ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L^-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L^-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L^-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）. ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.

Objective:To evaluate the efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy in elderly women with locally advanced cervical cancer.Methods:A retrospective analysis was conducted among elderly patients with cervical cancer who received nimotuzumab combined with concurrent chemoradiotherapy in the gynecology department of Beijing Hospital from November 2018 to March 2023.Efficacy assessments included the objective response rate(ORR), recurrence rates after 1-3 years of follow-up, and comparisons of the levels of squamous cell carcinoma antigen(SCC), carcino-embryonic antigen(CEA), and carbohydrate antigen 125(CA125)before and after treatment.Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 5.0.Results:A total of 47 elderly patients aged 60 years and older with stage ⅠB3-Ⅳa cervical cancer were included, with ages ranging from 60 to 76 years[mean age: (65.8±4.3) years; median age: 65(62, 70) years].The patients were divided into three age groups: 60-64 years(21 cases), 65-69 years(14 cases), and ≥70 years(12 cases).After treatment, SCC and CEA levels significantly decreased compared to pre-treatment levels, with statistically significant differences ( W=5.281 and 2.607, respectively; both P<0.05).However, there was no significant difference in CA125 levels before and after treatment( W=1.591, P=0.112).Among the 47 patients, 3 did not undergo post-treatment imaging examinations.Efficacy evaluation results were collected from 44 patients, including 21 cases of complete response(CR)(47.7%), 21 cases of partial response(PR)(47.7%), 1 case of stable disease(SD)(2.3%), and 1 case of progressive disease(PD)(2.3%).The ORR was 95.5%(42/44), and the diseae control rate was 97.7%(43/44).There were statistically significant differences in efficacy among different age groups(Fisher's exact test P=0.015).During the treatment process, a total of 36 patients experienced grade 3 or higher adverse reactions during treatment.Among them, 14 cases(29.8%)with grade 3 or higher acute hematological adverse reactions, 11 cases(23.4%)with grade 3 or higher acute gastrointestinal reactions, and 6 cases(12.8%)with grade 3 or higher acute urinary symptoms.Additionally, 2 cases of radiation cystitis and 3 cases of radiation proctitis were reported.There was no statistically significant difference in recurrence rates among different age groups(Fisher's exact test P=0.292).The highest recurrence rate among elderly patients was observed at the 2-3 year follow-up. Conclusions:For elderly patients with good organ function status, standard concurrent chemoradiotherapy combined with nimotuzumab may be an effective treatment for locally advanced cervical cancer.

Objective:To investigate the predictive value of the cancer antigen 125 (CA 125) elimination rate constant K (KELIM) score for no visible residual disease (R0) and prognosis in high-grade serous ovarian carcinoma (HGSOC) patients undergoing neoadjuvant chemotherapy (NACT)+interval debulking surgery (IDS). Methods:A retrospective analysis was conducted on 78 HGSOC patients treated with NACT+IDS at Beijing Hospital, from June 2014 to June 2024. The KELIM score was calculated, and its predictive value for R0 resection, chemotherapy response score (CRS), platinum-free interval (PFI), progression-free survival (PFS) time, and overall survival (OS) time was analyzed.Results:(1) The mean age at diagnosis was (61.9±9.9) years. The mean KELIM score was 1.1±0.4, with 44 patients having KELIM score≥1 and 34 having KELIM score <1. (2) Patients with KELIM score ≥1 had significantly higher rates of R0 resection (84% vs 56%; P=0.006), CRS3 grading (41% vs 0; P<0.001), and PFI ≥6 months (84% vs 53%; P=0.04) compared to those with KELIM score <1. Additionally, the median PFS time (18.7 vs 13.2 months; P<0.001) and OS time (34.8 vs 29.9 months; P=0.007) were significantly longer in the KELIM score ≥1 group. Chemosensitivity: patients with PFI <6 months had a significantly lower median KELIM score than those with PFI ≥6 months (0.8 vs 1.2; P=0.005). Surgical outcome: patients achieving R0 resection had a significantly higher median KELIM score than those without R0 (1.2 vs 0.7; P<0.001). (3) Univariate analysis identified non-R0 resection, CRS3 grading, lack of poly adenosine diphosphate ribose polymerase (PARP) inhibitor maintenance therapy, and KELIM score <1 as significant risk factors for OS time (all P<0.05). Multivariate analysis confirmed non-R0 resection ( HR=3.78,95% CI: 1.13-12.66; P=0.031), no PARP inhibitor maintenance ( HR=7.41,95% CI:1.82-30.15; P=0.005), and KELIM score <1 ( HR=5.14,95% CI:1.41-18.72; P=0.013) as independent risk factors for OS time. Conclusions:The KELIM score may serve as a predictive marker for chemosensitivity, R0 resection, PFS time, and OS time in HGSOC patients undergoing NACT+IDS. KELIM score<1 is an independent risk factor for OS.

