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Matrine (MT) is a major bioactive compound extracted from

The prognostic significance of conversion into a shockable rhythm in patients who experienced out-of-hospital cardiac arrest (OHCA) with an initially nonshockable rhythm is controversial, perhaps due to the timing of rhythm conversion not being considered previously. We aimed to compare the different prognoses of patients with OHCA and early and late conversion of their rhythm into a shockable rhythm.This was a single-centre retrospective cohort study. We enrolled patients with OHCA who were sent to a medical centre in central Taiwan from 2016 to 2020. Patients18 years old, those with cardiac arrest due to trauma or a circumstantial cause, and those for whom resuscitation was not attempted were excluded. Patients were divided into two groups in accordance with presentation with an initially shockable rhythm. Those with an initially nonshockable rhythm were divided into three subgroups: early-conversion, late-conversion, and nonconversion groups. The primary outcome was the neurological functional status upon discharge from hospital.A total of 1645 patients with OHCA were included: initially shockable rhythm group, 339; early conversion group, 68; late-conversion group, 166; and nonconversion group, 1072. After adjustment, multivariate logistic regression revealed that a favourable neurological outcome was more common in the early conversion group than the nonconversion group (odds ratio [OR] 2.4; 95% confidence interval [CI], 1.1-5.3; p = 0.035), whereas the late-conversion group did not significantly differ from the nonconversion group (OR 0.5; 95% CI, 0.1-1.5; p = 0.211). The proportions of sustained return of spontaneous circulation and survival to discharge were also higher in the early conversion group than the late-conversion group (OR 2.9 95% CI 1.6-5.5, p = 0.001 and OR 4.5, 1.8-11.0, p = 0.001, respectively).In patients who experience OHCA and have an initially nonshockable rhythm, early conversion into a shockable rhythm resulted in a better prognosis, whereas late conversion was not significantly different from nonconversion.

It is well-established that the lack of accurate diagnostic modalities for prostate cancer (PCa) leads to overdiagnosis and overtreatments. Accordingly, this study aimed to assess the value of urine-derived exosomal prostate-specific membrane antigen (PSMA) as a biomarker for the diagnosis of PCa and clinically significant prostate cancer (csPCa).A total of 284 urine samples were collected from patients after the digital rectal examination (DRE). Urinary exosomes were extracted using commercial kits, and urine-derived exosomal PSMA was determined via enzyme-linked immunosorbent assay (ELISA). Evaluation of diagnostic accuracy of PSMA was performed via receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and waterfall plots.We found that urine-derived exosomal PSMA was significantly higher in PCa and csPCa than in benign prostatic hyperplasia (BPH) and BPH + non-aggressive prostate cancer (naPCa) groups (P 0.001). Furthermore, the urine-derived exosome PSMA yielded area under the ROC curve (AUC) values of 0.876 and 0.826 for detecting PCa and csPCa, respectively, suggesting better performance than traditional clinical biomarkers. Besides, when the cutoff value used corresponded to a sensitivity of 95%, urine-derived exosomal PSMA could avoid unnecessary biopsies in 41.2% of cases and missed only 0.7% of csPCa cases.Urine-derived exosomal PSMA exhibits a good diagnostic yield for detecting PCa and csPCa. Findings of the present study provide the foothold for future studies on cancer management and research in this patient population.

Background. Immunotherapy has been considered as a promising cancer treatment for hepatocellular carcinoma (HCC). However, due to the particular immune environment of the liver, identifying patients who could benefit from immunotherapy is critical in clinical practice. Methods. The pyroptosis gene expression database of 54 candidates from The Cancer Genome Atlas (TCGA) were collected to discover the critical prognostic-related pyroptosis genes. A novel pyroptosis gene model was established to calculate the risk score. Kaplan–Meier analysis and receiver operating characteristic curve (ROC) were used to verify its predictive ability. The International Cancer Genome Consortium (ICGC) data was collected as external validation data to verify the model’s accuracy. We employed multiple bioinformatics tools and algorithms to evaluate the tumor immune microenvironment (TIME) and the response to immunotherapy. Results. Our study found that most pyroptosis genes were expressed differently in normal and tumor tissues and that their expression was associated with the prognosis. Then, a precise four-pyroptosis gene model was generated. The one-year area under the curves (AUCs) among the training, internal, and external validation patients were 0.901, 0.727, and 0.671, respectively. An analysis of survival data revealed that individuals had a worse prognosis than patients with low risk. The analysis of TIME revealed that the low-risk group had more antitumor cells, fewer immunosuppressive cells, stronger immune function, less immune checkpoint gene expression, and better immunotherapy response than the high-risk group. Immunophenoscore (IPS) analysis also demonstrated that the low-risk score was related to superior immune checkpoint inhibitors therapy. Conclusion. A nomogram based on the four-pyroptosis gene signature was a novel tool to predict the effectiveness of immunotherapy for HCC. Therefore, individualized treatment targeting the pyroptosis genes may influence TIME and play an essential role in improving the prognosis in HCC patients.

