The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic reticulum, resulting in endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). One of the important pathways by which UPR maintains intracellular homeostasis under ERS is activating protein kinase R-like endoplasmic reticulum kinase (PERK). The activation of the PERK pathway stimulates eukaryotic translation initiation factor 2 subunit-α (eIF2α) phosphorylation and the selective translation of active transcription factor 4 (ATF4), and PERK induces cell apoptosis by directly binding to the promoter of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This signaling pathway is also one of the important mechanisms by which UPR participates in the regulation of hematological malignancies and immune cells in a tumor microenvironment. This article provides an overview of advancements in research into the PERK-eIF2α-ATF4-CHOP signaling pathway in hematological malignancies and the potential therapeutic benefits of targeting this signaling pathway.

ObjectiveTo review the characteristics of interbrain synchrony between individuals with autism spectrum disorder (ASD) and healthy individuals during interactions. MethodsResearches on interbrain synchrony during interactions in individuals with ASD were retrieved from databases such as PubMed, Web of Science, Scopus and CNKI in November, 2023. Researches were screened and the relevant data were extracted. The quality of the methodology was evaluated using critical appraisal tool for analytic cross sectional study. ResultsFive researches were returned, publicated mainly from 2020 to 2023, including 130 individuals with ASD. Interbrain synchrony was lower during the interaction task in the individuals with ASD compared with the healthy, mainly involving the prefrontal and temporo-parietal joint regions; as well as the interbrain synchrony of theta, alpha and beta bands of electroencephalography. There was difference in interbrain synchrony between genders in individuals with ASD; furthermore, abnormal interbrain synchrony in individuals with ASD associated with social impairment. ConclusionInterbrain synchrony deficits may be a potential neural mechanism for social impairment in individuals with ASD, and the abnormalities mainly happen in the brain areas related with mirror nervous system and theories of mind network.

Background::Accurately and efficiently extracting microbial genomic sequences from complex metagenomic data is crucial for advancing our understanding in fields such as clinical diagnostics, environmental microbiology, and biodiversity. As sequencing technologies evolve, this task becomes increasingly challenging due to the intricate nature of microbial communities and the vast amount of data generated. Especially in intensive care units (ICUs), infections caused by antibiotic-resistant bacteria are increasingly prevalent among critically ill patients, significantly impacting the effectiveness of treatments and patient prognoses. Therefore, obtaining timely and accurate information about infectious pathogens is of paramount importance for the treatment of patients with severe infections, which enables precisely targeted anti-infection therapies, and a tool that can extract microbial genomic sequences from metagenomic dataset would be of help.Methods::We developed MetaGeneMiner to help with retrieving specific microbial genomic sequences from metagenomes using a k-mer-based approach. It facilitates the rapid and accurate identification and analysis of pathogens. The tool is designed to be user-friendly and efficient on standard personal computers, allowing its use across a wide variety of settings. We validated MetaGeneMiner using eight metagenomic samples from ICU patients, which demonstrated its efficiency and accuracy.Results::The software extensively retrieved coding sequences of pathogens Acinetobacter baumannii and herpes simplex virus type 1 and detected a variety of resistance genes. All documentation and source codes for MetaGeneMiner are freely available at https://gitee.com/sculab/MetaGeneMiner. Conclusions::It is foreseeable that MetaGeneMiner possesses the potential for applications across multiple domains, including clinical diagnostics, environmental microbiology, gut microbiome research, as well as biodiversity and conservation biology. Particularly in ICU settings, MetaGeneMiner introduces a novel, rapid, and precise method for diagnosing and treating infections in critically ill patients. This tool is capable of efficiently identifying infectious pathogens, guiding personalized and precise treatment strategies, and monitoring the development of antibiotic resistance, significantly impacting the diagnosis and treatment of severe infections.