Objective To introduce the application scene,operating steps and preliminary clinical effect of tibial bone mass preservation technique in medial unicompartmental knee arthroplasty(MUKA).Methods A total of 15 patients with antero-medial knee osteoarthritis(AMOA)treated in this hospital from May 2022 to May 2023 were selected as the study subjects.The tibial bone mass preservation technique was a-dopted to complete MUKA(fixed platform prosthesis).The operating time,intraoperative bleeding volume,hospitalization duration and operation complications were recorded.The VAS score before operation and in last follow up,range of motion(ROM)of knee joint,Knee Society Score(KSS),hip and knee stomping angle(HKA)of lower extremity in the operation side and image results were recorded to evaluate the clinical effect.Results The operations in 15 cases were successfully completed.The average operation time was(82.73±9.97)min,mean intraoperative bleeding volume was(21.00±9.49)mL and average hospital stay was(4.9±1.4)d.There was no intraoperative nerve,vascular and medial collateral ligament injury,no iatro-genic fracture,and no postoperative surgical site infection.All patients were followed up for average(5.87±2.77)months.The VAS score of knee joint,ROM,KSS and HKA angle of lower limb in the operated side were significantly improved compared with before operation(P<0.05).There was no prosthesis loosening,displacement or fragmentation,and no obvious degeneration aggravation of the lateral compartment of the knee joint.Conclusion The tibial bone mass preservation technique is a simple,effective and reliable method to deal with the slightly tight flexion space after tibial osteotomy during MUKA,and the postoperative clinical efficacy and imaging results are excellent.

Acute Kidney Injury (AKI) is a common and severe complication after cardiac surgery. The pathogenesis of cardiac surgery-associated AKI (CSA-AKI) is complex, and it is associated with increased patient mortality and poor renal prognosis. To identify high-risk patients as early as possible, numerous clinical studies have explored perioperative risk factors and developed a variety of biomarkers with good diagnostic capabilities. Currently, multiple prediction models for AKI after cardiac surgery have been developed internationally; however, there is no effective treatment for CSA-AKI. Therefore, implementing reasonable and comprehensive preventive strategies is crucial. In addition, the clinical application of some interventions is controversial, which means more research and exploration are needed to make more informed decisions regarding the prevention and treatment of CSA-AKI.

Objective:To evaluate the efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy in elderly women with locally advanced cervical cancer.Methods:A retrospective analysis was conducted among elderly patients with cervical cancer who received nimotuzumab combined with concurrent chemoradiotherapy in the gynecology department of Beijing Hospital from November 2018 to March 2023.Efficacy assessments included the objective response rate(ORR), recurrence rates after 1-3 years of follow-up, and comparisons of the levels of squamous cell carcinoma antigen(SCC), carcino-embryonic antigen(CEA), and carbohydrate antigen 125(CA125)before and after treatment.Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 5.0.Results:A total of 47 elderly patients aged 60 years and older with stage ⅠB3-Ⅳa cervical cancer were included, with ages ranging from 60 to 76 years[mean age: (65.8±4.3) years; median age: 65(62, 70) years].The patients were divided into three age groups: 60-64 years(21 cases), 65-69 years(14 cases), and ≥70 years(12 cases).After treatment, SCC and CEA levels significantly decreased compared to pre-treatment levels, with statistically significant differences ( W=5.281 and 2.607, respectively; both P<0.05).However, there was no significant difference in CA125 levels before and after treatment( W=1.591, P=0.112).Among the 47 patients, 3 did not undergo post-treatment imaging examinations.Efficacy evaluation results were collected from 44 patients, including 21 cases of complete response(CR)(47.7%), 21 cases of partial response(PR)(47.7%), 1 case of stable disease(SD)(2.3%), and 1 case of progressive disease(PD)(2.3%).The ORR was 95.5%(42/44), and the diseae control rate was 97.7%(43/44).There were statistically significant differences in efficacy among different age groups(Fisher's exact test P=0.015).During the treatment process, a total of 36 patients experienced grade 3 or higher adverse reactions during treatment.Among them, 14 cases(29.8%)with grade 3 or higher acute hematological adverse reactions, 11 cases(23.4%)with grade 3 or higher acute gastrointestinal reactions, and 6 cases(12.8%)with grade 3 or higher acute urinary symptoms.Additionally, 2 cases of radiation cystitis and 3 cases of radiation proctitis were reported.There was no statistically significant difference in recurrence rates among different age groups(Fisher's exact test P=0.292).The highest recurrence rate among elderly patients was observed at the 2-3 year follow-up. Conclusions:For elderly patients with good organ function status, standard concurrent chemoradiotherapy combined with nimotuzumab may be an effective treatment for locally advanced cervical cancer.

