Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

BACKGROUND:Osteoporosis is a high-risk factor for dental implant treatment.The preparation of tissue engineering scaffolds with sustained-release Alendronate and its application in oral implant surgery for osteoporosis patients is a current hot topic in oral bone tissue engineering research.OBJECTIVE:To prepare alendronate/chitosan/polyvinyl alcohol composite hydrogel film and characterize its sustained release properties.METHODS:(1)Chitosan/polyvinyl alcohol composite hydrogel films with varying mass ratios(mass ratios of chitosan and polyvinyl alcohol were 3:7,5:5,and 7:3,respectively),chitosan and polyvinyl alcohol hydrogel films were prepared using a physical crosslinking method.By characterizing the morphology,water contact angle,mechanical properties,swelling rate,and cell compatibility of the hydrogel film,a suitable hydrogel film was screened as a carrier of alendronate.(2)Chitosan/polyvinyl alcohol composite hydrogel films containing 0,0.4,1.2,and 2.0 mg/L alendronate were prepared,and rat bone marrow mesenchymal stem cells were co-cultured with the four groups of hydrogel films.The cytocompatibility of the hydrogel films was detected by CCK-8 assay and CD44 immunofluorescence staining.The drug-loaded chitosan/polyvinyl alcohol composite hydrogel films were immersed in PBS.The drug release performance of the composite hydrogel films was detected by ultraviolet-visible spectroscopy.RESULTS AND CONCLUSION:(1)The characterization results showed that with the increase of the mass of polyvinyl alcohol in the hydrogel film,the structural density of the hydrogel film increased,the porosity decreased,the water contact angle(all within 90°),the elongation at break and the compressive strength increased,and the equilibrium swelling rate decreased.It had no effect on the proliferation of rat bone marrow mesenchymal stem cells.Chitosan hydrogel film could promote the adhesion of rat bone marrow mesenchymal stem cells.The 3:7 and 5:5 ratio composite hydrogel films did not affect the adhesion of rat bone marrow mesenchymal stem cells.Polyvinyl alcohol hydrogel film and 7:3 ratio composite hydrogel film inhibited the adhesion of rat bone marrow mesenchymal stem cells.Based on the above results,the 5:5 composite hydrogel film was selected as the carrier of alendronate.(2)CCK-8 assay results showed that the composite hydrogel film containing 0.4 and 1.2 mg/L alendronate had no cytotoxicity.CD44 immunofluorescence staining results showed that the composite hydrogel film containing 0.4 mg/L alendronate did not affect the adhesion of rat bone marrow mesenchymal stem cells,while the composite hydrogel film containing 1.2 and 2.0 mg/L alendronate inhibited the adhesion of rat bone marrow mesenchymal stem cells.Chitosan/polyvinyl alcohol composite hydrogel film containing 0.4,1.2,and 2.0 mg/L alendronate released alendronate in the first 6 hours,and then released alendronate evenly and stably,with a release time of more than 96 hours.(3)The results showed that the chitosan/polyvinyl alcohol composite hydrogel film with a ratio of 5:5 had good physical and chemical properties and cytocompatibility,and could be used as a sustained-release carrier of alendronate.

BACKGROUND:Osteoporosis is a high-risk factor for dental implant treatment.The preparation of tissue engineering scaffolds with sustained-release Alendronate and its application in oral implant surgery for osteoporosis patients is a current hot topic in oral bone tissue engineering research.OBJECTIVE:To prepare alendronate/chitosan/polyvinyl alcohol composite hydrogel film and characterize its sustained release properties.METHODS:(1)Chitosan/polyvinyl alcohol composite hydrogel films with varying mass ratios(mass ratios of chitosan and polyvinyl alcohol were 3:7,5:5,and 7:3,respectively),chitosan and polyvinyl alcohol hydrogel films were prepared using a physical crosslinking method.By characterizing the morphology,water contact angle,mechanical properties,swelling rate,and cell compatibility of the hydrogel film,a suitable hydrogel film was screened as a carrier of alendronate.(2)Chitosan/polyvinyl alcohol composite hydrogel films containing 0,0.4,1.2,and 2.0 mg/L alendronate were prepared,and rat bone marrow mesenchymal stem cells were co-cultured with the four groups of hydrogel films.The cytocompatibility of the hydrogel films was detected by CCK-8 assay and CD44 immunofluorescence staining.The drug-loaded chitosan/polyvinyl alcohol composite hydrogel films were immersed in PBS.The drug release performance of the composite hydrogel films was detected by ultraviolet-visible spectroscopy.RESULTS AND CONCLUSION:(1)The characterization results showed that with the increase of the mass of polyvinyl alcohol in the hydrogel film,the structural density of the hydrogel film increased,the porosity decreased,the water contact angle(all within 90°),the elongation at break and the compressive strength increased,and the equilibrium swelling rate decreased.It had no effect on the proliferation of rat bone marrow mesenchymal stem cells.Chitosan hydrogel film could promote the adhesion of rat bone marrow mesenchymal stem cells.The 3:7 and 5:5 ratio composite hydrogel films did not affect the adhesion of rat bone marrow mesenchymal stem cells.Polyvinyl alcohol hydrogel film and 7:3 ratio composite hydrogel film inhibited the adhesion of rat bone marrow mesenchymal stem cells.Based on the above results,the 5:5 composite hydrogel film was selected as the carrier of alendronate.(2)CCK-8 assay results showed that the composite hydrogel film containing 0.4 and 1.2 mg/L alendronate had no cytotoxicity.CD44 immunofluorescence staining results showed that the composite hydrogel film containing 0.4 mg/L alendronate did not affect the adhesion of rat bone marrow mesenchymal stem cells,while the composite hydrogel film containing 1.2 and 2.0 mg/L alendronate inhibited the adhesion of rat bone marrow mesenchymal stem cells.Chitosan/polyvinyl alcohol composite hydrogel film containing 0.4,1.2,and 2.0 mg/L alendronate released alendronate in the first 6 hours,and then released alendronate evenly and stably,with a release time of more than 96 hours.(3)The results showed that the chitosan/polyvinyl alcohol composite hydrogel film with a ratio of 5:5 had good physical and chemical properties and cytocompatibility,and could be used as a sustained-release carrier of alendronate.

Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males. Immune-checkpoint inhibitors (ICIs) that target programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive efficacy in the treatment of non-small-cell lung cancer (NSCLC) (Pardoll, 2012; Champiat et al., 2016; Gao et al., 2022). Although ICIs are usually well tolerated, they are often accompanied by immune-related adverse events (irAEs) (Doroshow et al., 2019). Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system (O'Kane et al., 2017; Puzanov et al., 2017). Compared with adverse events caused by chemotherapy, irAEs are often characterized by delayed onset and prolonged duration and can occur in any organ at any stage of treatment, including after cessation of treatment (Puzanov et al., 2017; von Itzstein et al., 2020). They range from rash, pneumonitis, hypothyroidism, enterocolitis, and autoimmune hepatitis to cardiovascular, hematological, renal, neurological, and ophthalmic irAEs (Nishino et al., 2016; Kumar et al., 2017; Song et al., 2020). Hence, we conducted a retrospective study to identify validated factors that could predict the magnitude of the risk of irAEs in patients receiving PD-1/PD-L1 inhibitors; our approach was to analyze the correlation between the clinical characteristics of patients at the start of treatment and relevant indicators such as hematological indices and the risk of developing irAEs. Then, we developed an economical, practical, rapid, and simple model to assess the risk of irAEs in patients receiving ICI treatment, as early as possible.
Male ; Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/adverse effects* ; Programmed Cell Death 1 Receptor ; Retrospective Studies ; Apoptosis

Objective:To compare reconstruction of acromioclavicular ligament versus internal fixation of acromioclavicular joint with clavicle hook plate in the treatment of Rockwood Ⅲ-Ⅴ acromioclavicular dislocation by reconstruction of coracoclavicular ligament with suture anchor.Methods:A retrospective analysis was conducted of the 56 patients who had been treated for Rockwood Ⅲ-Ⅴ acromioclavicular dislocation from January 2015 to June 2019 at Department of Orthopaedic Trauma, Qilu Hospital of Shandong University (Qingdao). Of them, 26 were treated by reconstruction of coracoclavicular ligament with suture anchor plus reconstruction of acromioclavicular ligament (reconstruction group) and 30 by reconstruction of coracoclavicular ligament with suture anchor plus internal fixation of acromioclavicular joint with clavicle hook plate (plate group). The 2 groups were compared in terms of operation time, intraoperative blood loss, Constant-Murley score and Subjective Shoulder Rating System (SSRS) score at the last follow-up, and complications.Results:The 2 groups were comparable because there were no significant differences between them in the baseline data before operation ( P>0.05). The reconstruction group was followed up for 6 to 15 months (average, 7.9 months) while the plate group for 7 to 18 months (average, 11.3 months). The average operation time was (79.9±12.6) min for the reconstruction group and (69.1±8.5) min for the plate group, showing a significant difference ( P<0.05). No significant difference was found between the 2 groups in the intraoperative blood loss [(68.5±19.1) mL versus (65.0±16.6) mL] ( P>0.05). The differences were statistically significant between the 2 groups in Constant-Murley score (87.9±3.4 for the reconstruction group versus 91.9±3.5 for the plate group) and in SSRS score (85.1±4.1 for the reconstruction group versus 88.6±3.0 for the plate group) ( P<0.05). All the wounds healed well in the reconstruction group except for one patient who reported numbness around the wound which disappeared spontaneously 3 months postoperation. In the plate group, incision infection occurred in 2 cases, the redness and swelling in one which responded to dressing change 3 weeks later and numbness around the incision in one which was recovered 5 months after operation. Conclusions:Both surgical procedures can achieve good to excellent clinical outcomes. Although reconstruction of both acromioclavicular and coracoclavicular ligaments takes more operation time, it may lead to better Constant-Murley and SSRS scores and fewer complications, and spare secondary operation.

