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.

Major depressive disorder(MDD)is a prevalent con-dition associated with substantial impairment and low remission rates.Traditional antidepressants demonstrate delayed effects,low cure rate,and inadequate therapeutic effectiveness for man-aging treatment-resistant depression(TRD).Several studies have shown that ketamine,a non-selective N-methyl-D-aspartate receptor(NMDAR)antagonist,can produce rapid and sustained antidepressant effects.Ketamine has demonstrated efficacy for reducing suicidality in TRD patients.However,the pharmaco-logical mechanism for ketamine's antidepressant effects remains incompletely understood.Previous research suggests that the an-tidepressant effects of ketamine may involve the monoaminergic,glutamatergic and dopaminergic systems.This paper provides an overview of the pharmacological mechanism for ketamine's anti-depressant effects and discuss the potential directions for future research.

Glutamate,norepinephrine,and their receptors com-prise the glutamatergic and norepinephrine systems,which mu-tually affect each other and play essential roles in mediating vari-ous neuropsychiatric diseases.This paper reviews the functions of N-methyl-D-aspartate receptor(NMDA-R)and α2-adrenergic receptor(α2-AR)and their functional crosstalk at the molecular level in brain in common neuropsychiatric diseases,which would benefit our understanding of neuropathophysiology of psychiatric diseases,drug development and optimization of clinical neuro-psychopharmacology.

Objective:To establish a general method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops.Methods:The chromatographic analysis was per-formed on an Agilent C18 column(4.6 mm ×250 mm,5 μm)with 1％triethylamine solution(pH adjusted to 5.0 with phosphoric acid)as mobile phase A and methanol as mobile phase B.Gradient elution was performed at col-umn temperature of 40 ℃.The detection wavelength was 214 nm,the flow rate was 1 mL·min-1,and the injec-tion volume was 20 μL.Results:Methylparaben,ethylparaben,propylparaben,butylparaben,benzalkonium chlo-ride and benzalkonium bromide were 0.11-559.0,0.10-513.0,0.10-258.8,0.11-270.5,1.07-537.0 and 1.03-512.8 μg·mL-1,respectively.The linear range was good(r＞0.999).The average recoveries of meth-ylparaben,benzalkonium bromide and benzalkonium chloride were 104.7％(RSD=1.3％),102.6％(RSD=1.1％)and 100.9％(RSD=1.1％),respectively.The contents of bacteriostatic agent in 100 batches of eye drops from 36 varieties of 12 enterprises were determined,and the accurate results were obtained.Conclusion:This meth-od provides a reference for the content quality control and safety evaluation of bacteriostatic agents in eye drops.

Objective:To gain a deeper understanding of the cognitive differences between lactating women and obstetric nurses regarding their breastfeeding counselling abilities.Methods:This study was a descriptive phenomenology qualitative study. From October 2021 to June 2022, purposive sampling was used to select 11 lactating women who received breastfeeding counselling and 13 obstetric nurses who provided breastfeeding counselling services in Department of Obstetrics at Peking Union Medical College Hospital for semi-structured interviews. Giorgi analysis method was used to extract and analyze data.Results:The cognitive differences between lactating women and obstetric nurses regarding breastfeeding counselling abilities were mainly manifested in four aspects, namely breastfeeding knowledge and skills, counselling practice ability, improving counselling ability, and personality traits.Conclusions:Lactating women and obstetric nurses have cognitive differences in breastfeeding counselling abilities. Obstetric nurses should improve their breastfeeding counselling skills based on the needs of lactating women and provide personalized breastfeeding counselling services.

A triplex RT-qPCR assay with human genes as internal references was established for detection of the Dengue and Zika viruses(DENV and ZIKV,respectively).The conserved regions of the four serotypes of DENV,along with the NS1 gene of ZIKV and the human β-actin gene,which is stably ex-pressed in various human tissues,were targeted by three sets of specific primers and probes.Standard plasmids for four se-rotypes of DENV,ZIKV,and β-actin were constructed as pos-itive controls.Optimal reaction conditions were determined through an L9(34)orthogonal experiment.The specificity,sensitivity,and coverage of the assay were verified and evalua-ted clinically,and the consistency was evaluated against a com-mercial kit for detection of DENV.The triplex RT-qPCR assay established exhibited no non-specific cross reactions with 12 similar arboviruses.The detection sensitivity for DENV and ZIKV were 2.99 and 2.18 copies/μL,respectively,and the intra-group and inter-group repeatability coefficients of variation were within 1.5％.As compared to the commercial kit,the proposed assay obtained positive results for 13 epidemic strains of DENV.Bland-Altman consistency analysis confirmed that the consistency of the detection results of clinical positive samples between the commercial kit and the proposed assay was 92.59％.The highly specific and sensitive triplex RT-qPCR assay with internal references is an effective tool for early and rapid differential identification of DENV and ZIKV.

