This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis* ; Risk Assessment ; Minerals/chemistry* ; Fossils ; Humans ; Drug Contamination ; Mass Spectrometry

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVE: To explore the anti-photoaging properties of salvianolic acid B (Sal B). METHODS: The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking. RESULTS: Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol. CONCLUSION Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.
Humans ; Sirtuin 1/metabolism* ; Ultraviolet Rays ; Oxidative Stress/radiation effects* ; Keratinocytes/metabolism* ; Molecular Docking Simulation ; Benzofurans/pharmacology* ; Skin Aging/radiation effects* ; Reactive Oxygen Species/metabolism* ; Cell Survival/radiation effects* ; HaCaT Cells ; Hydroxyproline/metabolism* ; Glutathione Peroxidase/metabolism* ; Catalase/metabolism* ; Depsides

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

A high-performance liquid chromatography method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was developed to determine the content of 15 amino acids in the medicinal snakes Bungarus Parvus, Agkistrodon, and Zaocys. The results showed that the total amino acid(TAA) content ranged from 277.13 to 515.05 mg·g~(-1), with the top four amino acids in all three species being glutamic acid(Glu), glycine(Gly), aspartic acid(Asp), and lysine(Lys). The essential amino acid(EAA) content ranged from 74.56 to 203.94 mg·g~(-1), with Agkistrodon exhibiting the highest content. The non-essential amino acid(NEAA), semi-essential amino acid(semi-EAA), and medicinal amino acid(MAA) content ranged from 189.06 to 318.23, 12.89 to 33.53, and 179.83 to 342.33 mg·g~(-1), respectively, with Zaocys having the highest content in these categories. Amino acid nutritional value was evaluated using the amino acid ratio(RAA), amino acid ratio coefficient(RCAA), and amino acid ratio coefficient score(SRCAA), and the results indicated that all three medicinal snakes possessed good nutritional value. The amino acid composition was similar across the species, though significant differences in content were observed. Based on these differences, an orthogonal partial least squares-discriminant analysis(OPLS-DA) model was established, which could clearly distinguish between the three medicinal snake species. The key differences in amino acid content included Gly, tyrosine(Tyr), Glu, and serine(Ser), which may be related to the observed clinical application differences among the species. Further research into the mechanisms of these differential amino acids is expected to provide more insights into the clinical application disparities of these three medicinal snake species.
Amino Acids/chemistry* ; Animals ; Nutritive Value ; Chromatography, High Pressure Liquid ; Snakes/classification* ; Bungarus

