Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To explore the predictive value of triglyceride-glucose (TyG) index combined with low-density lipoprotein cholesterol (LDL-C) for major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD) complicated by type 2 diabetes mellitus (T2DM).Methods:A total of 248 patients with CHD and T2DM admitted to the First Affiliated Hospital of Xinjiang Medical University from July 2022 to January 2024 were retrospectively enrolled. All patients were followed up for 2 years and divided into MACE group (43 cases) and non-MACE group (205 cases) according to the occurrence of MACE. Indicators such as TyG index and LDL-C were compared between the two groups, and their correlations with MACE were analyzed. Multivariate logistic regression was used to screen the risk factors for MACE in patients with CHD and T2DM. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of TyG index, LDL-C, and their combination for MACE in these patients.Results:Compared with the non-MACE group, the MACE group had significantly higher LDL-C [2.63(2.23, 2.95)mmol/L vs 1.99(1.60, 2.66)mmol/L, P<0.001] and TyG index [9.30(8.80, 9.87) vs 8.60(8.09, 9.15), P<0.001]. Multivariate logistic regression showed that TyG index was an independent risk factor for MACE in patients with CHD and T2DM ( OR=10.49, P<0.001). ROC curve results indicated that the area under the curve (AUC) of TyG index and LDL-C for predicting MACE were 0.731 and 0.686, respectively. The combined AUC of the two indicators for predicting MACE was 0.769(95% CI: 0.698-0.840), showing better predictive performance. Conclusions:TyG index combined with LDL-C has high predictive value for the risk of MACE in patients with CHD complicated by T2DM.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

By elaborating on the theoretical framework of the pulse acupuncture based on systematic syndrome differentiation， this paper briefly analyzes the correspondence between pulse and acupuncture， and further explores its core principle of "establishing acupuncture based on pulse， and applying acupuncture when the pulse is balanced". This therapeutic system employs a three-step acupoint selection method， relying on the systematic integration and analysis of pulse elements at different levels to determine the nature of disease， syndrome type， and location. Treatment principles are guided by the concepts of form and spirit transformation， aiming to treat both simultaneously. Pulse diagnosis also serves as a standard for evaluating therapeutic efficacy and predicting prognosis， providing a theoretical basis for clinical acupuncture. Using stroke as a case example， this paper illustrates the practical clinical application of this approach， offering valuable insight for acupuncture.

Cancer is a serious global health problem and a major cause of human death. Conventional cancer treatments often run the risk of impairing vital organ functions. Anticancer peptides (ACPs) are considered to be one of the most promising therapeutic agents against common human cancers due to their small sizes, high specificity, and low toxicity. Since ACP recognition is highly limited to the laboratory, expensive, and time-consuming, we proposed pLM4ACP, a model for predicting ACPs based on machine learning and protein language models. In this model, the protein language model ProtT5 was used to extract the features of ACPs, and the extracted features were input into the support vector machine (SVM) classification algorithm for optimization and performance evaluation. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 0.763, F1-score of 0.767, Matthews correlation coefficient of 0.527, and area under the curve of 0.827 on the independent test set. This study constructs an efficient anticancer peptide prediction model based on protein language models, further advancing the application of artificial intelligence in the biomedical field and promoting the development of precision medicine and computational biology.
Machine Learning ; Antineoplastic Agents/chemistry* ; Humans ; Peptides/chemistry* ; Support Vector Machine ; Algorithms ; Computational Biology/methods* ; Neoplasms/drug therapy*

