Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To investigate the clinical efficacy of haploidentical high-dose in vitro non-T-cell-depleted peripheral blood hematopoietic stem cell transplantation (haplo-HDPSCT) in treating adult patients with Ph + acute lymphoblastic leukemia (Ph + ALL) . Method:This retrospective analysis was conducted on the clinical efficacy of 25 adult patients with Ph + ALL who underwent haplo-HDPSCT from July 2011 to June 2022 at our hospital. Results:This study included 25 patients with a median age of 27 (16-61) years, consisting of 12 males and 13 females. CR1 and ≥CR2 before transplantation were found in 23 and 2 cases, positive and negative minimal residual lesions were observed in 8 and 17 cases, and myeloablative conditioning and reduced-intensity conditioning were reported in 21 and 4 cases, respectively. Hematopoietic function was restored in all 25 patients after stem cell infusion. Of the 25 patients who underwent transplantation, 16 developed acute graft-versus-host disease (aGVHD). The cumulative incidence rates of Ⅱ-Ⅳ and Ⅲ-Ⅳ aGVHD were (40.4±11.3) % and (4.8±4.6) %, respectively. Four patients experienced relapse after transplantation, the cumulative relapse rates at 1 and 2 years after transplantation were (4.0±3.9) % and (14.5±7.9) %, respectively. The 2-year overall survival rate after transplantation was (81.3±8.5) % and the disease-free survival rate was (77.1±9.1) %.Conclusion:This study reveals that the unique haplo-HDPSCT protocol achieves good clinical efficacy in Ph + ALL treatment.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

Objective:To discuss the promotive effect of nerve growth factor(NGF),which is highly expressed in the adipose-derived stem cell(ADSC)-induced Schwann-like cells(SCLCs),on the growth of dorsal root ganglion(DRG)cell processes in the rats,and to clarify its mechanism.Methods:The ADSCs were extracted from the epididymal adipose tissue of the SD rats,and their multidirectional differentiation potential was identified through osteogenic,adipogenic,and chondrogenic induction.The ADSCs were induced to differentiate into the SCLCs,and the expression levels of glial fibrillary acidic protein(GFAP)and S100 calcium-binding protein β(S100β)protein in the ADSCs and SCLCs were detected by immunofluorescence staining and Western blotting methods.The DRG cells were isolated and cultured,and immunofluorescence staining was used to detect the βⅢ-tubulin expression in the DRG cells for identification.The SCLCs were co-cultured with the DRG cells(co-culture group),the single-culture DRG cells were regared as DRG group and toluidine blue staining was used to observe and measure the length of DRG cell processes under the optical microscope in co-culture group and DRG group.Small interfering RNA(siRNA)transfection was used to knock down NGF,and plasmid transfection was used to over-express NGF.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the NGF mRNA expression levels in the cells in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the NGF protein levels in the cell supernatants.The transfected SCLCs were co-cultured with DRG cells and divided into control group,siNC/vector group,NGF knockdown group(si-NGF group),and NGF over-expression group(oe-NGF group).The lengths of DRG cell processes in various groups were observed.Results:The primary ADSCs adhered within 24 h after seeding,with a small number of lipid droplets remaining.After 3 d of culture,the cells were mostly short spindle-shaped,fusiform,or polygonal,growing rapidly in a vortex pattern.After passaging,the cells exhibited a uniform morphology,appearing as long spindles arranged in a fish-school pattern.After 14 d of adipogenic induction,the cell morphology changed from spindle-shaped to flat-round,with translucent lipid droplets forming in the cytoplasm,which were stained red by Oil Red O.After 28 d of osteogenic induction,the cells appeared sand-like with blurred morphology,and calcified nodules were observed,which were stained red by Alizarin Red and deposited in the extracellular matrix.After 28 d of chondrogenic induction in a 3D culture system,millet-sized chondrogenic spheres formed.Frozen sections of the spheres were stained with Alcian Blue,and acidic mucopolysaccharides in the cartilage tissue were stained blue under the microscope.Under the fluorescence microscope,the third-passage purified ADSCs showed positive expression of CD29[fluorescein isothiocy anate(FITC)-labeled green fluorescence]and CD44(Cy3-labeled red fluorescence).The immunofluorescence staining results showed that GFAP was labeled with FITC(green fluorescence),and S100β was labeled with Cy3(red fluorescence).The Western blotting results showed that compared with ADSCs,the expression levels of S100β and GFAP proteins in the SCLCs were increased(P<0.05).The primary DRG cells began to adhere 6 h after conventional culture,and after 3 d,the cell bodies appeared round and bright,with two linear processes extending from them.Under fluorescence microscope,the cells positively expressed the neuron-specific marker βⅢ-tubulin,confirming that the isolated cells were DRG cells.Compared with the ADSCs,the NGF protein expression level in the SCLCs was increased(P<0.05).Compared with DRG group,the length of DRG cell processes in co-culture group was the highest when DRG cells and SCLCs were co-cultured at a 1∶2 ratio(P<0.05).The RT-qPCR results showed that compared with si-NC group,the expression levels of NGF mRNA in the cell supernatant in si-NGF-1,si-NGF-2,and si-NGF-3 groups were significantly decreased(P<0.05),with si-NGF-1 showing the highest knockdown efficiency,which was selected for subsequent experiments.The ELISA results showed that compared with si-NC group,the NGF levels in the cell supernatant of si-NGF-1,si-NGF-2,and si-NGF-3 groups were decreased(P<0.05).Compared with Vector group,the expression level of NGF mRNA and NGF protein level in the supernatant in oe-NGF group were increased(P<0.05).Compared with control group and siNC/vector group,the length of DRG cell processes in si-NGF group was decreased(P<0.05),while the length of DRG cell processes in oe-NGF group was increased(P<0.05).Conclusion:ADSCs can be directionally differentiated into SCLCs,and the differentiated cells highly express NGF.Knockdown or overexpression of NGF can affect the growth of DRG cell processes.