Activation of hepatic stellate cells (HSCs) is a key cause of liver fibrosis. However, the mechanisms leading to the activation of HSCs are not fully understood. In the pathological process, acid-sensing ion channel 1a (ASIC1a) is widely involved in the development of inflammatory diseases, suggesting that ASIC1a may play an important role in liver fibrosis. We found that in an acidic environment, ASIC1a leads to HSC-T6 cell activation. Meanwhile, exosomes produced by activated HSC-T6 cells (HSC-EXOs) can be reabsorbed by quiescent HSC-T6 cells to promote their activation. Exosomes mainly carry miRNAs involved in intercellular information exchange. We performed exosome miRNA whole transcriptome sequencing. The results indicated that the acidic environment could alter the miRNA expression profile in the exosomes of HSC-T6 cells. Further studies revealed that ASIC1a promotes the activation of HSCs by regulating miR-301a-3p targeting B-cell translocation gene 1 (BTG1). In conclusion, our study found that ASIC1a may affect HSC activation through the exosomal miR-301a-3p/BTG1 axis, and inhibiting ASIC1a may be a promising treatment strategy for liver fibrosis.

Equine coronavirus (ECoV) was first identified in the USA and has been previously described in several countries. In order to test the presence of ECoV in China, we collected 51 small intestinal samples from donkey foals with diarrhoea from a donkey farm in Shandong Province, China between August 2020 and April 2021. Two samples tested positive for ECoV and full-length genome sequences were successfully obtained using next-generation sequencing, one of which was further confirmed by Sanger sequencing. The two strains shared 100% sequence identity at the scale of whole genome. Bioinformatics analyses further showed that the two Chinese strains represent a novel genetic variant of ECoV and shared the highest sequence identity of 97.05% with the first identified ECoV strain - NC99. In addition, it may be a recombinant, with the recombination region around the NS2 gene. To our knowledge, this is the first documented report of ECoV in China, highlighting its risk to horse/donkey breeding. In addition, its potential risk to public health also warrants further investigation.

Shao-hua Ren,1,2 Ya-fei Qin,1,2 Hong Qin,1,2 Hong-da Wang,1,2 Guang-ming Li,1,2 Yang-lin Zhu,1,2 Cheng-lu Sun,1,2 Bo Shao,1,2 Jing-yi Zhang,1,2 Jing-peng Hao,3 Hao Wang1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Department of Anorectal Surgery, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Hao Wang, Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Tel/Fax +01186-22-60362502, Email hwangca272@hotmail.comBackground: The prognostic value of m6A-related genes in hepatocellular carcinoma (HCC) and its correlation with the immune microenvironment still requires further investigation.Methods: Consensus clustering by m6A related genes was used to classify 374 patients with HCC from The Cancer Genome Atlas (TCGA) database. Then we performed the least absolute shrinkage and selection operator (LASSO) to construct the m6A related genes model. The International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) datasets were used to verify and evaluate the model. ESTIMATE, CIBERSORTx, the expression levels of immune checkpoint genes, and TIDE were used to investigate the tumor microenvironment (TME) and the response to immunotherapy. Gene set enrichment analyses (GSEA), tumor-associated macrophages (TAMs), and gene-drug sensitivity were also analyzed.Results: By expression value and regression coefficient of five m6A related genes, we constructed the risk score of each patient. The patients with a higher risk score had a considerably poorer prognosis in the primary and validated cohort. For further discussing TME and the response to immunotherapy, we divided the entire set into two groups based on the risk score. Our findings implied that the tumor-infiltrating lymphocytes (TILs) were proportional to the risk scores, which seemed to contradict that patients with higher scores had a poor prognosis. Further, we found that the high-risk group had higher expression of PD-L1, CTLA-4, and PDCD1, indicating immune dysfunction, which may be a fundamental reason for poor prognosis. This was further reinforced by the fact that the low-risk group responded better than the high-risk group to monotherapy and combination therapy.Conclusion: The m6A related risk score is a new independent prognostic factor that correlates with immunotherapy response. It can provide a new therapeutic strategy for improving individual immunotherapy in HCC.Keywords: hepatocellular carcinoma, N6-methyladenine, tumor immune microenvironment, immunotherapy, drug sensitivity

Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been probed in cerebral ischemia, while the regulatory mechanism of ZFAS1 in focal cerebral ischemia (FCI) via binding to microRNA (miR)-144-5p remains rarely explored. This study aims to decipher the function of ZFAS1 on FCI via sponging miR-144-5p to modulate fibroblast growth factor 7 (FGF7). The focal cerebral ischemia rat model was established by occlusion of the middle cerebral artery (MCAO) Lentivirus vectors altering ZFAS1, miR-144-5p or FGF7 expression were injected into rats before MCAO. Then, ZFAS1, miR-144-5p, and FGF7 levels were detected, the inflammatory factor level, oxidative stress level, angiogenesis, neurological function injury and neuronal apoptosis were assessed. The binding relations among ZFAS1, miR-144-5p and FGF7 were validated. ZFAS1 and FGF7 expression was elevated, while miR-144-5p expression was reduced in FCI rats. Decreased ZFAS1 or FGF7 or enriched miR-144-5p repressed the inflammatory response, oxidative stress, neuronal apoptosis, while it improved angiogenesis, and neurological function recovery; while up-regulated ZFAS1 exerted opposite effects. The augmented miR-144-5p or silenced FGF7 reversed the effects of enriched ZFAS1. ZFAS1 sponged miR-144-5p that targeted FGF7. Inhibition of lncRNA ZFAS1 improves functional recovery and angiogenesis after FCI via miR-144-5p/FGF7 axis. This study provides novel therapeutic targets for FCI treatment., Graphical Abstract

