BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.

BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

AIM: To explore the effect of dihydroquercetin on visual function in mice with form deprivation myopia based on the NOD-like receptor thermoprotein domain-related protein 3(NLRP3)inflammasome pathway.METHODS: The C57BL/6 mice were randomly divided into control group and form deprivation myopia model group, and the form deprivation myopia model group was constructed by covering the right eye with a translucent eye patch. After successful modeling, the mice in the model group of form deprivation myopia were randomly divided into model group, low-, medium- and high-dose dihydroquercetin groups, and high-dose dihydroquercetin + NLRP3 agonist group. The diopter and axial length of mice in each group were detected. The kit was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in retinal tissue. RT-qPCR was used to detect the mRNA expressions of NLRP3, apoptosis-associated spot-like protein(ASC), Caspase-1, IL-1β and IL-18 in retinal tissues. Western blot was used to detect the expression of NLRP3, ASC, cleaved Caspase-1, IL-1β and IL-18 proteins in retinal tissues. TUNEL staining was used to detect apoptosis in retinal tissue.RESULTS: Compared with the control group, the diopter of the mice in the model group decreased, and axial length increased, and the SOD decreased whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 increased, and the rate of apoptosis in retinal tissue increased(all P<0.05). Compared with the model group, the diopter of mice in the low-, medium- and high-dose dihydroquercetin groups increased, axial length shortened, the SOD increased, whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 decreased, and the rate of apoptosis in retinal tissue decreased(all P<0.05). Compared with the high-dose dihydroquercetin group, the high-dose dihydroquercetin+NLRP3 agonist group had reduced diopter, increased axial length, decreased SOD levels, elevated MDA, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 levels, as well as increased apoptosis rate in retinal tissue(all P<0.05).CONCLUSION: Dihydroquercetin can improve visual function in mice with form deprivation myopia by inhibiting pyroptosis and oxidative stress responses, which may be related to the suppression of NLRP3 inflammasome. NLRP3 agonists can partially mitigate the effects of high-dose dihydroquercetin on form deprivation myopia in mice.

AIM: To compare the clinical efficacy of goniosynechialysis versus trabeculectomy combined with cataract phacoemulsification in treating glaucoma complicated with cataract.METHODS:From January 2019 to January 2024, patients with glaucoma complicated with cataract diagnosed in our hospital were included as the study subjects. They were assigned into trabeculectomy group and goniosynechialysis group based on different surgical methods. The trabeculectomy group was treated with cataract phacoemulsification combined with trabeculectomy, while the goniosynechialysis group was treated with cataract phacoemulsification combined with goniosynechialysis. The improvement of visual acuity, anterior chamber depth, chamber angle width, intraocular pressure, whole en face vessel density within the optic disc head and in the peripapillary region, and complications were compared between two groups.RESULTS: A total of 120 patients(120 eyes)with glaucoma combined with cataract were included in this study, among which 60 eyes were in the trabeculectomy group and 60 eyes in the goniosynechialysis group. The age of the trabeculectomy group was 60.72±6.16 years, including 28 males and 32 females. The age of the goniosynechialysis group was 61.04±6.24 years, including 31 males and 29 females. At 3 mo after surgery, the visual acuity of patients in both groups improved significantly, and the improvement of visual acuity in the goniosynechialysis group was significantly better than that in the trabeculectomy group(all P<0.01). At 3 mo after surgery, the anterior chamber depth and chamber angle width of patients in both groups were higher than those before surgery, and with the goniosynechialysis group being higher than the trabeculectomy group(all P<0.01), while the intraocular pressure was lower than that before surgery, and with the goniosynechialysis group being lower than the trabeculectomy group(all P<0.01). Before surgery, there was no significant difference in the whole en face vessel density within the optic disc head between the two groups(P>0.05), however, the whole en face vessel density within the optic disc head in both groups on 1 d after surgery were significantly lower than before surgery(all P<0.05); and compared with 1 d after surgery, there was a significant increase at 1 wk, 1, and 3 mo after surgery(all P<0.05); the whole en face vessel density within the optic disc head in the goniosynechialysis group was significantly higher than that in the trabeculectomy group at various time points after surgery(all P<0.05). However, there was no significant difference in the whole en face vessel density in the peripapillary region between the two groups before surgery and various time points after surgery(all P>0.05). Within 3 mo after surgery, the incidence of complications in the goniosynechialysis group(8.3%)was significantly lower than that in the trabeculectomy group(21.7%; P<0.05).CONCLUSION:Goniosynechialysis combined with phacoemulsification is more effective than trabeculectomy combined with phacoemulsification in the treatment of patients with glaucoma complicated with cataract in improving the visual acuity and whole en face vessel density within the optic disc head of patients, increasing the anterior chamber depth and chamber angle width, reducing intraocular pressure and the risk of complications. It has high safety and ideal short-term efficacy.

