Objective: To systematically evaluate the clinical efficacy of topical preparations of Mongolian medicine Manggari hot compress therapy (hereafter referred to as Manggari hot compress therapy) in treating cervical spondylotic radiculopathy (CSR) and explore the possible pharmacological material basis in the formula, providing evidence for the clinical application of Mongolian medicine in the treatment of CSR. Methods: The clinical trial employed a randomized, controlled, open-label, and outcome-assessor-blinded design. The CSR patients who were treated at the Department of Traditional Therapeutics Outpatient Clinic, Xilinguole Meng Mongolian General Hospital between July 1, 2024 and August 31, 2025, were enrolled. They were randomly assigned to three groups: an oral control group (administration of oral administration of mecobalamin tablets combined with cervical electric traction), an experimental group (Manggari external hot compress), and a patch control group (flurbiprofen gel plaster). The intervention lasted two weeks. Before and after treatment, the following subjective indicators were recorded: Mongolian Medicine Syndrome (MMS) score, Visual Analog Scale (VAS) score, Northwick Park Neck Pain Questionnaire (NPQ) score, and tongue morphology. Serum levels of inflammatory markers [tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β)] and oxidative stress markers [malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity] were measured using enzyme-linked immunosorbent assay (ELISA). Overall therapeutic efficacy was evaluated. One month after treatment completion, a follow-up assessment was conducted, and the MMS, VAS, and NPQ scores were recorded again for all patients. For the pharmacological substance exploration, ultra-high-performance liquid chromatography-Q-exactive orbitrap-mass (UHPLC-QE-MS) was employed to analyze blood-absorbed prototype components of Manggari, under both positive and negative ion modes. The targeting relationship between the core active compounds and the target protein was validated using molecular docking. Results: This study ultimately included 90 patients with CSR for analysis. Baseline characteristics showed no statistically significant differences among the three groups (P > 0.05). (i) Symptom scores. After treatment, the MMS, VAS, and NPQ scores decreased significantly from baseline in all three groups (P < 0.001). At follow-up, there was no significant difference in MMS, VAS, and NPQ scores of the experimental group compared with those at the end of the treatment (P > 0.05). After treatment, the experimental group showed significantly greater reductions in MMS, VAS, and NPQ scores than oral control and patch control groups (P < 0.001). At follow-up, these differences remained significant (P < 0.001). (ii) Inflammatory and oxidative stress markers. After treatment, serum levels of TNF-α, IL-6, and IL-1β, and MDA activity decreased significantly from baseline in all three groups (P < 0.001), and SOD content and GSH-Px activity increased significantly from baseline (P < 0.05). After treatment, the experimental group had significantly lower serum levels of TNF-α, IL-6, and IL-1β than oral and patch control groups. Additionally, it exhibited lower MDA activity and higher SOD content and GSH-Px activity compared with the two control groups. (P < 0.05). (iii) Overall efficacy. The total effective rate was 93.33% in the experimental group, 86.66% in the oral control group, and 83.33% in the patch control group. (iv) Pharmacological substance analysis. A total of 152 compounds were identified in the blood-absorbed components of Manggari. Among them, the core compounds—4-hydroxycoumarin, N-methylanthranilic acid, genistein, and ginsenoside-Rk1—showed binding energies to the key target proteins TNF-α and IL-1β range from − 4.7 to − 7.1 kcal/mol, with the majority of the binding energies being below − 5.0 kcal/mol, suggesting that it generally has a good binding affinity. Conclusion Mongolian medicine hot compress therapy effectively modulates inflammatory and oxidative stress responses through the combined action of its thermal effects and active pharmaceutical ingredients Manggari. It inhibits cervical nerve root inflammation and alleviates radicular pain, improving clinical symptoms, reducing pain severity, and alleviating neck functional disability.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Objective To evaluate the feasibility and efficacy of the three-guidewire technique for retrograde stent placement in the treatment of ureteral mucosal sleeve avulsion (UMSA). Methods A retrospective analysis was conducted on the clinical data of 12 patients with UMSA secondary to ureteroscopic lithotripsy for ureteral calculi in our hospital during Jul. 2010 and Oct. 2023. The three-guidewire technique was employed for retrograde stent placement during the procedure. A secondary ureteroscopic lithotripsy was performed one month postoperatively.Results Double-J stent was successfully placed in all 12 patients, with a mean stent insertion time of 23.3(16-30)minutes. No intraoperative exacerbation of mucosal avulsion occurred. One patient was lost to follow-up. At the one-month postoperative ureteroscopic examination and lithotripsy, 81.8% (9/11) cases exhibited unobstructed ureters, while 18.2%(2/11) developed annular membranous strictures, which were resolved following dilation. During subsequent follow-up, the postoperative creatinine level after double-J stent removal showed a mild decrease compared to the preoperative level [87.9(72-100)μmol/L vs. 90.1(69-108)μmol/L]. Up to 90.9%(10/11) patients remained free of hydronephrosis, with only 1 case (9.1%) requiring laparoscopic ureterovesical reimplantation for hydronephrosis 4 months postoperatively. Conclusion The three-guidewire technique for retrograde stent placement in the treatment of UMSA demonstrates strong operability, high success rates, favorable outcomes, and a low incidence of ureteral stricture, which warrant wide clinical promotion.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

