Objective:To investigate the clinical characteristics and prognostic significance of germline mutations in patients with myelodysplastic neoplasms (MDS) .Methods:Clinical data from 407 patients with MDS [male, 252; female, 155; median age, 64 (range, 19-85) years] diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The clinical features and prognostic effects of germline mutations were evaluated.Results:The prevalence of germline mutations in patients with MDS was 5.9% (24/407), peaking at 20.0% in the group aged 21-30 years. The spectrum of germline mutations comprised DDX41 (9 cases, 2.2%), TP53 (3 cases, 0.7%), and single cases of RUNX1, TET2, MPL, CBL, ATRX, CEBPA, ETV6, IDH1, KDM5C, SBDS, GNAS, and CTC1. Patients with germline mutations exhibited significantly lower peripheral WBC counts than those without (1.87×10 9/L vs 2.50×10 9/L, P=0.018), but showed comparable median overall survival (21.3 months vs 21.1 months, P=0.97). Patients with DDX41 germline mutations, compared with those with other germline mutations, had a significantly older median age (65 vs 54 years, P=0.010), lower WBC counts (1.51×10 9/L vs 2.31×10 9/L, P=0.040), increased mean corpuscular volume (111.80 fl vs 97.25 fl, P=0.003), and a higher prevalence of normal karyotypes (100.0% vs 53.3%, P=0.022). The most frequently co-occurring somatic mutations in DDX41 germline mutation carriers were ASXL1, TET2, and RUNX1. Conclusion:In this study, the detection rate of germline mutations in MDS patients was 5.9% (24/407), peaking at 20% in the group aged 21-30 years. DDX41 and TP53 were the most prevalent germline mutations. DDX41 mutation carriers displayed distinct clinical characteristics; however, germline mutations overall showed no significant prognostic effect.

Objective: To investigate the protective effects of morusin on lipopolysaccharide (LPS)-induced acute liver injury in mice and its underlying mechanisms. Methods: Thirty-two male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups (n = 8 per group): control, LPS, low-dose morusin (morusin-L, 10 mg/kg), and high-dose morusin (morusin-H, 20 mg/kg) groups. The mice in each group were administered the corresponding drugs or normal saline via continuous gavage daily for 16 consecutive days. Except for control group, which received an equal volume of normal saline, other groups were intraperitoneally injected with LPS (5 mg/kg) 2 h after the last gavage to establish the acute liver injury model. Serum and liver tissues were collected for subsequent analysis 6 h after LPS injection. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected with biochemical methods. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in serum were measured by enzyme-linked immunosorbent assay (ELISA). Hepatic pathological changes were evaluated by hematoxylin-eosin (HE) staining. The 16S ribosomal RNA (16S rRNA) sequencing was performed to assess the composition of intestinal flora, linear discriminant analysis effect size (LEfSe) was applied for multi-level species discrimination, and Spearman’s correlation analysis was performed. The liver tissues of mice with acute liver injury were analyzed by RNA sequencing (RNA-seq) technology to identify differentially expressed genes (DEGs), and then enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was conducted. The expression levels of selected genes was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), while immunohistochemistry (IHC) was performed to examine the expression levels of IL-6, myeloid differentiation primary response 88 (MYD88), and toll-like receptor 2 (TLR2). Results: Morusin significantly reduced the serum levels of ALT, AST, and inflammatory factors (TNF-α, IL-6, and IL-1β) (P < 0.05, P < 0.01, or P < 0.001), while alleviating the hepatic pathological damage in mice. Based on efficacy comparisons, morusin-H group was selected for subsequent microbiome and transcriptome analyses. Microbiome analysis revealed that morusin-H effectively mitigated LPS-induced gut dysbiosis and restored the Firmicutes/Bacteroidota balance (P < 0.01). At the genus level, morusin-H significantly reduced the abundances of norank_f_Muribaculaceae, Desulfovibrio, Parabacteroides, and Muribaculum (P < 0.05, P < 0.01, or P < 0.001). At the phylum, family, and genus levels, our findings indicated that morusin-H treatment caused a significant decrease in the abundance of Desulfobacterota, Desulfovibrionaceae, and Desulfovibrio (P < 0.01). Importantly, the abundance of Desulfovibrio was positively correlated with the levels of ALT, AST, TNF-α, IL-1β, and IL-6. Transcriptomic and molecular analyses showed that the therapeutic mechanism of morusin-H involved suppression of the IL-17/TNF signaling pathways and downregulating the mRNA levels of Tlr2, Tlr3, Myd88, Il6, and Cxcl10 (P < 0.05 or P < 0.001), as well as the protein levels of key inflammatory mediators (IL-6, MYD88, and TLR2) (P < 0.001). Conclusion Morusin demonstrates protective effects against LPS-induced acute liver injury, likely through modulation of gut microbiota and suppression of pro-inflammatory factor expression. These findings indicate that morusin exerts its effects through the "microbiota-inflammation-liver" axis, providing a theoretical basis for its use as a multi-target plant-based drug in the treatment of metabolic inflammation-related liver diseases.

