1.Influencing Factors of Depression in Patients with Postoperative Ovarian Cancer
Jialiang YAO ; Long ZHANG ; Jianhui TIAN ; Ze LIU ; Yun YANG ; Yiyang ZHOU ; Minghua LI ; Wang YAO ; Wenfei SHI ; Xinyi LU ; Pan YU ; Enchao CONG
Cancer Research on Prevention and Treatment 2026;53(5):349-359
Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.
2.Peripheral Immune Response Patterns Under Vital Qi-Strengthening and Toxin-Eliminating Therapy and Their Value in Assessing Vital Qi Deficiency in Lung Cancer Metastasis: A Group-Based Trajectory Modeling
Fan XU ; Jianhui TIAN ; Yuan YAO ; Zhenyang CHENG ; Yanhong WANG ; Bin LUO ; Jialiang YAO ; Wang YAO ; Xinyi LU ; Yuchen BAO ; Xiaoyu YANG ; Youjun LIU ; Yiyang ZHOU ; Jianchun WU ; Minghua LI ; Wenfei SHI ; Yajing CUI ; Qingzhong LIU ; Yan LI ; Yun YANG
Cancer Research on Prevention and Treatment 2026;53(9):711-717
Objective On the basis of the theory of the tumor metastatic state, this work aims to explore the metastasis trajectories and peripheral immune response patterns in patients with non-small cell lung cancer (NSCLC) receiving vital qi-strengthening and toxin-eliminating therapy (Fuzheng Juandu) and reveal the value of peripheral immunity in assessing vital qi deficiency during metastasis. Methods A retrospective study design was adopted. Patients with NSCLC admitted from January 1, 2018, to October 31, 2025 were enrolled. Data on metastasis status and peripheral immune indices were collected at the follow-up time points of one, two, three, and five years. Group-based trajectory modeling was used to fit metastasis trajectories, and the independent predictors of trajectory grouping were analyzed through multifactor and multiclassification logistic regression. Results A total of 184 patients with NSCLC were included, and three different groups of metastasis trajectories were identified, namely, the low-risk stable (46.74%, n=86), low-risk rising (13.59%, n=25), and high-risk stable (39.67%, n=73) groups. Univariate analysis revealed substantial differences in peripheral immune indices among the three trajectory groups. Multivariate analysis showed that TNM stage, absolute neutrophil count, lymphocyte count, absolute monocyte count, platelet volume, SAA:CRP ratio, and NLR were independent predictors of the low-risk rising group, whereas TNM stage, absolute monocyte count, basophil count, SII, and NLR were independent predictors of the high-risk stable group. Conclusion Under Fuzheng Juandu therapy, patients with NSCLC exhibit three distinct metastasis trajectories, each
3.Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults (version 2025)
Bobin MI ; Faqi CAO ; Weixian HU ; Wu ZHOU ; Chenchen YAN ; Hui LI ; Yun SUN ; Yuan XIONG ; Jinmi ZHAO ; Qikai HUA ; Xinbao WU ; Xieyuan JIANG ; Dianying ZHANG ; Zhongguo FU ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Tengbo YU ; Jinhai TAN ; Xi CHEN ; Fengfei LIN ; Zhangyuan LIN ; Dongfa LIAO ; Aiguo WANG ; Shiwu DONG ; Gaoxing LUO ; Zhao XIE ; Dong SUN ; Dehao FU ; Yunfeng CHEN ; Changqing ZHANG ; Kun LIU ; Deye SONG ; Yongjun RUI ; Fei WU ; Ximing LIU ; Junwen WANG ; Meng ZHAO ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Xiao CHEN ; Guandong DAI ; Shiyuan FANG ; Wenchao SONG ; Ming CHEN ; Guanghua GUO ; Yongqing XU ; Lei YANG ; Wenqian ZHANG ; Kun ZHANG ; Xin TANG ; Hua CHEN ; Weiguo XU ; Shuquan GUO ; Yong LIU ; Xiaodong GUO ; Zhewei YE ; Liming XIONG ; Tian XIA ; Hongbin WU ; Qisheng ZHOU ; Mengfei LIU ; Yiqiang HU ; Yanjiu HAN ; Hang XUE ; Kangkang ZHA ; Wei CHEN ; Zhiyong HOU ; Bin YU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Guohui LIU
Chinese Journal of Trauma 2025;41(5):421-432
Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.