Objective This project aimed to study the Miao medicine helleborus thibetanus franchon,including investigating its anti-inflammatory activity in collagen-induced arthritis CIA rats and its mechanism of VEGF/VEGFR2/P38 MAPK pathway regulation.Methods Sixty female Wistar rats were randomly divided into six groups:normal;model;positive drug;and low,medium,high dose groups,with 10 rats in each group.Bovine type Ⅱ collagen solution was injected into the tail of rats to construct the rheumatoid arthritis model,and the positive drug group was given MTX2.0 mg/(kg·d)by gavage once every other day.The three groups of helleborus thibetanus franchon low,medium,and high dose were gavaged with helleborus thibetanus franchon ethanol extract at 0.25,0.5 and 1 g/(kg·d)once a day.The normal and model groups were given an equivalent volume of NaCl solution,with continuous administration lasting for 28 days.During treatment,the general condition of the rats was observed,body weight changes recorded,and foot thickness measured.After treatment and euthanasia,the rats'hind limbs were removed for Micro-CT to detect bone destruction;hematoxylin and eosin staining for pathological investigattion of the synovial membrane;immunohistochemistry to observe neovascularization in the synovium;quantitative reverse-transcription PCR to detect mRNA levels of VEGF-A,VEGFR2,TNF-α in the synovial tissue;and Western Blot to detect the expression of VEGF,VEGFR2,p-P38,p-AKT.The analyses were used to explore the potential mechanisms of action of the Miao medicine helleborus thibetanus franchon in treating rheumatoid arthritis.Results Compared with the normal group,the model group showed significant weight loss(P＜0.01),increased foot swelling(P＜0.01),visible proliferative synovial tissue with inflammatory cell infiltration,erosive lesions on bone surfaces,increased neovascularization in the synovium,and significant bone destruction in Micro-CT,with reduced bone percentage,trabecular thickness,and bone density.The levels of VEGF-A,VEGFR2,TNF-α mRNA and VEGF-A,VEGFR2,p-P38,p-AKT proteins were significantly elevated(P＜0.01).Compared with the model group,the helleborus thibetanus franchon ethanol extract-treated groups showed improvements in these conditions in a dose-dependent manner,with the high-dose group receiving the best effect.There was a significant increase in the rats'body weight(P＜0.05);reduction in foot swelling(P＜0.05);amelioration of synovial and erosive bone lesions;reduction in neovascularization in the synovium;and significantly lower levels of VEGF-A,VEGFR2,and TNF-α mRNA,and VEGF-A,VEGFR2,p-P38,and p-AKT protein(P＜0.01).Conclusions The Miao medicine plant helleborus thibetanus franchon may alleviate joint inflammatory damage in CIA rats by modulating the VEGF/VEGFR2 signaling pathway,thereby exerting therapeutic effects on rheumatoid arthritis.

Objective To explore the application of cluster nursing mode in perioperative period of elderly patients with hip fracture.Methods A retrospective cohort study design was used.Through convenience sampling method,50 elderly patients admitted to the hospital for hip fractures from January 2018 to December 2019 were selected as the control group.Meanwhile,47 elderly patients admitted to hospital for hip fractures from January 2020 to December 2021 were selected as the experimental group.The experimental group received cluster nursing,while the control group received routine nursing measures.The outcomes compared between the 2 groups included the effective rate of pain intervention,functional exercise compliance,and the incidence of complications.Results The effective rate of pain intervention(χ2=5.922,P=0.015)and functional exercise compliance(χ2=9.685,P= 0.008)in the experimental group were higher than those in the control group.The number of perioperative complications(χ2=7.600,P=0.006)in the experimental group were lower than those in the control group.Conclusion The application of cluster nursing mode in the perioperative period of elderly patients with hip fractures can effectively control pain,improve functional exercise compliance,and reduce complications.