Rheumatoid Arthritis(RA)is a critical disease that endangers the health of the Chinese pop-ulation.At present,there are still many deficiencies in the diagnosis and treatment of RA in China.The 2024 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis addresses 10 important clinical issues in the diagnosis and treatment of RA,and provides evidence-based recommendations based on the latest domes-tic and international literature,with consideration of the actual situation of RA diagnosis and treatment in China.The guidelines comprehensively cover the diagnosis of RA,imaging examinations,treatment goals,follow-up monitoring,initial treatment plans,treatment adjustments,the application of glucocorticoids,drug tapering,and health education.They will promote the RA diagnosis and treatment levels and improve the prog-nosis of RA patients in China.

Objective:To investigate the feasibility of transcatheter edge-to-edge repair (TEER) using a short-clip strategy for patients with moderate-to-severe or greater degenerative mitral regurgitation caused by commissural prolapse.Methods:This retrospective study included patients with severe mitral regurgitation secondary to commissural prolapse who underwent TEER at the Second Affiliated Hospital of Zhejiang University School of Medicine between September 2022 and July 2024. Preoperative clinical and imaging data, intraoperative details, procedural outcomes, and 1-month postoperative follow-up results were collected.Results:A total of 19 patients were enrolled, aged (74.1±6.1) years, including 12 males. Among them, 10 patients had external commissural prolapse, and 9 patients had internal commissural prolapse. Preoperatively, all patients exhibited severe mitral regurgitation (4+), with an effective regurgitant orifice area of (0.55±0.17) cm2, left atrial volume of (104.77±36.57) ml, left ventricular end-diastolic volume of (102.29±32.47) ml, left ventricular end-diastolic dimension of (5.34±0.59) mm, and prolapse width of (1.18±0.34) cm. All procedures utilized short clips (NTR or NTW clips) to target the prolapsed commissural region and were completed successfully without intraoperative complications. At 1-month follow-up, no mortality, stroke, single-leaflet device attachment, myocardial infarction, or unplanned mitral reintervention occurred. Mitral regurgitation severity improved to ≤2+ in all patients, with left atrial volume of (74.49±33.83) ml, left ventricular end-diastolic volume of (85.90±18.05) ml, and left ventricular end-diastolic dimension of (4.93±0.37) mm (all P<0.05). Conclusion:The short-clip strategy, focusing on precise clip placement at the commissural interface, is feasible and effective for TEER in patients with severe mitral regurgitation due to commissural prolapse.

Objective:To investigate the clinical characteristics and prognostic significance of germline mutations in patients with myelodysplastic neoplasms (MDS) .Methods:Clinical data from 407 patients with MDS [male, 252; female, 155; median age, 64 (range, 19-85) years] diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The clinical features and prognostic effects of germline mutations were evaluated.Results:The prevalence of germline mutations in patients with MDS was 5.9% (24/407), peaking at 20.0% in the group aged 21-30 years. The spectrum of germline mutations comprised DDX41 (9 cases, 2.2%), TP53 (3 cases, 0.7%), and single cases of RUNX1, TET2, MPL, CBL, ATRX, CEBPA, ETV6, IDH1, KDM5C, SBDS, GNAS, and CTC1. Patients with germline mutations exhibited significantly lower peripheral WBC counts than those without (1.87×10 9/L vs 2.50×10 9/L, P=0.018), but showed comparable median overall survival (21.3 months vs 21.1 months, P=0.97). Patients with DDX41 germline mutations, compared with those with other germline mutations, had a significantly older median age (65 vs 54 years, P=0.010), lower WBC counts (1.51×10 9/L vs 2.31×10 9/L, P=0.040), increased mean corpuscular volume (111.80 fl vs 97.25 fl, P=0.003), and a higher prevalence of normal karyotypes (100.0% vs 53.3%, P=0.022). The most frequently co-occurring somatic mutations in DDX41 germline mutation carriers were ASXL1, TET2, and RUNX1. Conclusion:In this study, the detection rate of germline mutations in MDS patients was 5.9% (24/407), peaking at 20% in the group aged 21-30 years. DDX41 and TP53 were the most prevalent germline mutations. DDX41 mutation carriers displayed distinct clinical characteristics; however, germline mutations overall showed no significant prognostic effect.

