ObjectiveTo explore the potential mechanism of Weicanqing Formula （微残清方， WF） combined with chemotherapy in treating acute myeloid leukemia （AML） based on malic enzyme 2 （ME2）-mediated bone marrow immune-metabolic homeostasis and . MethodsSixty-five male C57BL/6N mice were randomly divided into control group， model group， WF group， chemotherapy group， and the combination group （WF plus chemotherapy）， with 13 mice per group. Except for the control group， mice were injected with C1498 cells （appro-ximately 1×10⁶ cells per mouse） via the tail vein on day 1 to establish an AML model. Starting from day 8， mice in the chemotherapy group and the combination group were administered with cytarabine at 30 mg/（kg·d） via subcutaneous injection， once daily for 3 consecutive days； WF group and the combination group received WF at 7.54 g/（kg·d） by gavage， once daily for 21 consecutive days. On days 1， 7， 14， 21 and 28， hemoglobin （Hb） and white blood cell （WBC） levels were determined in each group. On day 28， Giemsa staining was used to observe morphological changes in bone marrow cells. Flow cytometry was employed to detect the expression levels of bone marrow T lympthocyte subsets， including CD8⁺， CD4⁺， and regulatory T lymphocytes （Treg）. The contents of glutamine （Gln）， nicotinamide adenine dinucleotide phosphate （NADP⁺）， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in bone marrow were determined using visible spectrophotometry. Adenosine triphosphate （ATP） concentration in bone marrow was measured by chemiluminescence assay. The mRNA expression of malic enzyme 2 （ME2） in bone marrow was detected by RT-qPCR， and the protein expression level of ME2 was determined by Western blotting. ResultsCompared to the control group， the model group showed decreased Hb levels on day 14， 21， and 28， and increased WBC levels on day 7， 14， 21， and 28 （P＜0.05）. On day 28， bone marrow CD8⁺ and CD8⁺/CD4⁺ levels decreased， while Treg cells， ATP， Gln， NADP⁺， NADPH， ME2 mRNA， and their corresponding protein levels increased （P＜0.05）. Compared to the model group， the chemotherapy group and the combination group both exhibited reduced Hb level on day 14， 21 and 28， as well as the increased WBC level； the combination group showed increased CD8⁺ level， decreased Treg， ATP， Gln， and NADPH content， as well as reduced ME2 mRNA expression and protein levels （P＜0.05）. Compared to the chemotherapy group， the combination group showed significantly increased Hb level on days 21 and 28， and increased WBC level on day 28 （P＜0.05）. Bone marrow smear pathology revealed that， in the model group， myeloid blast cells exhibited cytoplasmic vacuoles indicative of abnormal metabolic activity. In contrast， both the chemotherapy group and the combination group showed large numbers of metamyelocytes and band neutrophils， with only a few immature granulocytic blast cells observed. ConclusionWF may improve the prognosis of AML when used as an adjunct to chemotherapy by modulating ME2 expression， inhibiting metabolic energy competition within the bone marrow microenvironment， and reshaping the distribution of T lymphocyte subsets in the bone marrow.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective:To investigate and analyze basic status of radiotherapy units in Hebei Province in 2024.Methods:Led by the Fourth Hospital of Hebei Medical University, the Radiation Oncology Branch of the Hebei Medical Association, and the Radiation Oncology Expert Committee of the Hebei Society of Clinical Oncology, a province-wide survey was conducted using structured questionnaires. The survey covered key aspects such as basic information of radiotherapy institutions, personnel allocation, equipment configuration, and implementation of radiotherapy techniques. Collected data were summarized and descriptively analyzed comparing with a 2013 survey of radiotherapy in Hebei Province.Results:All 158 radiotherapy institutions across Hebei Province participated in the survey. A total of 2273 radiotherapy professionals were reported, including 1317 radiation oncologists (57.94%), 332 medical physicists (14.61%), 71 radiotherapy engineers (3.12%), and 553 radiotherapy technologists (24.33%). The number of radiotherapy devices significantly increased from 121 in 2013 to 237 in 2024, including 68 domestic radiotherapy equipment. The current inventory includes 195 medical linear accelerators (2.61 units per million population), 2 cobalt-60 units, 27 afterloading machines, 9 tomotherapy (TOMO) systems, 3 CyberKnife units, and 1 proton therapy system. Three-dimensional conformal radiotherapy and stati intensity-modulated radiotherapy have been widely adopted across the province, while advanced techniques such as volumetric-modulated arc therapy, stereotactic body radiotherapy, and respiration-gated technology, and respiratory gating are gradually being implemented.Conclusions:In recent years, the configuration of radiotherapy personnel in Hebei Province has become more balanced, and the availability of precision radiotherapy equipment has significantly improved. There is a growing trend in the adoption of domestically manufactured radiotherapy equipment, marking substantial progress in the development of radiation oncology services in the region.

