Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Objective·To explore the effect of double homeobox(DUX)protein on the differentiation potential of mouse embryonic stem cells(mESCs)into extraembryonic endoderm(XEN)and the possible mechanism of its action.Methods·Overexpression of DUX cell lines in mESCs was achieved by using a lentiviral system.The proportion of 2-cell-like cells(2CLCs)before and after DUX overexpression was detected by flow cytometry,and the expression of 2-cell stage-specific genes,Dux,zinc finger and SCAN domain containing 4c(Zscan4c),zinc finger protein 352(Zfp352)and murine endogenous retrovirus-L polymerase(MERVL-pol),were detected by real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR).RT-qPCR assay was used to detect the expression of pluripotency factors,nanog homeobox(Nanog),kruppel-like transcription factor 4(Klf4),sex determining region Y-box 2(Sox2),and octamer-binding transcription factor 4(Oct4),in pluripotent state,as well as the expression of signature genes for different germ layers in the differentiated state[endodermal:GATA binding protein 4(Gata4),GATA binding protein 6(Gata6),and sex determining region Y-box 17(Sox17);ectodermal:Nestin and tubulin beta 3 class Ⅲ(Tubb3);mesodermal:heart and neural crest derivatives expressed 1(Hand1),myogenic differentiation 1(Myod1),and kinase insert domain protein receptor(Flk1)].Public RNA sequencing(RNA-seq)data were mined to further clarify the effect of DUX on the differentiation of mESCs into extraembryonic endoderm.Functional and pathway enrichment analyses of differentially expressed genes were performed using Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis(GSEA)to identify the signaling pathways regulated by DUX.Additionally,an in-depth analysis of existing chromatin immunoprecipitation sequencing(ChIP-seq)data was conducted to explore the potential target genes of DUX.Results·Molecular biology experiments showed that overexpression of DUX could effectively maintain the pluripotency of mESCs,which was consistent with the analysis of public RNA-seq data.Differential gene analysis revealed that endodermal genes were specifically upregulated.After differentiation assay of mESCs,RT-qPCR assay experiments showed that mRNA expression of the XEN marker genes(Gata4,Gata6,Sox17)was significantly upregulated(P<0.001).In contrast,there was no specific change in mesodermal and ectodermal genes.GSEA enrichment analysis indicated that DUX might activate the retinoid metabolism signaling pathway,and the analysis of the ChIP-seq data further revealed the presence of a large number of known retinoic acid receptor motif in DUX-bound peaks,which could activate downstream target genes related to the development of the XEN.Conclusion·DUX has a strong correlation with the retinoic acid signaling pathway and it is predicted to activate the retinoic acid signaling pathway,which could promote the tendency of mESCs toward XEN differentiation.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely.Methods:A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI.Results:Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T 0.5ALP and T 0.5ALT) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC)?=?0.787, 95%CI: 0.697~0.878, P ?

Objective To investigate the effect and mechanism of andrographolide(AG)on lipopolysaccharide(LPS)-induced ferroptosis in renal tubular epithelial cells(HK-2 cells).Methods HK-2 cells were treated with LPS to simulate the in vitro HK-2 injury model of sepsis.The cells were further treated with AG of 5,10,20,40 μmol/L and randomly divided into control group,LPS group,LPS+dimethyl sulfoxide group(DMSO group),and AG group.Cell viability was detected by the CCK-8 method,and the optimal concentrations of LPS and AG were screened.Cell morphological change,the levels of kidney injury markers,including neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),malondialdehyde(MDA),glutathione(GSH)and reactive oxygen species(ROS),as well as the expression levels of ferroptosis regulatory proteins such as solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and ferritin in each group were compared,and the pro-tective effect of AG treatment on the cells was evaluated.Results Compared with the control group,the cell viabi-lity and GSH content decreased significantly in HK-2 cells treated with 10 μg/mL LPS;cell shrinkage and adhesion ability were poor;the contents of oxidative products MDA and ROS,as well as the levels of kidney injury markers NGAL and KIM-1 increased significantly,while expression levels of SLC7A11 and GPX4 protein decreased;ferritin expression level increased;differences were all statistically significant(all P＜0.05).Compared with LPS group,the cell viability,GSH content,as well as protein expression levels of SLC7A11 and GPX4 increased significantly after AG intervention,while ferritin expression level decreased,differences were all significant(all P＜0.05).MDA content,ROS fluorescence intensity,and the levels of kidney injury markers NGAL and KIM-1 decreased sig-nificantly,difference were all significant(all P＜0.05).Conclusion AG has a protective effect on LPS-induced HK-2 cell injury,possibly by activating SLC7A11/GPX4 pathway,reducing oxidative stress,up-regulating antioxi-dant enzyme activity,and alleviating ferroptosis.

BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.