Aim To explore the mechanism of hydroxy-a-sanshool in the treatment of diabetic cardiomyopathy ( DCM) based on label-free quantitative proteomics detection technique. Methods DCM model was established by high fat diet and intraperitoneal injection of streptozotocin ( STZ) . They were divided into control group ( CON group ) , diabetic cardiomyopathy group (DCM group) and hydroxy-a-sanshool treatment group ( DCM + SAN group) . The cardiac function of mice was evaluated by echocardiography, the myocardial morphology was observed by pathology staining, the protective mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy was speculated by proteomic technique , and the expression level of cAMP/PKA signaling pathway and key proteins were verified by Western blotting. Results Cardiac ultrasound and pathology staining showed that hydroxy-a-sanshool had protective effect on the heart of DCM mice. Label-free quantitative proteomic analysis was carried out between DCM + SAN group and DCM group, and 160 differential pro-teins were identified by proteomics, in which 127 proteins were up-regulated and 33 proteins were down regulated ; GO secondary functional annotations showed the biological process, molecular function and cellular component; KEGG enrichment analysis showed that cAMP signaling pathway was the most abundant; protein interaction network showed that PKA as the central node interacted with many proteins in the cAMP signaling pathway. Western blot showed that the relative expression of с AMP, PKA protein in DCM group was significantly lower than that in CON group ( P < 0. 05 ) , while the relative expression of cAMP, PKA protein in DCM + SAN group was significantly higher than that in DCM group ( P < 0. 05 ) . Conclusions Hydroxy-a-sanshool has protective effect on heart function of mice with diabetes, which plays a role through cAMP signaling pathway.

The tumor microenvironment includes blood vessels， lymph， nerves， non-malignant cells， and their metabolites at and near the tumor lesion site， which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption， or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply， forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors， widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer， occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets， the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer， inhibit the proliferation， invasion， and metastasis of breast cancer cells in the hypoxia environment， induce apoptosis， reverse their drug resistance， intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment， and inhibit their angiogenesis， thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation， invasion， metastasis， drug resistance， immune function， metabolic reprogramming， non-coding RNA， iron death， and autophagy of breast cancer cells， which affected the occurrence and development of breast cancer， and it elaborated the mechanism behind it. Then， the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine， so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.

BACKGROUND:With the right bio-inks,3D printing can be used to create replacements for human tissues and organs that work inside the body.In recent years,3D printing technology has developed rapidly and has great application potential in regenerative medicine. OBJECTIVE:To introduce the types of bio-inks for 3D printing,and review the classification,application,advantages and disadvantages of bio-inks,as well as the future vision. METHODS:With"3D printing,biological ink,tissue engineering,hydrogel,synthetic material,cytoactive factor"as search terms,relevant articles published on PubMed and CNKI databases from 2000 to 2022 were searched by computer and finally 83 articles were included for review. RESULTS AND CONCLUSION:3D bioprinting technology has developed rapidly over the past few decades and has received great attention in various fields,including tissue engineering and biomedicine.Compared with the limitations of traditional biological scaffold manufacturing methods in terms of function and structure,3D printing can better simulate the complex structure of biological tissues and has appropriate mechanical,rheological and biological characteristics.Bio-ink is an essential part of 3D printing.Bioscaffolds produced by printing bio-ink prepared by biological materials have great scientific potential and clinical significance in tissue repair and regenerative medicine.The research of the materials itself is also getting more and more attention from experts.Bio-inks for 3D printing come in a variety of materials,from natural to synthetic,to aggregations of cells that do not require any additional biomaterials,and their usefulness in practical use varies.In the future,more and more bio-inks will be developed for tissue engineering.It is necessary to analyze the printability of bio-inks through sufficient experimental simulation and equipment testing to meet the actual medical needs.

