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:To investigate the mid-and long-term clinical efficacy of modified Colonna arthroplasty in the treatment of unilateral dislocation type developmental dysplasia of hip (DDH) in adolescents.Methods:A total of 28 adolescent DDH patients with unilateral dislocation who underwent modified Colonna capsular arthroplasty from January 2016 to January 2018 in the 920th Hospital of Joint Logistics Support Force of People's Liberation Army were retrospectively analyzed. There were 4 males and 24 females, aged 16.5±5.0 years (range, 10-25 years). The mean body mass index was 21.2±1.1 kg/m 2 (range, 18.7-24.1 kg/m 2). According to DDH classification, 10 cases were Tonnis type III and 18 cases were Tonnis type IV. The postoperative lateral center-edge angle, acetabular coverage, femoral anteversion angle and leg length discrepancy were measured. The operation time, intraoperative blood loss, visual analogue scale (VAS) of hip pain, Harris hip score (HHS) and congenital dislocation of the hip score were recorded. Results:All patients successfully completed the operation and were followed up for 72.1±5.2 months (range, 60-84 months). The operation time was 81.6±4.3 min (range, 70-90 min), the intraoperative blood loss was 177.5±12.6 ml (range, 160-200 ml), and the hospital stay was 6.8±0.7 days (range, 6-9 days). The VAS score of the hip joint was 1.8±0.6 before operation and 2.3±0.6 at the last follow-up, and the difference was not statistically significant ( t=2.845, P=0.224). The preoperative HHS score was 57.1±5.9, and it increased to 87.3±4.0 at the last follow-up, and the difference was statistically significant ( t=-22.141, P=0.001). At the last follow-up, the femoral anteversion angle was 17.0°±1.5°, which was lower than that before operation 41.6°±2.4°, with a statistically significant difference ( t=-44.868, P=0.008). The leg length discrepancy was 10.2±2.3 mm, which was lower than that before operation (26.4±6.1 mm), with a statistically significant difference ( t=-12.892, P<0.001). The lateral center-edge angle was 28° (26°, 30°), and the acetabular coverage rate was 78% (76%, 79%). The curative effect evaluation standard score of congenital dislocation of the hip was 24 (16.7, 25.7) points, including 7 excellent cases, 14 good cases, 4 fair cases, and 3 poor cases. The excellent and good rate was 75% (21/28). Conclusion:The modified Colonna arthroplasty for the treatment of unilateral dislocation DDH in adolescents has good mid-and long-term hip function recovery and radiographic improvement.

AIM To investigate the effects of Ophiopogonis Root Decoction on bleomycin(BLM)-induced idiopathic pulmonary fibrosis(IPF)in mice and to explore its metabolic modulation of immunity.METHODS The IPF mouse model was constructed by tracheal drip injection of BLM,and the mice were randomly divided into the control group,the model group,the pirfenidone group(0.3 g/kg)and the high,medium and low dose groups of Ophiopogonis Root Decoction(18,9,4.5 g/kg).HE and Masson staining,ELISA,flow cytometry and immunohistochemistry were used to detect the histopathological changes of the lung,the levels of Collagen I,HYP and TGF-β1,the proportion of PD-1+ CD4+T cells in plasma,and the expressions of p-STAT3,PD-1,PD-L1 and IL-17A in lung tissue,respectively.RESULTS Compared with the control group,the model group displayed significantly higher level of lung coefficients(P<0.01),more severe pulmonary inflammatory cell infiltration and collagen fiber deposition,and increased pulmonary fibrosis score(P<0.01),increased levels of Collagen I,HYP and TGF-β1(P<0.01),increased proportion of PD-1+ CD4+ T cells in plasma(P<0.01),increased pulmonary expression of p-STAT3,PD-1,PD-L1 and IL-17A(P<0.01).Compared with the model group,the Ophiopogonis Root Decoction groups shared lower levels of lung coefficients(P<0.05),less pulmonary inflammatory cell infiltration and collagen fiber deposition,decreased pulmonary fibrosis score(P<0.05),decreased levels of Collagen I,HYP and TGF-β1(P<0.05),decreased proportion of PD-1+ CD4+T cells in plasma(P<0.05),and decreased pulmonary expression of p-STAT3,PD-1,PD-L1,and IL-17A(P<0.05).CONCLUSION Ophiopogonis Root Decoction can significantly reduce extracellular matrix(ECM)deposition and curb the progression of IPF via inhibition of STAT3/PD-1/PD-L1 immunomodulatory signaling pathway.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*