Parkinson's disease （PD） is a common neurodegenerative disorder characterized by motor impairments， with its pathological mechanisms involving multiple processes such as the degeneration of dopaminergic neurons and the abnormal aggregation of α-synuclein. Current Western medical treatments face challenges including diminished long-term efficacy and motor complications. In recent years， Traditional Chinese Medicine （TCM） has demonstrated advantages in the prevention and treatment of PD through its systematic regulatory capabilities， featuring multi-component， multi-target， and multi-pathway approaches.This article systematically reviews the roles of seven key signaling pathways-NF-κB， AMPK/mTOR， PI3K/Akt， MAPKs， Nrf2/ARE， Wnt/β-catenin， and BDNF/TrkB-in the pathological process of PD and the regulatory mechanisms of TCM. Research indicates that active ingredients of Chinese herbs and compound formulations can synergistically modulate these pathways， exerting comprehensive effects in inhibiting neuroinflammation， alleviating oxidative stress， promoting autophagy to clear abnormal proteins， and enhancing neurotrophic support. These signaling pathways form a complex regulatory network through crosstalk among key nodal molecules， constituting an intricate regulatory system in PD pathology. The multi-target intervention characteristics of TCM align well with this network-based regulatory requirement， achieving integrated anti-inflammatory， antioxidant， autophagy-regulating， and neurorestorative effects through synergistic multi-pathway modulation. This article systematically outlines the mechanisms of TCM in the coordinated regulation of multiple pathways， providing a theoretical basis for elucidating the pathological process of PD and the intervention mechanisms of TCM， while also offering new perspectives and directions for modern research on TCM in the prevention and treatment of PD.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

With the ongoing reform of medical insurance policies and the growing prevalence of private hospitals,domes-tic public hospitals must explore a suitable development path tailored to their operational and management requirements.Aligning with the principles of high-quality development,this study identifies shortcomings in public hospital operation and management across five key areas:management systems,budget and cost management,business process management,performance manage-ment,and information system construction.Targeted solutions are proposed to facilitate the high-quality development of public hospitals.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Objective To investigate the transgenerational effects of paternal PM2.5 exposure on offspring growth and development,and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.Methods Eight-week-old male C57BL/6 mice were randomly divided into filtered air(FA),unfiltered air(UA),and concentrated PM2.5(CAP)groups,with 10 animals in each group.The exposure was conducted from November 2019 to April 2020,and then,these male mice were mated with unexposed females to generate F1 offspring,which were bred successively to produce F2 and F3 generations.All the offspring were living in PM2.5-free environment.The birth body weight,birth number,and sex ratio of the offspring were recorded,body weight growth was monitored,and organ coefficients of the heart,liver,lung,and brain were calculated.Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group,FA group,and their F1 generation offspring to screen for differentially methylated regions,and the genes and pathways associated with these regions were analyzed.Results When compared with the F1～F3 offspring of the FA group,the CAP group had significantly reduced birth body weight in the F1 generation(P<0.05),no statistical differences were observed in the birth body weight in the F2 and F3 generations(P>0.05),or either in the sex ratio and birth number among the F1,F2 and F3 generations.Compared with the FA group offspring,the F1～F3 offspring of CAP group exhibited delayed body weight gain,especially in the males(P<0.05),the CAP-F1 male generation had obviously elevated liver organ coefficient(P<0.01),but no statistical changes were observed in the heart,lung,or brain coefficients among the F1～F3 generations.Between the FA group and the CAP group,37 997 differentially methylated regions were detected,with a reduction of approximately 50%in the number of differentially methylated regions in the F1 generation.Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes,including imprinting genes(Gnas,Igf2)and metabolic genes(Ppard,Rps6kb1).Conclusion Paternal exposure to PM2.5 leads to reduced birth weight and intergenerational growth retardation in offspring.Its impact on phenotypic effects is gradually weakened during intergenerational transmission.Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

Objective:To build an internet hospital cost-benefit evaluation index system based on a large public tertiary hospital, for references for improving the operation and management of internet hospitals.Methods:From May to October 2024, this study identified the elements of cost-benefit through on-site investigation, literature analysis and expert discussion, and built an initial evaluation index system of cost-benefit of internet hospitals; Delphi method and Pareto chart method were used to determine indicators and their weights; This evaluation index system was used to quantitatively evaluate an internet hospital since its operation for two years (from May 2022 to April 2024).Results:Five profit entities and 26 cost-benefit components had been identified; The expert authority coefficient of the two rounds of Delphi method was 0.73, and the Kendall coefficient was 0.80 ( P<0.001). The costs and benefits of an internet hospital since its operation for two years were 14.06 million yuan and 134.95 million yuan, respectively, with a benefit cost ratio of 9.60. Conclusions:The cost-benefit evaluation index system of internet hospitals built in this study was suitable for these relying on physical hospitals. This system was scientific and practical, and could provide references for cost-benefit evaluation of other Internet hospitals.

