Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Cistanches Herba(CH) is a famous tonic traditional Chinese medicine, with the effects of tonifying kidney Yang, nourishing kidney Yin, replenishing essence and blood, and moistening the intestines to relieve constipation. Modern pharmacological studies have shown that CH has anti-aging, anti-fatigue, immunomodulatory, neuroprotective, and anti-aging activities, serving as an ideal raw material for the development of pharmaceuticals and health products. In 2023, CH was added in the catalog of medicinal and food substances, which provided policy support for its application in conventional food products and expanding pathways for industrial diversification. To comprehensively understand current development status of CH products, this review systematically investigated professional databases including Yaozhi(https://db.yaozh.com), Chinese Pharmacopoeia, Compendium of National Standards for Chinese Patent Medicines, and Kezhuang and collected market survey data to thoroughly review the applications of CH as a primary ingredient in domestic and international Chinese patent medicines, health foods, cosmetics, and common food products. Furthermore, this review points out challenges in the current industrial development and future potential market prospects, aiming to provide guidance for the development and industrialization of CH-based pharmaceuticals and health products, thereby promoting the vigorous growth of the CH industry.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Cistanche/chemistry* ; Animals ; Medicine, Chinese Traditional

PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67% in the TXA group and 47.95% in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.
Humans ; Tranexamic Acid/administration & dosage* ; Hip Fractures/surgery* ; Male ; Aged ; Female ; Fracture Fixation, Intramedullary/adverse effects* ; Blood Loss, Surgical/prevention & control* ; Antifibrinolytic Agents/administration & dosage* ; Aged, 80 and over ; Bone Nails ; Middle Aged ; Blood Transfusion/statistics & numerical data*

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVE: To investigate the effect of different previous treatments on the efficacy of flumatinib in patients with chronic myeloid leukemia (CML). METHODS: The clinical data of 69 patients with CML treated with flumatinib in the Affiliated Hospital of Xuzhou Medical University from 2019 to 2024 were retrospectively analyzed. The patients were divided into a first-line flumatinib group and a first-line non-flumatinib group according to whether flumatinib was used as first-line treatment. The molecular response (MR) at 3, 6 and 12 months of treatment was compared between the two groups to evaluate the early efficacy. The first-line non-flumatinib group was further divided into imatinib group, nilotinib group, and dasatinib group according to the previous first-line drugs used. The efficacy data of these three groups at 3, 6 and 12 months after switching to flumatinib were collected, and the MR was evaluated to compare efficacy differences. RESULTS: The rate of early molecular response (EMR) in the first-line flumatinib group was significantly higher than that in the first-line non-flumatinib group (P < 0.05). At 6 months and 12 months of treatment, the proportion of patients achieving MR 4.5 in the first-line flumatinib group was significantly higher than that in the first-line non-flumatinib group (P < 0.05). Compared with the imatinib and nilotinib groups, the previous dasatinib group showed a significantly higher proportion of patients achieving MR 5.0 at 3, 6, and 12 months after switching to flumatinib (P < 0.05). CONCLUSION Compared with the previous treatment with other tyrosine kinase inhibitors (TKIs), initial use of flumatinib at diagnosis enable patients to achieve deeper molecular remission more rapidly. Compared with previous use of imatinib or nilotinib, previous use of dasatinib is associated with deeper molecular remission after switching to flumatinib.
Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Retrospective Studies ; Imatinib Mesylate/therapeutic use* ; Dasatinib/therapeutic use* ; Treatment Outcome ; Pyrimidines/therapeutic use* ; Female ; Male ; Protein Kinase Inhibitors/therapeutic use* ; Middle Aged ; Antineoplastic Agents/therapeutic use*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

In the progression of end-stage liver disease,the incidence of sleep disorders in patients with liver cirrhosis is high.Currently,western medicine treatment has obvious liver and kidney damage and adverse reactions after discontinuation,which affects the therapeutic effect.Cirrhosis and sleep disorders can be separately attributed to the category of"abdominal mass"and"insomnia"in traditional Chinese medicine.The"abdominal mass"is caused by the disorder of liver and spleen qi movement,as well as the obstruction of phlegm-dampness and blood stasis.In the development of"abdominal mass",the liver failed in ensuring free movement of qi,the spleen failed in transportation and transformation,liver yin and liver blood became insufficiency and the imbalance of yin and yang in the zang-fu organs became imbalanced,and then the ethereal soul depart from the housing,which leads to"insomnia"as an outward manifestation.Professor ZHOU Xiao-Zhou focuses on the concept of qi and blood,and points out that the pathogenesis of sleep disorder in cirrhosis is characterized by liver stagnation and spleen deficiency.He proposed that the treatment principle is to regulate the liver and spleen simultaneously,as well as to nourish the heart and calm the mind.Professor ZHOU has developed Ganyinghua Anshen Formula for treating sleep disorders in cirrhosis,which is derived from the modification of Xiangsha Liujunzi Decoction,and is composed of 14 Chinese medicines of vinegar-prepared Cyperi Rhizoma,Amomi Fructus,Coicis Semen,Dioscoreae Rhizoma,bran-fried Atractylodis Macrocephalae Rhizoma,Galli Gigerii Endothelium Corneum,Gardeniae Fructus,Codonopsis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Citri Reticulatae Pericarpium,Sclerotium Poriae Pararadicis,Longan Arillus,Albiziae Cortex,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The formula has achieved remarkable clinical effect.The clinical experience of Professor ZHOU Xiao-Zhou for treating sleep disorders in cirrhosis through regulating the liver and spleen simultaneously will provide a reference for its clinical treatment with traditional Chinese medicine.