Objective To investigate the effects and molecular mechanisms of ginsenoside Rg1(GSRG1)on the proliferation,mi-gration,and inflammatory cytokine expression of human gingival fibroblasts(HGFs)induced by lipopolysaccharide(LPS).Methods HGFs were isolated and cultured using the tissue block method.The effects of different concentrations of LPS(0,1,5,10,20μg/mL)on inflammatory cytokines in HGFs were detected by ELISA.Cells were divided into three groups:control group(no treat-ment),LPS group(20 μg/mL LPS),and LPS+GSRG1 group(20 μg/mL LPS and 100 mg/L GSRG1).Cell proliferation was detec-ted by cell counting kit-8(CCK-8);cell migration was assessed by Transwell assay;intracellular reactive oxygen species(ROS)lev-els were compared using flow cytometry;and the expression levels of TNF-α,IL-6,NLRP3,p-p38,and p38 proteins were detected by Western blot.Results LPS concentrations of 5,10,and 20 μg/mL significantly increased the expression of IL-6 and TNF-α in HGFs(P＜0.05),with 20 μg/mL showing the strongest pro-inflammatory effect.Compared with the control group,there was no notable difference in the proliferation of HGFs in the LPS group at Day 1 and 2.However,on Day 3,4 and 5,decreased cell proliferation,re-duced migration,significantly increased ROS levels(P＜0.001),elevated protein expression of TNF-α,IL-6,and NLRP3(P＜0.001),and reduced p-p38 protein expression(P＜0.001)were exhibited.Compared with the LPS group,the LPS+GSRG1 group showed significantly enhanced cell proliferation and migration(P＜0.05),reduced ROS levels,decreased protein expression of TNF-α,IL-6,and NLRP3,and increased p-p38 protein expression(P＜0.001).There was no significant change in p38 expression among the three groups.Conclusion GSRG1 can alleviate the inhibitory effects of LPS on the proliferation and migration of HGFs and inhibit the inflammatory response,potentially through mechanisms involving p-p38 protein regulation.

Objective:To explore the causes of lack of compliance with life care in hematopoietic stem cell transplantation recipients while living alone in the transplant warehouse, and to provide a basis for developing targeted promotion measures.Methods:Using purposive sampling method, from June to December 2023, on-site observations were conducted on the voluntary completion of life care by hematopoietic stem cell transplant patients (with a 30 day observation period) admitted to the Blood Transplantation Center of the First Affiliated Hospital of Wenzhou Medical University. The compliance was calculated after the observation period. Patients with a compliance of less than 80% were selected, and semi-structured interviews were conducted with 17 of them after informed consent. The Colaizzi 7-step analysis method was applied to organize and analyze the interview data.Results:Three core themes on lack of compliance were distilled, namely physical factors impeding compliance (somatic specific symptoms leading to distraction, somatic non-specific symptoms leading to activity intolerance), psychological factors impeding compliance (negative emotions, comfort zone dilemmas, regression phenomena, constraints of personality psychological traits), and cognitive factors impeding compliance (subjective cognitive unperceived benefit, poor modeling resulting in cognitive biases, limited perceived attention) .Conclusions:The behavioral causes of lack of compliance with life care of hematopoietic stem cell transplant patients while living alone in the transplant warehouse are due to multiple factors of the body and mind, among which psychologically mediated mechanisms are key to compliance. Healthcare professionals should pay attention to both the physiological and psychological needs of patients, actively alleviate physical symptoms, appropriately provide psychological care to remove psychological barriers, help them actively seek family and social support, and promote cognitive improvement, thereby improving compliance.

