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.

Objective:This study aimed to clarify the clinical characteristics of children infected with rhinovirus in the context of the Corona Virus Disease 2019 (COVID-19) pandemic and to explore the impact of recent COVID-19 infection history on their clinical features.Methods:Clinical data and laboratory test result of 286 children diagnosed with rhinovirus infection at Hangzhou Children′s Hospital from July 2022 to October 2023 were collected. A retrospective survey was conducted to determine whether all study participants had a history of COVID-19 infection within the 6 months prior to hospitalization.Results:Among the 286 children with rhinovirus infection, 180 (62.94%) had simple rhinovirus infection, while 106 (37.06%) had co-infections with other pathogens; Among the 180 rhinovirus simplex-positive children, 56.67% had wheezing symptoms; among them, 15 cases (15/180, 8.33%) were diagnosed with acute asthma attacks; 7 cases (7/180, 3.88%) were diagnosed with severe pneumonia. Based on whether the children had a history of COVID-19 infection in the 6 months prior to hospitalization, they were divided into a group with previous COVID-19 infection and a group without previous COVID-19 infection. There were no significant differences between the two groups in terms of gender, age of onset, peak fever, incidence of wheezing, incidence of pneumonia, proportion of severe pneumonia, proportion of severe asthma attacks, duration of fever, time to relief of wheezing, length of stay, white blood cell count, eosinophil count, C-reactive protein, procalcitonin, immunoglobulin E, oxygen therapy requirements, and use of intravenous steroids ( P>0.05). Conclusions:A history of COVID-19 infection in the past 6 months does not exacerbate the clinical symptoms of children with rhinovirus infection, nor does it increase the incidence of wheezing.

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.

Objective To evaluate the application effect of broth microdilution(BMD)method in susceptibility testing of multidrug-resistant Mycobacterium tuberculosis(MDR-MTB).Methods The Roche's proportion method and BMD method were adopted in drug susceptibility testing on 108 MDR-MTB strains and 11 non-MDR-MTB strains in Hainan Province.Whole genome sequencing(WGS)was performed on strains with inconsistent results by the above two methods.Results The average time to acquire drug susceptibility testing results by Roche's propor-tional method and BMD method were 28.0 and 8.5 days,respectively.Roche's proportional method showed higher resistance rates to isoniazid(INH),rifampicin(RFP),ethambutol(EMB),kanamycin(KM),and capreomycin(CPM)than BMD method(all P＜0.001).BMD method showed higher resistance rates to protionamide(PTO)and para-aminosalicylic acid(PAS)than Roche's proportional method(both P＜0.001).Taking Roche's proportional method as the gold standard,the sensitivity and specificity of BMD method for testing drug resistance were 50.00％-100％and 95.69％-100％,respectively.Except EMB(87.39％)and INH(94.96％),the consistency rates of the BMD method in testing drug resistance of other drugs were all ≥95.00％.The overall consistency rate between Roche's proportional method and WGS was 76.19％(32/42),while the consistency rate between BMD method and WGS was 23.81％(10/42),difference was statistically significant(x2=23.048,P＜0.001).34 MTB strains showed inconsistent results by two drug susceptibility testing methods.Among the 26 MTB strains that were resis-tant in Roche's proportion method but sensitive in BMD method,22 strains(84.62％)had mutations in relevant re-sistance genes.Among the 11 MTB strains that were sensitive in Roche's proportion method but resistant in BMD method,5 strains(45.45％)had mutations in relevant resistance genes.Conclusion BMD method is an accurate and rapid MDR-MTB susceptibility testing method,but further improvement and optimization are still needed.Drug resistance is closely related to mutations in relevant resistance genes.

Objective To predict the mechanism of Chaihu Shugan Powder against depression based on network pharmacology and molecular docking technology;To verify them through animal experiment of chronic unpredictable mild stress(CUMS)depression model rats.Methods TCMSP was used to screen the active components of Chaihu Shugan Powder and the related targets were obtained.Disease targets were retrieved by DisGeNET,GeneCards and GEO databases.The protein-protein interaction(PPI)network construction,GO and KEGG pathway enrichment analyses were conducted to determine the action pathway of Chaihu Shugan Powder against depression.Molecular docking of main active components and potential targets was performed.The depression model was established by CUMS combined with solitary rearing method,in which Chaihu Shugan Powder and PI3K specific inhibitor LY294002 were used to intervene depression model rats.Western blot and qPCR were respectively used to detect the action pathway related proteins and mRNAs.ELISA was used to detect the contents of monoamine neurotransmitters 5-HT and NE in hippocampal tissue,and their pathways of action were integrated and analyzed.Results Totally 118 active components of Chaihu Shugan Powder against depression and 74 potential targets were screened;KEGG pathway enrichment analysis indicated that action pathway of Chaihu Shugan Powder against depression were closely related to PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,etc.Molecular docking showed that quercetin,kaempferol,β-sitosterol,isorhamnetin,naringenin had good binding activity with AKT1,PIK3CA,GSK3B,IL6,IL1B.The animal experiments showed that Chaihu Shugan Powder could improve the depression-like behavior of model rats,increase the phosphorylation levels of PI3K and Akt in hippocampal tissue,down-regulate the expression of GSK3β,and increase the contents of 5-HT and NE.LY294002 could reverse the effect of Chaihu Shugan Powder.The results of integration analysis showed that PI3K/Akt signaling pathway of Chaihu Shugan Powder was closely related to metabolism of 5-HT and NE.Conclusion Chaihu Shugan Powder can exert antidepressant effects by activating the PI3K/Akt signaling pathway,inhibiting the expression of GSK3β,and increasing the levels of monoamine neurotransmitters 5-HT and NE.