To analyze the epidemiological distribution, clinical characteristics, and prognostic risk factors of patients having severe fever with thrombocytopenia syndrome (SFTS).We enrolled 790 patients with SFTS divided into the ordinary group and the severe group, analyzed the clinical characteristics, and screened the risk factors of severious patients by univariate logistic regression analysis.Most of the 790 patients (SFTS) are farmers (84.56%). The proportion of patients with fieldwork history was 72.41%, of which 21.27% had a clear history of a tick bite and 98.61% were sporadic cases. The annual peak season is from April to November. 16.33% patients were not accompanied by fever. The incidence of severe thrombocytopenia was 47.59%. They were statistically significant between the 2 groups in indicators such as age, hypertension, coronary heart disease, diabetes mellitus, bunyavirus nucleic acid load and mean platelet count (P .05). Multivariate non conditional Logistic regression analysis showed that the risk factors of the mild patients deteriorating severe disease were age (OR = 1.985, P ≤ .003), diabetes mellitus (OR = 1.702, P ≤ .001), coronary heart disease (OR = 1.381, P ≤ .003), platelet count (OR = 2.592, P ≤ .001), viral nucleic acid loading (OR = 3.908, P ≤ .001).The incidence population and seasonal distribution characteristics of patients with SFTS are obvious. The risk factors for poor prognosis of severe patients are old age, multiple basic medical histories, high viral load, a serious decrease of mean platelet count, and delay of treatment time.

The application of Suzuki-Miyaura coupling reaction to forge the atropisomeric biaryls has seen remarkable progress but exploration of this chemistry to directly forge chiral C(aryl)-C(alkene) axis is underdeveloped. The replacement of arene substrates by alkenes intensifies the challenges in terms of reactivity, configurational atropostability of product and selectivity control. By meticulous ligand design and fine-tuning of reaction parameters, we identified a highly active 3,3'-triphenylsilyl-substituted phosphite ligand to realize arene-alkene Suzuki-Miyaura coupling of hindered aryl halides and vinyl boronates under very mild conditions. The axially chiral acyclic aryl-alkenes were generated in commendable efficiency, enantioselectivity and E/Z selectivity.

Over the past few decades, mechanisms of programmed cell death have attracted the scientific community because they are involved in diverse human diseases. Initially, apoptosis was considered as a crucial mechanistic pathway for programmed cell death; recently, an alternative regulated mode of cell death was identified, mimicking the features of both apoptosis and necrosis. Several lines of evidence have revealed that dysregulation of necroptosis leads to pathological diseases such as cancer, cardiovascular, lung, renal, hepatic, neurodegenerative, and inflammatory diseases. Regulated forms of necrosis are executed by death receptor ligands through the activation of receptor-interacting protein kinase (RIPK)-1/3 and mixed-lineage kinase domain-like (MLKL), resulting in the formation of a necrosome complex. Many papers based on genetic and pharmacological studies have shown that RIPKs and MLKL are the key regulatory effectors during the progression of multiple pathological diseases. This review focused on illuminating the mechanisms underlying necroptosis, the functions of necroptosis-associated proteins, and their influences on disease progression. We also discuss numerous natural and chemical compounds and novel targeted therapies that elicit beneficial roles of necroptotic cell death in malignant cells to bypass apoptosis and drug resistance and to provide suggestions for further research in this field.

Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp

BACKGROUND: Oxytocin (OXT) and corticotropin-releasing hormone (CRH) are both produced in hypothalamic paraventricular nucleus (PVN). Central CRH may cause depression-like symptoms, while peripheral higher OXT plasma levels were proposed to be a trait marker for bipolar disorder (BD). We aimed to investigate differential OXT and CRH expression in the PVN and their receptors in prefrontal cortex of major depressive disorder (MDD) and BD patients. In addition, we investigated mood-related changes by stimulating PVN-OXT in mice. METHODS: Quantitative immunocytochemistry and in situ hybridization were performed in the PVN for OXT and CRH on 6 BD and 6 BD-controls, 9 MDD and 9 MDD-controls. mRNA expressions of their receptors (OXTR, CRHR1 and CRHR2) were determined in anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) of 30 BD and 34 BD-controls, and 24 MDD and 12 MDD-controls. PVN of 41 OXT-cre mice was short- or long-term activated by chemogenetics, and mood-related behavior was compared with 26 controls. FINDINGS: Significantly increased OXT-immunoreactivity (ir), OXT-mRNA in PVN and increased OXTR-mRNA in DLPFC, together with increased ratios of OXT-ir/CRH-ir and OXTR-mRNA/CRHR-mRNA were observed in BD, at least in male BD patients, but not in MDD patients. PVN-OXT stimulation induced depression-like behaviors in male mice, and mixed depression/mania-like behaviors in female mice in a time-dependent way. INTERPRETATION: Increased PVN-OXT and DLPFC-OXTR expression are characteristic for BD, at least for male BD patients. Stimulation of PVN-OXT neurons induced mood changes in mice, in a pattern different from BD. FUNDING: National Natural Science Foundation of China (81971268, 82101592).