Objective:To investigate the correlation between transabdominal bowel ultrasongraphy (TBUS) parameters and disease activity of ulcerative colitis (UC).Methods:The results of TBUS, endoscopy and laboratory tests of 68 UC patients (108 examinations) who visited the Department of Gastroenterology of the Second Hospital (Eastern Campus) of Hebei Medical University From January 2022 to February 2024 were retrospectively analyzed. According to Mayo endoscopic score (MES), there were 10 cases of remission (MES=0) and 98 cases of active phase (MES>0); patients in active phase further classified into 16 cases of mild (MES=1), 19 cases of moderate (MES=2), and 63 cases of severe (MES=3). The TAUS parameters were compared between patients in remission and active phases. Spearman rank correlation analysis was used to analyze the correlation between the TBUS parameters including bowel wall thickness (BWT), Limberg score, wall layer stratification, fat wrapping and endoscopic activity score, laboratory inflammatory indicators. Receiver operating characteristic curve (ROC) analysis was applied to evaluate the predictive efficacy of the TBUS parameters and laboratory inflammatory indicators in identifying remission under endoscopy. Independent sample t-test and Fisher′s exact probability method were used to compare the two groups. Results:The BWT of patients in remission was significantly thinner than that of patients in active phase ((2.99±0.41) mm vs. (5.66±1.57) mm, t=-5.34, P<0.001). The proportions of patients in remisson with Limberg score ≤2, normal wall layer stratification, and absence of fat wrapping were significantly higher than those of patients in active phase (10/10 vs. 34/98, 10/10 vs. 48/98, 10/10 vs. 41/98, Fisher′s exact test, P<0.001, =0.002, =0.001). BWT, Limberg score, wall layer stratification, and fat wrapping were positively correlated with MES ( r=0.676, 0.677, 0.441, and 0.493, all P<0.001). BWT and Limberg score were moderate positively correlated with C-hypersensitive reactive protein, erythrocyte sedimentation rate and fecal calprotectin (BWT: r=0.561, 0.420 and 0.458, all P<0.001; Limberg score: r=0.576, 0.469 and 0.403, all P<0.001), and were negatively correlated with serum albumin and hemoglobin (BWT: r=-0.604 and -0.453, both P<0.001; Limberg score: r=-0.573 and -0.532, both P<0.001). The results of ROC analysis showed that BWT achieved the best predictive efficacy in identifying endoscopic remission, and the best cut-off value was 3.45 mm (area under the curve was 0.972, 95% confidence interval: 0.944 to 1.000, P<0.001), with a sensitivity of 93.9% and specificity of 100.0%. Conclusions:TBUS parameters can accurately reflect disease activity in UC. It is a powerful tool for UC monitoring. The BWT<3.45 mm is the best cut-off value in prediction of endoscopic remission.