BACKGROUND:In recent years,there have been many novel tympanic membrane repair materials,including patches and 3D-printed scaffolds.However,the tympanic membrane repaired by these materials is different from the natural tympanic membrane in terms of thickness and internal structure. OBJECTIVE:To explore the efficacy of bone marrow mesenchymal stem cells-loaded high-porosity polycaprolactone/collagen nanofiber membrane scaffolds in repairing chronic tympanic membrane perforation. METHODS:Polycaprolactone,polycaprolactone-collagen,and high-porosity polycaprolactone-collagen nanofiber membranes were prepared by electrospinning technology,and the surface morphology,porosity and cell compatibility of the scaffolds were characterized.The tympanic membrane perforation model of 50 male SD rats was established by puncturing the posterior lower part of both eardrums with a sterile 23-measure needle combined with mitomycin C and hydrocortisone.After 12 weeks of modeling,the rats were divided into five groups by the random number table method.The blank control group did not receive any treatment.In the other four groups,polycaprolactone nanofiber membrane(polycaprolactone group),polycaprolactone-collagen nanofiber membrane(polycaprolactone-collagen group),high-porosity polycaprolactone-collagen nanofiber membrane(high-porosity polycaprolactone-collagen group)and high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells(high-porosity polycaprolactone-collagen group)were implanted at the perforation of the tympanic membrane,respectively.Each group consisted of 10 animals.The healing of the tympanic membrane was examined by otoendoscopy after 1,2,3 and 4 weeks of stent implantation.Hematoxylin-eosin staining,Masson staining,and Ki-67 immunohistochemical staining were performed on the tympanic membrane after 4 weeks of implantation. RESULTS AND CONCLUSION:(1)Scaffold characterization:Scanning electron microscopy showed that compared with other nanofiber membranes,the high-porosity polycaprolactone-collagen nanofiber membranes had more orderly nanofiber structure,larger surface pore size,and higher porosity(P<0.001).Live/dead staining showed that bone marrow mesenchymal stem cells adhered well on the three scaffolds,and the number of living cells on the high-porosity polycaprolactone-collagen nanofiber membrane was more than that on the other two scaffolds.Almarin staining showed that the proliferation rate of bone marrow mesenchymal stem cells on the high-porosity polycaprolactone-collagen nanofiber membrane was higher than that of the other two fiber membranes.(2)Animal experiments:Except for the blank control group,the tympanic membrane of the other four groups healed gradually with the extension of the time of fibrous membrane implantation,among which the healing speed of the cell-loaded high-porosity polycaprolactone-collagen group was the fastest.Hematoxylin-eosin staining,Masson staining,and Ki-67 immunohistochemical staining showed that the tympanic membrane of rats in the cell-carrying high-porosity polycaprolactone-collagen group was moderate in thickness and a three-layer structure with uniform collagen fiber layers,similar to the normal tympanic membrane,and the repair quality of tympanic membrane was better than that of other fiber membrane groups.(3)The results showed that the high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells could not only rapidly repair the perforation of the tympanic membrane,but also the newly healed tympanic membrane was similar to normal tympanic membrane in structure and thickness.

BACKGROUND:Thromboelastography plays an important role in identifying the hypercoagulable state of blood and thrombosis in humans.Recent studies have shown a correlation between an increase in mean platelet volume and thrombosis.We can therefore ask whether the combined diagnosis of thromboelastography and mean platelet volume is a more accurate predictor of thrombosis. OBJECTIVE:To predict the status of blood and the occurrence of thrombosis after total knee arthroplasty by means of mean platelet volume combined with thromboelastography. METHODS:One hundred and twenty patients who underwent unilateral total knee arthroplasty between May 2015 and March 2022 were collected.Patients were divided into 60 patients in the thrombosis group and 60 patients in the control group based on ultrasound findings on postoperative day 7.Whole blood cell and thromboelastography were performed 1 day before,1 and 7 days after surgery,respectively.Multifactorial analysis was used to investigate independent predictors of thrombosis after total knee arthroplasty.The receiver operating characteristic curve and area under the curve were measured in the subjects. RESULTS AND CONCLUSION:Mean platelet volume correlated most strongly with maximum amplitude,followed by coagulation angle.Mean platelet volume and coagulation angle on postoperative day 1 were independent predictors of thrombosis.Mean platelet volume tended to rise and then fall in patients with thrombosis.The best critical value for mean platelet volume to predict thrombosis was 10.73 fL.The area under the receiver operating characteristic curve of subjects was 0.665(95%CI:0.568-0.762,P<0.05];whereas the area under the receiver operating characteristic curve for subjects using mean platelet volume combined with coagulation angle was 0.815(95%CI:0.750-0.879,P<0.05).In addition,the maximum amplitude,coagulation angle,coagulation index and mean platelet volume were significantly higher in the thrombosis group than in the control group postoperatively(P<0.05).The results suggest that the mean platelet volume can reflect the hypercoagulable state of blood after surgery,and the combination of mean platelet volume and coagulation angle on day 1 after total knee arthroplasty can improve the prediction of thrombosis.