4.Effect and prognosis of thoracolumbar fracture combined with incomplete spinal cord injury on male sexual function
Gao SI ; Yuexin WANG ; Daole HU ; Guojin HOU ; Zhongwei YANG ; Yan GUO ; Zhishan ZHANG ; Hongquan JI ; Fang ZHOU ; Yun TIAN ; Yang LYU
Chinese Journal of Orthopaedics 2025;45(9):552-560
Objective:To investigate the effects of thoracolumbar vertebral fracture with incomplete spinal cord injury on male sexual function and postoperative prognosis.Methods:A retrospective review was conducted on data from 144 male patients with thoracolumbar vertebral fractures and incomplete spinal cord injuries treated between May 2009 and May 2021 in the Department of Traumatology and Orthopedics at Peking University Third Hospital. Patients ranged in age from 19 to 55 years (mean: 38.6±10.6 years) and underwent posterior incision and reduction internal fixation. The International Index of Erectile Function-5 (IIEF-5), the Premature Ejaculation Diagnostic Tool (PEDT), and the International Spinal Cord Injury Male Sexual Function Basic Data Set were used for sexual function evaluation. Based on the American Spinal Injury Association (ASIA) Spinal Cord Injury classification, changes in neurological and sexual function were assessed at the pre-injury stage, 3 months post-injury, 2 years postoperatively, and at the final follow-up. Factors influencing sexual dysfunction and recovery were analyzed. Spearman correlation analysis was used to identify factors affecting sexual function injury and recovery.Results:A total of 117 patients were included in the final analysis. Follow-up duration ranged from 26.2 to 161.7 months (mean: 74.6±40.5 months). After injury, ASIA grades were distributed as follows: 43 patients with grade B, 41 with grade C, and 33 with grade D. At the 2-year follow-up, 30 patients were grade E, 63 grade D, 19 grade C, and 5 grade B. Improvement in ASIA classification was observed in 90.6% (106/117) of patients: 79 improved by one grade, 27 by two grades, 8 remained unchanged, 1 worsened by one grade, and 2 worsened by two grades. Mean IIEF-5 scores were 19.5±6.4 pre-injury, 8.7±8.0 at 3 months post-injury, and 17.5±7.1 at 2 years postoperatively, with statistically significant differences ( F=123.247, P<0.001). Differences between 3 months post-injury vs. pre-injury and 2 years postoperatively vs. 3 months post-injury were statistically significant ( P<0.05). Mean PEDT scores were 5.3±3.1 pre-injury, 6.9±5.2 at 3 months post-injury, and 6.4±5.1 at 2 years postoperatively, with statistically significant differences ( F=17.014, P<0.001). The difference between 3 months post-injury and pre-injury was statistically significant ( P<0.05), but not between 2 years postoperatively and 3 months post-injury ( P>0.05). At the 2-year follow-up, 96 patients had their IIEF-5 classification restored to pre-injury levels, 85 restored PEDT classifications, and 83 restored both. Post-injury ASIA classification was positively correlated with a decrease in IIEF-5 score and an increase in PEDT score at 3 months post-injury ( P<0.05). Injury segment was positively correlated with the decrease in IIEF-5 score ( P<0.05). Time from injury to surgery showed a positive correlation with increased PEDT score at 3 months ( P<0.05). Post-injury ASIA grade, injury segment, time to surgery, age, intraoperative decompression, and spinal cord function recovery all showed significant correlations with changes in IIEF-5 and (or) PEDT scores at 2 years postoperatively ( P<0.05). According to the International Spinal Cord Injury Male Sexual Function Basic Data Set, the proportion of patients willing to discuss sexual issues increased from 29.9% at 3 months post-injury to 47.9% at 2 years postoperatively ( P<0.05). The proportion of patients with absent or diminished psychogenic erections remained stable (48.7% vs. 48.9%, P>0.05), while those with normal reflexive erections increased from 34.2% to 65.0% ( P<0.05). Conclusion:Thoracolumbar fractures with incomplete spinal cord injury result in reduced erectile function and increased incidence of premature ejaculation. The degree of spinal cord injury and the level of the injured segment are strongly correlated with the extent of sexual dysfunction. At the 2-year postoperative follow-up, 70.9% of patients had recovered sexual function to pre-injury levels.
5.Diagnostic value of MRI in differentiating gastrointestinal stromal tumors and uterine adnexal tumors in female pelvis
Su-yun XIE ; Tian-sheng WEN ; Hua ZHOU
Chinese Medical Equipment Journal 2025;46(9):60-64
Objective To explore the diagnostic value of MRI in differentiating between gastrointestinal stromal tumors and uterine adnexal tumors in female pelvis.Methods Imaging data were retrospectively collected from 42 patients admitted for pelvic mass and diagnosed with gastrointestinal mesenchymal tumor or uterine adnexal tumor by postoperative pathology in some hospital from 2016-2022,including 12 patients with gastrointestinal stromal tumor and 30 patients with uterine adnexal tumor composed of 20 ones with malignant epithelial tumors of the ovary,5 ones with ovarian sex cord-stromal tumors and 5 ones with exophytic uterine fibroids.The tumor blood vessels and normal ovarian structures were observed,and the positive rates of tumor vascular display were calculated;the location distribution of the cystic portions of gastrointestinal stromal tumors and ovarian malignant epithelial tumors was inspected;gastrointestinal stromal tumors and uterine adnexal tumors were compared in terms of conventional MRI signs including cystic or solid mass,morphology,signal characteristics and pelvic lymph nodes,and the accuracy,specificity and sensitivity of MRI for differentiating between gastrointestinal stromal tumors and uterine adnexal tumors were calculated with the postoperative pathological results as the gold standard.SPSS 26.0 software was used for statistical analysis.Results The overall display rate of tumor vascular was 80.9%,and the display rates being 75%,100%,60%and 40%for pelvic gastrointestinal stromal tumors,ovarian malignant epithelial tumors,ovarian sex cord-stromal tumors and exophytic uterine fibroids,respectively.A significant difference was found in the locations of the cystic portions between pelvic gastrointestinal stromal tumors and ovarian malignant epithelial tumors(P<0.001),while no significant differences were observed in other conventional MRI signs between the two groups(P>0.05).MRI demonstrated an overall diagnostic accuracy of 95.2%,with a sensitivity of 100%and a specificity of 83.3%.Conclusion MRI shows clearly the normal ovarian structure,ovarian vascular bundles and tumor MRI signs and has high rates for tumor vascular display,which is of great value for differentiating between gastrointestinal stromal tumors and uterine adnexal tumors in female pelvis.[Chinese Medical Equipment Journal,2025,46(9):60-64]
6.Risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation.
