ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

ObjectiveTo observe the clinical efficacy of Anzi Tiaochong decoction combined with aspirin and the effects of this therapy on the peripheral blood phospholipid antibody titers， coagulation function， and CD19⁺CD24^hiCD27⁺regulatory B （Breg） cells in patients with obstetric antiphospholipid syndrome （OAPS） （pattern of kidney deficiency and blood stasis）. MethodsPatients who meet the inclusion criteria were randomly allocated into an observation group （50 patients， with 4 patients dropped out and 46 patients completed） and a control group （50 patients， with 2 patients dropped out， 1 patient excluded， and 47 patients completed） through a random number table method. The control group was treated with aspirin enteric-coated tablets， 75 mg/time， once a day， and the observation group with Anzi Tiaochong decoction， 1 bag/day on the basis of the therapy in the control group. The treatment course for both groups was 8 weeks， and the patients were followed up for 4 weeks. The traditional Chinese medicine （TCM） symptom scores， titers of peripheral blood phospholipid antibodies ［anti-cardiolipin antibody IgM （ACA IgM）， anti-cardiolipin antibody IgG （ACA IgG）， anti-β₂-glycoprotein 1 antibody IgM （β₂GP1-IgM）， and anti-β₂-glycoprotein 1 antibody IgG （β₂GP1-IgG）］， D-dimer （D-D）， thromboelastography parameters ［clotting factor activity （R）， platelet function maximum amplitude （MA）， coagulation composite index （CI）， and clot strength （G）］， CD19⁺CD24^hiCD27⁺ Breg expression rate， and adverse drug reactions were recorded for the two groups before and after treatment. ResultsAfter treatment， both groups showed decreased ACA IgM， ACA IgG， β₂GP1-IgM， β₂GP1-IgG， D-D， MA， and G （P<0.05） and increased R （P<0.05）. There was no statistically significant difference in CI. Compared with the control group， the observation group showed more significant decreases in TCM symptom scores and phospholipid antibody titers （P<0.05）. After treatment， the expression rate of Breg in the observation group was higher than that before treatment （P<0.05）.There was no significant difference in Breg expression rate before and after treatment in the control group. Neither group experienced significant adverse reactions. ConclusionAnzi Tiaochong decoction combined with aspirin can alleviate the symptoms， reduce the phospholipid antibody titers， and restore the coagulation status of patients with obstetric antiphospholipid syndrome （pattern kidney deficiency and blood stasis）. It may exert the therapeutic effects by regulating Breg to maintain the patient's immune balance.

Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

Objective:To compare the efficacy of oliceridine and sufentanil when combined with propofol for painless gastroscopy.Methods:In this randomized controlled trial, 66 patients of either sex, aged 18-64 yr, with a body mass index of 18-26 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, scheduled for elective painless gastroscopy from September 2024 to November 2024, were divided into 2 groups ( n=33 each) using a table of computer-generated random numbers: sufentanil combined with propofol group (SP group) and oliceridine combined with propofol group (OP group). Sufentanil 0.1 μg/kg was intravenously injected in group SP, oliceridine 0.02 mg/kg was intravenously injected in group OP, and 1 min later propofol 2 mg/kg was intravenously injected in both groups. When the modified Observer′s Assessment of Alertness and Sedation score ≤ 1, the painless gastroscopy was performed. Heart rate, mean arterial pressure and peripheral oxygen saturation were recorded on admission to the operating room, immediately after insertion of the gastroscope, and at the end of procedure. The success of sedation, time of gastroscopy, emergence time, consumption of propofol and use of vasoactive drugs were recorded. The occurrence of adverse events such as respiratory depression, hypotension, dizziness and nausea was also recorded. Results:Compared with group SP, the incidence of respiratory depression was significantly decreased in group OP ( P<0.05). There was no statistically significant difference in the incidence of hypotension, dizziness and nausea and heart rate, mean arterial pressure and peripheral oxygen saturation at different time points between the two groups ( P>0.05). Conclusions:Oliceridine provides better efficacy than sufentanil when combined with propofol in painless gastroscopy.