Background The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients’ adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (健脾补肾续贯方, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer. Methods A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy. Discussion This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518)

Glucagon-like peptide-1 (GLP-1), a novel type of glucose-lowering agent, has been reported to exert cardioprotective effects. However, the cardioprotective mechanism of GLP-1 on spontaneous hypertension-induced cardiac hypertrophy has not been fully elucidated. In this study, we revealed that liraglutide or alogliptin treatment ameliorated spontaneous hypertension-induced cardiac hypertrophy, as evidenced by decreased levels of cardiac hypertrophic markers (atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain), as well as systolic blood pressure, diastolic blood pressure, mean arterial pressure, and histological changes. Both drugs significantly reduced the levels of angiotensin II (AngII) and AngII type 1 receptor (AT1R) and upregulated the levels of AngII type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2), as indicated by a reduced AT1R/AT2R ratio. Simultaneously, treatment with liraglutide or alogliptin significantly increased GLP-1 receptor expression and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and downregulated the phosphorylation of mammalian target of rapamycin (mTOR), p70 ribosomal S6 protein kinase, and eukaryotic translation initiation factor 4E binding protein 1 in spontaneous hypertension rats. Furthermore, our data demonstrated that the AMPK inhibitor compound C or mTOR activator MHY1485 inhibited the anti-hypertrophic effect of GLP-1. In summary, our study suggests that liraglutide or alogliptin protects the heart against cardiac hypertrophy by regulating the expression of AngII/AT1R/ACE2 and activating the AMPK/mTOR pathway, and GLP-1 agonist can be used in the treatment of patients with cardiac hypertrophy.

BackgroundEmergency medical service (EMS) personnel have high COVID-19 risk during resuscitation. The resuscitation protocol for patients with out-of-hospital cardiac arrest (OHCA) was modified in response to the COVID-19 pandemic. However, how the adjustments in the EMS system affected patients with OHCA remains unclear.MethodsWe analysed data from the Taichung OHCA registry system. We compared OHCA outcomes and rescue records for 622 cases during the COVID-19 outbreak period (1 February to 30 April 2020) with those recorded for 570 cases during the same period in 2019.ResultsThe two periods did not differ significantly with respect to patient age, patient sex, the presence of witnesses or OHCA location. Bystander cardiopulmonary resuscitation and defibrillation with automated external defibrillators were more common in 2020 (52.81% vs 65.76%, pConclusionEMS response time for patients with OHCA was prolonged during the COVID-19 pandemic. Early advanced life support by EMS personnel remains crucial for patients with OHCA.

Purpose Due to shared hepatic metabolism, concomitant medication with a proton pump inhibitor (PPI) and clopidogrel might reduce the effectiveness of clopidogrel in the prevention of cardiovascular events after percutaneous coronary intervention (PCI). We aimed to examine the risk of major cardiovascular events after PCI comparing patients who used clopidogrel together with PPI with those who used clopidogrel alone. Methods This Swedish nationwide cohort study included patients who received clopidogrel after primary PCI in 2005–2019. Patients were followed for up to 12 months after PCI. Data were retrieved from the Swedish Prescribed Drug Registry, Patient Registry, Cancer Registry, and Cause of Death Registry. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events comparing PPI users (exposed) with non-users of PPI (non-exposed). The HRs were adjusted for sex, age, comorbidity, calendar period, obesity, diabetes, anti-diabetic medication, tobacco-related diseases, hypertension, and congestive heart failure. Results The cohort included 99,836 patients who received clopidogrel after primary PCI. Among these, 35,772 (35.8%) received concomitant PPI. Compared to non-users, PPI users had increased adjusted HRs of all study outcomes, i.e., the main outcome myocardial infarction (HR = 1.23, 95% CI 1.15–1.32) and the secondary outcomes coronary heart disease (HR = 1.28, 95% CI 1.24–1.33), stroke (HR = 1.21, 95% CI 1.05–1.40), and death due to coronary heart disease (HR = 1.52, 95% CI 1.37–1.69). The results were similar in analyses including both primary and secondary PCIs. Conclusions In patients who receive clopidogrel after PCI, concomitant use of PPI seems to increase the risk of major cardiovascular events.

The genus Paraconiothyrium has worldwide distribution with diverse host habitats and exhibits potential utilisation as biocontrol agent, bioreactor and antibiotic producer. In this review, we firstly comprehensively summarise the current taxonomic status of Paraconiothyrium species, including their category names, morphological features, habitats, and multigene phylogenetic relationships. Some Paraconiothyrium species possess vital biological functions and potential applications in medicine, agriculture, industry, and environmental protection. A total of 147 secondary metabolites have been reported so far from Paraconiothyrium, among which 95 are novel. This paper serves to provide an overview of their diverse structures with chemical classification and biological activities. To date, 27 species of Paraconiothyrium have been documented; however, only seven have been investigated for their secondary metabolites or biological functions. Our review is expected to draw more attention to this genus for providing a taxonomic reference, discovering extensive biological functions, and searching in-depth for new bioactive natural products.

BACKGROUND Familial hemophagocytic lymphohistiocytosis type 2 (FHL2) is a rare genetic disorder presenting with fever, hepatosplenomegaly, and pancytopenia secondary to perforin-1 (PRF1) mutation. FLH2 has been described in Chinese but usually presents after 1 year old. We describe a female Chinese neonate with FHL2 secondary to compound heterozygous PRF1 mutation with symptom onset before 1 mo old. We review Chinese FHL2 patients in the literature for comparison. CASE SUMMARY A 15-d-old female neonate was referred to our hospital for persistent fever and thrombocytopenia with diffuse petechiae. She was born to a G5P3 mother at 39 wk and 4 d via cesarean section secondary to breech presentation. No resuscitation was required at birth. She was described to be very sleepy with poor appetite since birth. She developed a fever up to 39.5°C at 7 d of life. Leukocytosis, anemia, and thrombocytopenia were detected at a local medical facility CONCLUSION A literature review identified 75 Chinese FHL2 patients, with only five presenting in the first year of life. Missense and frameshift mutations are the most common PRF1 mutations in Chinese, with 24.8% having c.1349C>T followed by 11.6% having c.65delC. The c.658G>C mutation has only been reported once in the literature and our case suggests it can be pathogenic, at least in the presence of another pathogenic mutation such as c.1066C>T.

