BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.

Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

The healing process of skin wounds caused by severe mechanical trauma and chronic diseases(e.g.,diabetic foot ulcers)is often accompanied by tissue injury,microbial infection,intense inflammatory reactions,hypertrophic scars,and other complications.Microneedles have been widely used to facilitate wound healing in recent years.According to their different modes of action,microneedle formulation can be categorized into five types:solid microneedles,hollow microneedles,coated microneedles,soluble microneedles,and hydrogel microneedles.This paper reviews the preparation methods and characteristics of microneedles,and summarizes their roles in hemostasis,bacteriostasis,anti-inflammation,enhancement of collagen deposition,and angiogenesis,in the hope of providing some reference for future research and development.

This paper outlines the common aspects of constructing integrated urban medical groups,focusing on governance,organizational restructuring,operational modes,and mechanism synergy.It then delves into the challenges in China's group construction,highlighting issues with power-responsibility alignment,capacity evolution,incentive alignment,and performance evaluation.Finally,the paper suggests strategies to enhance China's compact urban medical groups,focusing on governance reform,capacity building,benefit integration,and performance evaluation.

Objective:To analyze the connotation and realization path of high-quality development of primary health care under the new development pattern,and expects to give full play to the advantages of primary health in the construction of a high-quality,efficient and integrated medical and health service system.Methods:Based on the Donabedian structure-process-outcome three-dimensional quality theory,the core connotation and realization path of high-quality development of primary health care were analyzed.Results:The connotation of high-quality development of primary health care includes three aspects:integrated and collaborative resource structure,innovative connotative service process,and high-quality and efficient outcome output.Through system innovation and development,innovative supply-side structural reform,we will promote the implementation of the main responsibility of health on both the supply and demand sides,and establish an evaluation mechanism guided by health outcome assessment,so as to help grassroots health care achieve high-quality development.Conclusions:The high-quality development of primary health care requires the coordination and linkage between multiple elements,focusing on the coordination and balance between supply and demand,focusing on health goals,innovating service models,extending service provision,realizing the transformation of primary health care from treatment service to health management,and promoting the formation of a virtuous circle of survival and development of primary health care.

Objective:To analyze the key points and shortcomings of Traditional Chinese Medicine(TCM)science and technology innovation policy in China,and to provide reference for the subsequent policy optimization.Methods:Searching for TCM science and technology innovation policy texts released at the national level since 2007,and use the two-dimensional analysis framework for quantitative analysis.Results:Among 27 policies,In the X dimension,supply-based,environmental and demand-based policy tools respectively accounted for 48.98%,39.29%and 11.73%.In the Y dimension,the proportion of scientific and technological innovation and achievement transformation was the highest(29.03%);Promoting the development of integrated Chinese and Western medicine was the least used(1.08%).Conclusion:There is a structural imbalance in the application of policy tools,the distribution difference of policy objectives is significant,and the internal policy tools'usage is imbalanced regarding policy objectives.Suggestions:Optimize the internal structure of policy tools.Meanwhile,enhance the structure of policy objectives,and facilitate the dynamic integration and application of policy tools to achieve the policy objectives of scientific and technological innovation in TCM.

This study delineated the conceptual framework of Diagnostic and Treatment Difficulty(DTD)for disease categories for the first time and calculated the coefficient by utilizing disease occurrence probability,average total cost,and cure/improvement rate.The study employed the 2017 data from the New Rural Cooperative Medical Insurance in seven counties or districts to assess the DTD coefficient of inpatient disease categories.It also generated a distribution chart and fitted curve illustrating the relationship between the number of cases and DTD coefficient,in line with disease occurrence patterns.A paired sample Wilcoxon rank-sum test was performed on the DTD coefficient of the same disease categories calculated for two sample counties,yielding non-significant results(p =0.73).This suggests that the algorithm is robust and effectively portrays the occurrence and distribution patterns of disease categories.The measurement results can be utilized to define the scope of disease categories in healthcare institutions and characterize healthcare service supply and demand behavior.However,it's worth noting potential limitations,including a reliance on sample size and subjectivity in weight determination.

Objective:To clarify the spatio-temporal characteristics and changing trends of provincial health resources and medical pressure,and to provide suggestions for the high-quality development of medical and health services in China.Methods:Based on the panel data of 31 provincial administrative units from 2010 to 2020,a comprehensive evaluation system of provincial health resources and medical pressure was constructed.The global entropy method and exploratory spatial analysis were used to reveal the spatio-temporal differentiation and correlation pattern,and the Tapio decoupling index was illustrated to explain the evolution characteristics and trends.Results:During the observation period,health resources and medical pressure in the vast majority of provinces in China rose steadily,with positive spatial correlation and agglomeration,and a close relationship with economic development and population demand;the mainstream decoupling state of the country shifted from a negative decoupling to a positive decoupling,with an obvious progressive decoupling trend,and the development of regional health continued to improve.Conclusions and suggestions:Provinces need to take into account the status quo of health development in their own provinces,focus on the spatio-temporal coupling of elements and structures,and optimize the structure of health resource allocation and enhance the resilience of the health system as a means of bringing into play the comparative advantages of the regional health system.

Objective:To develop an evaluation index system on health education effect for adolescents with type 1 diabetes mellitus (T1DM).Methods:Using "knowledge-attitude/belief-practice"model and health belief model as the theoretical framework, the first draft of the expert consulation questionnaire for evaluation index system on health education effect for adolescents with type 1 diabetes mellitus was drawn up through literature review, qualitative interview, and repeated discussions between groups. Two rounds of expert consultation were conducted. The results of the consulation were sorted and analyzed, the index structure, item content, and sequence were discussed repeatedly, and the evaluation index system on health education effect for adolescents with T1DM was determined, and the analytic hierarchy process was used to determine its weight.Results:A total of 21 female experts participated in two rounds of survey whose age was (43.48 ± 5.84) years old. The questionnaire response rates of the two rounds of expert consultations were 84.00%(21/25) and 85.71%(18/21), the authoritative coefficients were 0.96 and 0.97, the Kendall coordination were 0.181 and 0.256, respectively ( P<0.05). The consistency test of the weight of each indicator showed that the consistency ratios were all <0.1. The evaluation index system on health education effect for adolescents with T1DM was constructed with 5 first-level indicators (health knowledge, health belief, health practice, physiological indexes and health education satisfaction), 38 second-level indicators. Conclusions:The method used to construct the evaluation index system on health education effect for adolescents with T1DM was highly scientific and reliable, which provides the basis for clinical nurses to evaluate and monitor the effect of health education in adolescents with T1DM.