Objective To analyze the evaluation value of whole brain computed tomography perfusion imaging(CTPI)scanning parameters on collateral circulation in ischemic stroke.Methods One hundred and two patients with ischemic stroke were selected,according to the condition they were divided into mild group(n=26),moderate group(n=56),and severe group(n=20).The col-lateral circulation status was evaluated based on the modified American Society of Interventional and Therapeutic Neuroradiology(ASITN)/Society of Interventional Radiology(SIR)score of dynamic CT angiography,and was divided into good group(n=61)and poor group(n=41).CTPI parameters were compared between different groups of patients with cerebral blood flow(CBF),cerebral blood volume(CBV),mean transit time(MTT),and time to peak(TTP).Results The CBF and CBV in the severe group were lower than those in the mild and moderate groups,while the MTT and TTP were higher than those in the mild and moderate groups(P<0.05);The CBF and CBV in the moderate group were lower than those in the mild group,while the MTT and TTP were higher than those in the mild group(P<0.05).The CBF and CBV in the good group were higher than those in the poor group,while the MTT and TTP were lower than those in the poor group(P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity of CBF,CBV,MTT,and TTP in predicting poor collateral circulation was 0.820,0.672,0.803,and 0.820,respectively;The specificity was 0.854,0.756,0.732,and 0.780,respectively.Conclusion CTPI scanning parameters have certain values to assess the intracranial collateral circulation status in patients with ischemic stroke.

Objective To investigate the effect of electroacupuncture(EA)on the behaviors of lipopolysaccharide(LPS)-induced depression-like mice and explore the potential molecular mechanism of the antidepressant effect of EA using transcriptomics sequencing technology.Methods Thirty-six male specific pathogen-free-grade C57BL/6J mice were divided into the normal,the model,and the EA groups using the random number table method,with 12 mice per group.The EA group received a daily 20-minute EA at the"Baihui"and"Yintang"acupoints for 7 days.After 7 days of EA treatment,1.5 mg/kg LPS was injected intraperitoneally into the model and EA groups,whereas the normal group received an injection of an equal volume of saline solution.Depressive behaviors were assessed using the open-field test,tail-suspension test,and other relevant tests.Pathologic morphology of the hippocampus tissue was determined using hematoxylin-eosin staining.Transcriptomics technology was used to identify differentially expressed genes in the hippocampus,and bioinformatics analysis was performed.Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of hematopoietic cell kinase(Hck),adhesion G protein-coupled receptor E1(Adgre1),Toll-like receptor 2(Tlr2),and Gm49037 in the hippocampus.Results Compared to the normal group,mice in the model group exhibited a decrease in total travel distance,central travel distance,center area time(P＜0.01),as well as an increase in tail-suspension immobility time(P＜0.05).Hippocampal neurons were loosely arranged,and some neurons had blurred boundaries.Compared to the model group,mice in the EA group showed an increase in open-field total travel distance,central travel distance,center area time(P＜0.05),as well as a decrease in tail-suspension immobility time(P＜0.01);Additionally,hippocampal neurons were more tightly arranged,exhibiting clearer morphology and structure.Transcriptomic analysis revealed that 779 differentially expressed genes were identified in the model group compared to the normal group,whereas 172 genes differed between the EA and model groups.Nineteen genes were upregulated in the model group but downregulated in the EA group,and ten genes were down-regulated in the model group but up-regulated in the EA group.Gene Ontology Functional Analysis indicated that these genes primarily function in immune responses,Toll-like receptor activity,cell surface receptor signaling pathways,and interleukin-10 production.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment in inflammation-related pathways,including Toll-like receptor signaling pathway and tumor necrosis factor signaling pathway.Compared to the normal group,Hck,Adgre1,and Tlr2 mRNA expressions were elevated in the model group(P＜0.01),whereas there was a decrease tendency for Gm49037 mRNA expression and there was no significant difference(P＞0.05);compared to the model group,Hck,Adgre1,and Tlr2 mRNA expressions were decreased in the EA group(P＜0.05),whereas there was an increase tendency for Gm49037 mRNA expression and there was no significant difference(P＞0.05).Conclusion EA alleviated depressive-like behavior and pathological damage in the hippocampus in LPS-induced mice,which may be related to attenuating hippocampal inflammatory pathways,and Hck,Adgre1,and Tlr2 genes may be the potential targets for its effect.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective To investigate the effect of ginsenoside Re on angiotensin Ⅱ(Ang Ⅱ)-induced proliferation,migration,and phenotype transformation of vascular smooth muscle cells(VSMCs)by regulating the Ras homologous gene family member A(RhoA)/mitogen activated protein kinase(MAPK)pathway.Methods MOVAS cells were divided into control group,Ang Ⅱ group,ginsenoside Re low dose group,ginsenoside Re medium dose group,ginsenoside Re high dose group,andginsenoside Re high dose+RhoA activator(U46619)group.MOVAS cell proliferation was detected by CCK-8.MOVAS cell migration was detected by scratch assay.Immunocytochemistry was used to detect the positive expression of α-smooth muscle actin(α-SMA)and osteopontin(OPN)proteins in MOVAS cells.qRT-PCR was used to detect the mRNA expression of PCNA,MMP-9,and MMP-2 in MOVAS cells.Western blot was used to detect RhoA,phosphorylated extracellular signal regulated kinase 1/2(p-ERK1/2),phosphorylated stress activated protein kinase 1(p-JNK1),and p-P38 protein in MOVAS cells.Results Compared with the control group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,RhoA,p-ERK1/2,p-JNK1,p-P38 protein expression of MOVAS cells in the Ang II group increased,while the positive expression of α-SMA protein decreased significantly(P<0.05).Compared with the Ang Ⅱ group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,and RhoA,p-ERK1/2,p-JNK1,and p-P38 proteins of MOVAS cells in the low,medium,and high dose groups of ginsenoside Re decreased,while the positive expression of α-SMA protein increased.The trend was most significant in the high dose group of ginsenoside Re(P<0.05).Compared with ginsenoside Re high-dose group,OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression and RhoA,p-ERK1/2,p-JNK1,p-P38 protein in ginsenoside Re high-dose+U46619 group increased,the positive expression of α-SMA protein decreased significantly(P<0.05).Conclusion Ginsenoside Re may inhibit the proliferation,migration,and phenotype transformation of Ang Ⅱ in MOVAS cells by suppressing the RhoA/MAPK pathway.

