IVC filter - assessing the readability and quality of patient information on the Internet.

OBJECTIVE: The internet is an increasingly favorable source of information regarding health-related issues. The aim of this study is to apply appropriate evaluation tools to assess the evidence available online about inferior vena cava (IVC) filters with a focus on quality and readability. METHODS: A search was performed during December 2022 using three popular search engines, namely Google, Yahoo, and Bing. Websites were categorized into academic, physician, commercial, and unspecified websites according to their content. Information quality was determined using Journal of the American Medical Association (JAMA) criteria, the DISCERN scoring tool, and whether a Health On the Net Foundation certification (HONcode) seal was present. Readability was established using the Flesch Reading Ease Score (FRES) and Flesch-Kincaid Grade Level (FKGL). Statistical significance was accepted as P < .05. RESULTS: In total, 110 websites were included in our study. The majority of websites were categorized as commercial (25%), followed by hospital (24%), academic (21%), unspecified (16%), and physician (14%). Average scores for all websites using JAMA and DISCERN were 1.93 ± 1.19 (median, 1.5; range, 0-4) and 45.20 ± 12.58 (median, 45.5; range, 21-75), respectively. The highest JAMA mean score of 3.07 ± 1.16 was allocated to physician websites, and the highest DISCERN mean score of 52.85 ± 12.66 was allocated to hospital websites. The HONcode seal appeared on two of the selected websites. Physician, hospital, and unspecified websites had a significantly higher mean JAMA score than academic and commercial websites (all with P < .001). Hospital websites had a significantly higher mean DISCERN score than academic (P = .007), commercial (P < .001), and unspecified websites (P = .017). Readability evaluation generated a mean FRES score of 51.57 ±12.04, which represented a 10th to 12th grade reading level and a mean FKGL score of 8.20 ± 1.70, which represented an 8th to 10th grade reading level. Only 12 sources were found to meet the ≤6th grade target reading level. No significant correlation was found between overall DISCERN score and overall FRES score. CONCLUSIONS: The study results demonstrate that the quality of online information about IVC filters is suboptimal, and academic and commercial websites, in particular, must enhance their content quality regarding the use of IVC filters. Considering the discontinuation of the HONcode as a standardized quality assessment marker, it is recommended that a similar certification tool be developed and implemented for the accreditation of patient information online.

Global research on portal vein thrombosis and liver transplantation: A bibliometric and visualized study.

In recent years, the association between portal vein thrombosis and liver transplantation has extensive attention from physicians worldwide. However, there is no available literature on bibliometric analysis in this research area. Herein, we aimed to conduct a bibliometric analysis to identify the hotspots and frontiers of research related to portal vein thrombosis and liver transplantation. Documents published between 2002 and 2022 were retrieved and downloaded from the Web of Science Core Collection database. VOSviewer was utilized to generate a visualization network map of authors, nations, institutions, journals, and keyword co-occurrence/clustering. Additionaly, CiteSpace was used to analyze the keywords with the strongest bursts. A total of 1272 articles and reviews were extracted from the database. The author Marco Senzolo published the largest number of papers. The United States was the most prolific country, and Hope-Bochon (France) was the top productive institution. Liver Transplantation was the most prolific journal in the field. The most commonly identified keywords in the study were cirrhosis, risk factors, portal vein thrombosis, and management, as revealed by the keyword co-occurrence analysis. It is suggested that patients with cirrhosis, portal vein thrombosis prevention, and management measures for portal vein thrombosis have been prominet topics in recent years. Furthermore, an analysis of keywords with the strongest citation bursts highlighted pediatric liver transplantation, direct oral anticoagulants, and nonalcoholic fatty liver disease as current research trends. Research in portal vein thrombosis and liver transplantation exhibits a general upward trend. The latest hot topics within this area of study involve pediatric patients and nonalcoholic fatty liver disease.

Impact of biomimetic electrical stimulation combined with Femoston on pregnancy rate and endometrium characteristics in infertility patients with thin endometrium: a prospective observational study.