Objective To evaluate the long-term follow-up results of foam sclerosing agent in the treatment ofincompetent perforating vein.Methods 153 cases (316 incompetent perforating veins)received the treatment of foam sclerotherapy.The closure of perforating branches was followed up by ultrasound.Results 12 cases (27 incompetent perforating veins) were lost to follow up.289 incompetent perforating veins got follow up,The median follow-up time was 17 months (11-36 months).Closure rate was 100％ in vessels less than 3 mm in diameter,while that was 76％ invessels with the diameter between 3-5 mm.Closure rate was 16％ in vessels larger than 5 mm in diameter.Conclusion The long-term efficacy of the foam sclerosing agent in the treatment of incompetent perforating vein depends on the diameter of the vein.

Objective To evaluate the effect of antiplatelet drugs and ischemic-events-free duration by thromboelastography (TEG) in patients undergoing peripheral endovascular treatment.Methods From Mar 2015 to Oct 2016,38 patients undergoing initial successful peripheral stenting and then coming back for recurrent ischemic events.TEG was used to evaluate the platelet inhibition rate induced by arachidonic acid (AA％) approach,the platelet inhibition rate induced by adenosine diphosphate (ADP％) approach,and the ADP-induced platelet-fibrin clot strength (MAADP).Clinical feature differences between patients with MAADP ＞ 47 mm and MAADP ≤ 47 mm were compared.Results AA％ less than 50％ was found in 9 patients(23.9％),and ADP％ less than 30％ in 14 patients(36.8％).5 patients met the two conditions.Patients with MAADp ＞ 47 mm had a significantly lower ADP％ (x2 =10.755,P ＜ 0.001),compared to patients with MAADP ≤47 mm.Univariate survival analysis showed ADP％ ＜ 30％ and MAADP ＞47 mm were risk factors for getting shorter ischemic-events-free duration,compared to patients with ADP％ ≥ 30 (P ＜ 0.001),with MAADP ≤47 mm (x2 =4.408,P =0.036).Conclusions TEG may detect those patients who has a low response to antiplatelet drugs,and some TEG parameters may have a ischemic predictive value.

Objective To construct a lentivirus vector over-expressing Tumor necrosis factor alpha induced protein 1 (TNFAIP1) gene and detect its expression level in vitro.Methods The full length of TNFAIP1 gene fragments were amplified by polymerase chain reaction (PCR).The pEZ-Lv105 vectors were digested by restriction endonuclease which was then linked to the full length of TNFAIP1 gene fragments by using T4DNA ligase.The plasmids were transfected into E.coli stbl3 and then we obtained the highly expressing positive clones by screening and identifying.The lentivirus vectors containing TNFAIP1 gene were transfected into 293T cells for package according to the packing kit manual.Results TNFAIP1 gene was amplified and successfully bound to the pEZ-Lv105 lentivirus vectors.The sequences of the recombinant plasmids were confirmed correctly by PCR and DNA sequence.The enhanced green fluorescent protein (eGFP) could be observed after recombinant lentiviruses were cotransfected into 293T cells.Conclusions The TNFAIP1 overexpressed lentivirus vector is successfully constructed,which provides a molecular tool for further study of TNFAIP1 gene in optic nerve glioma.

OBJECTIVE: To sum up experience in unibody bifurcation stent graft in the treatment of abdominal aortic aneurysm with aortic bifurcation stenosis. METHODS: Clinical data of 19 cases of abdominal aortic aneurysm and aortic bifurcation stenosis received endovascular treatment using unibody bifurcation stent graft in Zhejiang Provincial People's Hospital during March 2009 and March 2018 were collected. The clinical characteristics, surgery procedure and follow-up results were reviewed. RESULTS: Stent graft was successful in all patients, and the average operation time was (70.0±2.3) min. Leakage was found in 3 patients, in which 2 patients with type Ⅰ leakage and 1 patient with type Ⅱ leakage. All leakage disappeared 15 days after surgery. The 19 cases were followed-up for 9-48 months with the median follow-up time of 27 months, and no displacement, leakage and lower limb ischemia was observed. CONCLUSIONS Unibody bifurcation stent graft is of satisfactory long-term effect for patients with abdominal aortic aneurysm and aortic bifurcation stenosis, and can avoid displacement of stent graft after operation.
Aortic Aneurysm, Abdominal ; surgery ; Aortic Valve Stenosis ; surgery ; Blood Vessel Prosthesis Implantation ; Humans ; Stents ; Treatment Outcome

Objective To discuss the curative effect and clinical significance of sclerosing foam agent in the treatment of chronic venous diseases (CVD) with incompetent perforating veins.Methods 65 cases of C4,C5,C6 CVD (a total of 84 limbs) underwent foam sclerotherapy closure for incompetent perforating vein.Patients were followed-up for 3 months,ultrasonography was used to observe the closure of perforating veins and the curative effect.Results 7 patients (9 limbs) were lost to follow-up,all with grade C4.In the 66 (C4,C5) limbs,pigmentation significantly subsided in 45,partial regression in 9,no change in 2.In the 9 limbs with grade C6,complete healing of ulcer in 5,partially healed in 3.Ultrasound observed satisfactory perforating vein closure.Conclusion Foam sclerotherapy closure for incompetent perforating vein has satisfactory effect,with good short-term curative result.