BACKGROUND:Pure titanium and titanium alloy implants are widely used in the field of implant restoration due to their excellent biocompatibility and elastic modulus.However,the biological inertness of the surface of titanium-based implants leads to poor integration with surrounding bone tissues,and surface modification is required to improve the bone integration ability of titanium-based implants.OBJECTIVE:To fabricate hydroxyapatite/graphene oxide/interleukin-4 composite coatings on pure titanium substrates,and to investigate their physicochemical properties and biocompatibility of the coating materials.METHODS:Hydroxyapatite/graphene oxide/interleukin-4 composite coatings were prepared on pure titanium substrates by electrochemical deposition and freeze-drying.Titanium sheets loaded with interleukin-4 and titanium sheets loaded with hydroxyapatite/graphene oxide coatings were prepared at the same time,and the physicochemical properties of pure titanium sheets and the above three titanium sheets were characterized.MC3T3-E1 cells were inoculated on the surfaces of pure titanium sheets and the above three titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell activity was detected by Calcein-AM/PI staining.Cell morphology and adhesion were observed by scanning electron microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscopy,energy-dispersive X-ray spectroscopy,X-ray photoelectron spectroscopy,X-ray diffraction,and Raman spectroscopy confirmed the successful fabrication of the hydroxyapatite/graphene oxide/interleukin-4 composite coating on the titanium surface.The water contact angle of hydroxyapatite/graphene oxide/interleukin-4 group was larger than that of pure titanium group and hydroxyapatite/graphene oxide group,and smaller than that of interleukin-4 group.(2)CCK-8 assay and DAPI staining results showed that hydroxyapatite/graphene oxide/interleukin-4 coating could promote the proliferation of MC3T3-E1 cells.Calcein-AM/PI staining results showed that MC3T3-E1 cells in hydroxyapatite/graphene oxide/interleukin-4 coating group had higher activity and fewer dead cells.Scanning electron microscopy showed that MC3T3-E1 cells adhered to the surfaces of the four groups of materials with good cell morphology.Compared with the pure titanium group,the MC3T3-E1 cells in the interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger;compared with the hydroxyapatite/graphene oxide group,the MC3T3-E1 cells in the hydroxyapatite/graphene oxide/interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger.(3)These findings indicate that the hydroxyapatite/graphene oxide/interleukin-4 composite coating possesses favorable physicochemical and biological properties.

BACKGROUND:Pure titanium and titanium alloy implants are widely used in the field of implant restoration due to their excellent biocompatibility and elastic modulus.However,the biological inertness of the surface of titanium-based implants leads to poor integration with surrounding bone tissues,and surface modification is required to improve the bone integration ability of titanium-based implants.OBJECTIVE:To fabricate hydroxyapatite/graphene oxide/interleukin-4 composite coatings on pure titanium substrates,and to investigate their physicochemical properties and biocompatibility of the coating materials.METHODS:Hydroxyapatite/graphene oxide/interleukin-4 composite coatings were prepared on pure titanium substrates by electrochemical deposition and freeze-drying.Titanium sheets loaded with interleukin-4 and titanium sheets loaded with hydroxyapatite/graphene oxide coatings were prepared at the same time,and the physicochemical properties of pure titanium sheets and the above three titanium sheets were characterized.MC3T3-E1 cells were inoculated on the surfaces of pure titanium sheets and the above three titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell activity was detected by Calcein-AM/PI staining.Cell morphology and adhesion were observed by scanning electron microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscopy,energy-dispersive X-ray spectroscopy,X-ray photoelectron spectroscopy,X-ray diffraction,and Raman spectroscopy confirmed the successful fabrication of the hydroxyapatite/graphene oxide/interleukin-4 composite coating on the titanium surface.The water contact angle of hydroxyapatite/graphene oxide/interleukin-4 group was larger than that of pure titanium group and hydroxyapatite/graphene oxide group,and smaller than that of interleukin-4 group.(2)CCK-8 assay and DAPI staining results showed that hydroxyapatite/graphene oxide/interleukin-4 coating could promote the proliferation of MC3T3-E1 cells.Calcein-AM/PI staining results showed that MC3T3-E1 cells in hydroxyapatite/graphene oxide/interleukin-4 coating group had higher activity and fewer dead cells.Scanning electron microscopy showed that MC3T3-E1 cells adhered to the surfaces of the four groups of materials with good cell morphology.Compared with the pure titanium group,the MC3T3-E1 cells in the interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger;compared with the hydroxyapatite/graphene oxide group,the MC3T3-E1 cells in the hydroxyapatite/graphene oxide/interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger.(3)These findings indicate that the hydroxyapatite/graphene oxide/interleukin-4 composite coating possesses favorable physicochemical and biological properties.