OBJECTIVE: To explore the impact of biomimetic electrical stimulation combined with Femoston (estradiol tablets/estradiol and dydrogesterone tablets) on pregnancy rate and endometrium characteristics (endometrial thickness and type) in patients with infertility and a thin endometrium. METHODS: This prospective study enrolled patients with infertility and a thin endometrium admitted to Urumqi Maternal and Child Health Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China, between May 2021 and January 2022. The patients received Femoston alone (Femoston group) or Femoston combined with biomimetic electrical stimulation (electrotherapy group). The outcomes were the pregnancy rate and endometrium characteristics. RESULTS: Finally, 120 patients were enrolled (60/group). Before treatment, the endometrial thickness (p = 0.515) and the percentages of patients with endometrial types A + B and C (p = 0.769) were comparable between the two groups. After treatment, the endometrium of the patients in the electrotherapy group was thicker than those in the Femoston group (6.48 ± 0.96 mm vs. 5.27 ± 0.51 mm, p < 0.001). Furthermore, the percentages of patients with endometrial types A + B and C in the electrotherapy group were larger than in the Femoston group (p = 0.027). In addition, the pregnancy rates between the two groups (28.33% vs. 16.67%, p = 0.126) were similar. CONCLUSIONS: The results suggest the possibility that biomimetic electrical stimulation combined with Femoston could improve endometrial type and thickness in patients with infertility and thin endometrium compared with Femoston alone, but the pregnancy rate showed no significant improvement. The results need to be confirmed.

Executive function characteristics of preschool children with high functioning autism and children with global developmental delay / 中华行为医学与脑科学杂志

Objective:To investigate the characteristics of executive function of preschool children with high functioning autism spectrum disorder (HFA) and with global developmental delay (GDD), and the differences among HFA, GDD and typically developmental (TD) children.Methods:From January 2020 to January 2021, 20 male HFA, 20 male GDD and 20 male TD children aged 4-6 years who visited the Psychological Behavior Clinic of the Child Health Department of Guiyang Maternal and Child Health Hospital and the Developmental Behavior Clinic of the Children Health Department of the Ninth People's Hospital in Chongqing were selected for comparative study.The executive function of HFA, GDD and TD children was assessed with the behavior rating scale of executive function-preschool version(BRIEF-P) and the executive function task program (EF-TOUCH). SPSS 26.0 software was used for statistical analysis, including variance test, independent sample t-test, χ2 test, Kruskal Wallis test and Mann-Whitney U test. Results:In the EF-TOUCH program task, the accuracy of the three groups of children's performance in the pig task (Pig), the silly sounds game (SSG), the working memory task (pick the picture, PTP) and the task of cognitive flexibility (something's the same, STS) were statistically different(Pig: HFA group: 0.87(0.76, 0.99), GDD group: 0.97(0.85, 0.99), TD group: 1.00(0.98, 1.00), χ2=15.646, P<0.001; SSG: HFA group: 0.76(0.53, 0.91), GDD group: 0.76(0.65, 0.99), TD group: 0.94(0.76, 1.00), χ2=6.448, P=0.040; PTP: HFA group: 0.66±0.18, GDD group: 0.66±0.19, TD group: 0.78±0.11; F=3.221, P=0.048; STS: HFA group: 0.67(0.63, 0.70), GDD group: 0.72(0.46, 0.78), TD group: 0.87(0.83, 0.90), χ2=26.898, P<0.001). The accuracies of Pig, SSG, PTP and STS in HFA group were significantly lower than those in TD group(all P<0.05), and the accuracies of Pig and STS in GDD group were significantly lower than those in TD group(both P<0.05). In inhibition control, there were statistically differences in response time of Pig and SSG among the three groups (Pig: HFA group: (1 694.36±222.83)ms, GDD group: (1 513.46±244.91)ms, TD group: (1 444.84±197.95)ms, F=5.810, P=0.005; SSG: HFA group: (2 202.42±195.58)ms, GDD group: (2 116.52±323.27)ms, TD group: (1 937.17±252.74)ms, Z=4.610, P=0.014). There were no significant differences in the reaction time of Arrows task ( P>0.05). There were significant differences in BRIEF-P inhibition control, organizational planning, inhibition self-regulation, cognitive flexibility and total scores among the three groups ( P<0.05), while there were no significant differences in the scores of other factors and dimensions ( P>0.05). Conclusion:The executive function of pre-school children with high functioning autism spectrum disorder and children with global developmental delay is impaired.The executive function of children with high functioning autism spectrum disorder and children with global developmental delay is significantly different from that of typically developmental children of the same age.Moreover, the executive function of children with HFA is more severely damaged from all components than that of children with GDD.

Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland / 医学前沿

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai / 医学前沿

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai / 医学前沿

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Guild-level microbiome signature associated with COVID-19 severity and prognosis

COVID-19 severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples collected from 300 in-hospital COVID-19 patients at time of admission. Among the 2,568 high quality metagenome-assembled genomes (HQMAGs), Redundancy Analysis identified 33 HQMAGs which showed differential distribution among mild, moderate, and severe/critical severity groups. Random Forest model based on these 33 HQMAGs classified patients from different severity groups (average AUC = 0.79). Co-abundance network analysis found that the 33 HQMAGs were organized as two competing guilds. Guild 1 harbored more genes for short-chain fatty acid biosynthesis, and fewer genes for virulence and antibiotic resistance, compared with Guild 2. Random Forest regression showed that these 33 HQMAGs at admission had the capacity to predict 8 clinical parameters, which are predictors for COVID-19 prognosis, at Day 7 in hospital. Moreover, the dominance of Guild 1 over Guild 2 at admission predicted the death/discharge outcome of the critical patients (AUC = 0.92). Random Forest models based on these 33 HQMAGs classified patients with different COVID-19 symptom severity, and differentiated COVID-19 patients from healthy subjects, non-COVID-19, and pneumonia controls in three independent datasets. Thus, this genome-based guild-level signature may facilitate early identification of hospitalized COVID-19 patients with high risk of more severe outcomes at time of admission.

Immune Infiltration and Clinical Outcome of Super-Enhancer-Associated lncRNAs in Stomach Adenocarcinoma.

Super-enhancers (SEs) comprise large clusters of enhancers that highly enhance gene expression. Long non-coding RNAs (lncRNAs) tend to be dysregulated in cases of stomach adenocarcinoma (STAD) and are vital for balancing tumor immunity. However, whether SE-associated lncRNAs play a role in the immune infiltration of STAD remains unknown. In the present study, we identified SE-associated lncRNAs in the H3K27ac ChIP-seq datasets from 11 tumor tissues and two cell lines. We found that the significantly dysregulated SE-associated lncRNAs were strongly correlated with immune cell infiltration through the application of six algorithms (ImmuncellAI, CIBERSORT, EPIC, quantiSeq, TIMER, and xCELL), as well as immunomodulators and chemokines. We found that the expression of SE-associated lncRNA TM4SF1-AS1 was negatively correlated with the proportion of CD8+ T cells present in STAD. TM4SF1-AS1 suppresses T cell-mediated immune killing function and predicts immune response to anti-PD1 therapy. ChIP-seq, Hi-C and luciferase assay results verified that TM4SF1-AS1 was regulated by its super-enhancer. RNA-seq data showed that TM4SF1-AS1 is involved in immune and cancer-related processes or pathways. In conclusion, SE-associated lncRNAs are involved in the tumor immune microenvironment and act as indicators of clinical outcomes in STAD. This study highlights the importance of SE-associated lncRNAs in the immune regulation of STAD.

Integrated analysis of gut microbiome and host immune responses in COVID-19 / 医学前沿

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

PathogenTrack and Yeskit: tools for identifying intracellular pathogens from single-cell RNA-sequencing datasets as illustrated by application to COVID-19 / 医学前沿

Pathogenic microbes can induce cellular dysfunction, immune response, and cause infectious disease and other diseases including cancers. However, the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods. Taking advantage of single-cell RNA-sequencing (scRNA-seq) analysis, we can assess the transcriptomic features at the single-cell level. Still, the tools used to interpret pathogens (such as viruses, bacteria, and fungi) at the single-cell level remain to be explored. Here, we introduced PathogenTrack, a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level. In addition, we established an R package named Yeskit to import, integrate, analyze, and interpret pathogen abundance and transcriptomic features in host cells. Robustness of these tools has been tested on various real and simulated scRNA-seq datasets. PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track, and the first tools for identifying bacteria at the single-cell level. Using the raw data of bronchoalveolar lavage fluid samples (BALF) from COVID-19 patients in the SRA database, we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages. SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module. Additionally, we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells, indicating a co-infection of the bacterium in some severe cases of COVID-19. The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.

Mycena subpiligera sp. nov., a Symbiotic Species from China Associated with the Seed Germination of Gastrodia elata

Mycena subpiligera, a new taxon in sect. Fragilipedes that can strongly enhance the germination efficiency of Gastrodia elata seeds, was discovered in subtropical areas of China. As revealed by a morphological comparison with related Mycena species as well as maximum likelihood (ML) and Bayesian phylogenetic analyses based on sequences of the internal transcribed spacer (ITS) and the large subunit (LSU) regions of nuclear ribosomal RNA, the new taxon can be distinguished from phenotypically similar and phylogenetically related species. Optimal cultural conditions for M. subpiligera basidiomata are reported, and the germination rate of the new species is compared with that of M. citrinomarginata.

