ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective:To explore the efficacy and feasibility of hypomethylating agent (HMA) as preventive therapy in children with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study. Data from 173 children who underwent allo-HSCT for high-risk AML at Children′s Hospital of Soochow University between August 2019 and April 2023 were analyzed. Participants were categorized into a trial group receiving HMA and a control group. Further classification was based on HMA courses:≥4 and <4 courses. The efficacy and safety of HMA preventive treatment after allo-HSCT were evaluated. Survival analysis was performed using the Kaplan-Meier method with Log-Rank testing, the Fine-Gray model was used to assess cumulative relapse rates and Cox regression was used to identify prognostic factors. Adverse events during HMA were descriptively analyzed.Results:Among 173 patients, there were 100 males (57.8%) and 73 females (42.2%), with the age of 81 (34,127) months. The starting time of HMA was 123 (91, 191) d post-transplant, continuing 4.0 (3.0, 6.5) courses and the follow-up period was 24 (13, 32) months. The trial group (53 cases) showed better 2-year overall survival (OS) rate ((88.6±5.6)% vs. (76.6±4.3)%, χ 2=5.00, P=0.025) and relapse-free survival (RFS) rate ((89.2±4.7)% vs. (56.2±4.8)%, χ 2=15.75, P<0.001) than control group (120 cases). The 2-year OS rates and RFS rates were similar between ≥4 courses group (31 cases) and <4 courses group (22 cases)(both P>0.05). The cumulative relapse rate in the trial group was significantly lower ((10.8±0.2)% vs. (35.2±0.2)%, χ 2=10.84, P=0.001) than control group. Among children with molecular relapse, 8 cases (8/30, 26.7%) in the control group had hematological relapse compared to 1 case (1/2) in the trial group ( χ 2=0.81, P=0.369). The differences in incidence of acute and chronic graft-versus-host disease (GVHD) were not statistically significant (all P>0.05). Cox regression analysis revealed that minimal residual disease (MRD) positivity detected by flow cytometry before allo-HSCT and chronic GVHD were independent risk factors for OS (both P<0.05).The HMA preventive treatment was an independent protective factor for RFS, while age ≥10 years and MRD positivity detected by PCR before allo-HSCT were independent risk factors for RFS (all P<0.05). In trial group, 38 cases experienced grade 3 to 4 adverse events (71.7%). Conclusion:HMA is safe as preventive treatment in post-transplant children with high-risk AML, which can reduce the relapse risk and doesn't increase the risk of GVHD.

Objective:To explore the efficacy and feasibility of hypomethylating agent (HMA) as preventive therapy in children with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study. Data from 173 children who underwent allo-HSCT for high-risk AML at Children′s Hospital of Soochow University between August 2019 and April 2023 were analyzed. Participants were categorized into a trial group receiving HMA and a control group. Further classification was based on HMA courses:≥4 and <4 courses. The efficacy and safety of HMA preventive treatment after allo-HSCT were evaluated. Survival analysis was performed using the Kaplan-Meier method with Log-Rank testing, the Fine-Gray model was used to assess cumulative relapse rates and Cox regression was used to identify prognostic factors. Adverse events during HMA were descriptively analyzed.Results:Among 173 patients, there were 100 males (57.8%) and 73 females (42.2%), with the age of 81 (34,127) months. The starting time of HMA was 123 (91, 191) d post-transplant, continuing 4.0 (3.0, 6.5) courses and the follow-up period was 24 (13, 32) months. The trial group (53 cases) showed better 2-year overall survival (OS) rate ((88.6±5.6)% vs. (76.6±4.3)%, χ 2=5.00, P=0.025) and relapse-free survival (RFS) rate ((89.2±4.7)% vs. (56.2±4.8)%, χ 2=15.75, P<0.001) than control group (120 cases). The 2-year OS rates and RFS rates were similar between ≥4 courses group (31 cases) and <4 courses group (22 cases)(both P>0.05). The cumulative relapse rate in the trial group was significantly lower ((10.8±0.2)% vs. (35.2±0.2)%, χ 2=10.84, P=0.001) than control group. Among children with molecular relapse, 8 cases (8/30, 26.7%) in the control group had hematological relapse compared to 1 case (1/2) in the trial group ( χ 2=0.81, P=0.369). The differences in incidence of acute and chronic graft-versus-host disease (GVHD) were not statistically significant (all P>0.05). Cox regression analysis revealed that minimal residual disease (MRD) positivity detected by flow cytometry before allo-HSCT and chronic GVHD were independent risk factors for OS (both P<0.05).The HMA preventive treatment was an independent protective factor for RFS, while age ≥10 years and MRD positivity detected by PCR before allo-HSCT were independent risk factors for RFS (all P<0.05). In trial group, 38 cases experienced grade 3 to 4 adverse events (71.7%). Conclusion:HMA is safe as preventive treatment in post-transplant children with high-risk AML, which can reduce the relapse risk and doesn't increase the risk of GVHD.

Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective To investigate the relationship between serum solute carrier family 7 member 11(SLC7A11)and Janus kinase 2(JAK2)levels and the severity and prognosis of acute non-variceal upper gas-trointestinal bleeding(ANVUGIB).Methods A total of 108 patients with ANVUGIB who were treated in the hospital from April 2019 to April 2023 were selected and divided into severe group(31 cases),moderate group(44 cases)and mild group(33 cases)according to the severity of ANVUGIB.The patients were divided into poor prognosis group(41 cases)and good prognosis group(67 cases)according to their prognosis.An-other 50 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the control group.Serum SLC7A11 and JAK2 levels were detected by enzyme-linked immunosor-bent assay.Spearman correlation analysis was used to analyze the correlation between serum SLC7A11 and JAK2 levels and Framingham risk score(FRS)and Glasweg-Blatchford bleeding score(GBS).Multivariate Logistic regression was used to analyze the influencing factors of poor prognosis in patients with ANVUGIB.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum SLC7A11 and JAK2 for poor prognosis in patients with ANVUGIB.Results The serum SLC7A11 level was significantly lower and the serum JAK2 level was significantly higher in the three groups of ANVUGIB patients than in the control group(all P＜0.05).As the severity of the disease increased,the serum SLC7A11 level gradually de-creased,and the serum JAK2 level,FRS and GBS scores gradually increased(all P＜0.05).In ANVUGIB pa-tients,serum SLC7A11 level was negatively correlated with FRS and GBS scores,and serum JAK2 level was positively correlated with FRS and GBS scores(all P＜0.05).Compared with the good prognosis group,the poor prognosis group had significantly higher proportion of patients with bleeding volume＞400 mL,red blood cell distribution width,FRS score,GBS score,and JAK2 level,and significantly lower levels of hemoglo-bin and SLC7A11(P＜0.05).Bleeding volume＞400 mL and elevated JAK2 level were risk factors for poor prognosis in ANVUGIB patients,while elevated SLC7A11 level was a protective factor(all P＜0.05).The ar-ea under the curve of combined SLC7A11 and JAK2 in predicting poor prognosis of ANVUGIB patients was better than that of each index alone(Zcombination-SLC7A11=3.086,Zcombination JAK2=2.330,P=0.020,0.030).Conclu-sion The decrease of SLC7A11 level and increase of JAK2 level in patients with ANVUGIB can effectively e-valuate the severity and prognosis of patients,and the combination of the two can predict the prognosis of pa-tients with ANVUGIB.

AIM:To investigate the effects of curcumin on cardiac dysfunction induced by chronic restraint stress in a depression rat model.METHODS:Thirty-two Wistar rats weighing(200±20)g were randomly divided into control,model,low-dose curcumin,and high-dose curcumin groups(n=8 per group).The rats in model and curcumin groups were subjected to chronic restraint stress for 5 h daily at random time,while those in control group were maintained under normal conditions.Following daily stress exposure,the rats in low-and high-dose curcumin groups received 100 and 200 mg/kg curcumin daily,respectively,and those in control and model groups received the same volume of normal saline daily.The above treatments lasted for 28 d.Body weight of the rats was measured weekly.Sucrose preference test was performed on days 14 and 28 of the experiment.Serum corticosterone content was determined to evaluate depression.Histological changes of cardiac tissues were observed using HE and Masson staining.Echocardiography was conducted to examine heart function.The related mRNA and protein levels were detected using RT-qPCR and Western blot,respective-ly.RESULTS:Compared with control group,the rats in model group exhibited significantly slower weight gain(P<0.05),impaired sucrose preference(P<0.01),and increased corticosterone levels(P<0.01).HE staining revealed myo-cardial hypertrophy in model group but not in control group.Masson staining indicated significantly higher cardiac fibrosis in model group than control group(P<0.01).Immunohistochemical staining demonstrated a significant increase in posi-tive collagen type I expression(P<0.01).RT-qPCR results showed significantly elevated mRNA levels of inflammatory cytokines(tumor necrosis factor-α,interleukin-6,and interleukin-1β)and fibrosis factors(α-smooth muscle actin,colla-gen type I,and collagen type Ⅲ)in model group compared with control group(P<0.05 or P<0.01).Western blot re-vealed a significant increase in c-Jun N-terminal kinase(JNK)phosphorylation level in model group(P<0.01).Treat-ment with low-and high-dose curcumin reversed the above indicators.CONCLUSION:Curcumin treatment attenuated cardiac inflammation and fibrosis in rats subjected to chronic restraint stress,possibly by inhibiting JNK signaling pathway.