Two new nucleoside derivatives, kipukasins O (1) and P (2), one new cyclohexenone derivative, arthropsadiol D (5), and one new natural product, (+)-2,5-dimethyl-3(2H)-benzofuranone (6), together with eleven known compounds (3, 4, 7-15), were obtained from the culture broth of the endophytic fungus Aspergillus polyporicola R2 isolated from the roots of Synsepalum dulcificum. Among them, the absolute configuration of compound 5 was determined by quantum chemical calculations of NMR chemical shifts and ECD spectrum. The antimicrobial activities of these compounds were evaluated. Compound 11 exhibited obvious inhibitory activity against MRSA, Staphylococcus aureus, Salmonella typhimurium, Botrytis cinerea, and Fusarium graminearum with MIC values of 4, 4, 4, 32, and 16 μg/mL, respectively. Compound 12 exhibited antibacterial activity against S. typhimurium and MRSA with MIC values of 4 and 16 μg/mL. Compound 6 exhibited antifungal activity against F. graminearum with MIC value of 32 μg/mL.

African swine fever, a serious infectious disease, has been found in many countries around the world over the last nearly 100 years, and causes untold damage to the economy wherever it occurs. Diagnosis is currently performed by real-time PCR, which is highly sensitive but can only be carried out in a diagnostic laboratory environment with sophisticated equipment and expertise. A sensitive, rapid diagnostic method that can be implemented in agricultural settings is thus urgently needed for the detection and control of African swine fever virus (ASFV) infection. In this study, we developed an isothermal amplification technology to achieve molecular diagnosis of ASFV in clinical samples, using recombinase-aided amplification (RAA) assay combined with a portable instrument. This assay method avoids the limitations of traditional real-time PCR and offers detection times within 20 min, enabling detection of as few as 10 copies of ASFV DNA molecules per reaction without cross-reaction with other common swine viruses. We evaluated clinical performance using 200 clinical blood samples. The coincidence rate of the detection results between rt-RAA and RT-qPCR was 96.94% positive, 100% negative, and 97.50% total. We have also developed an rt-RAA system for the detection of ASFV targeting the EP402R gene, with detection of as few as 10 copies of DNA per reaction; this offers the possibility of DIVA (differentiating infected from vaccinated animals) diagnosis, because CD2V gene-deleted ASFV could soon be approved to be the leading candidate for live attenuated vaccine in China. The rt-RAA assay is a reliable, rapid, highly sensitive method, and it offers a reasonable alternative to RT-qPCR for point-of-care detection of ASFV. KEY POINTS: • The RT-RAA assay can detect as few as 10 copies of ASFV genome per reaction within 20 min. • The rt-RAA assay system targeting different genes can achieve differentiating infected from vaccinated diagnosis.

Objective: The present study aimed to evaluate the association between hematocrit (HCT) levels and all-cause mortality in geriatric hip fractures. Methods: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of these patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between HCT levels and mortality. Analyses were performed using EmpowerStats and the R software. Results: A total of 2589 patients were included in this study. The mean follow-up period was 38.94 months. Eight hundred and seventy-five (33.8%) patients died due to all-cause mortality. Linear multivariate Cox regression models showed that HCT level was associated with mortality (hazard ratio [HR] = 0.97, 95% confidence interval [CI]: 0.96–0.99, p = 0.0002) after adjusting for confounding factors. However, the linear association was unstable and nonlinearity was identified. A HCT level of 28% was the inflection point for prediction. A HCT level of 28% was not a risk factor for mortality (HR = 0.99, 95% CI: 0.97–1.01, p = 0.3792). We found that the nonlinear association was very stable in the propensity score-matching sensitivity analysis. Conclusions: The HCT level was nonlinearly associated with mortality in geriatric hip fracture patients and could be considered a predictor of mortality in these patients. Registration: ChiCTR2200057323.

Metabolism affects the development, progression, and prognosis of various cancers, including breast cancer (BC). Our aim was to develop a metabolism-related long non-coding RNA (lncRNA) signature to assess the prognosis of BC patients in order to optimize treatment. Metabolism-related genes between breast tumors and normal tissues were screened out, and Pearson correlation analysis was used to investigate metabolism-related lncRNAs. In total, five metabolism-related lncRNAs were enrolled to establish prognostic signatures. Kaplan-Meier plots and the receiver operating characteristic (ROC) curves demonstrated good performance in both training and validation groups. Further analysis demonstrated that the signature was an independent prognostic factor for BC. A nomogram incorporating risk score and tumor stage was then constructed to evaluate the 3 – and 5-year recurrence-free survival (RFS) in patients with BC. In conclusion, this study identified a metabolism-related lncRNA signature that can predict RFS of BC patients and established a prognostic nomogram that helps guide the individualized treatment of patients at different risks., GRAPHICAL ABSTRACT