Objective To investigate the correlation between different TCM syndrome types and RNF180/Septin9 gene methylation in patients with chronic gastritis.Methods Hospitalized cases diagnosed with chronic gastritis from March 2022 to July 2024 were retrieved through the information system of Wangjing Hospital,China Academy of Medical Sciences.Information such as general conditions,pathological findings and RNF180/Septin9 gene methylation detection results were collected.A total of 441 patients with chronic gastritis were finally collected according to the attrition criteria,and were divided into 5 types:liver-stomach disharmony syndrome,spleen-stomach damp-heat syndrome,spleen-stomach weakness syndrome,stomach-collateral stasis syndrome and stomach-yin deficiency syndrome.SPSS 25.0 was used to analyze the correlation between TCM syndrome types of chronic gastritis and methylation of RNF180/Septin9 gene.Results The majority of 441 patients with chronic gastritis were spleen-stomach damp-heat syndrome.The results of statistical analysis showed that there were differences in gender,smoking and drinking history and age distribution among different TCM syndrome types(P<0.05).The positive rate of RNF180/Septin9 gene methylation in stomach-collateral stasis syndrome was significantly higher than that in other syndrome types(P<0.01).Correlation analysis further showed that spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome were positively correlated with RNF180/Septin9 gene methylation(P<0.05),and the correlation of stomach-collateral stasis syndrome was particularly significant(P<0.01).Conclusion Spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome are positively correlated with RNF180/Septin9 gene methylation in patients with chronic gastritis.Pathological products such as blood stasis and damp-pathogenic bacteria can increase the risk of"inflammatory-cancer"transformation,and its prognosis is worse than other syndrome types.Timely intervention and regular examination should be conducted to achieve early diagnosis and treatment.

Objective To investigate the effects and molecular mechanisms of ginsenoside Rg1(GSRG1)on the proliferation,mi-gration,and inflammatory cytokine expression of human gingival fibroblasts(HGFs)induced by lipopolysaccharide(LPS).Methods HGFs were isolated and cultured using the tissue block method.The effects of different concentrations of LPS(0,1,5,10,20μg/mL)on inflammatory cytokines in HGFs were detected by ELISA.Cells were divided into three groups:control group(no treat-ment),LPS group(20 μg/mL LPS),and LPS+GSRG1 group(20 μg/mL LPS and 100 mg/L GSRG1).Cell proliferation was detec-ted by cell counting kit-8(CCK-8);cell migration was assessed by Transwell assay;intracellular reactive oxygen species(ROS)lev-els were compared using flow cytometry;and the expression levels of TNF-α,IL-6,NLRP3,p-p38,and p38 proteins were detected by Western blot.Results LPS concentrations of 5,10,and 20 μg/mL significantly increased the expression of IL-6 and TNF-α in HGFs(P＜0.05),with 20 μg/mL showing the strongest pro-inflammatory effect.Compared with the control group,there was no notable difference in the proliferation of HGFs in the LPS group at Day 1 and 2.However,on Day 3,4 and 5,decreased cell proliferation,re-duced migration,significantly increased ROS levels(P＜0.001),elevated protein expression of TNF-α,IL-6,and NLRP3(P＜0.001),and reduced p-p38 protein expression(P＜0.001)were exhibited.Compared with the LPS group,the LPS+GSRG1 group showed significantly enhanced cell proliferation and migration(P＜0.05),reduced ROS levels,decreased protein expression of TNF-α,IL-6,and NLRP3,and increased p-p38 protein expression(P＜0.001).There was no significant change in p38 expression among the three groups.Conclusion GSRG1 can alleviate the inhibitory effects of LPS on the proliferation and migration of HGFs and inhibit the inflammatory response,potentially through mechanisms involving p-p38 protein regulation.

Objective To investigate the correlation between different TCM syndrome types and RNF180/Septin9 gene methylation in patients with chronic gastritis.Methods Hospitalized cases diagnosed with chronic gastritis from March 2022 to July 2024 were retrieved through the information system of Wangjing Hospital,China Academy of Medical Sciences.Information such as general conditions,pathological findings and RNF180/Septin9 gene methylation detection results were collected.A total of 441 patients with chronic gastritis were finally collected according to the attrition criteria,and were divided into 5 types:liver-stomach disharmony syndrome,spleen-stomach damp-heat syndrome,spleen-stomach weakness syndrome,stomach-collateral stasis syndrome and stomach-yin deficiency syndrome.SPSS 25.0 was used to analyze the correlation between TCM syndrome types of chronic gastritis and methylation of RNF180/Septin9 gene.Results The majority of 441 patients with chronic gastritis were spleen-stomach damp-heat syndrome.The results of statistical analysis showed that there were differences in gender,smoking and drinking history and age distribution among different TCM syndrome types(P<0.05).The positive rate of RNF180/Septin9 gene methylation in stomach-collateral stasis syndrome was significantly higher than that in other syndrome types(P<0.01).Correlation analysis further showed that spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome were positively correlated with RNF180/Septin9 gene methylation(P<0.05),and the correlation of stomach-collateral stasis syndrome was particularly significant(P<0.01).Conclusion Spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome are positively correlated with RNF180/Septin9 gene methylation in patients with chronic gastritis.Pathological products such as blood stasis and damp-pathogenic bacteria can increase the risk of"inflammatory-cancer"transformation,and its prognosis is worse than other syndrome types.Timely intervention and regular examination should be conducted to achieve early diagnosis and treatment.