BACKGROUND: Medical informatics accumulated vast amounts of data for clinical diagnosis and treatment. However, limited access to follow-up data and the difficulty in integrating data across diverse platforms continue to pose significant barriers to clinical research progress. In response, our research team has embarked on the development of a specialized clinical research database for cardiology, thereby establishing a comprehensive digital platform that facilitates both clinical decision-making and research endeavors. METHODS: The database incorporated actual clinical data from patients who received treatment at the Cardiovascular Medicine Department of Chinese PLA General Hospital from 2012 to 2021. It included comprehensive data on patients' basic information, medical history, non-invasive imaging studies, laboratory test results, as well as peri-procedural information related to interventional surgeries, extracted from the Hospital Information System. Additionally, an innovative artificial intelligence (AI)-powered interactive follow-up system had been developed, ensuring that nearly all myocardial infarction patients received at least one post-discharge follow-up, thereby achieving comprehensive data management throughout the entire care continuum for high-risk patients. RESULTS: This database integrates extensive cross-sectional and longitudinal patient data, with a focus on higher-risk acute coronary syndrome patients. It achieves the integration of structured and unstructured clinical data, while innovatively incorporating AI and automatic speech recognition technologies to enhance data integration and workflow efficiency. It creates a comprehensive patient view, thereby improving diagnostic and follow-up quality, and provides high-quality data to support clinical research. Despite limitations in unstructured data standardization and biological sample integrity, the database's development is accompanied by ongoing optimization efforts. CONCLUSION The cardiovascular specialty clinical database is a comprehensive digital archive integrating clinical treatment and research, which facilitates the digital and intelligent transformation of clinical diagnosis and treatment processes. It supports clinical decision-making and offers data support and potential research directions for the specialized management of cardiovascular diseases.

Objective To investigate the effects and mechanisms of ubiquitin-associated domain-containing protein 2(UBAC2)mediated by m6A methylation modification on the invasion and migration abilities of colorectal cancer cells.Methods The GEPIA2.0 database was utilized to analyze the expression differences of UBAC2 mRNA between colorectal cancer tissues and adjacent normal tissues,as well as its expression in colorectal cancer tissues at different stages.The correlation between Wilms tumor 1-associated protein(WTAP)and UBAC2 expression was analyzed.The Kaplan-Meier plotter online tool was applied to analyze the correlation between UBAC2 and the overall survival rate of colorectal cancer patients.The RMVar and SRAMP databases were employed to predict potential m6A methylation modification sites in the UBAC2 gene.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to detect the expression levels of UBAC2 mRNA and protein in colorectal cancer cell lines.For UBAC2 knockdown experiments,SW480 cells were divided into control group(no treatment),sh-NC group(transfected with sh-NC negative control plasmid),and sh-UBAC2 group(transfected with sh-UBAC2 plasmid).For WTAP knockdown experiments,groups included control group(no treatment),si-NC group(transfected with negative control siRNA),and si-WTAP group(transfected with WTAP-targeting siRNA).For UBAC2 overexpression experiments,groups were control group(no treatment),si-WTAP group(transfected with pcDNA3.1 empty plasmid),and si-WTAP+OE-UBAC2 group(transfected with UBAC2 overexpression plasmid pcDNA3.1-UBAC2).Western blotting was used to detect the protein expression levels of UBAC2,WTAP,E-cadherin,N-cadherin,and Vimentin;qRT-PCR was applied to detect the expression level of UBAC2 mRNA;Transwell assays were conducted to assess cell invasion and migration abilities.MeRIP-qPCR was employed to detect the m6A methylation modification of UBAC2 mRNA;RIP-qPCR experiments were conducted to verify the binding of WTAP to UBAC2 mRNA.In nude mouse colorectal cancer lung metastasis experiments,groups included LV-sh-NC group(tail vein injection of SW480 cells stably infected with LV-sh-NC)and LV-sh-UBAC2 group(tail vein injection of SW480 cells stably infected with LV-sh-UBAC2).After 42 d of tumor-implantation in nude mice,lung tissues were harvested:the number of lung nodules observed by hematoxylin/eosin(HE)staining,and the expression level of Luc2 mRNA detected by qRT-PCR.Results GEPIA2.0 database analysis revealed that the expression level of UBAC2 mRNA in colorectal cancer tissues was significantly higher than that in adjacent normal tissues,and it gradually increased with the progression of tumor stage(P<0.05).The expression levels of UBAC2 mRNA and protein in multiple colorectal cancer cell lines were significantly higher than those in normal colonic epithelial cells(P<0.05).Compared with sh-NC group,sh-UBAC2 group showed significantly increased E-cadherin protein expression,significantly decreased N-cadherin and Vimentin protein expression,and significantly reduced number of invaded and migrated SW480 cells(P<0.05).GEPIA2.0 database analysis results indicated a positive correlation between WTAP and UBAC2 expression(r=0.24,P<0.001).Compared with si-NC group,si-WTAP group showed significantly decreased expression levels of WTAP and UBAC2 mRNA and protein in SW480 cells(P<0.05).MeRIP-qPCR results demonstrated that the m6A modification level of UBAC2 mRNA in si-WTAP group was significantly lower than that in si-NC group(P<0.05).RIP-qPCR further confirmed that WTAP could bind to UBAC2 mRNA.Compared with control group,si-WTAP group showed significantly increased E-cadherin protein expression and significantly decreased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05);compared with si-WTAP group,si-WTAP+OE-UBAC2 group showed significantly decreased E-cadherin protein expression and significantly increased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05).The number of lung nodules in LV-sh-UBAC2 group was significantly fewer than that in LV-sh-NC group,and the expression level of Luc2 mRNA in lung tissues was significantly lower than that in LV-sh-NC group(P<0.05).Conclusion UBAC2 mediated by m6A methylation modification can regulate the epithelial-mesenchymal transition(EMT)process in colorectal cancer cells,thereby affecting the invasion and migration abilities of colorectal cancer cells.