In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds 5 g (IC50: 7.54 ± 1.10 μM), 5e (IC50: 9.00 ± 0.97 μM), and 5 h (IC50: 9.57 ± 0.62 μM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC50: 32.18 ± 1.66 µM), 5 h (IC50: 31.47 ± 1.42 µM), and 5 s (IC50: 30.91 ± 0.86 µM) showed strongest inhibitory activities towards α-amylase, ∼ 2.5 times stronger than acarbose. The mechanisms and docking simulation of the compounds were also studied. Compounds 5 g and 5 h exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells.HighlightsA series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against α-glucosidase and α-amylase.Compound 5g exhibited promising activity (IC50 = 7.54 ± 1.10 μM) against α-glucosidase.Compound 5s exhibited promising activity (IC50 = 30.91 ± 0.86 μM) against α-amylase.In silico studies were performed to confirm the binding interactions of synthetic compounds with the enzyme active site., Graphical Abstract

The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABA(A) receptor (GABA(A)R) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

Background Hypoxemia due to respiratory depression and airway obstruction during upper gastrointestinal endoscopy with sedation is a common concern. The Wei nasal jet tube (WNJT) is a new nasopharyngeal airway with the ability to provide supraglottic jet ventilation and oxygen insufflation via its built-in wall channel. The available evidence indicates that with a low oxygen flow, compared with nasal cannula, the WNJT does not decrease the occurrence of hypoxemia during upper gastrointestinal endoscopy with propofol sedation. To date, there has been no study assessing the performance of WNJT for supplemental oxygen during upper gastrointestinal endoscopy with sedation when a moderate oxygen flow is used. Aim To determine whether the WNJT performs better than the nasal prongs for the prevention of hypoxemia during gastroscopy with propofol mono-sedation when a moderate oxygen flow is provided in patients with a normal body mass index. Methods This study was performed in 291 patients undergoing elective gastroscopy with propofol mono-sedation. Patients were randomized into one of two groups to receive either the WNJT (WNJT group, n = 147) or the nasal cannula (nasal cannula group, n = 144) for supplemental oxygen at a 5-L/min flow during gastroscopy. The lowest SpO2 during gastroscopy was recorded. The primary endpoint was the incidence of hypoxemia or severe hypoxemia during gastroscopy. Results The total incidence of hypoxemia and severe hypoxemia during gastroscopy was significantly decreased in the WNJT group compared with the nasal cannula group (P = 0.000). The lowest median SpO2 during gastroscopy was significantly higher (98%; interquartile range, 97-99) in the WNJT group than in the nasal cannula group (96%; interquartile range, 93-98). Epistaxis by device insertion in the WNJT group occurred in 7 patients but stopped naturally without any treatment. The two groups were comparable in terms of the satisfaction of physicians, anesthetists and patients. Conclusion With a moderate oxygen flow, the WNJT is more effective for the prevention of hypoxemia during gastroscopy with propofol mono-sedation compared with nasal prongs, but causing slight epistaxis in a few patients.

Increased plasma homocysteine (Hcy) levels have been widely documented in patients with overt hypothyroidism; however, the significance of Hcy level changes in patients with subclinical hypothyroidism (SCH) remains controversial. The aim of this meta-analysis was to determine the Hcy status in patients with SCH compared with euthyroid subjects. We searched PubMed, Embase, and Cochrane Library databases prior to December 2019 to identify eligible studies and assessed the quality of selected studies using the Newcastle-Ottawa Quality Assessment Scale. Publication bias was evaluated by Begg’s test and Egger’s test. Meta-regression analysis was conducted to investigate the source of heterogeneity. A likely source of heterogeneity was the year of the study. All statistical analyses were performed with RevMan 5.3 and Stata 12.0 software. Our meta-analysis of twelve observational studies with 684 patients showed that those with SCH aged between 18 and 65 years old were associated with a slightly increased plasma Hcy level compared with euthyroid controls. The pooled result of the weighted mean difference (WMD) of increased tHcy levels was 1.16 μmol/l (95% CI: 0.51, 1.82; p=0.0005). The Hcy level in patients with SCH aged between 18 and 65 years old is significantly increased compared to euthyroid controls.

Aim Primary thyroid lymphoma (PTL) is a rare malignant disease. Its prognosis depends on early diagnosis. The role of fine-needle aspiration (FNA), including smear cytology, cell block (CB) techniques, and immunohistochemistry (IHC) sections in the diagnosis of PTL is still unclear. Here we reported 19 cases of PTL and literature review to evaluate the diagnostic accuracy for lymphoma by cytology. Methods Our study retrospectively reviewed 19 patients diagnosed with PTL at the affiliated hospital of Southwest Medical University in China from June 2011 to May 2019. According to the Bethesda system for reporting thyroid cytopathology, the CB sections were evaluated for the presence of single tumor cells. IHC was performed on CB. Results The diagnostic accuracy for PTL of FNA, CB with smears, and the joint application of the three methods (FNA + CB + IHC) of our study with 19 cases was 68.4% (13/19), 83.3% (15/18), and 100% (17/17), respectively. Conclusion The present study demonstrates that FNA has low sensitivity in diagnosing PTL, but the joint application of FNA, CB, and IHC might provide high diagnostic accuracy for lymphoma and should be applied in all cases where the clinical suspicion is high regardless of the FNA findings.