This study employed the α-glucosidase inhibitory activity model as an anti-diabetic assay and implemented a bioactivity-guided isolation strategy to identify novel natural compounds with potential therapeutic properties. Hypericum sampsoniiwas investigated, leading to the isolation of two highly modified seco-polycyclic polyprenylated acylphloroglucinols (PPAPs) (1 and 2), eight phenolic derivatives (3-10), and four terpene derivatives (11-14). The structures of compounds 1 and 2, featuring an unprecedented octahydro-2H-chromen-2-one ring system, were fully characterized using extensive spectroscopic data and quantum chemistry calculations. Six compounds (1, 5-7, 9, and 14) exhibited potential inhibitory effects against α-glucosidase, with IC₅₀ values ranging from 0.050 ± 0.0016 to 366.70 ± 11.08 μg·mL^-1. Notably, compound 5 (0.050 ± 0.0016 μg·mL^-1) was identified as the most potential α-glucosidase inhibitor, with an inhibitory effect about 6900 times stronger than the positive control, acarbose (IC₅₀ = 346.63 ± 15.65 μg·mL^-1). A docking study was conducted to predict molecular interactions between two compounds (1 and 5) and α-glucosidase, and the hypothetical biosynthetic pathways of the two unprecedented seco-PPAPs were proposed.
Molecular Structure ; Hypericum/chemistry* ; alpha-Glucosidases ; Magnetic Resonance Spectroscopy ; Glycoside Hydrolase Inhibitors/pharmacology*

Objective:To evaluate the ultrasound diagnostic value of portal vein complications after liver transplantation by monitoring changes in portal vein hemodynamic parameters using the color Doppler ultrasound technology and to determine its clinical significance.Methods:The clinical data of 99 patients who underwent liver transplantation at the Organ Transplantation Center of the Affiliated Hospital of Qingdao University from July 2015 to December 2018 were analyzed retrospectively. There were 81 males and 18 females, aged (51±9) years old. These patients were divided into the portal vein complication ( n=23) and the non-portal vein complication ( n=76) groups, based on whether portal vein complications had developed within 2 years after surgery. In addition, 30 healthy volunteers at the Affiliated Hospital of Qingdao University, including 16 males and 14 females, aged (40±14) years old were selected to form the control group. The patients’ morphology of liver was studied using color Doppler ultrasound at days 1, 7, 14, 30, 180, 365 and 730 after liver transplantation, and the maximum portal vein blood flow velocity and portal blood flow were recorded. Results:Compared with the control group, the maximum portal venous flow velocity and portal venous blood flow significantly increased on days 1, 7, 14, 30, and 180 after liver transplantation in the non-portal complication group (all P<0.05). With time, these changes showed a decreasing trend. By day 365 after surgery, the differences between the maximum portal venous flow velocity and the portal venous blood flow between the two groups became not significant ( P>0.05). Of the 23 patients in the portal vein complication group, 9 developed portal vein stenosis (PVS) and 14 portal vein embolism. The 9 patients with PVS had a maximum portal flow velocity of 63.8 (46.0, 78.6) cm/s at 1 month after surgery, and this flow velocity was significantly higher than that in the non-portal complication group [35.0(29.6, 41.8) cm/s, Z=-3.35, P<0.001]. The portal blood flow was 993 (887, 1168) ml/min in the 9 patients with portal vein stenosis at 1 month after surgery, and it was significantly higher than those in the non-portal complication group [811(682, 1 018) ml/min, Z=-2.37, P=0.020]. Conclusions:After liver transplantation, both the portal venous blood flow velocity and the blood flow were at high levels in the early postoperative period and they returned to normal levels with time. Ultrasound dynamic monitoring of portal venous blood flow changes was of clinical significance in diagnosing portal vein stenosis and portal vein embolism after liver transplantation.