BACKGROUND:Previous studies on the effects of valgus and varus angles of tibial component on short-term postoperative outcomes after mobile bearing unicompartmental knee arthroplasty have been reported in and outside China.However,there are few reports on the effect of the valgus and varus angles of tibial component on short-term postoperative outcomes after fixed bearing unicompartmental knee arthroplasty. OBJECTIVE:To investigate the effect of valgus and varus angles of tibial component on short-term clinical outcomes in patients with medial knee osteoarthritis undergoing fixed bearing unicompartmental knee arthroplasty. METHODS:120 patients(122 knees)who underwent fixed bearing unicompartmental knee arthroplasty for medial knee osteoarthritis in Department of Orthopedic Surgery,Affiliated Hospital of Xuzhou Medical University from August 2020 to January 2023 were selected as the study subjects.Two physicians measured the varus angle of femoral prosthesis,valgus and varus angles of tibial prosthesis,flexion and extension angles of femoral prosthesis,and posterior inclination angle of tibial prosthesis after unicompartmental knee arthroplasty based on postoperative X-ray.After excluding the influence of the other three angles,the measurement results of the tibial component varus angle were divided into three groups:<-2°,-2° to 2°,>2°,which were denoted as groups 1,2,and 3,respectively.The range of knee motion,the hospital for special surgery knee score,the American knee society score,and forgotten joint score were recorded and compared before and after the operation. RESULTS AND CONCLUSION:(1)A total of 120 patients(122 knees)were enrolled in this study.They were divided into three groups according to the size of the valgus and varus angles of the tibial prosthesis after operation:37 patients in the first group,60 patients in the second group,and 23 patients in the third group.There was no significant difference between the three groups in terms of baseline information such as age,gender,and side of surgery(P>0.05).(2)Patients were followed up for 3-30 months after arthroplasty.(3)The hospital for special surgery knee score of the second group was higher than that of the first group(P=0.015)and the third group(P=0.012).The American knee society score of the second group was significantly higher than that of the first group(P=0.014)and the third group(P<0.001).The forgotten joint score of the second group was higher than that of the first group(P=0.033)and the third group(P=0.016).(4)After fixed bearing unicompartmental knee arthroplasty,when the valgus angle of tibial prosthesis was-2° to 2°,which can achieve better short-term clinical results,the degree of prosthesis self-realization is higher.

BACKGROUND:Tissue engineering has brought new hope to the clinical challenge of liver failure,and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE:To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate,and assess its biocompatibility. METHODS:Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution,separately.Afterwards,the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline.Subsequently,scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials.Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice,and their expression of stem cell-related markers(CD45,CD34,CD73,CD90,and CD105)was identified through flow cytometry.The cells were then divided into a scaffold-free control group and a scaffold group.Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups.The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay,hematoxylin-eosin staining,and phalloidine staining.Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy.Furthermore,the scaffold was subdivided into the non-induced group and the hepatogenic-induced group.Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold,and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison.Immunofluorescent staining using liver cell markers,including albumin,cytokeratin 18,and CYP1A1,was performed.Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin.Additionally,scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold,verifying the expression of liver cell-related genes on the decellularized scaffold material.Finally,the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size,with no residual cells observed.(2)Through flow cytometry analysis,the cultured cells were identified as adipose-derived mesenchymal stem cells.(3)CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity.Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold.(4)The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins,including albumin,alpha-fetoprotein,cytokeratin 18,and CYP1A1.These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells.(5)The decellularized apple scaffold implanted at 7 days has integrated with the liver,with partial degradation of the scaffold observed.By 28 days,the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue.(6)The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility,promoting the proliferation,adhesion,and hepatic differentiation of adipose-derived mesenchymal stem cells.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective:To assess the feasibility and application of mixed reality combined with surgical navigation technology in parapharyngeal space tumor surgery, and to provide a reference for the development and promotion of this technology.Methods:In this study, retrospective data collection was conducted on 16 patients with parapharyngeal space tumors who were treated at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from June 2020 to June 2023. The patient′s age was (39.6±17.8) years, with 4 males and 12 females. Mixed reality combined with surgical navigation technology was utilized to assist physicians in the treatment of these patients. Mixed reality combined with surgical navigation technology was used to assist physicians in treatment of these patients. The application steps included acquisition of image data, processing of image data [three-dimensional (3D) reconstruction, image fusion, and virtual surgical design], development of surgical navigation plan, connection of mixed reality and navigation system, automatic registration and intraoperative guidance and validation. In the preoperative plan, landmark points were placed on the virtual tumor and surrounding important structures reconstructed using digital software, serving to guide the localization of crucial anatomical structures. Intraoperative positioning deviation, surgical time, intraoperative blood loss, and postoperative complications were recorded and analyzed to evaluate the clinical application effectiveness of mixed reality combined with surgical navigation technology.Results:With the assistance of mixed reality combined with surgical navigation technology, 16 patients successfully underwent tumor resection. All patients were accurately diagnosed preoperatively by 3D reconstruction and image fusion technology, and a comprehensive preoperative plan was formulated; intraoperatively, mixed reality combined with surgical navigation technology was utilized for the localization of important structures. The average localization deviation of 38 landmark points during the operation were (4.43±1.96) mm, with 62% (26/42) of the points having a deviation of ≥0 and<5 mm. The average duration of the operation was (149.6±53.9) min and the blood loss was 70 (45, 150) ml. The average postoperative follow-up was 16 months, and five patients experienced postoperative complications involving facial paralysis, hoarseness, and choking.Conclusions:Mixed reality combined with surgical navigation technology can achieve the three-dimensional visualization of oral and maxillofacial anatomical structures to achieve precise preoperative diagnosis. During surgery, the technology can real-time display the relationship between soft tissue tumors and the surrounding important anatomical structures, guide surgical operation, and enhance the safety of surgery.

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS). Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of 151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cfPWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling. Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2 rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a 19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.