In this study, the secondary metabolites of a lichen-derived actinomycete strain Amycolatopsis sp. YIM 130687 were investigated intensively by using three different media (4#, 302#, and 312#) for fermentation. A total of 21 compounds were isolated from the fermented extraction of the strain. The structures of all compounds were identified by the examination of HRESIMS and NMR spectra. Compounds 1–3, 5, 6, 21 were only found in the cultivation on 302# medium, while compounds 4, 9–11 were only obtained when the strain was cultured on 312# medium. On the other hand, compounds 7, 8, and 20 were only isolated from the fermentation product on 4# medium. The antimicrobial activity test showed that compound 9 had significant inhibitory effects on bacterial pathogens of Staphylococcus aureus and MRSA with the MICs of 2 μg/ml and fungal pathogens of Botrytis cinerea and Fusarium graminearum with the MICs of 1 μg/ml.

Using Fiber as the based material for photocatalyst particles is favorable for their recovery, thereby avoiding the photocatalyst particles cause secondary pollution to water environment. In this work, the AgBr and Ag3PO4 photocatalyst particles were loaded onto the surface of chitosan fiber (CF) via chelation and in situ anion-exchange method. The photocatalytic results illustrated that the AgBr/Ag3PO4/CF composites displayed the best photocatalytic performance when the mass ratio of Ag3PO4 and AgBr onto the CF was approximately 1:0.15, their degradation rate can reach 98.1% for the methyl orange (MO) solution, this value far exceeded those of pure CF, AgBr/CF composites, and Ag3PO4/CF composites. Besides, the AgBr/Ag3PO4/CF composites also shown excellent durability, after the fifth cycle, they still maintained a decolorization rate of 86.4% for the MO solution, while the Ag3PO4/CF composites maintained a decolorization rate of only 70.7%. Based on these results, we consider that the AgBr/Ag3PO4/CF composites have high practical interest in environmental remediation.

Epilepsy is a prevalent neurological disorder and it is a significant health risk, affecting >50 million people worldwide. The development of novel and appropriate strategies is required for ameliorating the progression and/or limiting the detrimental consequences of epilepsy. In the current study, kainic acid (KA), a neurotoxin, was used to induce seizures in mice. The flavonoid quercetin has recently been reported to have neuroprotective effects. Therefore, the effects of quercetin on KA-induced epilepsy and the potential underlying molecular mechanisms were examined. It was noted that quercetin attenuated the KA-induced seizure score and proinflammatory cytokine production, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and activation of nuclear factor κB (NF-κB) in mice. Quercetin attenuated KA-induced proinflammatory cytokine (TNF-α and IL-1β) release from microglia cells, as well as activation of NF-κB and ionized calcium binding adapter molecule 1 in microglia cells. Therefore, quercetin inhibited KA-induced epilepsy by microglia cell inactivation and the production of NF-κB, TNF-α and IL-1β.

The causes of death in patients with gastric adenocarcinoma have not been well characterized. This nationwide population‐based cohort study included 56 240 patients diagnosed with gastric adenocarcinoma in 1970‐2014 in Sweden. We used competing‐risks regression to compare cause‐specific risks of death in patients with different characteristics and a multiple‐cause approach to assess proportions of deaths attributable to each cause. Among 53 049 deaths, gastric cancer was the main (77.7% of all deaths) underlying cause. Other major underlying causes were nongastric malignancies (8.0%), ischemic heart disease or cerebrovascular disease (6.5%), and respiratory diseases (1.4%). Risk of death from gastric cancer steadily decreased in patients with cardia adenocarcinoma over the study period, but remained relatively stable in patients with noncardia adenocarcinoma since the 1980s. Risk of death from other malignancies increased during later calendar periods (subhazard ratio [SHR] = 2.16, 95% confidence interval [CI] 1.97‐2.38, comparing 2001‐2014 with 1970‐1980). Compared with men, the risk of death in women with cardia adenocarcinoma was higher from gastric cancer (SHR = 1.18, 95% CI 1.10‐1.27), but lower from other malignancies (SHR = 0.80, 95% CI 0.71‐0.91). In multiple‐cause models, 60.4%‐71.2% of all deaths were attributable to gastric cancer and 9.5%‐12.1% to other malignancies. The temporal trends of cause‐specific risks from multiple‐cause models were similar to those of underlying causes. Our findings suggest that although most deaths in patients with gastric adenocarcinoma are due to gastric cancer, other causes of death are common. Patients with cardia adenocarcinoma face considerable increasing risk of death from other causes over time, particularly from other malignancies., Causes of death in patients with gastric adenocarcinoma have not been well described. In this nationwide population‐based cohort study of 56,240 patients, we found that most deaths in patients with gastric adenocarcinoma were due to gastric cancer, but other causes of death were common, and increasingly so in patients with cardia adenocarcinoma. Attention to common comorbidities may benefit the follow‐up and survival of patients with gastric adenocarcinoma.

Myocardial hypertrophy is a major pathological and physiological process during heart failure. Glucagon-like peptide 1 (GLP-1) is a glucagon incretin hormone released from the gut endocrine L-cells that has protective effects on various cardiovascular diseases, including hypertension, atherosclerosis, and myocardial hypertrophy. However, the protective mechanisms of GLP-1 in myocardial hypertrophy remain unclear. Here, we showed that the GLP-1 agonist liraglutide and dipeptidyl peptidase 4 inhibitor alogliptin decreased heart weight and cardiac muscle cell volume in spontaneously hypertensive rats (SHR). In H9C2 cell hypertensive models induced by angiotensin II, GLP-1 treatment reduced myocardial cell volume, inhibited the expressions of atrial natriuretic peptide, brain/B-type natriuretic peptide, β-myosin heavy chain, RhoA, and ROCK2, and decreased MLC and MYPT1 phosphorylation. When H9C2 cells were treated with H89, a PKA inhibitor, the inhibitory effect of GLP-1 disappeared, while the inhibitory role was enhanced under the treatment of Y-27632, a ROCK2 inhibitor. These results suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway.