Objective:To investigate the predictive value of the cancer antigen 125 (CA 125) elimination rate constant K (KELIM) score for no visible residual disease (R0) and prognosis in high-grade serous ovarian carcinoma (HGSOC) patients undergoing neoadjuvant chemotherapy (NACT)+interval debulking surgery (IDS). Methods:A retrospective analysis was conducted on 78 HGSOC patients treated with NACT+IDS at Beijing Hospital, from June 2014 to June 2024. The KELIM score was calculated, and its predictive value for R0 resection, chemotherapy response score (CRS), platinum-free interval (PFI), progression-free survival (PFS) time, and overall survival (OS) time was analyzed.Results:(1) The mean age at diagnosis was (61.9±9.9) years. The mean KELIM score was 1.1±0.4, with 44 patients having KELIM score≥1 and 34 having KELIM score <1. (2) Patients with KELIM score ≥1 had significantly higher rates of R0 resection (84% vs 56%; P=0.006), CRS3 grading (41% vs 0; P<0.001), and PFI ≥6 months (84% vs 53%; P=0.04) compared to those with KELIM score <1. Additionally, the median PFS time (18.7 vs 13.2 months; P<0.001) and OS time (34.8 vs 29.9 months; P=0.007) were significantly longer in the KELIM score ≥1 group. Chemosensitivity: patients with PFI <6 months had a significantly lower median KELIM score than those with PFI ≥6 months (0.8 vs 1.2; P=0.005). Surgical outcome: patients achieving R0 resection had a significantly higher median KELIM score than those without R0 (1.2 vs 0.7; P<0.001). (3) Univariate analysis identified non-R0 resection, CRS3 grading, lack of poly adenosine diphosphate ribose polymerase (PARP) inhibitor maintenance therapy, and KELIM score <1 as significant risk factors for OS time (all P<0.05). Multivariate analysis confirmed non-R0 resection ( HR=3.78,95% CI: 1.13-12.66; P=0.031), no PARP inhibitor maintenance ( HR=7.41,95% CI:1.82-30.15; P=0.005), and KELIM score <1 ( HR=5.14,95% CI:1.41-18.72; P=0.013) as independent risk factors for OS time. Conclusions:The KELIM score may serve as a predictive marker for chemosensitivity, R0 resection, PFS time, and OS time in HGSOC patients undergoing NACT+IDS. KELIM score<1 is an independent risk factor for OS.

Acute Kidney Injury (AKI) is a common and severe complication after cardiac surgery. The pathogenesis of cardiac surgery-associated AKI (CSA-AKI) is complex, and it is associated with increased patient mortality and poor renal prognosis. To identify high-risk patients as early as possible, numerous clinical studies have explored perioperative risk factors and developed a variety of biomarkers with good diagnostic capabilities. Currently, multiple prediction models for AKI after cardiac surgery have been developed internationally; however, there is no effective treatment for CSA-AKI. Therefore, implementing reasonable and comprehensive preventive strategies is crucial. In addition, the clinical application of some interventions is controversial, which means more research and exploration are needed to make more informed decisions regarding the prevention and treatment of CSA-AKI.

Objective To investigate the role of bufalin(BU)in inhibiting M2-type macrophage-mediated colorec-tal cancer metastasis.Methods Human acute leukemia mononuclear cells(THP-1)were differentiated into M0 macrophages using phorbol ester induction(PMA)for 48 hours.The M0 macrophages were then treated with IL-4 and IL-13 medium.Surface markers and morphological changes were observed through ELISA,morphology,and RT-qPCR experiments.RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages.The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA.Additionally,the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell,Wound healing,RT-qPCR,and Western blot experiments.Subsequent-ly,bufalin was added to the conditioned medium and the changes in AKT/PI3K protein,migration,and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot,Transwell,Wound healing and RT-qPCR experiments.Results THP-1 were successfully differentiated into M2 macrophages.The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages,which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells.The migration and epithelial-mes-enchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin.Conclu-sion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells,thereby promoting their migration and epithelial-mesenchymal transition capacity.Moreover,bufalin exhibits inhibitory effects on this effect.