ObjectiveTo investigate the effect and potential mechanism of Dihuangyin on 2， 4-dinitrochlorobenzene （DNCB） -induced model mice with atopic dermatitis （AD）. MethodA mouse model with AD was established by repeatedly stimulating the back skin of mice with DNCB. After successful modeling， the mice were randomly divided into model group， Runzao group （0.78 g·kg^-1）， and high， medium， and low dose （40.30， 20.15， and 10.08 g·kg^-1） groups of Dihuangyin， with 12 mice in each group， and the blank group consisted of 12 mice， 72 in total. The administration groups were given the corresponding liquid by dose， and the blank group and model group were given the same dose of pure water by intragastric administration， once a day. The skin lesions and scratching times of mice were observed after continuous administration for two weeks. The back skin lesions of mice were stained with hematoxylin-eosin （HE） and toluidine blue to observe the pathology. The contents of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， and interferon-γ （IFN-γ） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of IFN-γ， IL-4， IL-6， Janus kinase 1 （JAK1）， and transcriptional activator 3 （STAT3） in skin lesion tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of JAK1， phosphorylation（p）-JAK1， STAT3， and p-STAT3 proteins in skin lesion tissue were detected by Western blot. ResultCompared with the blank group， the back skin of the model group showed large-scale scab， dryness， erosion， hypertrophy with scratching， epidermal hyperplasia with hyperkeratosis and parakeratosis， hyperacanthosis with edema， and a large number of mast cell infiltration in the dermis， some of which were degranulated. The contents of IgE， IL-4， IL-6， and IFN-γ in the serum of mice were significantly increased （P<0.01）， and the protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly increased （P<0.01）. Compared with the model group， only a small amount of dryness and desquamation were observed in the back skin of mice in each administration group， and cell edema was reduced. The inflammatory infiltration was significantly reduced， and the number of mast cell infiltration was significantly decreased. The serum IgE， IL-4， IL-6， and IFN-γ of mice were decreased to varying degrees （P<0.05， P<0.01）. The protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly decreased， and the effect of high dose group of Dihuangyin was the best （P<0.01）. ConclusionDihuangyin can improve skin lesions and pruritus in mice with AD， and its mechanism may be related to the effective regulation of cytokines on the helper T cells （Th1）/Th2 axis by interfering with the JAK1/STAT3 signaling pathway and affecting skin barrier function.

Objective To investigate and analyze the behavioral and pathological differences in early-stage mouse models of epilepsy established by 2 different administration routes for kainic acid(KA),intracerebroventricular(ICV)injection and intraperitoneal(IP)injection.Methods A total of 100 male C57BL/6N wild-type(WT)mice(20～22 g)were randomly divided into ICV+normal saline(NS)control group(n=10),ICV+KA model group(n=40),IP+NS control group(n=10)and IP+KA model group(n=40).The ICV+KA model group was given 600 nL of KA(0.5 mg/mL)via ICV injection,and the IP+KA model group was injected with different dose of KA(25 mg/kg).Two control groups were administered equal volumes of NS via corresponding routes.After 3 d of modeling,the evaluation of behavioristics,molecular biology(including Western blotting),and neuropathological assessments(including FJB staining,TUNEL staining and immunofluorescence staining)were performed.Results No epileptic seizures were observed in both 2 control groups,while exhibited seizures were observed in both model groups.The mortality rates of the IP+KA group and the ICV+KA group were 47.50%and 65.00%respectively,while the success rates of modeling were 80.00%and 60.00%respectively.Compared with the IP+KA group,the ICV+KA group showed a significant increase in success rate and a significant reduction in mortality rate.FJB and TUNEL staining results showed that,compared with the IP+KA group,the severity of neurodegeneration and apoptotic changes in the hippocampus of the ICV+KA group were more significant(P＜0.05).Compared with the IP+KA group,there was also a significant difference in the expression of apoptotic proteins in the hippocampus of the ICV+KA group(P＜0.05).Immunofluorescence results showed that the astrocytes and microglia in the hippocampus and cortex of the ICV+KA and IP+KA groups were significantly activated compared with the control groups(P＜0.05),but the activation of glial cells in the hippocampus and cortex of the ICV+KA group was stronger than that of the IP+KA model group(P＜0.05)and the activation levels in the ICV+KA group were higher than in the IP+KA model group(P＜0.01).Moreover,expression levels of GFAP and Iba-1 proteins in the hippocampus and cortex were higher in the ICV+KA group than the IP+KA group(P＜0.05).Conclusion Two routes of KA administration are effective in construct epilepsy models.The mice with ICV administration route show a higher success rate and lower mortality rate,and more significant neuropathological damage and glial cell activation.