Background Tumor recurrence or residual tumor after targeted therapy is common in patients with advanced non-small cell lung cancer (NSCLC). There is a lack of high-level evidence on which type of treatment should be employed for these patients and the role of salvage surgery has not been well reported in the literature. Methods A retrospective analysis of patients who underwent salvage surgery in our center between January 2016 and June 2019 for advanced NSCLC after targeted therapy was performed. Results A total number of nine patients were identified, including five males and four females, with a median age of 56 years (range, 40-65 years), all diagnosed with lung adenocarcinoma stage IIIa-IVb. All patients had received targeted therapy according to individual positive mutation of driver gene(s). Salvage surgery was performed for tumor recurrence or residual tumor after a duration of 2-46 months of targeted therapy. A negative surgical margin was achieved in all cases. Postoperative complication rate was 11.1% (1/9). All patients were alive at the time of this analysis and two patients had disease progression. After a median follow-up of 17 months (range: 5-44 months), the median event-free survival and postoperative survival was 14 months (range: 2-44 months) and 17 months (range: 5-44 months) respectively. Conclusions Salvage surgery may be a feasible and promising therapeutic option for tumor recurrence or residual tumor in advanced NSCLC in selective patients after targeted therapy. Key points Salvage surgery is feasible in selected patients with advanced NSCLC and provides promising survival outcomes after targeted therapy failure. Salvage surgery provides precise molecular and pathological information which is most important for subsequent therapy.

In this work, a novel "turn-on" mode Au nanocubes (AuNCs) enhanced surface-enhanced Raman scattering (SERS) biosensing platform coupled with heated Au electrode (HAuE) and strand displacement amplification (SDA) strategy was proposed for highly sensitive detection of DNA adenine methylation (Dam) Methyltransferase (MTase) activity. The Dam MTase and DpnI enzyme activities were significantly increased by elevating the HAuE surface temperature, resulting in the rapid production of template DNA for later SDA. During the SDA process, the released single-stranded DNA (ssDNA) could be amplified exponentially, and its concentration was positively related to the Dam MTase activity. The plasmonic AuNCs in SERS tags could provide significant SERS enhancement due to their "lightning rod" effect resulting from the sharp feature of the edges and corners of AuNCs. Because of these factors, the proposed biosensors exhibited high sensitivity in detecting the Dam MTase activity. The limit of detection was estimated to be 8.65 × 10

Long non-coding RNA ELFN1 antisense RNA 1 (ELFN1-AS1) has been reported as a cancer driver in many human malignancies. This study was conducted to investigate the function of ELFN1-AS1 in gastric cancer (GC) and its mechanism of action. Bioinformatics analysis revealed increased expression of ELFN1-AS1 in GC, and abundant expression of ELFN1-AS1 was observed in the acquired GC cell lines. Knockdown of ELFN1-AS1 in GC cells weakened cell proliferation, invasion, migration, and resistance to apoptosis. ELFN1-AS1 was mainly localized in the nuclei of GC cells. ELFN1-AS1 recruited DNA methyltransferases to the promoter region of ZBTB16 and induced transcriptional repression of ZBTB16 through methylation modification. Furthermore, downregulation of ZBTB16 activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and restored the proliferation and invasiveness of GC cells. In vivo, downregulation of ELFN1-AS1 reduced the growth rate of xenograft tumors in mice. In summary, this study demonstrates that ELFN1-AS1 recruits DNA methyltransferases to the promoter region of ZBTB16 to induce its transcriptional repression, which further augments the development of GC by activating the PI3K/AKT signaling pathway.

Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury (TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.

Background Low-dose aspirin use may reduce cancer incidence and mortality, but its influence on gastric adenocarcinoma survival is unclear. This study aimed to assess whether aspirin use improves long-term survival following gastrectomy for gastric adenocarcinoma. Methods This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden from 2006 to 2015, with follow-up throughout 2020. Preoperative exposure to a daily low-dose (75–160 mg) aspirin for 1 (main exposure), 2 and 3 years and for 1 year after gastrectomy was examined in relation to 5-year all-cause mortality (primary outcome) and disease-specific mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, statin use, tumour location, tumour stage, neoadjuvant chemotherapy, surgeon volume of gastrectomy and surgical radicality. Results Among 2025 patients, 545 (26.9%) used aspirin at the date of gastrectomy. Aspirin use within 1 year before surgery did not decrease the adjusted risk of 5-year all-cause mortality (HR = 0.98, 95% CI 0.85–1.13) or disease-specific mortality (HR = 1.00, 95% CI 0.86–1.17). Preoperative aspirin use for 2 years (HR = 0.98, 95% CI 0.84–1.15) or 3 years (HR = 0.94, 95% CI 0.79–1.12) did not decrease the risk of 5-year all-cause mortality. Patients remaining on aspirin during the first year after gastrectomy had a similar 5-year all-cause mortality as non-users of aspirin (HR = 1.01, 95% CI 0.82–1.25). Conclusions Low-dose aspirin use might not improve long-term survival after gastrectomy for gastric adenocarcinoma and may thus not be a target for adjuvant therapy in this group of patients.