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

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

Multiple myeloma is a common and refractory hematological malignancy for which there is currently no radical treatment, and it is prone to relapse. Patients with relapsed and refractory myeloma have often been previously treated with multiple drugs including proteasome inhibitors and / or immunomodulatory drugs. Therefore, for such patients, the primary goal of treatment is to achieve disease control with acceptable toxicity and maintenance of quality of life. In this paper, the aim is to review the clinical effect of selinexor in treating patients with RRMM. As a novel treatment for RRMM, selinexor has a unique pharmacological mechanism that may further improve the clinical response rate of RRMM patients and enhance patients' quality of life. Although selinexor can cause a series of adverse reactions, most of these adverse reactions can be alleviated or disappear after clinical targeted treatment, and effective preventive measures can also minimize the occurrence of adverse reactions. In conclusion, selinexor has shown broad application prospects in RRMM patients, and further research will be conducted in the future to optimize the treatment regimen of selinexor, so that more RRMM patients can benefit from it.
Humans ; Multiple Myeloma/drug therapy* ; Hydrazines/therapeutic use* ; Triazoles/therapeutic use* ; Quality of Life ; Recurrence

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Objective To observe the clinical efficacy of acupuncture combined with western medicine in the treatment of rheumatoid arthritis(RA)complicated with mild anemia under the guidance of"Dongyuan acupuncture".Methods A total of 80 cases of patients definitively diagnosed as RA complicated with mild anemia of deficiency of qi and blood were selected and randomly divided into the observation group and the control group according to the random number table method,those who were admitted to the wards and outpatient clinics of the Department.of Rheumatology,Chongqing Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine from February 2024 to September 2024,with 40 cases in each group.The control group was given conventional treatment with western medicines,while the observation group was additionally treated with acupuncture under the guidance of"Dongguan acupuncture".The course of treatment covered four consecutive weeks.After one month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in traditional Chinese medicine(TCM)syndrome scores and Visual Analogue Scale(VAS)of pain scores,as well as Disease Activity Scores(DAS-28)before and after treatment were observed in the two groups.The changes of rheumatoid factor(RF),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),red blood cell count(RBC),and hemoglobin(Hb)levels before and after treatment were compared between the two groups.The safety and incidence of adverse reactions in the two groups were also evaluated.Results(1)After treatment,the TCM syndrome scores of the patients in the observation group were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(2)After treatment,the VAS scores and DAS-28 scores of the patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the RF,CRP,and ESR levels of patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05);after treatment,there was a significant improvement in the RBC level of the observation group(P＜0.05),but the difference was not statistically significant when compared with the control group(P＞0.05);after treatment,the Hb level of patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(4)The total effective rate was 95.00％(38/40)in the observation group and 87.50％(35/40)in the control group,and the efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P＜0.05).(5)The incidence of adverse reactions was 7.50％(3/40)in the observation group and 27.50％(11/40)in the control group,the incidence of adverse reactions in the observation group was significantly lower than that in the control group,the difference being statistically significant(P＜0.05).Conclusion Under the guidance of"Dongyuan acupuncture",the application of acupuncture combined with western medicine in the treatment of RA complicated with mild anemia can not only realize the complementarity of acupuncture and medicine,improve the clinical efficacy,reduce the level of inflammatory factors,and significantly alleviate the joint symptoms of the patients,but also increase the level of blood cells,improve the anemia condition of the patients and have fewer adverse reactions,thus enhancing their quality of life.