Perceived stress and associated factors among healthcare workers in a primary healthcare setting: the Psychological Readiness and Occupational Training Enhancement during COVID-19 Time (PROTECT) study

INTRODUCTION@#Disease outbreaks such as the COVID-19 pandemic significantly heighten the psychological stress of healthcare workers (HCWs). The objective of this study was to understand the factors contributing to the perceived stress levels of HCWs in a public primary care setting during the COVID-19 pandemic, including their training, protection and support (TPS), job stress (JS), and perceived stigma and interpersonal avoidance.@*METHODS@#This cross-sectional study using an electronic self-administered questionnaire was conducted at the National Healthcare Group Polyclinics in March 2020. Data was collected anonymously. Analysis was performed using regression modelling.@*RESULTS@#The response rate was 69.7% (n = 1,040). The mean perceived stress level of HCWs in various departments ranged from 17.2 to 20.3. Respondents who reported higher perceived stress were those who made alternative living arrangements, were more affected by the current pandemic, reported higher JS and were Muslims. Respondents who reported lower perceived stress were those who had been through the severe acute respiratory syndrome epidemic in 2003 and H1N1 pandemic in 2009 as HCWs, and those who had higher confidence in the organisation's TPS.@*CONCLUSION@#All HCWs, regardless of their scope of work, were similarly stressed by the current pandemic compared to the general population. Improving the confidence of HCWs in their training, protection and the support of personal protective equipment, and retaining experienced HCWs who can provide advice and emotional support to younger colleagues are important. Adequate psychological support for HCWs in the pandemic can be transformed into reserves of psychological resilience for future disease outbreaks.

Healthcare cost of patients with multiple chronic diseases in Singapore public primary care setting

INTRODUCTION@#The rising prevalence of multiple chronic diseases is an important public health issue as it is associated with increased healthcare utilisation. This paper aimed to explore the annual per capita healthcare cost in primary care for patients with multiple chronic diseases (multimorbidity).@*METHODS@#This was a retrospective cohort study conducted in a cluster of public primary care clinics in Singapore. De-identified data from electronic medical records were extracted from July 2015 to June 2017. Only patients with at least 1 chronic disease were included in the study. Basic demographic data and healthcare cost were extracted. A list of 20 chronic diseases was considered for multimorbidity.@*RESULTS@#There were 254,377 patients in our study population, of whom 52.8% were female. The prevalence of multimorbidity was 62.4%. The median annual healthcare cost per capita for patients with multimorbidity was about twice the amount compared to those without multimorbidity (SGD683 versus SGD344). The greatest percentage increment in cost was when the number of chronic diseases increased from 2 to 3 (43.0%).@*CONCLUSION@#Multimorbidity is associated with higher healthcare cost in primary care. Since evidence for the optimal management of multimorbidity is still elusive, prevention or delay in the onset of multimorbidity in the general population is paramount.

Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection / 医学前沿

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4

Ferroptosis in Carcinoma: Regulatory Mechanisms and New Method for Cancer Therapy.

Ferroptosis is a new form of programmed cell death with characteristic accumulation of reactive oxygen species (ROS) resulting from iron accumulation and lipid peroxidation. Ferroptosis is involved in many diseases, including cancer, and induction of ferroptosis has shown attractive antitumour activities. In this review, we summarize recent findings on the regulatory mechanisms of key regulators of ferroptosis, including the catalytic subunit solute carrier family 7 member 11 (SLC7A11), the glutathione peroxidase 4 (GPX4), p53 and non-coding RNAs, the correlations between ferroptosis and iron homeostasis or autophagy, ferroptosis-inducing agents and nanomaterials and the diagnostic and prognostic value of ferroptosis-associated genes in TCGA data.

Effects of Buyang Huanwu Decoction on Endothelial-mesenchymal Transformation of Lung Tissue in Idiopathic Pulmonary Fibrosis Model Rats and Mechanism Study / 中国药房

