BACKGROUND: Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation. METHODS: Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD). RESULTS: We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion. CONCLUSION Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.

BACKGROUND: Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation. METHODS: Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD). RESULTS: We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion. CONCLUSION Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.

BACKGROUND: Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation. METHODS: Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD). RESULTS: We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion. CONCLUSION Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.

BACKGROUND: Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation. METHODS: Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD). RESULTS: We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion. CONCLUSION Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.

BACKGROUND: Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation. METHODS: Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD). RESULTS: We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion. CONCLUSION Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

[摘 要] 目的：基于蛋白质组学技术探讨麻疹减毒活疫苗191株（MV-Hu191）在体内外对三阴性乳腺癌MDA-MB-231、4T1细胞的影响及其作用机制。方法：采用CCK-8法检测MV-Hu191对MDA-MB-231和4T1细胞增殖的影响；液相色谱-质谱联用技术分析MV-Hu191处理对MDA-MB-231细胞中蛋白质谱的影响，多重数据库筛选蛋白质谱中的典型差异蛋白质并进行GO、KEGG、亚细胞定位与功能注释。瘤内注射1×106 TCID50 MV-Hu191干预4T1细胞移植瘤模型小鼠，流式细胞术检测小鼠脾组织中T细胞亚群，ELISA法检测小鼠血清TNF-α和IL-6含量。结果：体外实验结果表明，MV-Hu191具有抑制MDA-MB-231和4T1细胞增殖的作用，差异均具有统计学意义（P<0.01）。蛋白质组学分析结果显示，MV-Hu191作用MDA-MB-231细胞后明显上调蛋白质有38个、下调有12个；差异表达的蛋白质主要参与细胞黏附、信号受体激活、细胞代谢、应激反应等生物学过程，22个差异蛋白质亚细胞定位位于细胞外，KEGG功能分类显示与免疫调节功能相关的差异蛋白质最多且均为上调蛋白，包括C4A、C8B、SERPINF2、A2M、SERPINC1、CTSB、SERPING1、C5；PPI预测发现免疫相关差异蛋白与CD4、CD8、TNF-α及IL-6相互关联。体内实验结果显示，MV-Hu191干预组小鼠脾组织中CD4+ T细胞数量略高于对照组，但差异无统计学意义（P>0.05），CD4+/CD8+ T细胞比值明显高于对照组（P<0.05），血清TNF-α和IL-6含量显著上升（均P<0.01）。结论：MV-Hu191显著抑制MDA-MB-231、4T1细胞增殖及拮抗4T1细胞荷瘤小鼠成瘤性，其机制可能是MV-Hu191通过激活免疫效应分子实现抗肿瘤作用。

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Introduction: Bosworth fracture dislocations of the ankle are rare injuries of the ankle caused by extreme external rotation of the supinated foot where the proximal fibula fracture fragment is posteriorly dislocated and entrapped behind the posterior-lateral ridge of the tibia. This case series aims to document three such cases treated in our institution over a nine year period. We also provide a review of 129 cases in the existing literature. Materials and methods: Medical records and relevant radiographs for each patient were analysed and collected from the time of presentation till the point of latest followup. During each clinic visit, all physical exam findings as well as all complications were recorded. The American Foot and Ankle Society (AOFAS) Hindfoot score was also tabulated for each patient at the point of latest review. Results: Closed reduction was unsuccessful in all three patients, and all required open reduction. One patient had an uncomplicated recovery whilst the remaining two suffered significant soft tissue complications. One patient suffered severe soft tissue swelling preventing primary closure at the time of surgery, whilst another suffered post-operative wound dehiscence and infection. Eventually all fractures healed, and all three patients obtained satisfactory AOFAS scores. Conclusion: The diagnosis of Bosworth fracture dislocations of the ankle is often delayed or missed, due to its rare occurrence. Closed reduction is often unsuccessful, and early open reduction is required to avoid poor clinical outcomes due to severe soft tissue damage or even compartment syndrome.

OBJECTIVE：To establish the method for the content determination of 7 components，such as puerarin ， 3′-methoxypuerarin，daidzein，rutin，hesperidin，salvianolic acid A and quercetin ，in Zhengxin jiangzhi tablets ，and conduct cluster heatmap analysis. METHODS ：HPLC method was adopted. The separation was performed on Kromasil C 18 column with mobile phase consisted of acetonitrile- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.8 mL/min. The detection wavelength was set at 280 nm，and the column temperature was 25 ℃. The sample size was 10 μL. Taking the content data as the object，the cluster heatmap was drawn by Hiplot scientific research mapping platform. RESULTS ：The linear range of puerarin ， 3′-methoxypuerarin，daidzein，rutin，hesperidin，salvianolic acid A and quercetin were 17.00-170.00（r＝0.999 9），5.14-51.40（r＝ 0.999 8），3.00-30.00（r＝0.999 8），153.00-1 530.00（r＝0.999 9），7.88-78.75（r＝0.999 8），2.85-28.50（r＝0.999 9）and 11.34-113.40 μg/mL（r＝0.999 8），respectively. RSDs of precision ，stability（24 h）and repeatability tests were all less than 2％； the average recoveries were 99.58％（RSD＝0.83％，n＝6），100.31％（RSD＝1.17％，n＝6），100.61％（RSD＝1.08％，n＝6）， 100.05％（RSD＝0.82％，n＝6），100.31％（RSD＝1.38％，n＝6），100.31％（RSD＝0.85％，n＝6），99.85％（RSD＝1.01％， n＝6），respectively. The contents of above components in 10 batches of samples were 7.262 5-8.941 5，2.464 9-3.068 9，1.478 9- 1.883 4，58.632 8-79.408 3，3.569 4-4.500 6，1.077 6-1.341 5，1.139 7-5.957 0 mg/g，respectively. Results of cluster heatmap analysis showed that 10 batches of samples could be divided into 4 categories，including S 1-S3 as one category ，S4 as one category，S5-S6 as one category and S 7-S10 as one category. CONCLUSIONS ：The established method is simple ，accurate and specific，which can be used for the quality control of Zhengxin jiangzhi tablets ，combined with cluster heatmap analysis. There are some differences in the quality of different batches of samples.