In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans ; Glioma/psychology* ; Palliative Care/methods* ; Quality of Life ; Psychometrics ; Brain Neoplasms/psychology*

OBJECTIVES: To evaluate the photothermal and antibacterial activities of polydopamine-modified phycocyanin nanoparticles (PDA@PC NPs) and their capacity for promoting wound healing. METHODS: PDA@PC NPs were synthesized from phycocyanin (C-PC) and dopamine hydrochloride using a one-pot method. The photothermal activity of the nanoparticles was assessed in vitro by 808 nm laser irradiation, their biocompatibility was evaluated using CCK-8 assay, and their photothermal antibacterial activity by plate colony counting. In adult male BALB/c mice, two symmetrical full-thickness skin wounds (1.0 cm ×1.0 cm) were created on both sides of the spine, and 200 μL of Staphylococcus aureus suspension was inoculated into the wounds. The mice were divided into control group, PDA@PC NPs group, and PDA@PC NPs with laser irradiation group, and wound healing rates and histomorphological changes in the wound tissues were evaluated on days 0, 7 and 14 after modeling. RESULTS: The synthesized PDA@PC NPs exhibited no obvious cytotoxicity up to a concentration of 500 μg/mL and showed strong photothermal and antibacterial activities in response to 808 nm laser irradiation. In the mouse models, the size of the infected skin wounds showed substantial reduction at 7 and 14 days in PDA@PC NPs group and PDA@PC NPs with laser irradiation group, and the mean wound healing rate was faster in the latter group. HE staining and Masson's trichrome staining revealed extensive granulation tissue formation and collagen deposition on the wound surfaces in both of the treatment groups, and these changes were more obvious in the PDA@PC NPs with laser irradiation group. CONCLUSIONS PDA@PC NPs possess excellent photothermal and antibacterial activities and can effectively promote wound healing in mice.
Animals ; Indoles/chemistry* ; Wound Healing/drug effects* ; Mice ; Mice, Inbred BALB C ; Male ; Nanoparticles ; Polymers/chemistry* ; Phycocyanin/chemistry* ; Skin/injuries* ; Staphylococcus aureus/drug effects* ; Anti-Bacterial Agents/pharmacology*