[摘 要] 目的：探讨高良姜素（Gal）调控AMPK/mTOR/ULK1信号通路对胃癌细胞凋亡和自噬的影响及其机制。方法：将胃癌NCI-N87细胞分为对照组、多索吗啡（DM）组、Gal低剂量（Gal-L）组、Gal高剂量（Gal-H）组、Gal-H + DM组。采用MTT法、流式细胞术、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测PCNA、C-caspase-3、免疫逃逸相关蛋白（B7H1）、EMT和AMPK/mTOR/ULK1信号通路蛋白的表达水平。建立裸鼠NCI-N87细胞移植瘤模型，观察Gal和5-FU对移植瘤的抑制效果。结果：与对照组比较，DM组NCI-N87细胞增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著升高（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著降低（均P < 0.05）；Gal-L组和Gal-H组NCI-N87细胞的增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著降低（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著升高（均P < 0.05）；DM可部分逆转Gal对NCI-N87细胞恶性生物学行为的抑制作用（P < 0.05）；与对照组比较，Gal组和5-FU组裸鼠移植瘤体积和质量均显著降低，肿瘤组织细胞凋亡率显著升高（P < 0.05）。结论：Gal可促进胃癌NCI-N87细胞自噬和凋亡，抑制其增殖、迁移和侵袭，可能与激活AMPK/mTOR/ULK1信号通路有关。

ObjectiveTo investigate the effects of exogenous nitric oxide （NO） on the accumulation and quality formation mechanism of flavonoids in Scutellariae Radix. MethodsFresh roots of Scutellaria baicalensis were treated with sodium nitroprusside （SNP） solutions at concentrations of 0.0， 7.5， and 20 mmol·L^-1， respectively. Kits and supporting reaction systems were used to determine the following indicators of samples in each group， including （1） reactive oxygen species： changes in the content of nitric oxide （NO）， superoxide anion （O2-·）， and hydrogen peroxide （H₂O₂）， （2） lipid oxidation products： changes in the content of malondialdehyde （MDA）， （3） antioxidant enzymes： changes in the activity of superoxide dismutase （SOD）， catalase （CAT）， and peroxidase （POD）， and （4） metabolic key enzymes and metabolic intermediates： Changes in the activity of phenylalanine ammonia-lyase （PAL） and the content of 1，3-diphosphoglycerate （1，3-DPG）. High-performance liquid chromatography （HPLC） was used to determine the changes in the content of secondary metabolites in flavonoids such as baicalin， wogonoside， baicalein， and wogonin in each group. ResultsCompared with that on day 0， during the treatment with 20 mmol·L^-1 SNP solution， the content of NO， O2-·， H₂O₂， and MDA in fresh roots of Scutellaria baicalensis increased significantly （P<0.01）， by 138.7%， 75.7%， 292.9%， and 140.3% respectively. The activity of SOD， CAT， and POD increased by 100.7%， 41.4%， and 70.4% respectively （P<0.01）， and that of PAL increased by 111.1% （P<0.01）. The content of the secondary metabolites baicalin and wogonoside remained basically unchanged， while that of baicalein and wogonin increased by 401.3% and 457.9% respectively （P<0.01）. The content of 1，3-DPG increased by 165.0% （P<0.01）. In the 7.5 mmol·L^-1 SNP solution treatment group， the stress degree was relatively mild. Compared with that on day 0， the content of NO， O2-·， H₂O₂， and MDA increased by 76.2%， 57.7%， 221.4%， and 99.7% respectively （P<0.01）. The activity of antioxidant enzymes SOD， CAT， and POD increased by 79.5%， 55.6%， and 51.9% respectively （P<0.01）， and that of PAL increased by 69.0% （P<0.01）. The content of baicalein and wogonin increased by 204.7% and 272.2% respectively （P<0.01）， and that of 1，3-DPG increased by 128.0% （P<0.01）. The 20 mmol·L^-1 SNP group showed better performance than the 7.5 mmol·L^-1 SNP group. ConclusionSNP can simulate the physiological state of Scutellaria baicalensis under stress conditions， activate the antioxidant protection mechanism， promote the biosynthesis of flavonoids in Scutellariae Radix， and significantly improve the quality of medicinal materials in Scutellariae Radix.

Natural products have shown great potential in the research and development of antitumor drugs. However， their clinical application is severely limited by inherent drawbacks such as poor water solubility， low stability， and low bioavailability. Cell membrane biomimetic nanoparticles， as a novel drug delivery system， have provided new strategies to overcome this bottleneck. This review systematically summarizes the preparation methods （e.g.， membrane extrusion， ultrasonic fusion， and microfluidic electroporation） and characterization techniques （e.g.， particle size， Zeta potential， and membrane surface protein detection） of cell membrane biomimetic nanoparticles， with a focus on the application of these derived from various sources in delivering antitumor natural products. Cell membrane biomimetic nanoparticles are endowed with unique biological functions， including low immunogenicity conferred by stem cell membranes， prolonged systemic circulation enabled by red blood cell membranes， and homologous targeting facilitated by tumor cell membranes. Despite these advancements， the technology still faces challenges such as difficulties in large-scale production， high costs， and limited characterization methods. Future research needs to further optimize the relevant processes to promote the clinical translation of cell membrane-biomimetic nanoparticles， thereby offering an efficient and safe novel delivery approach for antitumor therapy using natural products.

BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.