after inhibition of SIX1 expression. CONCLUSION: Inhibition of SIX1 expression can improve cell sensitivity to adriamycin, and its role in reversing drug resistance may be related to the promotion of apoptosis gene expression.

Synthesis, Characterization and Biosafety Evaluation of Hollow Gold Nanospheres.

Objectives In order to assess the biosafety of HAuNS using zebrafish models and the cancer cell lines HepG2, HEK293, and A549, this study prepared HAuNS in a variety of sizes and alterations. Methods By oxidizing cobalt nanoparticles encased in gold shells, HAuNS were created. In the meantime, PEG- and PEI-coated HAuNS were created. The diameters of the HAuNS that were produced were 30~40 nm, 50~60 nm, and 70~80 nm. MTT assay was used to assess the toxicity of HAuNS on HepG2, HEK293, and A549 cells. For the investigation of their toxicities, HAuNS (50~60 nm) of various concentrations were incubated with zebrafish embryos. Then, cell death was determined using acridine orange staining.

Bidirectional crosstalk of the cAMP/ROS-dependent signaling pathways in inflammatory macrophage: An activation of formononetin.

Bacterial lipopolysaccharide (LPS) is a toxic stimulant to macrophage inflammation. Inflammation intersects cell metabolism and often directs host immunopathogenesis stress. We aim here at pharmacological discovering of formononetin (FMN) action, to which anti-inflammatory signaling spans across immune membrane receptors and second messenger metabolites. In ANA-1 macrophage stimulated by LPS, and simultaneous treatment with FMN, results show the Toll-like receptor 4 (TLR4) and estrogen receptor (ER) signals, in concert with reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP), respectively. LPS stimulates inactivation of the ROS-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) by upregulating TLR4, but it does not affect cAMP. However, FMN treatment not only activates Nrf2 signaling by TLR4 inhibition, but also it activates cAMP-dependent protein kinase activities by upregulating ER. The cAMP activity gives rise to phosphorylation (p-) of protein kinase A, liver kinase B1 and 5'-AMP activated protein kinase (AMPK). Moreover, bidirectional signal crosstalk is amplified between p-AMPK and ROS, as FMN combinational validation with AMPK activator/inhibitor/target small-interfering RNA or ROS scavenger. The signal crosstalk is well positioned serving as the 'plug-in' knot for rather long signaling axis, and the immune-to-metabolic circuit via ER/TLR4 signal transduction. Collectively, convergence of the FMN-activated signals drives significant reduction of cyclooxygenase-2, interleukin-6 and NLR family pyrin domain-containing protein 3, in LPS-stimulated cell. Although anti-inflammatory signaling is specifically related to the immune-type macrophage, the p-AMPK antagonizing effect arises from FMN combination with ROS scavenger H-bond donors. Information of our work assists in predictive traits against macrophage inflammatory challenges, using phytoestrogen discoveries.

16α-OHE1, a novel oestrogen metabolite, attenuates dysfunction of left ventricle contractility via regulation of autophagy after myocardial ischemia and reperfusion.

BACKGROUND: Myocardial ischemia-reperfusion (MI/R) can exacerbate the initial cardiac damage in the myocardial functional changes, including dysfunction of left ventricular contractility. Oestrogen has been proven to protect the cardiovascular system. However, whether the oestrogen or its metabolites play the main role in attenuating dysfunction of left ventricular contractility is unknown. METHODS AND RESULTS: This study used the LC-MS/MS to detect oestrogen and its metabolites in clinical serum samples (n = 62) with heart diseases. After correlation analysis with markers of myocardial injury including cTnI (P < 0.01), CK-MB (P < 0.05), and D-Dimer (P < 0.001), 16α-OHE1 was identified. The result from LC-MS/MS in female and ovariectomised (OVX) rat serum samples (n = 5) matched the findings in patients. In MI/R model of animal, the recovery of left ventricular developed pressure (LVDP), rate pressure product (RPP), dp/dtmax and dp/dtmin after MI/R in OVX or male group were worsened than those in female group. Also, the infarction area of OVX or male group was larger than that in females (n = 5, p < 0.01). Furthermore, LC3 II in the left ventricle of OVX and male group was lower than that in females (n = 5, p < 0.01) by immunofluorescence. In H9C2 cells, after the application of 16α-OHE1, the number of autophagosomes was further increased and other organelles improved in MI/R. Simultaneously, LC3 II, Beclin1, ATG5, and p-AMPK/AMPK were increased, and p-mTOR/mTOR was decreased (n = 3, p < 0.01) by Simple Western. CONCLUSION: 16α-OHE1 could attenuate left ventricle contractility dysfunction via autophagy regulation after MI/R, which also offered fresh perspectives on therapeutical treatment for attenuating MI/R injury.

[Determination of seven paraben preservatives in aquatic seasoning using solid-phase extraction coupled with high performance liquid chromatography].

Seven parabens are widely used in soy sauce, vinegar, jam, oyster sauce, stuffing, and other foods. The long-term intake of large amounts of parabens and similar substances may be harmful to the human body. Therefore, the addition of paraben preservatives to food should be strictly controlled. The current detection method is applicable to single target compound and several food categories, and the experimental pretreatment method involves extraction with anhydrous ethyl ether, which is a toxic reagent. Moreover, interferences in the analysis of parabens via gas chromatography limit the versatility and accuracy of the detection method. Herein, a novel method based on solid-phase extraction (SPE) coupled with high performance liquid chromatography (HPLC) was developed for the determination of seven paraben preservatives (methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate, and heptyl p-hydroxybenzoate) in oyster sauce, shrimp sauce, and fish sauce. Compared with the conventional method, the proposed work enables the determination of more compounds, thereby expanding its scope of application to different food types. This strategy also optimizes the pretreatment method and device parameters. The samples were extracted with methanol and 20% methanol aqueous solution by ultrasonication, respectively, and then centrifuged. The experimental pretreatment method was enriched, and sample clean-up was conducted using a MAX SPE column. The seven parabens were separated using a Chromcore 120 C18 column (150 mm×4.6 mm, 3.0 µm). Gradient elution was performed with acetonitrile-5 mmol/L ammonium acetate aqueous solution as the mobile phase (initial mobile phase volume ratio, 30∶70). The flow rate was 0.7 mL/min, and the column temperature was 35 ℃. A diode array detector with a detection wavelength of 254 nm was also used. The seven paraben preservatives showed good linearity in the range of 0.5-50.0 mg/L, with correlation coefficients greater than 0.9999. The limits of detection (LODs) and quantification (LOQs) for the seven paraben preservatives were 0.2-0.4 mg/kg and 0.5-1.3 mg/kg, respectively. A spiked recovery test was conducted using oyster sauce, shrimp sauce, and fish sauce at three spiked levels of 2, 40, and 200 mg/kg. Good recoveries for the seven paraben preservatives were obtained and the recoveries of the analytes in oyster sauce, shrimp sauce, and fish sauce were 91.0%-102%, 95.5%-106%, and 95.0%-105%, respectively, with relative standard deviations of ≤6.97%. Compared with the liquid-liquid extraction method, the proposed method demonstrated better purification effects. The recoveries of the seven paraben preservatives extracted using this method were also much higher than those obtained from liquid-liquid extraction. We determined the contents of these preservatives in 135 food products using the method established in this study and detected methyl p-hydroxybenzoate and ethyl p-hydroxybenzoate in soy sauce, vinegar, and pickles. Thus, the established method can be used for the effective determination of seven parabens in aquatic seasoning such as oyster sauce, shrimp sauce, and fish sauce.