[摘 要] 目的：探讨高良姜素（Gal）调控AMPK/mTOR/ULK1信号通路对胃癌细胞凋亡和自噬的影响及其机制。方法：将胃癌NCI-N87细胞分为对照组、多索吗啡（DM）组、Gal低剂量（Gal-L）组、Gal高剂量（Gal-H）组、Gal-H + DM组。采用MTT法、流式细胞术、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测PCNA、C-caspase-3、免疫逃逸相关蛋白（B7H1）、EMT和AMPK/mTOR/ULK1信号通路蛋白的表达水平。建立裸鼠NCI-N87细胞移植瘤模型，观察Gal和5-FU对移植瘤的抑制效果。结果：与对照组比较，DM组NCI-N87细胞增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著升高（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著降低（均P < 0.05）；Gal-L组和Gal-H组NCI-N87细胞的增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著降低（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著升高（均P < 0.05）；DM可部分逆转Gal对NCI-N87细胞恶性生物学行为的抑制作用（P < 0.05）；与对照组比较，Gal组和5-FU组裸鼠移植瘤体积和质量均显著降低，肿瘤组织细胞凋亡率显著升高（P < 0.05）。结论：Gal可促进胃癌NCI-N87细胞自噬和凋亡，抑制其增殖、迁移和侵袭，可能与激活AMPK/mTOR/ULK1信号通路有关。

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

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.

Objective:To investigate the biomechanical correlation between ankle instability and osteochondral lesions of the talus (OLT) under loading conditionsMethods:A healthy 29-year-old male volunteer was selected for the study. A 64-slice spiral CT scan of the right lower limb was performed to construct a detailed finite element model of the ankle joint, including ligaments and cartilage. Three injury models were created: models of distal tibiofibular syndesmosis injury, lateral collateral ligament injury, and a combined injury of the distal tibiofibular syndesmosis and lateral collateral ligament. Differences in stress distribution on the tibiotalar joint surface, talus stress, and talus displacement were analyzed through anterior drawer test, inversion stress test, and external rotation stress test.Results:In the anterior drawer test, as the forward traction force increased (40, 60, 80, 100, 120, 140, and 150 N), all the injury models showed a progressive increase in tibiotalar joint surface stress, talus stress, and talus displacement. The combined injury model showed the highest tibiotalar joint surface stress (32.6 MPa), while the lateral collateral ligament injury model demonstrated the highest talus stress (56.5 MPa). Talus displacement increased significantly with traction, reaching the maximum (4.88 mm) in the combined injury model under 150 N. In the inversion stress test, stress on the tibiotalar joint surface in the lateral collateral ligament injury model was concentrated on the posterior-lateral and posterior-medial regions, whereas in the combined injury model, stress on the tibiotalar joint surface was predominantly concentrated in the posterior-medial region. Talus stress was localized to the talus neck and body in all the models, with the combined injury model showing the largest talus displacement (8.46 mm). In the external rotation stress test, stress on the tibiotalar joint surface was mainly distributed in the posterior-medial, posterior-lateral, and anterior-lateral regions in all the models. Talus stress was concentrated at the talus neck and body. The combined injury model exhibited the greatest talus displacement (12.50 mm).Conclusion:Ankle instability, particularly from combined injuries of the distal tibiofibular syndesmosis and lateral collateral ligament, significantly increases the stress concentration and talus displacement under loading conditions, thus elevating the risk of OLT.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.