Objective:To investigate the feasibility of transcatheter edge-to-edge repair (TEER) using a short-clip strategy for patients with moderate-to-severe or greater degenerative mitral regurgitation caused by commissural prolapse.Methods:This retrospective study included patients with severe mitral regurgitation secondary to commissural prolapse who underwent TEER at the Second Affiliated Hospital of Zhejiang University School of Medicine between September 2022 and July 2024. Preoperative clinical and imaging data, intraoperative details, procedural outcomes, and 1-month postoperative follow-up results were collected.Results:A total of 19 patients were enrolled, aged (74.1±6.1) years, including 12 males. Among them, 10 patients had external commissural prolapse, and 9 patients had internal commissural prolapse. Preoperatively, all patients exhibited severe mitral regurgitation (4+), with an effective regurgitant orifice area of (0.55±0.17) cm2, left atrial volume of (104.77±36.57) ml, left ventricular end-diastolic volume of (102.29±32.47) ml, left ventricular end-diastolic dimension of (5.34±0.59) mm, and prolapse width of (1.18±0.34) cm. All procedures utilized short clips (NTR or NTW clips) to target the prolapsed commissural region and were completed successfully without intraoperative complications. At 1-month follow-up, no mortality, stroke, single-leaflet device attachment, myocardial infarction, or unplanned mitral reintervention occurred. Mitral regurgitation severity improved to ≤2+ in all patients, with left atrial volume of (74.49±33.83) ml, left ventricular end-diastolic volume of (85.90±18.05) ml, and left ventricular end-diastolic dimension of (4.93±0.37) mm (all P<0.05). Conclusion:The short-clip strategy, focusing on precise clip placement at the commissural interface, is feasible and effective for TEER in patients with severe mitral regurgitation due to commissural prolapse.

OBJECTIVE To investigate the changes in serum metabolites of mice with radiation-induced intestinal injury under the intervention of baicalein and the changing characteristics of endogenous biological small molecules during the process of baicalein's participation in the prevention and treatment of radiation-induced intestinal injury through the metabolomics method based on GC-MS technology,in order to explore the potential regulatory mechanism of baicalein.METHODS A mouse radioactive intestinal injury model was established and randomly divided into normal control group,model group,low-dose baicalein group and high-dose baica-lein group.Baicalein was administered by gavage.Gas chromatography-mass spectrometry(GC-MS)technology was used to analyze the serum samples of mice in each group,and differential metabolites were screened through partial least squares-discriminant analysis(PLS-DA).Potential metabolic pathways were analyzed with MetaboAnalyst.RESULTS The pathological sections of mouse intesti-nal tissue showed that the high-dose and low-dose baicalein groups had a certain protective effect on radiation-induced intestinal dam-age.Metabolomic analysis showed that there were significant differences in the metabolic profiles of the blank control group,model group,low-dose and high-dose baicalein administration groups.After intragastric administration of baicalein,the endogenous metabo-lites in mice with radiation intestinal injury tended to normalize.The study screened out a total of 11 potential metabolic markers and 5 related metabolic pathways,among which pathways related to glucose metabolism,glutathione pathway,and ammonia metabolism were particularly significant.CONCLUSION Baicalein has a certain preventive and therapeutic effect on radiation-induced intestinal in-jury;baicalein participates in glucose metabolism and glutathione metabolism,and improving the endogenous substance disorder caused by radiation is its potential mechanism of action.

Rheumatoid Arthritis (RA) is a critical disease that endangers the health of the Chinese population. At present, there are still many deficiencies in the diagnosis and treatment of RA in China. The 2024 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis addresses 10 important clinical issues in the diagnosis and treatment of RA, and provides evidence-based recommendations based on the latest domestic and international literature, with consideration of the actual situation of RA diagnosis and treatment in China. The guidelines comprehensively cover the diagnosis of RA, imaging examinations, treatment goals, follow- up monitoring, initial treatment plans, treatment adjustments, the application of glucocorticoids, drug tapering, and health education. They will promote the RA diagnosis and treatment levels and improve the prognosis of RA patients in China.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.