Objective:To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF) autophagy on papillary thyroid cancer(PTC).Methods:CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients. Expressions of fibroblast activation protein(FAP) and α-smooth muscle actin in cells were assessed. Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells. The effects of CAF and normal fibroblasts on survival, proliferation, migration, invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay, cell scratch assay, cell invasion assay, and cell iodine uptake assay. The autophagy level of CAF was also evaluated. Autophagy inhibition and activation were used to regulate the autophagy of CAF, and then their effects on PTC cell proliferation, migration and invasion were further evaluated. The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results:CAF exhibited higher FAP expression and basal autophagy levels. PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation, migration, invasion, and reduced iodine uptake. Autophagy inhibition reduced these effects, while autophagy activation further promoted them. In vivo, inhibiting CAF autophagy suppressed tumor growth.Conclusions:CAF promotes PTC cell malignancy through autophagy activation, enhancing proliferation, migration, and invasion while reducing iodine uptake.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.

Objective:To analyze the effects of electrophysiological combined therapy on pelvic floor function and electrophysiological indexes of pelvic floor in elderly patients with pelvic prolapse.Methods:A total of 46 elderly patients with pelvic prolapse admitted to Noncommissioned Officer School Hospital, Army Medical University from Jan. 2022 to Jul. 2023 were selected as subjects. All patients were divided into control group and study group by random number table method, with 23 cases in each group. The control group was treated with conventional operation, and the study group was treated with electrophysiological combination. The therapeutic effect, psychological state, pelvic floor electrophysiology and pelvic floor muscle function before and after treatment were compared between the two groups.Results:The treatment efficacy rate in the observation group was 95.65%, while that in the control group was 73.91%, with the observation group showing a significantly higher rate than the control group ( P<0.05). There were no statistically significant differences between the two groups in terms of psychological state scores, pelvic floor electrophysiological indicators, or pelvic floor muscle function before treatment ( P>0.05). After treatment, the SAS score, SDS score, fatigue degree of Type I muscle fibers, fatigue degree of Type II muscle fibers, and absolute values of gh scores in the observation group were lower than those in the control group ( P<0.05) ; The observation group had higher Type I muscle fiber strength, Type II muscle fiber strength, Ba point, Bp point, pb point, TVL point, pelvic floor contraction pressure, rapid contraction pressure, resting pressure, and number of contractions than the control group ( P<0.05) . Conclusion:Electrophysiological combined therapy is helpful to improve the therapeutic effect of elderly patients with pelvic prolapse, improve their psychological state, pelvic floor electrophysiological indexes and pelvic floor muscle function.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.

Objective To investigate their potential differences in brain functional characteristics from a neuroimaging perspective,functional magnetic resonance imaging(fMRI)was employed.Methods Twenty chronic fatigue syndrome(CFS)patients were recruited and underwent assessments of traditional Chinese medicine(TCM)syndrome patterns,fatigue severity scores,and resting-state fMRI scans.First,correlation analysis was performed between fatigue scores and TCM symptom scores.Symptom clusters significantly associated with fatigue were categorized into spleen deficiency and liver stagnation groups.Principal component analysis(PCA)was then applied to identify the dominant symptom components for each group.These components were subsequently mapped onto whole-brain functional activity to compare the neural signatures between the two syndromes.Finally,the brain functional profiles of spleen deficiency and liver stagnation were compared with publicly available neurotransmitter receptor maps to explore their distinct neurochemical substrates.Results Symptoms correlated with fatigue severity included exhaustion,dizziness,chest tightness,bitter taste in the mouth,epigastric fullness,poor appetite,irritability,lumbar soreness,sallow complexion,dry eyes,and five-center-heat.The brain mapping results revealed that spleen deficiency-related symptoms(poor appetite,sallow complexion,reduced food intake,dizziness)were primarily associated with the left thalamus and left parahippocampal gyrus.Liver stagnation-related symptoms(dry eyes,chest tightness,irritability,bitter taste)were linked to the left parahippocampal gyrus and right middle occipital gyrus(lingual region).The functional brain spectrum of the two syndromes showed significant negative correlations.Moreover,the spleen deficiency spectrum was closely associated with vesicular acetylcholine transporter(VAChT)receptor density.The liver stagnation spectrum correlated with D2 dopamine receptor density.Both spectrums were significantly related to glucose metabolic density but exhibited opposing directional trends.Conclusion CFS patients with spleen deficiency and liver stagnation demonstrate distinct central functional activities and neurochemical substrates,along with opposing brain activity patterns.Clinically,differentiating between these two syndrome patterns is critical for applying targeted TCM interventions.