OBJECTIVE: To elucidate the rules of temporal and spatial variations in distal skin potential at Hegu (LI4) under different stimulation modes by extracting nonlinear characteristic parameters from array multichannel data and adopting multivariate statistical analysis. METHODS: Seven healthy subjects were selected and the surface potential at the left Quchi (LI11) was collected using 14×9 array multichannel electrodes. Using Hegu (LI4) on the left as the stimulation point, four stimulation modes were applied, i.e. being quiescent, point pressing, moxibustion, and manual needling manipulation. Electrical signals were collected for 30 s in each mode, with a 5-min interval between operations, and a sampling frequency of 16 384 Hz. The data was denoised using ensemble empirical mode decomposition (EEMD), and sample entropy (SaEn) features were extracted. Statistical analysis was conducted on these data using factor analysis and multivariate analysis of variance. RESULTS: The SaEn values of most electrode channels were higher under point pressing, moxibustion and manual needling manipulation compared with those under quiescent condition. Under manual needling manipulation, the SaEn value of the electrode channel reached the peak in the first time interval (1-5 s) and it was declining thereafter. Factor analysis showed that the specificity of activation channels was concentrated at the left Quchi (LI11) (loading capacity ≥0.90). Analysis of variance indicated that the significant differences were presented in average sample entropy (SaEn()) values of activation channels among different stimulation modes at Hegu (LI4) (P<0.001), but there was no statistically significant interaction effect between groups and time intervals (P>0.05). CONCLUSION Through nonlinear characteristic parameter extraction and multivariate statistical analysis, we have uncovered the complex temporal and spatial dynamical rules of distal skin potential at Hegu (LI4) under various stimulation modes and successfully identified the specific activation characteristics at Quchi (LI11).
Humans ; Moxibustion ; Acupuncture Points ; Male ; Adult ; Female ; Young Adult ; Acupuncture Therapy/instrumentation*

OBJECTIVE: To explore the pain-location interaction between pressure-sensitive points on the body surface and traditional acupoints in patients with chronic non-specific low back pain (CNLBP) under different disease courses, using Euclidean distance and multivariate statistical analysis. METHODS: A pressure-sensitive point detection was performed on 30 CNLBP patients with varying disease courses. A constant pressure was applied using an FDK20 algometer within a designated lumbar area, a total of 50 points were tested, and the tested points were numbered; the visual analogue scale (VAS) pain score was recorded simultaneously. MatlabR2022a9.12. software was used to extract the positions of pressure-sensitive points, and preprocessing and normalization of point location and VAS scores data were conducted. Under constraint conditions (VAS≥8.0 ∩ Euclidean distance to acupoint≤0.5), the proportion of pressure-sensitive points within the Euclidean distance threshold to each acupoint (PVD_acupoint) was calculated, followed by multivariate statistical analysis. RESULTS: ①Constrained analysis of PVD_acupoint showed that PVD_{Qihaishu (BL24)} and PVD_{Dachangshu (BL25)} were positively correlated with disease course (r=0.55, P<0.01). ②Factor analysis and silhouette analysis revealed that PVD_{Shenshu (BL23)} and PVD_{Dachangshu (BL25)} exhibited trends consistent with disease course progression (P>0.05), with different degree (P<0.01). CONCLUSION The PVD_acupoint value based on Euclidean distance can characterize the pressure sensitivity features of traditional acupoints associated with disease. Multivariate statistical analysis of PVD_acupoint confirms that selecting the acupoint combination of Shenshu (BL23) and Dachangshu (BL25) for CNLBP is associated with the distribution of surrounding pressure-sensitive points and the pathological characteristics of the condition.
Humans ; Acupuncture Points ; Low Back Pain/physiopathology* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Acupuncture Therapy ; Young Adult ; Pressure