Objective To investigate the clinical efficacy of modified Fuzheng Yiliu Decoction(composed of Astragali Radix,Codonopsis Radix,Ligustri Lucidi Fructus,Hedyotis Diffusae Herba,Moutan Cortex,Visci Herba,etc.)combined with XELOX regimen(Oxaliplatin plus Capecitabine)for the treatment of postoperative patients with advanced gastric cancer of qi and yin deficiency type.Methods A total of 80 postoperative patients with advanced gastric cancer of qi and yin deficiency type were randomly divided into the Chinese medicine group and the control group,with 40 cases in each group.Both groups received chemotherapy with XELOX regimen,while the Chinese medicine group was given modified Fuzheng Yiliu Decoction.Three weeks constituted a course of treatment,the medication of Chinese medicine decoction lasted for two weeks or more in each course of treatment,and a total of 8 courses of treatment were performed.The incidence of adverse reactions during chemotherapy was monitored and changes in serum tumor markers of serum carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and alpha-fetoprotein(AFP)were observed in the two groups before and after treatment.Moreover,the patients'quality of life was assessed by the scores of Karnofsky's Performance Status(KPS)and World Health Organization Quality of Life Measurement Scale(WHOQOL-100).Long-term follow-up was carried out for the evaluation of the prognostic indicators such as overall survival and one-year and 2-year overall survival rates.Results(1)Patients in the two groups were all followed up,and the median follow-up time was 27 months(95%CI:23.59-27.86).(2)After treatment,the levels of serum CEA and AFP in the Chinese medicine group were significantly lower than those before treatment(P＜0.05 or P＜0.01),while serum CA199 tended to decrease compared with those before treatment,but the difference was not statistically significant(P＞0.05);in the control group,the levels of serum CEA,CA199,and AFP were not significantly decreased after treatment(P＞0.05).The intergroup comparison showed that the decrease of serum CEA,CA199 and AFP levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The adverse reactions during chemotherapy in the two groups mainly involved bone marrow suppression,gastrointestinal reactions and liver function abnormalities,etc.The incidences of all adverse reactions in the Chinese medicine group tended to be lower than those in the control group,but the differences were not statistically significant(P＞0.05).(4)After treatment,the KPS scores of patients in both groups were improved compared with those before treatment(P＜0.01),and the improvement in the Chinese medicine group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the scores of the four dimensions of WHOQOL-100 such as health status,mobility,life feelings,and other activities of daily life in the Chinese medicine group were significantly improved compared with the pre-treatment(P＜0.05),whereas there was no significant improvement in the control group(P＞0.05).The intergroup comparison showed that the improvement of the scores of each dimension of the WHOQOL-100 in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(6)The median survival in the Chinese medicine group was 29.0 months(95%CI:25.95-31.70)and that in the control group was 22.0 months(95%CI:19.67-25.58),indicating that the median survival was significantly prolonged in Chinese medicine group(P＜0.01).The one-year and 2-year postoperative survival rates were 97.5%and 77.5%in the Chinese medicine group and 92.5%and 47.5%in the control group,respectively.The intergroup comparison showed that the one-year and 2-year postoperative survival rates in the Chinese medicine group were higher than those in the control group(P＜0.01).Conclusion Modified Fuzheng Yiliu Decoction can effectively alleviate the adverse reactions during adjuvant chemotherapy for postoperative patients with advanced gastric cancer of qi and yin deficiency type,improve the quality of life of patients,and prolong the survival time of patients.

Objective To observe the regulating effect and mechanism of Yichang Sanjie Granules on intestinal flora and immune function in mice with colon cancer.Methods Sixty mice were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Yichang Sanjie Granules,and the overexpression of melanoma absent gene 2(AIM2)plasmid(pcDNA-AIM2)intervention group,with 10 mice in each group.Colorectal cancer model was prepared by oxidized azomethine(AOM)/dextran sulfate sodium(DSS)induction method in all groups except normal group.After drug administration,the survival curves of mice in each group were plotted and the tumor volume was calculated;serum levels of immunoglobulin(Ig)G,IgM,interleukin(IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA);peripheral blood levels of CD3+,CD4+,CD8+ T cells were detected by flow cytometry;the splenic index was determined;Hematoxylin-eosin(HE)staining was used to observe the pathological changes in colon tissues;16S-rDNA intestinal flora sequencing was used to detect the α-diversity of intestinal flora and the structure of intestinal flora communities;and protein immunoblotting(Wetsern Blot)was used to detect the protein expressions of AIM2,apoptosis-associated speckled-like protein containing a CARD(ASC),and cystatinase-1(caspase-1)in colon tissues.Results Compared with the normal group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the model group were significantly decreased,and the tumor volume,serum levels of IL-1β and IL-18,peripheral blood level of CD8+,and splenic index were significantly increased(all P＜0.05),and the HE staining results showed the characteristic manifestations of colon cancer;compared with the model group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group were significantly increased,and the tumor volume,serum levels of IL-1β and IL-18,level of peripheral blood CD8+,and splenic index were significantly decreased(all P＜0.05),and the HE staining results showed the manifestations of colon cancer were improved.Compared with the normal group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group,and Ruminiclostridium in the model group were significantly decreased,while the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was increased in the model group(P＜0.05);compared with the model group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group and Ruminiclostridium were significantly increased,and the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was decreased in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group(all P＜0.05).Conclusion Yichang Sanjie Granules can increase autoimmunity and improve intestinal flora structure in mice with colon cancer,and its mechanism is related to the activation of AIM2 inflammatory vesicles.