ObjectiveTo explore the possible mechanism of action of Bushen Huoxue Granules （补肾活血颗粒， BHG） in the treatment of Parkinson's disease （PD） through the Nrf2/NLRP3 inflammasome axis. MethodsA total of 84 male C57/BL 6 mice were randomly divided into blank group， model group， Madopar group， dimethyl fumarate group， and low-， medium， and high-dose BHG group， with 12 mice in each group. Except for the blank group， all groups were induced into PD models by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 30 mg/ml for 7 consecutive days. The blank group received an equal volume of saline. After model establishment， the low-， medium， and high-dose BHG groups were treated with 1.5， 3， and 6 g/（kg·d） of the BHG by gavage， respectively. The Madopar group was given 0.113 g/（kg·d） of Madopar tablets by gavage， and the dimethyl fumarate group was given 50 mg/（kg·d） of dimethyl fumarate solution. The blank group and the model group were given 10 ml/（kg·d） of distilled water by gavage. Gavage was administered once daily for 14 days. Behavioral changes were evaluated using the open field test （total distance， central area distance， and average speed）， rotarod test （time on the rod）， and climbing pole test （climbing time）. Serum levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and myeloperoxidase （MPO） were measured by ELISA. Immunohistochemistry was used to detect tyrosine hydroxylase （TH） expression in the brain substantia nigra. Immunofluorescence was used to detect α-synuclein （α-syn） expression. Western Blot was used to detect Nrf2， NLRP3， Caspase-1， and α-syn protein levels in the brain substantia nigra. RT-PCR was used to detect mRNA expression levels of Nrf2， NLRP3， and Caspase-1 in the brain substantia nigra. ResultsCompared with the blank group， the model group showed decreased total distance， central area distance， and average speed， reduced time on the rotarod， prolonged climbing time， reduced TH expression， increased α-syn expression， decreased Nrf2 protein and mRNA expression， increased NLRP3 and Caspase-1 protein and mRNA expression， and elevated serum IL-1β， IL-18， and MPO levels （P＜0.05）. Compared with the model group， all drug interventions significantly improved the above indicators （P＜0.05）. There was no significant differences in all indicators between the high-dose BHG group and the Madopar group （P＞0.05）. Compared with the dimethyl fumarate group， the medium and high-dose BHG groups showed increased Nrf2 mRNA expression in the brain substantia nigra （P＜0.05）. Compared with the high-dose BHG group， the low-dose group showed decreased total distance， central area distance， and average speed， reduced serum IL-18 levels， decreased α-syn， Nrf2， NLRP3， and Caspase-1 protein levels， and lower Nrf2 mRNA expression （P＜0.05）. ConclusionThe mechanism by which BHG treat PD may involve activating the Nrf2/NLRP3 inflammasome axis in the brain substantia nigra， thereby reducing neuroinflammation and α-syn aggregation. The high-dose group showed the best effects.

Objective : To explore the changes of periodontal soft and hard tissue parameters of the maxillary central incisors after the distant migration of the maxillary total dentition in adult patients with different periodontal phenotypes, so as to provide a reference for orthodontic treatment. Methods: The study was approved by the hospital ethics committee, and the patients signed the informed consent form. Fifty-two adult patients in the orthodontic department of Hefei Stomatological Hospital were selected and divided into thick gingival and thin gingival groups, with 26 cases in each group. The labial and palatal alveolar bone parameters and various periodontal indexes of the maxillary central incisor teeth of the two groups were collected and recorded before and after treatment. SPSS 26.0 statistical software was used to statistically analyze the intra-group and inter-group differences. Results: After orthodontic treatment, the differences in sella-nasion-subspinale angle (SNA), sella-nasion-supramental angle (SNB), and subspinale-nasion-supramental angle (ANB) were not statistically significant (P > 0.05). However, the inclination of the upper middle incisor teeth (U1-NA) decreased significantly (P < 0.05), and there was no significant difference in SNA, SNB, ANB, and U1-NA between the two groups after treatment (P > 0.05). The thickness of the labial alveolar bone of the maxillary central incisors in both groups increased at the labial neck 1/3 and labial middle 1/3 (P < 0.05), and decreased at the apical 1/3 (P < 0.05). The thickness of the palatal alveolar bone decreased at the labial neck 1/3 and labial middle 1/3 (P < 0.01), and increased at the apical 1/3 (P < 0.01). In both groups, the height of the lip and palate of the upper jaw decreased to different degrees, and the height of the palatal alveolar bone was lower in the thin gingival group (P < 0.05). There were no significant differences in maxillary central incisor probing depth (PD), lip keratinized tissue width (KTW), or lip gingival recession (GR) between the two groups after treatment (P > 0.05). Conclusion In the process of maxillary central incisor adduction, the labial-palatine alveolar bone remodeling is not uniform, and the alveolar bone of palatine side is mainly absorbed, which should be paid attention to clinically. Palatal alveolar bone height decreased more significantly in patients with thin gingiva after orthodontic treatment, and the risk of bone fenestration and bone dehiscence was greater.

