Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

As one of the most common solid organ malignant tumors in the world， hepatocellular carcinoma has climbed to the fourth place in incidence rate and the second place in mortality in China， which seriously threatens people’s health. Terpenoids are natural active substances widely present in nature， among which sesquiterpenoids are numerous. They exhibit a variety of pharmacological activities， such as anti-tumor， antibacterial， anti-inflammatory， antiviral and antioxidant activities. This article reviews the research progress on the anti-hepatocellular carcinoma mechanism of sesquiterpenes from 2015 to 2024. The results showed that 24 sesquiterpenoids for the treatment of hepatocellular carcinoma have been reported in the literature in the past 10 years， and these compounds have shown potential in treating hepatocellular carcinoma by inhibiting cancer cell proliferation， inducing apoptosis， preventing invasion and metastasis， regulating immunity， and enhancing anti-drug resistance. The mechanism of anti-hepatocellular carcinoma mainly involves three regulatory pathways: phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin signaling pathway， nuclear factor kappa-B signaling pathway， and mitochondrial pathway. In the future， it is necessary to continue to explore new anti-hepatocellular carcinoma drugs with high research value， conduct in-depth analysis on the mechanism of synergistic anti-hepatocellular cancer effects of multiple components， targets， pathways， and accelerate the development of finished products in order to be widely used in clinical practice.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.

Objective To analyze the current situation of pediatric CT examination protection and cognition in Linyi City, China, and to promote the safe and standardized development of pediatric CT examination. Methods The radiation protection facilities of 58 medical institutions, the use of protective equipment among 158 pediatric patients undergoing CT examinations, and the cognition of radiation knowledge by 188 radiographers were investigated, and the data were analyzed. Results All 58 medical institutions installed ionizing radiation warning signs according to the standards, the normal operation rate of the work indicator lights was 81.0%, and the proper provision rate of protective equipment was 72.4%. The utilization rate of protective equipment was 59.5%, and there were significant differences among hospitals at different levels (P < 0.05). Radiographers had the highest awareness rate of radiation hazards (93.6%). The awareness rate of radiation basic knowledge differed significantly among radiographers with variuos educational backgrounds and professional titles (P < 0.05). The awareness rate of protection knowledge differed significantly with sex, age, and professional title (P < 0.05). There were significant differences in the awareness rate of emergency knowledge and laws and regulations based on age, educational background, and professional title (P < 0.05). Conclusion The availability and utilization of protective facilities and equipment for pediatric CT examinations in medical institutions in Linyi City require further improvement. Radiographers have a high level of awareness of radiation hazards. However, there remain gaps in their awareness rates of fundamental radiation hygiene knowledge, radiation protection knowledge, emergency knowledge, and laws and regulations. Increased efforts in education and training are recommended.

Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

Quality control is a key link in the modernization process of traditional Chinese medicine(TCM). Studies have shown that the effects of active components in TCM depend on not only their chemical composition but also their suitable physical forms and states. The physical phase structures, such as micelles, vesicles, gels, and nanoparticles, can improve the solubility, delivery efficiency, and targeting precision of active components. These structures significantly enhance the pharmacological activity while reducing the toxicity and side effects, demonstrating functional activity surpassing that of active components and highlighting the key effects of "structures" on "functions" of active components. Taking the physical phase structure as a breakthrough point, this paper outlines the common types of TCM physical phase structures. Furthermore, this paper explores how to realize the quality upgrading of TCM through the precise regulation of physical phase structures based on the current applications and potential of TCM physical phase structures in processing to increase the efficacy and reduce the toxicity, compounding and decocting processes, drug delivery systems, and quality control, aiming to provide novel insights for the future quality control of TCM.
Quality Control ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional/standards* ; Humans ; Drug Delivery Systems

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.