Objective:To analyze the research trends and hotspots of bupivacaine liposomes from 1994 to 2023 using bibliometrics.Methods:A comprehensive search was conducted for the literature related to bupivacaine liposomes in the Web of Science Core Collection from 1994 to 2023. The CiteSpace software was used to conduct an in-depth analysis of the included literature data, including publication year, country, institution, author, journal, cited references, keywords, etc.Results:A total of 875 papers related to bupivacaine liposomes were included. The research and development of bupivacaine liposomes were divided into 3 stages: slow development (1994-2011), a sharp rise (2011-2021), and stabilization (2021-2023). The United States was in a leading position in terms of the number of publications, centrality, and author cooperation, and Harvard University had the largest number of publications. de Paula E had the most publications, Bramlett K had the highest number of citations, and Boogaerts J had the highest centrality of publications. Journals such as Anesthesia and Analgesia made significant contributions to this field. The most cited references focused on the infiltration of wounds and the periprosthetic injection of bupivacaine liposomes. The keyword analysis showed that local anesthetics, postoperative pain, etc. were commonly used keywords, and enhanced recovery after surgery was an emerging hotspot. Conclusions:Bupivacaine liposomes show good application prospects in the field of peripheral nerve block due to their unique pharmacological properties and safety characteristics and are expected to prolong the duration of postoperative analgesia. However, there is a difference between the actual effect and the expectation, and more clinical trials are needed to evaluate the curative effect, providing a more solid and reliable theoretical basis and practical guidance for clinical practice.

Objective:To analyze the research trends and hotspots of bupivacaine liposomes from 1994 to 2023 using bibliometrics.Methods:A comprehensive search was conducted for the literature related to bupivacaine liposomes in the Web of Science Core Collection from 1994 to 2023. The CiteSpace software was used to conduct an in-depth analysis of the included literature data, including publication year, country, institution, author, journal, cited references, keywords, etc.Results:A total of 875 papers related to bupivacaine liposomes were included. The research and development of bupivacaine liposomes were divided into 3 stages: slow development (1994-2011), a sharp rise (2011-2021), and stabilization (2021-2023). The United States was in a leading position in terms of the number of publications, centrality, and author cooperation, and Harvard University had the largest number of publications. de Paula E had the most publications, Bramlett K had the highest number of citations, and Boogaerts J had the highest centrality of publications. Journals such as Anesthesia and Analgesia made significant contributions to this field. The most cited references focused on the infiltration of wounds and the periprosthetic injection of bupivacaine liposomes. The keyword analysis showed that local anesthetics, postoperative pain, etc. were commonly used keywords, and enhanced recovery after surgery was an emerging hotspot. Conclusions:Bupivacaine liposomes show good application prospects in the field of peripheral nerve block due to their unique pharmacological properties and safety characteristics and are expected to prolong the duration of postoperative analgesia. However, there is a difference between the actual effect and the expectation, and more clinical trials are needed to evaluate the curative effect, providing a more solid and reliable theoretical basis and practical guidance for clinical practice.

Objective:To investigate and analyze basic status of radiotherapy units in Hebei Province in 2024.Methods:Led by the Fourth Hospital of Hebei Medical University, the Radiation Oncology Branch of the Hebei Medical Association, and the Radiation Oncology Expert Committee of the Hebei Society of Clinical Oncology, a province-wide survey was conducted using structured questionnaires. The survey covered key aspects such as basic information of radiotherapy institutions, personnel allocation, equipment configuration, and implementation of radiotherapy techniques. Collected data were summarized and descriptively analyzed comparing with a 2013 survey of radiotherapy in Hebei Province.Results:All 158 radiotherapy institutions across Hebei Province participated in the survey. A total of 2273 radiotherapy professionals were reported, including 1317 radiation oncologists (57.94%), 332 medical physicists (14.61%), 71 radiotherapy engineers (3.12%), and 553 radiotherapy technologists (24.33%). The number of radiotherapy devices significantly increased from 121 in 2013 to 237 in 2024, including 68 domestic radiotherapy equipment. The current inventory includes 195 medical linear accelerators (2.61 units per million population), 2 cobalt-60 units, 27 afterloading machines, 9 tomotherapy (TOMO) systems, 3 CyberKnife units, and 1 proton therapy system. Three-dimensional conformal radiotherapy and stati intensity-modulated radiotherapy have been widely adopted across the province, while advanced techniques such as volumetric-modulated arc therapy, stereotactic body radiotherapy, and respiration-gated technology, and respiratory gating are gradually being implemented.Conclusions:In recent years, the configuration of radiotherapy personnel in Hebei Province has become more balanced, and the availability of precision radiotherapy equipment has significantly improved. There is a growing trend in the adoption of domestically manufactured radiotherapy equipment, marking substantial progress in the development of radiation oncology services in the region.