ObjectiveTo systematically analyze the global policy framework, standard systems and application technology models of digital rehabilitation within the framework of the World Health Organization (WHO) Global Digital Health Strategy and propose policy recommendations for the future development of digital rehabilitation. MethodsBased on the policies on digital health and rehabilitation development issued by the WHO, focusing on the Global Digital Health Strategy, Rehabilitation 2030 Initiative, Rehabilitation in Health Systems, Rehabilitation in Health Systems: A Guide for Action, and World Report on Disability, a systematic review was conducted, to explore the policy architecture and core content of digital rehabilitation, the standard system for digitalizing rehabilitation, and key technological models for the development of digital rehabilitation. ResultsIn the context of global health and digital transformation, the development of digital rehabilitation services was an essential component of the global digital health strategy. Building a comprehensive policy framework and content system for digital rehabilitation was critical for strengthening rehabilitation data governance, enhancing data utilization efficiency, and ensuring data privacy and security. Empowering rehabilitation with digital technology was vital for improving the standardization, effectiveness, coverage, quality and safety of rehabilitation services. International digital rehabilitation policies primarily involved the following areas: policy and governance, digital standard systems, data privacy, security and ethics, digital talent cultivation and capacity building, and monitoring, evaluation and continuous improvement of digitally empowered rehabilitation services. The standard system for rehabilitation digitization covered the three major reference classifications of the WHO Family of International Classifications, including International Classification of Diseases Eleventh Revision (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI), especially ICF. It also included international data interoperability standards, data security and privacy protection standards, data quality and certification standards, and health information standards, etc. The application technology models of digital rehabilitation primarily included data-driven service models, artificial intelligence -enabled models, and remote rehabilitation models combined with virtual reality, augmented reality technologies, and Internet of Things support. ConclusionThe establishment and implementation of comprehensive policies, standards and technological models for digital rehabilitation are crucial for driving the digital transformation and development of global rehabilitation services. Under the framework of the WHO Global Digital Health Strategy, it is necessary to build adaptive digital rehabilitation policy frameworks, and enhance digital governance capabilities and levels, establishing and improving digital rehabilitation standard systems, and promoting the interoperability and integration of rehabilitation data with other health big data. Meanwhile, it is essential to actively develop data-driven technological models for rehabilitation services to comprehensively improve the accessibility, availability, quality and safety of rehabilitation services.