Objective To evaluate the clinical efficacy of Shengqing Jiangzhuo(lifting lucid yang and lowering turbid yin)Acupuncture Method,based on the"turbidity-clearness interaction"theory,combined with western medicine in treating gouty nephropathy(GN)patients with damp-heat accumulation syndrome.Methods A total of 117 patients diagnosed with GN from September 2023 to September 2024 at the First Affiliated Hospital of Guangzhou University of Chinese Medicine Chongqing Hospital were enrolled and randomly divided into three groups,with 39 cases in each group.The western medicine group received Febuxostat Tablets,the control group was given western medicine+conventional acupuncture,and observation group was given western medicine+Shengqing Jiangzhuo Acupuncture Method.All groups received 4 weeks of treatment.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,visual analogue scale(VAS)of pain scores,and laboratory parameters—including serum uric acid(UA),blood urea nitrogen(BUN),creatinine(Scr),estimated glomerular filtration rate(eGFR),β2-microglobulin(β2-MG),24-hour urinary protein(24h-UTP),cystatin C(CysC)were assessed.The erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)were compared before and after treatment.Results(1)The total effective rate was 71.79%(28/39)in the western medicine group,84.62%(33/39)in the control group,and 92.31%(36/39)in the observation group.The observation group demonstrated statistically significant superiority over the western medicine group(P＜0.05),while showing marginally better efficacy than the control group without statistical significance(P＞0.05).(2)After treatment,all three groups exhibited significant improvements in ESR,CRP,and UA levels(P＜0.05).The observation group significantly outperformed the other two groups in reducing ESR and CRP levels(P＜0.05),and was statistically superior to the western medicine group in lowering UA levels(P＜0.05),though no significant difference was observed versus the control group for UA improvement(P＞0.05).The control group showed significantly greater reductions in ESR,CRP,and UA levels than the western medicine group(P＜0.05).(3)After treatment,Scr,BUN,and eGFR levels were significantly improved in all groups(P＜0.05).The observation group achieved significantly better improvements in Scr and eGFR than the other two groups(P＜0.05).However,no statistical difference existed between the control and western medicine groups for Scr or eGFR enhancement(P＞0.05).No intergroup differences were detected in BUN improvement(P＞0.05).(4)Significant differences emerged in β2-MG and CysC levels among all groups after treatment(P＜0.05).Both observation and control groups demonstrated statistically significant improvements in 24-hour 24h-UTP(P＜0.05),whereas the western medicine group showed no significant change(P＞0.05).The observation group significantly outperformed the other groups in reducing 24h-UTP and β2-MG levels(P＜0.05),and was superior to the western medicine group in lowering CysC(P＜0.05),though no difference versus the control group was observed for CysC reduction(P＞0.05).The control group showed no statistical advantage over the western medicine group in improving 24h-UTP,β 2-MG,or CysC(P＞0.05).(5)After treatment,TCM syndrome scores and VAS scores were significantly improved in all groups(P＜0.05).The observation group achieved significantly greater reductions in TCM syndrome scores and VAS scores than the western medicine group(P＜0.05).The control group showed statistically superior VAS score improvement versus the western medicine group(P＜0.05),but no significant differences emerged in TCM syndrome score improvement compared to either group(P＞0.05).No statistical difference existed between observation and control groups for VAS score reduction(P＞0.05).Conclusion Shengqing Jiangzhuo Acupuncture Method,grounded in the"turbidity-clearness interaction"theory,effectively reduces serum UA,controls inflammation,and preserves renal function in damp-heat accumulation type of GN,demonstrating significant therapeutic benefits.

Objective To observe the clinical effect of Dongjing Tiaoshen Comprehensive Therapy combined with computerized cognitive behavioral therapy for insomnia(CCBT-I)in the treatment of chronic insomnia patients with liver depression and spleen deficiency syndrome.Methods A total of 60 patients with chronic insomnia of liver depression and spleen deficiency type were randomly divided into observation group and control group,30 cases in each group.Both groups of patients were treated with CCBT-I as the basic treatment,the observation group was additionally treated with Dongjing Tiaoshen Comprehensive Therapy,i.e.,mind-regulating acupuncture therapy combined with regular aerobic exercises and Dantian Qigong exercises,and the control group was additionally treated with cranial electrotherapy stimulation.The course of treatment for the two groups covered 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)score,Self-rating Anxiety Scale(SAS)score and Self-rating Depression Scale(SDS)score in the two groups were observed before and after treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 86.67%(26/30),and that of the control group was 70.00%(21/30).The intergroup comparison(tested by rank sum test)showed that the curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the PSQI scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of PSQI scores in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the SAS and SDS scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of SAS and SDS scores in the observation group tended to be superior to that in the control group,but there was no significant difference between the two groups(P＞0.05).Conclusion For the treatment of chronic insomnia of liver depression and spleen deficiency type,the combination of Dongjing Tiaoshen Comprehensive Therapy with CCBT-I can significantly improve the sleep quality,relieve anxiety and depression,and improve the quality of life of the patients,which exerts significant efficacy.

Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.