As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

ObjectiveTo analyze the research status and development trends of non-pharmacological therapies for post-stroke spasticity (PSS) over the past two decades. MethodsRelevant literatures on non-pharmacological rehabilitation of PSS published from January, 2004 to June, 2024 were retrieved from Web of Science Core Collection. CiteSpace 6.3.R6 and VOSviewer 1.6.18 were used for visualization analysis. ResultsA total of 780 publications were included. The annual number of publications showed an overall upward trend. China, the USA, and Italy contributed the highest number of publications. The Hong Kong Polytechnic University and researcher Noureddin Nakhostin Ansari were identified as the most influential institution and author, respectively. High-frequency keywords and cluster labels included electric stimulation, transcranial magnetic stimulation, robot and acupuncture. ConclusionOver the past 20 years, researches on non-pharmacological therapies for PSS have remained active, with hotspots focusing on diverse interventions such as electrical stimulation, magnetic stimulation and robot-assisted therapy.

OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

The promulgation of the Technical Specifications for Clinical Use of Blood (2025 Edition) signifies that China's clinical blood transfusion management has transitioned from mere technical operations to a new stage centered on patient blood management (PBM). Through an in-depth comparison of the new and old specifications, this paper analyzes the core transformations regarding conceptual reconstruction, legal alignment, technological upgrades, and closed-loop management. The new specifications establish PBM principles, reinforce legal safeguards for informed consent and emergency treatment, and construct a comprehensive, refined quality control system by specifying compatibility testing standards and introducing a post-transfusion evaluation system. Medical institutions should seize this opportunity to update management protocols and information systems, deepen multidisciplinary collaboration, and drive the profound transformation of clinical blood use from focusing solely on safety assurance to placing equal emphasis on science and value.

Objective To study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.

ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

The chapter Zhouyu in Guoyu says "Qi of the heaven and the earth moves without losing its order." With lucidity ascending and turbidity descending， Qi moves in a normal state， and Yin and Yang consolidate the foundation of the body. The mutual interference between lucidity and turbidity leads to the disorder of Qi movement， thus causing diseases. It is a pathological state of disorder between ascending and descending， as well as between entering and exiting， gradually evolving into a state of turbidity affecting lucidity and transforming into pathogen， which can be used to interpret and analyze the core of disease pathogenesis. The theory of lucidity and turbidity is connected with the harmony of nutrient and defensive aspects， Qi circulation， and sweat pore associating with Qi movement， and it has common implications with immune responses and nutrient metabolism system， intestinal mucosal barrier function， and mitochondrial energy synthesis. Modern studies have shown that intestinal flora imbalance， bile acid receptor inactivation， macrophage polarization imbalance， epithelial-mesenchymal transition， ferroptosis and other related microscopic pathological mechanisms are involved in the development and progression of ulcerative colitis. By delving into the common meaning of the classic theory of mutual interference between lucidity and turbidity in traditional Chinese medicine and modern medical pathological mechanisms， this paper summarizes the correspondence between the micropathological mechanism and the theory of mutual interference between lucidity and turbidity in the regulation and mamagement of ulcerative colitis. The combined use of sweet and warm medicinal materials consolidates the middle Qi and activates Qi circulation， thus ascending lucidity and descending turbidity. The combined use of pungent medicinal materials for dispersing and bitter medicinal materials for descending simultaneously raises warm and clear Qi. Wind-extinguishing medicinal materials facilitate the ascending of Qi and the opening of sweat pores. Accordingly， turbidity descends and lucidity ascends. The prescriptions incorporating these medication principles are in agreement with the therapeutic approach of following the normal flow of lucidity and turbidity. This paper clarifies the scientific connotation and micropathologic mechanism of ulcerative colitis from the perspective of mutual interference between lucidity and turbidity， providing new theories and prescriptions for the clinical diagnosis， treatment， and prevention of ulcerative colitis.