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on endothelial-mesenchymal transformation （EndMT） of lung tissue in idiopathic pulmonary fibrosis （IPF） model rats， and to explore its potential mechanism. METHODS： Male SD rats were randomly divided into normal group， model gorup， dexamethasone group [0.405 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6.435， 12.87， 25.74 g/（kg·d）， by raw material]， with 8 rats in each group. Except for normal group， other groups were given endotracheal injection of bleomycin to induce IPF model. On the second day after modeling， normal group and model group were given water intrgastrically [10 mL/（kg·d）]； administration groups were given relevant medicine intragastrically， once a day， for consecutive 28 days. 24 h after last medication， the expression of endothelial cell markers [platelet endothelial cell adhesion molecule 1， vascular endothelial cell cadherin] and interstitial cell markers [α-smooth muscle actin， fibroblast specific protein 1] were detected by immunohistochemistry method. The expression of Notch4 and DLL4 in lung tissue of rats were detected by Western blotting assay. RESULTS： Compared with normal group， the expression of endothelial cell markers were decreased significantly in lung tissue of model group， while the expressipon of interstitial cell markers， Notch4 and DLL4 were increased significantly （P＜0.01）. Compared with model group， the expression of endothelial cell markers in lung tissue of rats were increased significantly in administration groups， while Buyang huanwu decoction low-dose group was significantly lower than dexamethasone group； the expression of interstitial cell markers， Notch4 and DLL4 were decreased significantly， while Buyang huanwu decoction low-dose group was significantly higher than dexamethasone group （P＜0.05 or P＜0.01）. CONCLUSIONS： Buyang huanwu decoction can relieve IPF of model rats by intervening in EndMT， the mechanism of which may be associated with inhibiting DLL4/Notch4 singaling pathway.

Post-translational Modifications of PML in Regulating the Functions of Nuclear Bodies --Review / 中国实验血液学杂志

Abstract　　The promyelocytic leukemia (PML) gene encoded PML protein as a tumor suppressor protein, plays important roles in the occurrence and development of various cancers including acute promyelocytic leukemia. Recent studies have indicated that there are a variety of post-translational modifications of the PML protein, such as SUMOylation, ubiquitination, phosphorylation, and acetylation in cells. These modifications of the PML protein can directly affect the formation of PML nuclear bodies (PML-NBs), repair DNA damage, and modulate cell apoptosis. Furthermore, the abnormal modifications of PML not only result in the occurrence of hematopoietic tumors, but also are closely related to the drug-resistance of cancer. Therefore, investigating the post-translational modifications of PML is significant to uncover the mechanism of formation and functions of PML-NBs, thus contributing to the prevention and treatment of related hematopoietic tumors. In this review, the characteristics of the post-translational modifications of PML protein and the relationship between these modifications and functions of PML-NBs are summarized so as to provide the potential targets for the treatment of related cancers.

Frequent hospital admissions in Singapore: clinical risk factors and impact of socioeconomic status

<p><b>INTRODUCTION</b>Frequent admitters to hospitals are high-cost patients who strain finite healthcare resources. However, the exact risk factors for frequent admissions, which can be used to guide risk stratification and design effective interventions locally, remain unknown. Our study aimed to identify the clinical and sociodemographic risk factors associated with frequent hospital admissions in Singapore.</p><p><b>METHODS</b>An observational study was conducted using retrospective 2014 data from the administrative database at Singapore General Hospital, Singapore. Variables were identified a priori and included patient demographics, comorbidities, prior healthcare utilisation, and clinical and laboratory variables during the index admission. Multivariate logistic regression analysis was used to identify independent risk factors for frequent admissions.</p><p><b>RESULTS</b>A total of 16,306 unique patients were analysed and 1,640 (10.1%) patients were classified as frequent admitters. On multivariate logistic regression, 16 variables were independently associated with frequent hospital admissions, including age, cerebrovascular disease, history of malignancy, haemoglobin, serum creatinine, serum albumin, and number of specialist outpatient clinic visits, emergency department visits, admissions preceding index admission and medications dispensed at discharge. Patients staying in public rental housing had a 30% higher risk of being a frequent admitter after adjusting for demographics and clinical conditions.</p><p><b>CONCLUSION</b>Our study, the first in our knowledge to examine the clinical risk factors for frequent admissions in Singapore, validated the use of public rental housing as a sensitive indicator of area-level socioeconomic status in Singapore. These risk factors can be used to identify high-risk patients in the hospital so that they can receive interventions that reduce readmission risk.</p>

miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence. We also found that miR-125b-5p reduced the expressions of cell cycle regulatory genes including CCNA2, CCND1 and CCNE1, and regulated the markers of epithelial to mesenchymal transition (EMT) including E-cadherin, N-cadherin and EMT associated transcription factor Slug, and also decreased the MMPs including MMP2, MMP7 and MMP13. Furthermore, the candidate target gene HMGA2 was negatively regulated by miR-125b-5p both in mRNA and protein levels. Importantly, knockdown of HMGA2 partially phenocopied the effects of miR-125b-5p overexpression on cell cycle regulators and EMT markers. In conclusion, our results suggested that overexpression of miR-125b-5p inhibited cell proliferation, migration and invasion partially by down-regulating HMGA2 in ESCC.