Objective:To investigate the effect of macrophage polarization mediated by Jumonji domain containing-3(JMJD3)-interferon regulatory factor 4(IRF4)signaling pathway on the malignant biological behavior of multiple myeloma(MM)cells.Methods:THP-1 monocytes were induced to differentiate into macrophages by phorbol myristate acetate(PMA).THP-1 macrophages were divided into control group(normal culture),M2 induction group[added recombinant human interleukin(IL)-4,IL-13 proteins],M2+JMJD3 protein group(added recombinant human IL-4,IL-13 and JMJD3 proteins)and M2+JMJD3 inhibitor group(added recombinant human IL-4,IL-13 proteins and JMJD3 inhibitor),the proportion of CD206+cells was detected by flow cytometry,the levels of IL-10 and transforming growth factor-β(TGF-β)in the culture supernatant were detected by ELISA assay,the expression levels of arginase-1(Arg-1),JMJD3 and IRF4 mRNA were detected by real-time quantitative PCR(qRT-PCR),and the expression levels of Arg-1,JMJD3 and IRF4 proteins were detected by Western blot.Correspondingly,human MM cells U266 were cultured with THP-1 macrophage culture supernatant of each group,Methyl thiazolyl tetrazolium(MTT)method and plate colony formation assay were used to detect cell proliferation,cell apoptosis was detected by flow cytometry,Western blot was used to detect the expression levels of apoptosis-promoting protein Bcl-2-associated X protein(Bax)and cleaved caspase-3 in cells,and Transwell assay was used to detect cell migration and invasion.Results:Compared with the control group,the proportion of CD206+cells in THP-1 macrophages,the mRNA and protein expression levels of Arg-1,JMJD3 and IRF4,and the levels of IL-10 and TGF-β in the cell culture supernatant in M2 induction group were significantly increased(P＜0.001),meanwhile,the proliferation activity and the number of clones of U266 cells were significantly increased(P＜0.01),the apoptosis rate and the expression levels of apoptosis-promoting protein Bax and cleaved caspase-3 were significantly decreased(P＜0.001),the numbers of migrated cells and invasive cells were increased(P＜0.001).Compared with M2 induction group,the proportion of CD206+cells in THP-1 macrophages,the mRNA and protein expression levels of Arg-1,JMJD3 and IRF4,and the levels of IL-10 and TGF-β in the cell culture supernatant in M2+JMJD3 protein group were further increased(P＜0.01),meanwhile,the proliferation activity and the number of clones of U266 cells were further increased(P＜0.05),the apoptosis rate and the expression levels of apoptosis-promoting protein Bax and cleaved caspase-3 were further decreased(P＜0.01),the numbers of migrated cells and invasive cells were further increased(P＜0.001);However,the change trends of the above indexes in M2+JMJD3 inhibitor group were opposite to those in M2+JMJD3 protein group.Conclusion:M2 polarization of macrophages mediated by JMJD3-IRF4 signaling pathway can promote the proliferation,migration and invasion of MM cells,and inhibit cell apoptosis.

Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease. TAO is clinically classified into active and inactive stage, and the accurate judgment is the key point of treatment choice. Clinical activity score (CAS) is often used for the assessment of TAO activity, which is subjective to some extent. With the development of imaging techniques, ultrasonography, CT, MRI and radionuclide imaging have gradually been applied into the diagnosis and treatment of TAO. What′s more, the imaging is an important complement to CAS from the aspects of anatomical and functional metabolism, which can better assess the activity and the therapy response of TAO. The clinical value of medical imaging in activity and treatment efficacy evaluation of TAO is reviewed in this article.