AIM To study the chemical constituents from Euphorbia humifusa Willd.and their in vitro anti-hepatoma activity.METHODS Silica gel,D101 macroporous adsorption resin and semi-preparative RP-HPLC were used for isolated and purified,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-hepatocellular carcinoma activity was determined by MTT mothod.RESULTS Eighteen compounds were isolated and identified as 22-O-angeloyl-R1-barrigenol(1),dimethyl 3,3'-[oxybis(4,1-phenylene)](2E,2'E)-diacrylate(2),N-(3-methoxy-1,3-dioxopropyl)-D-tryptophan methyl ester(3),N-acetyltryptophan methyl ester(4),N-(methoxycarbonyl)-tryptophan methyl ester(5),(3β,5α,17β)-4,4,8,14-tetramethyl-18-norandrostane-3,17-diol(6),3β,18,19β-trihydroxylupane(7),pregnenolone(8),3-hydroxy-5,6-epoxy-7-megastigmen-9-one(9),dehydrovomifoliol(10),loliolide(11),2,2'-oxybis(1,4-di-tert-butylbenzene)(12),dibutyl phthalate(13),4-methoxycinnamic acid(14),3,4-dimethoxycinnamic acid(15),methyl 4-hydroxybenzoate(16),kaempferol(17),quercetin(18).The IC50 values of compounds 1,7 and 8 on HepG2 cells were(17.27±0.92),(19.11±2.14)and(7.53±1.09)μmol/L,respectively.CONCLUSION Compounds 1-16 are first isolated from this plant.Compounds 1,7 and 8 have anti-hepatoma activity.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Blue light inactivation technology, particularly at the 405 nm wavelength, has demonstrated distinct and multifaceted mechanisms of action against both Gram-positive and Gram-negative bacteria, offering a promising alternative to conventional antibiotic therapies. For Gram-positive pathogens such as Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus (MRSA), the bactericidal effects are primarily mediated by endogenous porphyrins (e.g., protoporphyrin III, coproporphyrin III, and uroporphyrin III), which exhibit strong absorption peaks between 400-430 nm. Upon irradiation, these porphyrins are photoexcited to generate cytotoxic reactive oxygen species (ROS), including singlet oxygen, hydroxyl radicals, and superoxide anions, which collectively induce oxidative damage to cellular components. Early studies by Endarko et al. revealed that (405±5) nm blue light at 185 J/cm² effectively inactivated L. monocytogenes without exogenous photosensitizers, supporting the hypothesis of intrinsic photosensitizer involvement. Subsequent work by Masson-Meyers et al. demonstrated that 405 nm light at 121 J/cm² suppressed MRSA growth by activating endogenous porphyrins, leading to ROS accumulation. Kim et al. further elucidated that ROS generated under 405 nm irradiation directly interact with unsaturated fatty acids in bacterial membranes, initiating lipid peroxidation. This process disrupts membrane fluidity, compromises structural integrity, and impairs membrane-bound proteins, ultimately causing cell death. In contrast, Gram-negative bacteria such as Salmonella, Escherichia coli, Helicobacter pylori, Pseudomonas aeruginosa, and Acinetobacter baumannii exhibit more complex inactivation pathways. While endogenous porphyrins remain central to ROS generation, studies reveal additional photodynamic contributors, including flavins (e.g., riboflavin) and bacterial pigments. For instance, H. pylori naturally accumulates protoporphyrin and coproporphyrin mixtures, enabling efficient 405 nm light-mediated inactivation without antibiotic resistance concerns. Kim et al. demonstrated that 405 nm light at 288 J/cm² inactivates Salmonella by inducing genomic DNA oxidation (e.g., 8-hydroxy-deoxyguanosine formation) and disrupting membrane functions, particularly efflux pumps and glucose uptake systems. Huang et al. highlighted the enhanced efficacy of pulsed 405 nm light over continuous irradiation for E. coli, attributing this to increased membrane damage and optimized ROS generation through frequency-dependent photodynamic effects. Environmental factors such as temperature, pH, and osmotic stress further modulate susceptibility, sublethal stress conditions (e.g., high salinity or acidic environments) weaken bacterial membranes, rendering cells more vulnerable to subsequent ROS-mediated damage. The 405 nm blue light inactivates drug-resistant Pseudomonas aeruginosa through endogenous porphyrins, pyocyanin, and pyoverdine, with the inactivation efficacy influenced by bacterial growth phase and culture medium composition. Intriguingly, repeated 405 nm exposure (20 cycles) failed to induce resistance in A. baumannii, with transient tolerance linked to transient overexpression of antioxidant enzymes (e.g., superoxide dismutase) or stress-response genes (e.g., oxyR). For Gram-positive bacteria, porphyrin abundance dictates sensitivity, whereas in Gram-negative species, membrane architecture and accessory pigments modulate outcomes. Critically, ROS-mediated damage is nonspecific, targeting DNA, proteins, and lipids simultaneously, thereby minimizing resistance evolution. The 405 nm blue light technology, as a non-chemical sterilization method, shows promise in medical and food industries. It enhances infection control through photodynamic therapy and disinfection, synergizing with red light for anti-inflammatory treatments (e.g., acne). In food processing, it effectively inactivates pathogens (e.g., E. coli, S. aureus) without altering food quality. Despite efficacy against multidrug-resistant A. baumannii, challenges include device standardization, limited penetration in complex materials, and optimization of photosensitizers/light parameters. Interdisciplinary research is needed to address these limitations and scale applications in healthcare, food safety, and environmental decontamination.

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

OBJECTIVES: To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. METHODS: Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. RESULTS: At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). CONCLUSIONS Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals ; Rats, Sprague-Dawley ; Magnetic Resonance Imaging/methods* ; Rats ; White Matter/injuries* ; Animals, Newborn ; Female ; Multimodal Imaging ; Male ; Hypoxia-Ischemia, Brain/pathology*

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Objective:To evaluate the role of a single PET-CT scan in predicting survival and prognosis in patients with non-small cell lung cancer (NSCLC) who did not undergo surgery but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy.Methods:A retrospective analysis was conducted on the data of 23 NSCLC patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from May 2022 to June 2024. All patients were pathologically confirmed, received neoadjuvant chemotherapy combined with immunotherapy, did not undergo surgery for various reasons, and instead received radiotherapy. Each patient underwent only one PET-CT scan after neoadjuvant chemotherapy combined with immunotherapy and before radiotherapy. According to the maximum standardized uptake value (SUV max) on PET-CT, patients were divided into the low-uptake group (SUV max < 8, n=12) and high-uptake group (SUV max ≥ 8, n=11). Survival analysis was performed using the Kaplan-Meier method with survival curves plotted. Univariate analysis of influencing factors of survival was conducted using the Cox proportional hazards regression model. Clinical characteristics and survival outcomes of the two groups were compared, including progression-free survival (PFS) and overall survival (OS). Results:The 1-year PFS rates were 100% in the low-uptake group, 54.5% in the high-uptake group. This difference was statistically significant ( P=0.007). The 1-year and 2-year OS rates were both 100% in the low-uptake group, the 1-year and 2-year OS rates were both 90.9% in the high-uptake group, with no statistically significant difference ( P=0.394). Univariate Cox analysis identified age as an independent factor affecting PFS. Conclusions:For NSCLC patients who did not undergo surgical resection but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy, a single PET-CT scan before radiotherapy has potential value in predicting PFS. However, clinical studies with larger sample size and longer follow-up are required to evaluate its predictive value for OS.