BACKGROUND: The addition of growth factiors is commonly applied to improve the osteogenic differentiation of stem cells. However, for human pluripotent stem cells (hPSCs), their complex differentiation processes result in the unknown effect at different stages. In this study, we focused on the widely used bone forming peptide-1 (BFP-1) and investigated the effect and mechanisms of its addition on the osteogenic induction of hPSCs as a function of the supplementation period. METHODS: Monolayer-cultured hPSCs were cultured in osteogenic induction medium for 28 days, and the effect of BFP-1 peptide addition at varying weeks was examined. After differentiation for varying days (0, 7, 14, 21 and 28), the differentiation efficiency was determined by RT–PCR, flow cytometry, immunofluorescence, and alizarin red staining assays. Moreover, the expression of marker genes related to germ layers and epithelial-mesenchymal transition (EMT) was investigated at day 7. RESULTS: Peptide treatment during the first week promoted the generation of mesoderm cells and mesenchymal-like cells from hiPSCs. Then, the upregulated expression of osteogenesis marker genes/proteins was detected in both hESCs and hiPSCs during subsequent inductions with BFP-1 peptide treatment. Fortunately, further experimental design confirmed that treating the BFP-1 peptide during 7–21 days showed even better performance for hESCs but was ineffective for hiPSCs. CONCLUSION The differentiation efficiency of cells could be improved by determining the optimal treatment period.Our study has great value in maximizing the differentiation of hPSCs by adding osteogenesis peptides based on the revealed mechanisms and promoting the application of hPSCs in bone tissue regeneration.

Objective : To investigate and analyze the root and root canal morphology of mandibular first molars (MFMs) in the Tibetan population using cone-beam computed tomography (CBCT) and to provide references for clinical root canal treatment in the Tibetan population. Methods: This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. CBCT imaging data of 300 mandibular first molars from 300 Tibetan patients were included. Patient age, the number of roots in mandibular first molars were recorded. The morphology and incidence of mesial root and mesial root canals and the morphology and incidence of distal root and distal root canals were statistically analyzed by Vertucci classification. Results : There were 198 double-root teeth and 102 three-root teeth in the 300 mandibular first permanent molars. Among the three-rooted molars, 1 case had mesiolingual roots, and the rest had distolingual roots. The incidence rate of the distolingual root was 33.7%(101/300). The most common root canal configuration was Vertucci Ⅳ 65.7% (197/300), followed by Vertucci Ⅱ 20.3% (61/300) in the mesial roots. The overall incidence of middle mesial canals (MMCs) was 6% (18/300), with the highest incidence of MMCs in the 20-40 year-old group at 9% (9/100). The distal roots canals of single-distal-rooted mandibular first molars were mainly Vertucci Ⅰ 66.8% (133/199), followed by Vertucci Ⅱ 14.6% (29/199) and Vertucci Ⅳ 11.6% (23/199). For the mandibular first permanent molars with two distal roots, 96% (97/101) of the distal buccal roots and 100% (101/101) of the distal lingual roots were Vertucci Ⅰ root canals. Conclusion The root and root canal morphology of mandibular first permanent molars in a Tibetan population is complex and variable. Approximately one-third of patients have distolingual roots, and clinicians should carefully explore the root canals under the guidance of CBCT.

Objective: To investigate the effect of acid-sensing ion channel 1 (ASIC1) gene knockout on articular cartilage injury in adjuvant arthritis (AA) of mice． Methods: Wild-type mice and ASIC1 knockout mice were divided into normal group and model group．Arthritis score was performed by observing the inflammation of paws，and the right paw swelling was measured．HE staining，immunohistochemistry，TUNEL and ELISA were used to detect the injury of articular cartilage and arthritic inflammation. Results : The arthritis score and paw swelling of AA mice with ASIC1 knockout was lower than that of the AA wild-type mice．AA mice with ASIC1 knockout showed less destruction and increased expression of collagen-Ⅱin articular cartilage． Moreover ，the lower apoptosis rate was observed by TUNEL assay in AA mice with ASIC1 knockout by comparing with AA wild-type mice．Furthermore，ELISA assay showed that the levels of IL-1 β、TNF-α in the serum decreased in AA mice with ASIC1 knock- out． Conclusion Knockout of ASIC1 may have protective effect on articular cartilage injury.