Two new coumarin glycosides were isolated and purified from the dichloromethane fraction of Angelica biserrata 75% ethanol extract using silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Through the comprehensive use of modern spectroscopic methods, their structures were identified as angelmanetin A (1) and angelmanetin B (2), respectively.

Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

Objective: To compare the clinical efficacy of visual dilated sheath combined with needle nephroscope percutaneous nephrolithotomy (PCNL) with traditional PCNL for renal calculi，so as to enhance the intraoperative safety and puncture accuracy. Methods: A retrospective analysis was conducted on 100 patients with renal calculi treated on hospital during Sep.2022 to Sep.2023.Based on the surgical approaches，patients were divided into the needle nephroscope group (PCNL with visual dilator sheath and needle nephroscope，n=52) and traditional group (traditional PCNL，n=48).Clinical characteristics，surgical parameters，and outcomes were compared between the two groups. Results: There were no significant differences between the two groups in baseline data，total operation time and hospital stay (P>0.05).The needle nephroscope group had a longer channel establishment time compared to the traditional group [20.0(17.0-22.0) min vs.16.0 (15.0-21.0) min，P=0.002]，but significantly shorter puncture time [2.0 (1.0-2.6) min vs. 2.8(2.0-3.5) min，P<0.001]，and fewer adjustments of the puncture needle (9.6% vs. 64.6%，P<0.001).The channel was successfully established on the first attempt in all patients in the needle nephroscope group，while only 41 of patients in the traditional group achieved success on the first attempt，6 cases needed 2 attempts，and 1 case needed 3 attempts.Postoperative complications were absent in the needle nephroscope group，whereas postoperative bleeding requiring interventional treatment occurred in 1 case in the traditional group.There was no significant difference in the first-stage stone-clearance rate between the two groups (88.4%vs. 85.4%，P=0.872). Conclusion: PCNL using a visual dilator sheath combined with a needle nephroscope achieves a comparable first-stage stone-clearance rate to traditional PCNL.However，it offers significant advantages in terms of shorter puncture time，fewer adjustments of the puncture needle，and lower postoperative complication rate.These findings suggest superior safety and precision，making it a valuable technique for clinical application.

Objective To systematically evaluate the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer. Methods PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang, VIP, CNKI and Chinese Biomedical Literature database were searched for literature on the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer published from the establishment to May 2023. Newcastle-Ottawa Scale was used to evaluate the quality of researches, and meta-analysis was performed using RevMan5.4. Results A total of 9 articles were included, involving 3687 patients including 1019 in the McKeown group and 2668 in the Sweet group. NOS score was 8-9 points. There were no statistical differences in the age, sex or American Joint Committee on Cancer stage between the two groups (P>0.05). Patients in the McKeown group had longer operative time and hospital stay, more intraoperative blood loss, and higher Eastern Cooperative Oncology Group scores than those in the Sweet group (P<0.05). However, the McKeown operation could remove more lymph nodes (P=0.001). In terms of safety, the incidences of pulmonary complications [OR=2.20, 95%CI (1.40, 3.46), P=0.001] and postoperative anastomotic leakage [OR=2.06, 95%CI (1.45, 2.92), P=0.001] were higher in the McKeown group than those in the Sweet group. In addition, there were no statistical differences between the two groups in the Karnofsky score, cardiac complications, vocal cord injury or paralysis, chylous leakage, or gastric emptying (P>0.05). Conclusion Compared with McKeown, Sweet method has advantages in operation time, intraoperative blood loss and hospital stay, and has lower incidence of postoperative pulmonary complications and anastomotic leakage. However, McKeown has more lymph node dissection.

Objective To investigate the correlation between levels of intercellular adhesion molecule-1 (ICAM-1), platelet surface P-selectin (CD62P), and inflammatory factors and cerebral artery stenosis in patients with acute cerebral infarction (ACI). Methods A total of 305 patients with ACI complicated with cerebral artery stenosis admitted to Zhongwu Hospital of Suqian City and Xinyi People's Hospital from January 2021 to December 2023 were selected as the research subjects. According to the degree of cerebral artery stenosis, they were divided into grade I group (stenosis degree<50%, n=85), grade II group (stenosis degree of 50%-75%, n=128), and grade III group (stenosis degree>75%, n=92). Sixty-eight ACI patients without cerebral artery stenosis during the same period were included in the reference group. The levels of serum inflammatory factors [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8)], ICAM-1 and CD62P were compared among the four groups. Spearman analysis was used to analyze the correlation between each factor and degree of cerebral artery stenosis. Results The levels of CRP, TNF-α, IL-6, IL-8, ICAM-1 and CD62P in the grade I, II and III groups were higher than those in the reference group. The levels of these factors were higher in the grade II and III groups than those in the grade I group, while the levels of various factors were higher in the grade III group than those in the grade II group (P<0.05). Spearman analysis showed that CRP, TNF-α, IL-6, IL-8, ICAM-1, and CD62P were positively correlated with the degree of cerebral artery stenosis in patients with ACI complicated with cerebral artery stenosis (P<0.05). Conclusion The levels of serum inflammatory factors, ICAM-1 and CD62P are significantly correlated with cerebral artery stenosis degree in patients with ACI.

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.