The Hippo-YAP/TEAD pathway plays a central role in melanoma progression by regulating tumor cell proliferation, survival, and migration. Using a NanoLuc Binary Technology (NanoBiT) protein-protein interaction assay, we screened honokiol-based small molecules and identified several analogues that disrupt the YAP-TEAD interaction. HK03 was the most effective analogue, leading to a pronounced reduction in Cyr61 levels and diminished Erk and Akt phosphorylation in B16-F10 melanoma cells. HK03 also blocked epithelial–mesenchymal transition (EMT) and impaired melanoma cell migration in wound-healing assays. In vivo, HK03 treatment markedly reduced metastatic burden in a B16-F10 lung metastasis model. These findings suggest that honokiol derivatives, particularly HK03, represent potential lead compounds for targeting the YAP-TEAD axis in melanoma therapy.

Objective: To determine the clinical efficacy of platelet-rich plasma (PRP) injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome. Methods: One hundred and twenty-eight patients with knee osteoarthritis and cold dampness obstruction syndrome who visited the Rehabilitation Department and Orthopedics Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to March 2024 and who met the inclusion and exclusion criteria were randomly divided into an experimental (n=64) and control group (n=64) using the random number table method. The experimental group was treated with PRP injection combined with warm acupuncture and moxibustion, whereas the control group was treated with normal saline injection combined with warm acupuncture and moxibustion treatment. PRP and normal saline injections were administered once every two weeks, a total of four times. Patients were treated with warm acupuncture and moxibustion once a day, six times a week, for four consecutive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Traditional Chinese Medicine (TCM) syndrome, visual analog scale (VAS), and Lysholm scores were determined before treatment, at week 4 and week 8 of treatment, and week 16 of follow-up. Serum interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), bone gla protein(BGP), and cartilage oligomeric matrix protein (COMP) levels were compared between the two groups before and after 8 weeks of treatment. The clinical efficacy and safety indicators between the two groups were also compared. Results: There was no statistical difference in baseline data such as gender, age, disease duration, and body mass index between the two groups of patients. Compared with before treatment, both groups showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm scores at 4, 8, and 16 weeks after treatment. After treatment, serum IL-6, MMP-3, TNF-α, and COMP levels decreased, whereas serum OPG and BGP levels increased (P<0.05). Compared with the control group, patients in the experimental group showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm score at 4, 8, and 16 weeks after treatment. Compared with the control group, patients in the experimental group showed decreased serum IL-6, MMP-3, TNF-α, and COMP levels and an increase in serum OPG and BPG levels after treatment (P<0.05). The total effective rate of the experimental group was 91.94%, higher than that of the control group (81.97%; P<0.05). Conclusion PRP injection combined with warm acupuncture and moxibustion can improve various TCM symptoms, improve knee joint function and bone metabolism, and reduce inflammation in patients with knee osteoarthritis and cold dampness obstruction syndrome.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

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

Objective To investigate the correlations of the expression levels of serum silencing in-formation regulatory factor 2-related enzyme 1(SIRT1),endothelial cell-specific molecule-1(ESM-1),and fibroblast growth factor-21(FGF21)with therapeutic outcome in patients with sepsis-related acute respiratory distress syndrome(ARDS).Methods A total of 140 patients with sepsis-related ARDS were selected and divided into good outcome group(n=96)and poor outcome group(n=44)accord-ing to the therapeutic outcome.The levels of serum SIRT1,ESM-1 and FGF21 were compared between the two groups,and the correlations of serum SIRT1,ESM-1 and FGF21 with the severity of the dis-ease and therapeutic outcome were analyzed.The predictive values of serum SIRT1,ESM-1 and FGF21 for therapeutic outcome were evaluated.Results The serum SIRT1 level in the poor outcome group was significantly lower,while the levels of ESM-1 and FGF21 were significantly higher than those in the good outcome group(P＜0.05).The serum SIRT1 level showed a significant gradual downward trend in mild,moderate,and severe patients,while the ESM-1 and FGF21 levels showed a significant gradual upward trend in mild,moderate,and severe patients(P＜0.05).Spearman corre-lation analysis showed that serum SIRT1 was significantly negatively correlated with disease severity,while ESM-1 and FGF21 were significantly positively correlated with disease severity(P＜0.05).Partial correlation analysis showed that serum SIRT1,ESM-1 and FGF21 were significantly correla-ted with the therapeutic outcome of ARDS patients with sepsis(P＜0.05).The receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)of serum SIRT1,ESM-1 and FGF21 for predicting the treatment outcome of sepsis-related ARDS patients was 0.742,0.838 and 0.796 respectively,with sensitivities of 77.27％,77.27％and 70.45％,and specificities of 64.58％,81.25％and 87.50％.The AUC of the combination of three indexes for predicting the therapeutic outcome of sepsis-related ARDS patients was 0.939,with a sensitivity of 88.64％and a specificity of 83.33％,which was significantly higher than the predictive value of the three indexes alone(P＜0.05).Conclusion The levels of SIRT1,ESM-1 and FGF21 in the serum of sepsis-re-lated ARDS patients are significantly correlated with the severity of the disease and the therapeutic outcome,and have the abilitis to independently predict the therapeutic outcome.The combined pre-dictive value is even higher.

Objective:To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient.Methods:A patient sent from the Blood Transfusion Department of Shanxi Provincial People′s Hospital to Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient′s blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient′s blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)].Results:①The patient′s blood type was B, RhD positive. Initial screening of the patient′s serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient′s serum showed varying reaction intensities with red blood cells treated with different enzymes. ②MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c. 376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient′s son was found to have a heterozygous variant c. 376C>T (p.Gln126Ter), and another heterozygous variant c. 421C>A (p.Gln141Lys), which predicted a Jr(a+ w) phenotype. ③Crossmatch tests confirmed the compatibility of blood from the patient′s son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient′s ongoing treatment, saving the patient′s life. Conclusion:Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.

Objective:To compare the efficacy of the transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 66 patients with OVCF admitted to the Second People′s Hospital of Hefei from December 2021 to June 2023, including 9 males and 57 females aged 60-89 years [(75.6±7.5)years]. The injured segments included T 11 in 17 patients, T 12 in 17, L 1 in 17, and L 2 in 15. Among them, 33 patients underwent vertebroplasty via the transverse process-lateral pedicle approach (lateral approach group), while other 33 patients underwent curved vertebroplasty (curved group). The surgical duration, number of X-ray fluoroscopy, bone cement injection volume, and length of hospital stay were compared between the two groups. Additionally, the restoration efficiency of vertebral height and the correction degree of spinal scoliosis Cobb angle at 2 days postoperatively were compared between the two groups. The changes in serum levels of stress factors including noradrenaline, adrenaline, and cortisol preoperatively and at 2 days postoperatively, the visual analogue scale (VAS) and Oswestry disability index (ODI) preoperatively, at 2 days, 6 months postoperatively, and at the last follow-up were compared between the two groups. The incidence of complications was assessed in the two groups. Results:All the patients were followed up for 12-14 months [(13.2±0.5)months]. The surgical duration and number of X-ray fluoroscopy in the lateral approach group were (30.9±4.1)minutes and (5.9±3.3)times, which were significantly lower than (35.8±3.9)minutes and (9.9±4.4)times in the curved group ( P<0.01). There were no statistically significant differences between the two groups in terms of bone cement injection volume, length of hospital stay, restoration efficiency of vertebral height at 2 days postoperatively, or the correction degree of spinal scoliosis Cobb angle ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively were (57.3±4.8)ng/ml, (49.9±4.2)ng/ml, (159.3±20.5)nmol/L in the lateral approach group, and (64.3±4.5)ng/ml, (58.3±4.4)ng/ml, (183.5±21.2)nmol/L in the curved group, which were all significantly increased compared with those preoperatively [(42.3±3.5)ng/ml, (38.5±2.8)ng/ml, (128.4±12.3)nmol/L in the lateral approach group and (42.0±3.5)ng/ml, (39.0±3.0)ng/ml, (128.5±12.3)nmol/L in the curved group] ( P<0.01). There were no significant differences between the two groups in terms of the levels of noradrenaline, adrenaline, and cortisol preoperatively ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively in the lateral approach group were significantly lower than those in the curved group ( P<0.01). The VAS scores for low back pain in the lateral approach group and the curved group were 3(2, 5)points and 5(3, 6)points at 2 days postoperatively, 3(2, 4)points and 3(2, 4)points at 6 months postoperatively, and 2(2, 3)points and 2(2, 4)points at the last follow-up, which were all significantly lower than those preoperatively [7(7, 9)points and 8(6, 9)points] ( P<0.05). Moreover, the VAS scores for low back pain were further decreased over time postoperatively ( P<0.05). The ODI values in the lateral approach group and curved group were (33.4±4.4)% and (33.7±4.3)% at 2 days postoperatively, (23.8±1.6)% and (23.8±1.7)% at 6 months postoperatively, and (15.6±0.9)% and (15.6±0.9)% at the last follow-up, which were all significantly lower than (67.4±4.3)% and (67.5±4.3)% preoperatively ( P<0.05). Moreover, the ODI values were further decreased over time postoperatively ( P<0.05). There were no significant differences between the two groups in terms of the VAS scores for low back pain or ODI values preoperatively, at 2 days, 6 months postoperatively or at the last follow-up ( P>0.05). The complication rate was 12.1% (4/33) in the lateral approach group, which was significantly lower than 51.5% (17/33) in the curved group ( P<0.05). Conclusion:Although both the transverse process-lateral pedicle approach vertebroplasty and the curved vertebroplasty can achieve good therapeutic effects in the treatment of OVCF, the former has shorter surgical duration, fewer times of X-ray fluoroscopy, lower trauma stress levels at 2 days postoperatively, and fewer complications.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Circadian rhythms are core regulatory mechanisms that evolved to align biological functions with the Earth's rotation. These rhythms are conserved across organisms from unicellular life to multicellular species and play essential roles in metabolism, immune responses, and sleep-wake cycle. Circadian disruptions are strongly associated with various diseases. Over the past decades, genetic studies in Drosophila and mice have identified key conserved clock genes and uncovered transcription-translation feedback loops governing circadian regulation. Additionally, rhythmic neurons in the brain integrate complex neural circuits to precisely regulate physiological and behavioral rhythms. This review highlights recent advances in understanding the neuronal circuit mechanisms of rhythmic neurons in the Drosophila brain and discusses future directions for translating circadian rhythm research into chronomedicine and precision therapies.
Animals ; Circadian Rhythm/genetics* ; Neurons/physiology* ; Drosophila/physiology* ; Brain/physiology* ; Nerve Net/physiology*