OBJECTIVE To study the effects of Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells. METHODS The rats were given Sanchong tongluo sanjie formula powder [0.946 g/（kg·d）]， Sanchong tongluo sanjie formula decoction [2.730 g/（kg·d）]， and normal saline intragastrically， and injected with Cisplatin injection （4.2 mg/kg） intra-peritoneally to prepare powder-containing serum， decoction-containing serum， positive control serum and negative control serum. Lewis lung cancer cells were divided into negative control serum group， positive control serum group， and 5%， 10%， 20% drug-containing serum groups. The cell proliferation inhibition rates at 24， 48， and 72 hours post- intervention were measured to screen the optimal intervention concentrations of powder-containing serum and decoction-containing serum. The cell invasion ability， metastasis ability and apoptotic rate were detected in the negative control serum group， positive control serum group， 20% powder-containing serum group， and 20% decoction-containing serum group. Protein expressions of vascular endothelial growth factor （VEGF）， hypoxia-inducible factor-1α （HIF-1α）， prolyl hydroxylase-2 （PHD2）， matrix metalloproteinase-2 （MMP-2）， extracellular regulated protein kinases （ERK），c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK） were detected. RESULTS The cell proliferation inhibition rates for both the 20% powder-containing serum group and the 20% decoction-containing serum group， when intervened for 48 hours， were not less than 50%. Compared with negative control serum group， the number of invasive Lewis lung cancer cells and migration distance were decreased significantly， while the apoptotic rate was increased significantly （P＜0.05）； the apoptotic rate in the 20% powder- containing serum group was significantly higher than 20% decoction-containing serum group （P＜0.05）. The protein expressions of PHD2 and p38 MAPK were increased significantly in the 20% powder-containing serum group （P＜0.05）， while the protein expression of HIF-1α was decreased significantly in the 20% decoction-containing serum group （P＜0.05）. CONCLUSIONS Sanchong tongluo sanjie formula can inhibit the proliferation， invasion and metastasis of Lewis lung cancer cells while promoting their apoptosis. The mechanism of action may be related to regulating the PHD2/HIF-1α signaling pathway. Furthermore， the powder demonstrates superior efficacy compared to the decoction， suggesting that they may possess different mechanisms of action.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Over the past three decades， China has made significant progress in the prevention and control of viral hepatitis， and the incidence rates of new-onset pediatric hepatitis B virus infections and acute viral hepatitis in the population have reduced to a relatively low level； however， there is still a heavy disease burden of chronic viral hepatitis in China， which severely affects the health status of the population. This study systematically summarizes the achievements of viral hepatitis prevention and control in China， analyzes existing problems and challenges， and proposes comprehensive prevention and control strategies and measures to eliminate viral hepatitis as a public health threat based on the national conditions of China， in order to provide a reference for related departments in China on how to achieve the action targets for eliminating viral hepatitis as a public health threat by 2030.

ObjectiveTo evaluate the safety/efficacy of compound Kushen injection （CKI） by zebrafish model and explore the possible mechanism. MethodsZebrafish were exposed to different concentrations of CKI solution， and the mortality rate after 24 h was calculated. After exposure to sublethal concentration （10） and safe dose concentration （0） for 24 h， the safety of CKI was evaluated based on acridine orange staining for the liver， liver area changes， and liver histological sections. The inflammatory bowel disease （IBD） model of zebrafish was established with 2，4，6-trinitrobenzenesulfonic acid sol （TNBS）. The efficacy of CKI in the treatment of IBD was evaluated by the changes in the area of neutral red staining， the number of neutrophils， the area of alcian blue staining， and the contents of tight junction protein （Occludin）， zonula occludens-1 （ZO-1）， tumor necrosis factor（TNF）-α， and prostaglandin E₂（PGE₂） in the intestine of zebrafish. The mechanism of CKI in the treatment of IBD was predicted by network pharmacology and verified by real-time polymerase chain reaction（Real-time PCR）. ResultsIn the safety evaluation， compared with the blank group， the sublethal concentration of CKI could cause liver cell apoptosis， liver area reduction， loose and disordered arrangement of liver cell structure， obvious vacuolation， and other pathological characteristics of zebrafish， while these indicators showed no significant changes under safe dose conditions. In the effectiveness evaluation， compared with the model group， the safe dose of CKI could increase the neutral red staining area of the intestine in a dose-dependent manner and improve the intestinal phagocytosis function. It could reduce the accumulation of intestinal neutrophils， increase the alcian blue staining area， enhance intestinal goblet cell secretion， improve the contents of Occludin and ZO-1， and decrease the contents of TNF-α and PGE₂. Network pharmacology analysis identified 288 potential targets for CKI treatment of IBD. The top five targets obtained by protein-protein interaction （PPI） network analysis were epidermal growth factor receptor A（EGFRA）， protein kinase B1（Akt1）， heat shock protein 90（HSP90AA1）， homologous oncogene of avian sarcoma virus（SRC）， and protooncogene （JUN）. Kyoto encyclopedia of genes and genomes（KEGG） results showed that CKI may be related to the Wnt signaling pathway and cholinergic synaptic pathway in the treatment of IBD， and Real-time PCR results verified the above pathways. ConclusionExcessive use of CKI can induce obvious liver injury in zebrafish， while the rational use of CKI does not cause obvious toxic reactions and can achieve a therapeutic effect on IBD by regulating the Wnt pathway.

[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.