With the ongoing reform of medical insurance policies and the growing prevalence of private hospitals,domes-tic public hospitals must explore a suitable development path tailored to their operational and management requirements.Aligning with the principles of high-quality development,this study identifies shortcomings in public hospital operation and management across five key areas:management systems,budget and cost management,business process management,performance manage-ment,and information system construction.Targeted solutions are proposed to facilitate the high-quality development of public hospitals.

Objective:To build an internet hospital cost-benefit evaluation index system based on a large public tertiary hospital, for references for improving the operation and management of internet hospitals.Methods:From May to October 2024, this study identified the elements of cost-benefit through on-site investigation, literature analysis and expert discussion, and built an initial evaluation index system of cost-benefit of internet hospitals; Delphi method and Pareto chart method were used to determine indicators and their weights; This evaluation index system was used to quantitatively evaluate an internet hospital since its operation for two years (from May 2022 to April 2024).Results:Five profit entities and 26 cost-benefit components had been identified; The expert authority coefficient of the two rounds of Delphi method was 0.73, and the Kendall coefficient was 0.80 ( P<0.001). The costs and benefits of an internet hospital since its operation for two years were 14.06 million yuan and 134.95 million yuan, respectively, with a benefit cost ratio of 9.60. Conclusions:The cost-benefit evaluation index system of internet hospitals built in this study was suitable for these relying on physical hospitals. This system was scientific and practical, and could provide references for cost-benefit evaluation of other Internet hospitals.

Objective To evaluate the stability and aesthetic effect of a xenogeneic collagen matrix(mucograft)on achieving an adequate keratinized mucosa width(KMW)around implants and to provide a reference basis for the clini-cal application of xenogeneic collagen matrix materials.Methods The hospital ethics committee approved the study protocol,and the patients provided informed consent.Twenty patients with a KMW＜2 mm at the buccal implant site who were treated in Binzhou Medical University Affiliated Yantai Stomatological Hospital from July 2020 to September 2022 were included,and a total of 36 implants were included.The mean age of the patients was(52.0±10.4)years,of which 18 were females and 2 were males.They were divided into a free gingival graft group(FGG,control group)and a xenogeneic collagen matrix group(test group)according to different graft materials.The incremental effect of the KMW on the buccal side of the implant and the mucosal shrinkage rate was measured at 1 month and 3 months after the opera-tion.The mucosal scar index(MSI)was evaluated after the operation.Results At 3 months postoperatively,the KMW was(3.67±1.06)mm in the control group and(2.96±0.98)mm in the test group,and the difference was statistically significant(t=2.076,P＜0.05).The KMW shrinkage rate was(33.34±16.30)％in the test group and(22.05± 15.47)％in the control group at 1 month postoperatively and(51.95±12.60)％in the test group and(37.44±16.30)％in the control group at 3 months postoperatively,with statistically significant differences between the two groups at the same time points(P＜0.05).Three months after surgery,the test group showed significantly better outcomes than the control group in terms of the five scar indicators(scar width,scar convexity,scar color,scar trace,and overall appear-ance),and the difference was statistically significant(P＜0.05).Conclusion Xenogeneic collagen matrix can increase the peri-implant KMW and achieve a more natural and coordinated soft tissue aesthetic effect but with a higher shrink-age rate.

Objective The progressive loading process of implants was simulated,and the influence of progressive loading method on peri-implant bone reconstruction was evaluated.Methods Using finite element analysis combined with the ANSYS parametric design language(APDL),the average bone density of the peri-implant regions was observed using conventional loading(control group)and progressive loading(experimental group)within six months of implant placement.The stress distributions of bone tissues in a 1 mm3 region of interest(ROI)around the implant and variations in bone density were observed.Results Within six months after implantation,the cortical bone density of the control group decreased by 0.19 g/cm3,whereas that of the experimental group decreased by 0.15 g/cm3.The trabecular bone density of each area in the experimental group increased by 0.4 g/cm3 compared with that in the control group.The bone density in the experimental group was lower than that in the control group.The increase in cancellous bone in the experimental group was higher than that in the control group.The finite element analysis revealed that the equivalent stress distribution range and maximum value of the experimental group(8.9 MPa)were significantly higher than those of the control group(6.68 MPa).Conclusions The use of the progressive loading method within six months after implantation was conducive to the distribution of stress on the bone tissues around the implant.This reduced the variation in bone density at the edge of the implant.The peri-implant bone density increased more under progressive loading than under conventional loading.The effect is superior to that of the conventional loading method.