Objectives:To evaluate the accuracy and safety of cervical pedicle screw implantation in chil-dren with O-arm navigation assistance.Methods:This study retrospectively analyzed 27 pediatric patients with cervical spine disease who underwent cervical pedicle screw implantation with O-arm navigation assis-tance between January 2015 and December 2021.The patients aged 4-15(8.2±3.2)years,among which,there were 7 cases of atlantoaxial dislocation,12 cases of congenital cervical-thoracic deformity,4 cases of neurofi-bromatosis with cervicothoracic atrophic scoliosis,2 cases of Gorham's disease,and 2 cases of neoplasms.All the patients were treated with O-arm navigation-assisted posterior cervical pedicle screw internal fixation.Pre-operatively,the pedicle width of each segment was measured on the widest cross-sectional image of cervical CT scans,and pedicles＜3.5mm in width were defined as high-risk pedicles,and during operation,cervical pedicle screws(CPS)were inserted under O-arm navigation guidance.The accuracy of CPS implantation was e-valuated immediate postoperatively by CT scans(grade 0:no breach;grade 1:breach＜25％screw diameter;grade 2:breach by 25％-50％the screw diameter and invading the internal or lower wall;grade 3:breach by 25％-50％the screw diameter and invading the external or upper wall;grade 4:breach＞50％screw diameter).The CPS breach numbers and grades of different levels,as well as complications were recorded.Results:A total of 109 CPSs were implanted,the mean preoperative pedicle diameter was 3.49±0.58mm(C3-6),including 36 high-risk screws.And the screw distributions by segments were C1 13(11.9％),C2 25(22.9％),C3 8(7.3％),C4 17(15.6％),C5 14(12.8％),C6 17(15.6％),and C7 15(13.8％).Postoperative CT scan showed that 100(91.7％)CPSs were well positioned(≤grade 2),5(4.6％)CPSs were of grade 3,and 4(3.7％)CPSs were of grade 4.No surgical complications such as vertebral artery or nerve root injury were found.The C4 vertebra was relatively more likely to undergo wall breakage due to positional influence and navigational excursions.Breach of grade 4 was due to extremely thin preoperative pedicles(mean 2.78mm),which did not require immediate secondary surgical adjustment or removal in the absence of significant neurologic complications.Conclusions:O-arm navigation-assisted CPS placement has a high accuracy in different cervical diseases in children,and therefore is endowed with high safety.

Objectives:To evaluate the accuracy and safety of cervical pedicle screw implantation in chil-dren with O-arm navigation assistance.Methods:This study retrospectively analyzed 27 pediatric patients with cervical spine disease who underwent cervical pedicle screw implantation with O-arm navigation assis-tance between January 2015 and December 2021.The patients aged 4-15(8.2±3.2)years,among which,there were 7 cases of atlantoaxial dislocation,12 cases of congenital cervical-thoracic deformity,4 cases of neurofi-bromatosis with cervicothoracic atrophic scoliosis,2 cases of Gorham's disease,and 2 cases of neoplasms.All the patients were treated with O-arm navigation-assisted posterior cervical pedicle screw internal fixation.Pre-operatively,the pedicle width of each segment was measured on the widest cross-sectional image of cervical CT scans,and pedicles＜3.5mm in width were defined as high-risk pedicles,and during operation,cervical pedicle screws(CPS)were inserted under O-arm navigation guidance.The accuracy of CPS implantation was e-valuated immediate postoperatively by CT scans(grade 0:no breach;grade 1:breach＜25％screw diameter;grade 2:breach by 25％-50％the screw diameter and invading the internal or lower wall;grade 3:breach by 25％-50％the screw diameter and invading the external or upper wall;grade 4:breach＞50％screw diameter).The CPS breach numbers and grades of different levels,as well as complications were recorded.Results:A total of 109 CPSs were implanted,the mean preoperative pedicle diameter was 3.49±0.58mm(C3-6),including 36 high-risk screws.And the screw distributions by segments were C1 13(11.9％),C2 25(22.9％),C3 8(7.3％),C4 17(15.6％),C5 14(12.8％),C6 17(15.6％),and C7 15(13.8％).Postoperative CT scan showed that 100(91.7％)CPSs were well positioned(≤grade 2),5(4.6％)CPSs were of grade 3,and 4(3.7％)CPSs were of grade 4.No surgical complications such as vertebral artery or nerve root injury were found.The C4 vertebra was relatively more likely to undergo wall breakage due to positional influence and navigational excursions.Breach of grade 4 was due to extremely thin preoperative pedicles(mean 2.78mm),which did not require immediate secondary surgical adjustment or removal in the absence of significant neurologic complications.Conclusions:O-arm navigation-assisted CPS placement has a high accuracy in different cervical diseases in children,and therefore is endowed with high safety.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.