You-Liang HAO ; Fang ZHOU ; Hong-Quan JI ; Yun TIAN ; Zhi-Shan ZHANG ; Yan GUO ; Yang LYU ; Zhong-Wei YANG ; Guo-Jin HOU
China Journal of Orthopaedics and Traumatology 2025;38(2):141-147
OBJECTIVE:
To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation.
METHODS:
A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure.
RESULTS:
There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure.
CONCLUSION
The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans
;
Male
;
Female
;
Hip Fractures/surgery*
;
Aged, 80 and over
;
Aged
;
Risk Factors
;
Retrospective Studies
;
Fracture Fixation, Intramedullary/adverse effects*
;
Bone Nails
;
Bone Screws
7.Clinical implication of post-angioplasty quantitative flow ratio in the patients with coronary artery de novo lesions underwent drug-coated balloons treatment.
Yun-Hui ZHU ; Xu-Lin HONG ; Tian-Li HU ; Qian-Qian BIAN ; Yu-Fei CHEN ; Tian-Ping ZHOU ; Jing LI ; Guo-Sheng FU ; Wen-Bin ZHANG
Journal of Geriatric Cardiology 2025;22(3):332-343
BACKGROUND:
Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions.
METHODS:
Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization.
RESULTS:
A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026).
CONCLUSIONS
In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.
8.Bear Bile Powder Ameliorates LPS-Induced Acute Lung Injury by Inhibiting CD14 Pathway and Improving Intestinal Flora: Exploration of "Fei (Lung)-Dachang (Large Intestine) Interaction" Theory.
Long CHENG ; Hui-Ling TIAN ; Hong-Yuan LEI ; Ying-Zhou WANG ; Ma-Jing JIAO ; Yun-Hui LIANG ; Zhi-Zheng WU ; Xu-Kun DENG ; Yong-Shen REN
Chinese journal of integrative medicine 2025;31(9):821-829
OBJECTIVE:
To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism.
METHODS:
The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS).
RESULTS:
UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05).
CONCLUSIONS
BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals
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Acute Lung Injury/pathology*
;
Lipopolysaccharides
;
Ursidae
;
Gastrointestinal Microbiome/drug effects*
;
Bile/chemistry*
;
Lipopolysaccharide Receptors/metabolism*
;
Powders
;
Male
;
Lung/drug effects*
;
Mice
;
Peroxidase/metabolism*
;
Signal Transduction/drug effects*
;
Cytokines/metabolism*
9.Sini Powder Alleviates Stress Response and Suppresses Hepatocellular Carcinoma Development by Restoring Gut Microbiota.
Si MEI ; Zhe DENG ; Fan-Ying MENG ; Qian-Qian GUO ; He-Yun TAO ; Lin ZHANG ; Chang XI ; Qing ZHOU ; Xue-Fei TIAN
Chinese journal of integrative medicine 2025;31(9):802-811
OBJECTIVES:
To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC).
METHODS:
The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice.
RESULTS:
The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased.
CONCLUSION
SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals
;
Gastrointestinal Microbiome/drug effects*
;
Liver Neoplasms/microbiology*
;
Carcinoma, Hepatocellular/microbiology*
;
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Powders
;
Cell Proliferation/drug effects*
;
Mice
;
Molecular Docking Simulation
;
Cell Line, Tumor
;
Hep G2 Cells
;
Receptors, Adrenergic, beta-2/genetics*
;
Stress, Physiological/drug effects*
;
Cell Movement/drug effects*
;
Male
;
Protein Interaction Maps/drug effects*
;
Cell Survival/drug effects*
;
Proto-Oncogene Mas
10.PROTAC-loaded nanocapsules degrading BRD4 for radio-chemotherapy sensitization in glioblastoma.
Yun GUO ; Mingzhu FANG ; Shilin ZHANG ; Zheng ZHOU ; Zonghua TIAN ; Haoyu YOU ; Yun CHEN ; Jingyi ZHOU ; Xiaobao YANG ; Yunke BI ; Chen JIANG ; Tao SUN
Acta Pharmaceutica Sinica B 2025;15(10):5050-5070
Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

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