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Glioblastoma (GBM), one of the most common malignant tumors in the central nervous system (CNS), is characterized by diffuse and invasive growth as well as resistance to various combination therapies. GBM is the most prevalent type with the highest degree of malignancy and the worst prognosis. While current clinical treatments include surgical resection, radiotherapy, temozolomide chemotherapy, novel molecular targeted therapy, and immunotherapy, the median survival time of GBM patients is only about one year. Radiotherapy is one of the important treatment modalities for GBM, which relies on ionizing radiation to eradicate tumor cells. Approximately 60% to 70% of patients need to receive radiotherapy as postoperative radiotherapy or neoadjuvant radiotherapy during the treatment process. However, during radiotherapy, the radioresistant effect caused by DNA repair activation and cell apoptosis inhibition impedes the therapeutic effect of malignant glioblastoma.Ferroptosis was first proposed by Dr. Brent R. Stockwell in 2012. It is an iron-dependent mode of cell death induced by excessive lipid peroxidation. Although the application of ferroptosis in tumor therapy is still in the exploratory stage, it provides a completely new idea for tumor therapy as a novel form of cell death. Ferroptosis has played a significant role in the treatment of GBM. Specifically, research has revealed the key processes of ferroptosis occurrence, including intracellular iron accumulation, reactive oxygen species (ROS) generation, lipid peroxidation, and a decrease in the activity of the antioxidant system. Among them, glutathione peroxidase 4(GPX4) in the cytoplasm and mitochondria, ferroptosis suppressor protein 1 (FSP1) on the plasma membrane, and dihydroorotate dehydrogenase (DHODH) in the mitochondria constitute an antioxidant protection system against ferroptosis. In iron metabolism, nuclear receptor coactivator 4 (NCOA4) can mediate ferritin autophagy to regulate intracellular iron balance based on intracellular iron content. Heme oxygenase1 (HMOX1) catalyzes heme degradation to release iron and regulate ferroptosis. Radiation can trigger ferroptosis by generating ROS, inhibiting the signaling axis of the antioxidant system, depleting glutathione, upregulating acyl-CoA synthase long chain family member 4 (ACSL4), and inducing autophagy. Interestingly, some articles has documented that exposure to low doses of radiation (6 Gy for 24 h or 8 Gy for 4-12 h) can induce the expression of SLC7A11 and GPX4 in breast cancer and lung cancer cells, leading to radiation resistance, while radiation-induced ferroptosis occurs after 48 h. In contrast, high doses of ionizing radiation (20 Gy and 50 Gy) increase lipid peroxidation after 24 h. This suggests that radiation-induced oxidative stress is a double-edged sword that can regulate ferroptosis in both directions, and the ultimate fate of cells after radiation exposure——developing resistance and achieving homeostasis or undergoing ferroptosis——depends on the degree and duration of membrane lipid damage caused by the radiation dose. In addition, during the process of radiotherapy, methods such as inducing iron overload, damaging the antioxidant system, and disrupting mitochondrial function are used to target ferroptosis, thereby enhancing the radiosensitivity of glioblastoma. By promoting the occurrence of ferroptosis in tumor cells as a strategy to improve radiotherapy sensitivity, we can enhance the killing effect of ionizing radiation on tumor cells, thus providing more treatment options for patients with glioblastoma. In this paper, we reviewed ferroptosis and its mechanism, analyzed the molecular mechanism of radiation-induced ferroptosis, and discussed the effective strategies to regulate ferroptosis in enhancing the sensitivity of radiotherapy, with a view to providing an important reference value for improving the current status of glioblastoma treatment.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

Objective:To investigate the effect of astragaloside IV (AS-IV) regulating the signal axis of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) on the mobilization of bone marrow endothelial progenitor cells (EPCs) to peripheral blood in diabetes skin ulcer (DSU) rats.Methods:Twenty four SPF grade male Sprague Dawley (SD) rats were selected to make the model of type 2 diabetes rats by intraperitoneal injection of 30 mg/kg 1% (plastid ratio) streptozotocin, and then round full-thickness skin with a diameter of 2 cm was cut on both sides of the waist and back to make the skin ulcer model of diabetes rats. After that, they were randomly divided into AS-IV group (50 mg/kg AS-IV), blocker group (50 mg/kg AS-IV+ 5 mg/kg AMD3100) and model group. At the same time, a blank group ( n=8) was set up, The drug was administered via intraperitoneal injection, and the model group and blank group were treated with 0.9% NaCl of equal volume. On the 10th day, peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats were collected. The number of EPCs in peripheral blood of each group of rats was measured by flow cytometry, and the protein expression of SDF-1α and CXCR4 in peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats was detected by enzyme-linked immunosorbent assay (ELISA); At the same time, the wound healing rates of each group were tested. Results:On the 10th and 21st day after modeling, the wound healing rate of each group of rats was compared. The blank group healed the fastest, while the model group healed the slowest. The AS-IV group had better healing than the model group and the blocker group, and the difference was statistically significant (all P<0.05). On the 10th day after modeling, the positive rates of peripheral blood EPCs in the white group, AS-IV group, and blocker group were significantly higher than those in the model group (all P<0.05), while the positive rates of peripheral blood EPCs in the blocker group were significantly lower than those in the AS-IV group (all P<0.05). On the 10th day after modeling, the protein expression of SDF-1α and CXCR4 in the wound, serum, and bone marrow of the model group was the lowest, while the protein expression in the blank group was the highest (all P<0.05). The protein expression of SDF-1α and CXCR4 in the wound, serum, bone marrow of the AS-IV group was significantly higher than that of the blocker group and model group, and the difference was statistically significant (all P<0.05). Conclusions:Astragaloside IV can promote the mobilization and migration of endothelial progenitor cells from bone marrow to peripheral blood in diabetes ulcer rats by regulating SDF-1α/CXCR4 signal axis, and can participate in angiogenesis of diabetes ulcer wounds as seed cells to promote the healing of diabetes skin ulcers.