Objective To analyze the evaluation value of whole brain computed tomography perfusion imaging(CTPI)scanning parameters on collateral circulation in ischemic stroke.Methods One hundred and two patients with ischemic stroke were selected,according to the condition they were divided into mild group(n=26),moderate group(n=56),and severe group(n=20).The col-lateral circulation status was evaluated based on the modified American Society of Interventional and Therapeutic Neuroradiology(ASITN)/Society of Interventional Radiology(SIR)score of dynamic CT angiography,and was divided into good group(n=61)and poor group(n=41).CTPI parameters were compared between different groups of patients with cerebral blood flow(CBF),cerebral blood volume(CBV),mean transit time(MTT),and time to peak(TTP).Results The CBF and CBV in the severe group were lower than those in the mild and moderate groups,while the MTT and TTP were higher than those in the mild and moderate groups(P<0.05);The CBF and CBV in the moderate group were lower than those in the mild group,while the MTT and TTP were higher than those in the mild group(P<0.05).The CBF and CBV in the good group were higher than those in the poor group,while the MTT and TTP were lower than those in the poor group(P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity of CBF,CBV,MTT,and TTP in predicting poor collateral circulation was 0.820,0.672,0.803,and 0.820,respectively;The specificity was 0.854,0.756,0.732,and 0.780,respectively.Conclusion CTPI scanning parameters have certain values to assess the intracranial collateral circulation status in patients with ischemic stroke.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective To investigate the effect of ginsenoside Re on angiotensin Ⅱ(Ang Ⅱ)-induced proliferation,migration,and phenotype transformation of vascular smooth muscle cells(VSMCs)by regulating the Ras homologous gene family member A(RhoA)/mitogen activated protein kinase(MAPK)pathway.Methods MOVAS cells were divided into control group,Ang Ⅱ group,ginsenoside Re low dose group,ginsenoside Re medium dose group,ginsenoside Re high dose group,andginsenoside Re high dose+RhoA activator(U46619)group.MOVAS cell proliferation was detected by CCK-8.MOVAS cell migration was detected by scratch assay.Immunocytochemistry was used to detect the positive expression of α-smooth muscle actin(α-SMA)and osteopontin(OPN)proteins in MOVAS cells.qRT-PCR was used to detect the mRNA expression of PCNA,MMP-9,and MMP-2 in MOVAS cells.Western blot was used to detect RhoA,phosphorylated extracellular signal regulated kinase 1/2(p-ERK1/2),phosphorylated stress activated protein kinase 1(p-JNK1),and p-P38 protein in MOVAS cells.Results Compared with the control group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,RhoA,p-ERK1/2,p-JNK1,p-P38 protein expression of MOVAS cells in the Ang II group increased,while the positive expression of α-SMA protein decreased significantly(P<0.05).Compared with the Ang Ⅱ group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,and RhoA,p-ERK1/2,p-JNK1,and p-P38 proteins of MOVAS cells in the low,medium,and high dose groups of ginsenoside Re decreased,while the positive expression of α-SMA protein increased.The trend was most significant in the high dose group of ginsenoside Re(P<0.05).Compared with ginsenoside Re high-dose group,OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression and RhoA,p-ERK1/2,p-JNK1,p-P38 protein in ginsenoside Re high-dose+U46619 group increased,the positive expression of α-SMA protein decreased significantly(P<0.05).Conclusion Ginsenoside Re may inhibit the proliferation,migration,and phenotype transformation of Ang Ⅱ in MOVAS cells by suppressing the RhoA/MAPK pathway.

ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

Objective:To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and chronic idiopathic intestinal pseudo-obstruction (CIIPX).Methods:A pedigree presented at the First Hospital of Lanzhou University in June 2024 for CVDPX combined with CIIPX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15).Results:Both the proband and his affected younger brother were found to harbor a hemizygous c. 443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded by the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+ PS4+ PP2+ PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. Conclusion:This study confirmed the diagnosis of CVDPX/CIIPX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.