Objective:To preliminarily analyze the expression of angiotensin-converting enzyme 2 (ACE2) and to investigate its potential regulatory mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from February 2020 to May 2021 were selected, including 17 males and 6 females, aging from 23 to 66 years old. Expression of ACE2 was evaluated via immunohistochemical staining in controls with non-chronic rhinosinusitis, non-eosinophilic CRSwNP (non-ECRSwNP), and eosinophilic CRSwNP (ECRSwNP) tissue, respectively. Correlations between ACE2 and the indicated Th1/Th2-related cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-25, IL-33, TSLP and periostin) were analyzed based on GSE72713 dataset. Protein-protein interaction (PPI) network was constructed via string database, immune infiltration of GSE72713 dataset was evaluated using cibersort algorithm. ACE2 was comprehensively analyzed by microRNA regulatory network, gene set enrichment analysis (GSEA) and pharmacological analysis. Statistical analysis was performed using GraphPad 7.0 and SPSS 20.0 software.Results:ACE2 was up-regulated in non-ECRSwNP compared with ECRSwNP. Microarray analysis showed that ACE2 was positively correlated with IFN-γ while inversely correlated with IL-5, IL-13 and periostin significantly. Analysis of immune infiltration suggested that ACE2 expression correlated positively with the number of M1 macrophage while negatively with M2 macrophage. GSEA demonstrated that interferon-related signaling pathways were up-regulated in non-ECRSwNP, and miRNA-200B/miRNA-200C/miRNA-429 pathways targeting ACE2 were enriched in ECRSwNP. Results of pharmacological analysis indicated that ampicillin was able to promote the expression of ACE2 whereas acetaminophen could down regulated the expression of ACE2.Conclusion:Expression pattern of ACE2 is varied in non-ECRSwNP and ECRSwNP, which may be related to the different infiltration of indicated cytokines and different regulatory pathways of miRNA.

Objective:To summarize the publications in the field of neurofibroma and malignant peripheral nerve sheath tumor in the past 25 years, to illuminate the cooperation among countries, academic institutions and researchers, and to compare the research topics between Chinese and English databases, and to predict the research trend.Methods:Web of Science and CNKI databases were searched, and literature about neurofibroma and malignant peripheral nerve sheath tumor(MPNST) resection from January 1st, 1997 to September 2nd, 2021 were included. Excel 2017 was used for statistical analysis. VOSviewer 1.6.16 software was used for clustering and visualization of countries, institutions, authors, and keywords.Results:A total of 9 620 English articles and 957 Chinese articles were included. Over the past 25 years, Chinese and English publications have been increasing quickly. In terms of countries and institutions, most of the countries with a large number of documents published in English literature (top 10) are developed countries and the institutional cooperation between them is relatively close. In terms of keywords clustering, the result of English literature are more comprehensive, including the pathogenesis, clinical manifestations, diagnosis and treatment of complications. The clustering result suggest that the potential research hotspots in the future may be the impact of tumor microenvironment on the development of neurofibroma and MPNST, molecular typing of neurofibroma, drug resistance mechanism of neurofibroma and so on. The clustering of Chinese literature can be summarized as the auxiliary diagnosis of neurofibroma and the treatment of complications.Conclusions:In the future, researchers may pay more attention to the role of tumor microenvironment in the development of neurofibroma, driving factors of neurofibroma and MPNST, molecular typing and drug resistance mechanism of neurofibroma.

Objective:To summarize the publications in the field of neurofibroma and malignant peripheral nerve sheath tumor in the past 25 years, to illuminate the cooperation among countries, academic institutions and researchers, and to compare the research topics between Chinese and English databases, and to predict the research trend.Methods:Web of Science and CNKI databases were searched, and literature about neurofibroma and malignant peripheral nerve sheath tumor(MPNST) resection from January 1st, 1997 to September 2nd, 2021 were included. Excel 2017 was used for statistical analysis. VOSviewer 1.6.16 software was used for clustering and visualization of countries, institutions, authors, and keywords.Results:A total of 9 620 English articles and 957 Chinese articles were included. Over the past 25 years, Chinese and English publications have been increasing quickly. In terms of countries and institutions, most of the countries with a large number of documents published in English literature (top 10) are developed countries and the institutional cooperation between them is relatively close. In terms of keywords clustering, the result of English literature are more comprehensive, including the pathogenesis, clinical manifestations, diagnosis and treatment of complications. The clustering result suggest that the potential research hotspots in the future may be the impact of tumor microenvironment on the development of neurofibroma and MPNST, molecular typing of neurofibroma, drug resistance mechanism of neurofibroma and so on. The clustering of Chinese literature can be summarized as the auxiliary diagnosis of neurofibroma and the treatment of complications.Conclusions:In the future, researchers may pay more attention to the role of tumor microenvironment in the development of neurofibroma, driving factors of neurofibroma and MPNST, molecular typing and drug resistance mechanism of neurofibroma.