Objective:To investigate the correlation between transabdominal bowel ultrasongraphy (TBUS) parameters and disease activity of ulcerative colitis (UC).Methods:The results of TBUS, endoscopy and laboratory tests of 68 UC patients (108 examinations) who visited the Department of Gastroenterology of the Second Hospital (Eastern Campus) of Hebei Medical University From January 2022 to February 2024 were retrospectively analyzed. According to Mayo endoscopic score (MES), there were 10 cases of remission (MES=0) and 98 cases of active phase (MES>0); patients in active phase further classified into 16 cases of mild (MES=1), 19 cases of moderate (MES=2), and 63 cases of severe (MES=3). The TAUS parameters were compared between patients in remission and active phases. Spearman rank correlation analysis was used to analyze the correlation between the TBUS parameters including bowel wall thickness (BWT), Limberg score, wall layer stratification, fat wrapping and endoscopic activity score, laboratory inflammatory indicators. Receiver operating characteristic curve (ROC) analysis was applied to evaluate the predictive efficacy of the TBUS parameters and laboratory inflammatory indicators in identifying remission under endoscopy. Independent sample t-test and Fisher′s exact probability method were used to compare the two groups. Results:The BWT of patients in remission was significantly thinner than that of patients in active phase ((2.99±0.41) mm vs. (5.66±1.57) mm, t=-5.34, P<0.001). The proportions of patients in remisson with Limberg score ≤2, normal wall layer stratification, and absence of fat wrapping were significantly higher than those of patients in active phase (10/10 vs. 34/98, 10/10 vs. 48/98, 10/10 vs. 41/98, Fisher′s exact test, P<0.001, =0.002, =0.001). BWT, Limberg score, wall layer stratification, and fat wrapping were positively correlated with MES ( r=0.676, 0.677, 0.441, and 0.493, all P<0.001). BWT and Limberg score were moderate positively correlated with C-hypersensitive reactive protein, erythrocyte sedimentation rate and fecal calprotectin (BWT: r=0.561, 0.420 and 0.458, all P<0.001; Limberg score: r=0.576, 0.469 and 0.403, all P<0.001), and were negatively correlated with serum albumin and hemoglobin (BWT: r=-0.604 and -0.453, both P<0.001; Limberg score: r=-0.573 and -0.532, both P<0.001). The results of ROC analysis showed that BWT achieved the best predictive efficacy in identifying endoscopic remission, and the best cut-off value was 3.45 mm (area under the curve was 0.972, 95% confidence interval: 0.944 to 1.000, P<0.001), with a sensitivity of 93.9% and specificity of 100.0%. Conclusions:TBUS parameters can accurately reflect disease activity in UC. It is a powerful tool for UC monitoring. The BWT<3.45 mm is the best cut-off value in prediction of endoscopic remission.

Prostate cancer is a prevalent malignant tumor in the male genitourinary system,characterized by a high propensity for bone metastasis.It is a leading cause of mortality,with approximately 70％of deaths attributed to this form of metastasis.Mouse models provide a crucial tool in the investigation of prostate cancer bone metastasis,and play a pivotal role in elucidating the underlying pathophysiological mechanisms and in the development and assessment of therapeutic agents.In this review,we summarize research progress in the construction method and evaluation strategies used in establishing prostate cancer bone metastasis mouse models.Notably,this review focuses on the exploration of the mechanisms responsible for prostate cancer bone metastasis,using mouse models,with the aim of offering insights and serving as a valuable reference for prostate cancer bone metastasis.