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Background Shoemaking industry workers are prone to work-related musculoskeletal disorders (WMSDs) due to long-term awkward postures during the work process. There is little research on the prevalence and influencing factors of WMSDs in the knee region of this industry, and it should be taken seriously. Objective To estimate the prevalence of work-related knee pain among shoemaking workers and analyze the related influencing factors. Methods A total of 6982 shoemaking workers were selected from 26 shoemaking factories in Guangdong, Hubei, Fujian, Chongqing, Shandong, Zhejiang, and Jingxi by convenience sampling. Prevalence of work-related knee pain in past year, demographic characteristics, occupational related factors, and work posture were collected by a cross-sectional survey using the electronic version of Musculoskeletal Disorder Questionnaire. Logistic regression analysis was used to analyze the influencing factors that may lead to work-related knee pain. Results This survey collected 6982 valid questionnaires with a recovery rate of 98.3%. The prevalence of work-related knee pain of shoemaking workers in the past 12 months was 13.0% (908/6982). According to the results of logistic regression analysis, compared with workers with less than 5 years of service, workers with 5-10 years of service (OR=1.21, 95%CI: 1.02, 1.45) and more than 10 years (1.53, 95%CI: 1.27, 1.83) showed a higher risk of knee WMSDs; sometimes, often and very frequent (reference : rarely or never) long-term standing (OR=1.33, 95%CI: 1.08, 1.64; OR=2.67, 95%CI: 2.10, 3.39; OR=2.75, 95%CI: 2.08, 3.63) and sometimes, often and very frequent (reference: rarely or never) long-term squatting or kneeling (OR=1.80, 95%CI: 1.47, 2.21; OR=2.43, 95%CI: 1.58, 3.75; OR=3.22, 95%CI: 1.66, 6.24) increased the risk of knee pain: long-term bending (OR=1.59, 95%CI: 1.34, 1.89) and often repeated movement of lower limbs and ankles (OR=1.48, 95%CI: 1.25, 1.75) were also risk factors for knee WMSDs among shoemaking industry workers (P<0.05). Adequate rest time (OR=0.58, 95%CI: 0.49, 0.68) and able to stretch or change leg posture (OR=0.75, 95%CI: 0.64, 0.88) reduced the risk of knee WMSDs (P<0.05). Conclusion In the shoemaking industry, length of service and awkward postures are risk factors for knee pain. The shoemaking enterprises should ensure that workers have sufficient rest time, reduce long-term standing, squatting, kneeling, and bending postures, as well as lower limbs repetition in order to reduce the occurrence of knee WMSDs of workers.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective To predict and verify the mechanism of Naoan capsules(NAC)in treatment of ischemic stroke(IS)by network pharmacology,Gene Expression Omnibus(GEO)database,and molecular docking technology.Methods The active components in NAC were collected using the Traditional Chinese Medicine System Pharmacological Analysis Platform,and the disease-related differential genes were screened using GEO database.After screening and obtaining the common targets of the two,the compound disease network was constructed by Cytoscape 3.8.2 software.At the same time,protein-protein interaction networks were created to identify candidate targets for NAC treatment of IS,and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed.Finally,core targets were verified by molecular docking technology.Results A total of 56 candidate compounds and 18 544 disease-related differential genes were screened.Further,quercetin,kaempferol,luteolin and baicalein were found to be the key active compounds of NAC in the treatment of IS through the compound disease network.In the search of PPI network core,eight key targets for NAC treatment of IS were screened,including mitogen-activated protein kinase 1(MAPK1),B-cell lymphoma factor 2(Bcl-2),cysteinylaspartate specific protease 3(CASP3),etc.In addition,the key pathways of NAC treatment of IS are mainly concentrated in lipid and atherosclerosis,advanced glycation end products and receptor for advanced glycation end products(AGE-RAGE),tumor necrosis factor(TNF),interleukin17(IL-17),C-type lectin receptor,apoptosis,hypoxia-inducing factor-1(HIF-1),MAPK and other signaling pathways.Finally,the molecular docking results showed that the key active compounds(quercetin,kaempferol,luteolin and baicalein)had good binding force with the 8 key targets,which initially verified the results of network pharmacology.Conclusion NAC plays a role in the treatment of IS through multi-component,multi-target and multi-pathway.

Objective To investigate the effects of palmatine on migration,invasion and epithelial mesenchymal transformation(EMT)in human oral cancer KB cells.Methods KB cells were divided into control group and palmatine-L,-M,-H groups,cultured with 0,4,8 and 16 μmol·L-1 palmatine.After incubation for 48 h,scratch assay was used to detect migration;Traswell assay was used to detect invasion;matrix metalloproteinase 2(MMP-2),MMP-9 and fibronectin(FN)contents were detected by enzyme-linked immunosorbent assay;the expression of Vimentin,N-cadherin and E-cadherin mRNA were detected by real-time quantitative polymerase chain reaction;the expression of Vimentin,N-cadherin,E-cadherin,Wnt3 and β-catenin protein were detected by Western blot.Results Cell mobility in control group and palmatine-L,-M,-H groups were(69.27±8.62)％,(52.94±4.49)％,(45.22±5.05)％and(37.63±4.88)％;the number of transmembrane cells were 197.33±20.26,125.33±12.01,97.00±9.17 and 62.67±7.51;the content of MMP-2 were(2.93±0.21),(1.49±0.13),(1.16±0.15)and(0.95±0.09)ng·mL-1;the content of MMP-9 were(3.51±0.36),(2.37±0.23),(2.06±0.35)and(1.72±0.16)ng·mL-1;the content of FN were(41.28±4.02),(24.03±3.17),(20.67±2.63)and(13.82±2.19)ng·mL-1;the above indexes in palmatine-L,-M,-H groups were compared with the control group,and the differences were statistically significant(P＜0.05,P＜0.01).The mRNA and protein expressions of Vimentin,N-cadherin and E-cadherin,and the expressions of Wnt3 and β-catenin protein in palmatine-L,-M,-H groups were statistically significant compared with those in control group(P＜0.05,P＜0.01).Conclusion Palmatine can inhibit the migration,invasion and EMT of human oral cancer KB cells,and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway.