The blood-brain barrier （BBB） is a physical and biochemical barrier that precisely regulates brain homeostasis and plays a central role in controlling the transport of endogenous and exogenous drugs and related metabolites across the blood-brain interface. These functions of the BBB are mediated by its major components， including brain microvascular endothelial cells （BMECs）， tight junction protein complexes， and influx and efflux transporter proteins. One of the pathological features of ischemic stroke （IS） is BBB disruption， which plays an important role in the development of post-stroke brain injury and subsequent neurological dysfunction. Therefore， given the increasing incidence of IS， there is an urgent need to develop new therapeutic strategies to prevent BBB dysfunction and thereby protect injured brain tissue after IS. This study describes the pathological mechanisms by which BMEC injury after IS leads to BBB dysfunction and elucidates the association between BMECs and IS， including the regulation of apoptosis， autophagy， inflammatory responses， oxidative stress， neurotoxic effects， and cerebral edema. In addition， this article summarizes Chinese herbal medicines that may prevent and treat IS by targeting BMECs. These include monomeric compounds and single herbs such as flavonoids， glycosides， phenols， phthalides， terpenoids， and Styrax. Traditional Chinese medicine （TCM） compound formulas and preparations include oral formulations such as Buyang Huanwu decoction， Sailuotong， Naoxintong capsules， Dandeng Tongnao capsules， and Shexiang Tongxin dropping pills， as well as injectable preparations such as Tongluo Jiunao injection， Xingnaojing injection， Danshen polyphenolic acid for injection， Yiqi Fumai injection， and Shuxuetong injection. This study aims to explore the protective effects of TCM against IS through targeted regulation of BMEC function， providing new insights into the mechanisms of IS and endovascular therapeutic strategies.

The aim of this research was to investigate the mechanism of chelidonine on H2 O2-in-duced inflammatory injury in porcine intestinal epithelial cells(IPEC-J2)through transcriptome sequencing.IPEC-J2 cells in the logarithmic growth phase were divided into the blank group(K group),H2O2 group(S group)and chelidonine group(L group),with three replicates in each group.Total RNA was isolated from each group for the purpose of constructing a sequencing li-brary.The assembled data underwent functional annotation,differential gene analysis,as well as GO and KEGG enrichment analyses.qPCR was used to confirm the expression of key differentially expressed genes(DEGs),and ELISA was utilized to assess the effect of chelidonine on the permea-bility of IPEC-J2 cells.The results indicated that the sequencing data met the necessary criteria and demonstrated a strong correlation between samples.The GO functional annotation results suggest that the intervention effects of chelidonine involve biological processes such as oxidative stress re-sponse and G2/M phase transition regulation of the mitotic cycle,and are closely associated with molecular functions,such as transmembrane transport activity.The KEGG enrichment analysis indicates that following H2 O2 treatment,DEGs in IPEC-J2 cells are predominantly enriched in the p53 signaling pathway,the coagulation cascade,the FoxO signaling pathway,and various other sig-naling pathways.Following pretreatment with chelidonine,the DEGs exhibit significant enrichment in several signaling pathways related to inflammation,including the TNF signaling pathway,syn-aptic vesicle cycle,and IL-17 signaling pathway.The results of qPCR were consistent with the se-quencing results.Chelidonine has also been found to effectively inhibit LDH release,elevate GLN content,and decrease DOA content.In conclusion,it can be seen that chelidonine can reduce cell permeability and alleviate H2 O2-induced inflammatory injury in IPEC-J2 cells by modulating in-flammation-related pathways such as the TNF signaling pathway.

The aim of this research was to investigate the mechanism of chelidonine on H2 O2-in-duced inflammatory injury in porcine intestinal epithelial cells(IPEC-J2)through transcriptome sequencing.IPEC-J2 cells in the logarithmic growth phase were divided into the blank group(K group),H2O2 group(S group)and chelidonine group(L group),with three replicates in each group.Total RNA was isolated from each group for the purpose of constructing a sequencing li-brary.The assembled data underwent functional annotation,differential gene analysis,as well as GO and KEGG enrichment analyses.qPCR was used to confirm the expression of key differentially expressed genes(DEGs),and ELISA was utilized to assess the effect of chelidonine on the permea-bility of IPEC-J2 cells.The results indicated that the sequencing data met the necessary criteria and demonstrated a strong correlation between samples.The GO functional annotation results suggest that the intervention effects of chelidonine involve biological processes such as oxidative stress re-sponse and G2/M phase transition regulation of the mitotic cycle,and are closely associated with molecular functions,such as transmembrane transport activity.The KEGG enrichment analysis indicates that following H2 O2 treatment,DEGs in IPEC-J2 cells are predominantly enriched in the p53 signaling pathway,the coagulation cascade,the FoxO signaling pathway,and various other sig-naling pathways.Following pretreatment with chelidonine,the DEGs exhibit significant enrichment in several signaling pathways related to inflammation,including the TNF signaling pathway,syn-aptic vesicle cycle,and IL-17 signaling pathway.The results of qPCR were consistent with the se-quencing results.Chelidonine has also been found to effectively inhibit LDH release,elevate GLN content,and decrease DOA content.In conclusion,it can be seen that chelidonine can reduce cell permeability and alleviate H2 O2-induced inflammatory injury in IPEC-J2 cells by modulating in-flammation-related pathways such as the TNF signaling pathway.

[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

ObjectiveTo explore the possible mechanism of Shipi Xiaoji Beverage （实脾消积饮） in treating primary liver cancer from the perspective of mitochondrial dynamics imbalance and ferroptosis. MethodsThe Shipi Xiaoji Beverage-containing serum was prepared， and liver cancer HepG2 cells were cultured in vitro. The blank group， control group， cisplatin group （10 µg/ml）， and 5%， 10%， and 15% medicated serum groups were set， with 4 duplicate holes in each group. After adding the corresponding medicinals to each group， the cell survival rate was calculated using the CCK-8 test after 24-hour culture at 37 ℃ with 5% CO₂. Using transwell invasion assay， the number of cells that reached the upper chamber membrane through penetrating the Matrigel was calculated after culturing for 48 hours. The scratch migration rate was calculated after incubation for 24 h and 48 h in the scratch experiment， and the concentration of the medicated serum was screened for subsequent experiments. The control group， 10% medicated serum group （the screened concentration） and 10% medicated serum+Mdivi-1 group were set up. After culturing for 24 hours， the average fluorescence intensity of mitochondria and reactive oxygen species （ROS）， adenosine triphosphate （ATP） content and level were measured， and the protein expression of cytoplasmic and mitochondrial dynein-related protein 1 （Drp1） and mitochondrial phosphorylated dynamin-related protein 1 （p-Drp1） was detected. The control group， 10% medicated serum group， ferroptosis activator group （Erastin， 10 μmol/L） and 10% medicated serum+ferroptosis inhibitor group （fer-1，10 μmol/L） were set up， and after adding the corresponding medicinals to each group and culture for 24 hours， the intracellular glutathione （GSH）， malondialdehyde （MDA） content and ferrous ion level were detected， as well as the protein expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4） in cells. ResultsCompared to those in the control group， the cell survival rate， invasion number， 24 h and 48 h scratch migration rate in all medicated serum groups and cisplatin group significantly decreased （P＜0.01）； as the concentration of medicated serum increased， the cell survival rate， invasion number and 48h scratch migration rate of each medicated serum group gradually decreased （P＜0.01）， and finally， 10% of Shipi Xiaoji Beverage-containing serum was selected for subsequent experimental concentration. Compared to the control group， the 10% medicated serum group had decreased average fluorescence intensity of mitochondria and ATP content and increased average fluorescence intensity of ROS （P＜0.05）； compared to the 10% medicated serum group， the 10% medicated serum+Mdivi-1 group had higher average fluorescence intensity of mitochondria and ATP content and lower average fluorescence intensity of ROS （P＜0.05 or P＜0.01）. Compared to those in the control group， GSH content and protein expression of SLC7A11 and GPX4 in other groups significantly decreased， while MDA content and ferrous ion level increased （P＜0.05 or P＜0.01）； compared to the ferroptosis activator group， the 10% medicated serum group and the 10% medicated serum+ferroptosis inhibitor group had decreased MDA content and ferrous ion level， and increased protein expression of SLC7A11 and GPX4 （P＜0.05 or P＜0.01）； the 10% medicated serum+ferroptosis inhibitor group had higher GSH level than the 10% medicated serum group （P＜0.01）. ConclusionShipi Xiaoji Beverage may inhibit the proliferation， infestation， migration of HepG2 cells by causing mitochondrial dynamics imbalance and inducing ferroptosis， thereby playing against liver cancer.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.