Infections associated with orthopaedic implants are currently one of the major concerns of orthopaedic surgeons. Metallic antimicrobial nanocoatings have demonstrated great potential in preventing implant infections due to their excellent antimicrobial properties and biocompatibility. However, there are potential risks associated with these metal nanoparticles, such as cytotoxicity of silver and copper, and rapid dissolution of zinc and magnesium which affects implant stability. Therefore, the clinical application of nanometallic coatings still faces challenges in how to better enhance biosafety, regulate degradation rate, and enhance osseointegration. This paper reviews the progress and challenges in the application of antimicrobial nanometallic coatings on implants to provide a reference for related research.

Objective:To investigate the effects of dual vascularized tissue-engineered bone constructed by vascular bundles and endothelial progenitor cells (EPCs) on repair of large bone defects and vascular regeneration.Methods:EPCs were seeded on the demineralized bone matrix (DBM) scaffolds and cultured for 6 days. The attachment and morphology of EPCs on DBM scaffolds were observed by electron microscopy. Next, the radial artery was implanted into a vascular groove opened inside the DBM-EPCs composite scaffolds. Finally, models of a large segmental bone defect were constructed using the radii from 18 New Zealand white rabbits. The rabbits were randomly divided into 4 groups using a simple random sampling method: DBM group, DBM+EPCs group, DBM+vascular bundle group, and DBM+EPCs+vascular bundle group. The DBM group and DBM+EPCs group shared the same rabbits so that transplantations were conducted into the left and right forearms respectively; the DBM+vascular bundle group and DBM+EPCs+vascular bundle group also shared the same rabbits so that transplantations were conducted into the left and right forearms respectively. Consequently, there were 9 experimental sites in each group. X-ray examination and gross morphological observation were performed to evaluate the bone regeneration in the experimental rabbits in each group at 4, 8, and 12 weeks after surgery, and CD31 immunofluorescence staining was used to evaluate the vascular regeneration. Micro-CT was used to analyze bone tissue parameters and reconstruct the three-dimensional structures of the defects site at 12 weeks after surgery.Results:Compared with the DBM, DBM+EPCs and DBM+vascular bundle groups, the DBM+EPCs+vascular bundle group showed new bone tissue crawling on the scaffold surface at 4 weeks after surgery, almost complete healing of the bone defect area at 8 weeks, and forming of a complete and dense bone bridge and appearance of a bone marrow cavity at 12 weeks. Micro-CT data at 12 weeks after surgery showed regular arrangement of the trabeculae, significantly improved mineralization, and increased thickness of the bone cortex in the DBM+EPCs+vascular bundle group. Additionally, in the DBM+EPCs+vascular bundle group, the number of microvessels was significantly higher than that in the other groups at 4, 8, 12 weeks after surgery ( P<0.05), and the angiogenesis and bone tissue regeneration were particularly prominent at 12 weeks after surgery. The number of CD31 cells in the DBM+EPCs+vascular bundle group increased significantly more than that in the DBM, DBM+EPCs and DBM+vascular bundle groups ( P<0.05). Conclusion:As the dual vascularized tissue-engineered bone constructed by vascular bundles and EPCs can significantly promote bone tissue regeneration and angiogenesis, it may be a potential therapeutic strategy for repair of large bone defects.

Objective To investigate prognostic value of serum levels of cathepsin B(CTSB)and NADPH oxidase 4(NOX4)in patients with sepsis associated acute kidney injury(S-AKI).Methods A total of 306 pa-tients with sepsis treated to the hospital from June 2023 to June 2024 were selected,including 192 patients with S-AKI(S-AKI group)and 114 patients without S-AKI(non-S-AKI group).According to the prognosis of S-AKI patients,they were divided into poor prognosis group(n=127)and non-poor prognosis group(n=65).The differences of CTSB and NOX4 in different groups were compared.Pearson analysis was conducted to analyze the correlation between CTSB,NOX4 and clinical indicators.The influencing factors of poor prognosis in S-AKI patients was analyzed according to multivariate Logistic regression.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTSB and NOX4 on the poor prognosis of S-AKI pa-tients.Results Th e serum levels of CTSB,NOX4 and serum creatinine(SCr)in S-AKI group were signifi-cantly higher than those in non-S-AKI group(P＜0.05),while the mean arterial pressure and oxygenation in-dex were lower than those in non-S-AKI group(P＜0.05).Serum levels of CTSB and NOX4 in patients with sepsis were positively correlated with SCr(P＜0.05).Compared to non-poor prognosis group,the age,SCr,CTSB and NOX4 of patients in the poor prognosis group were higher,while the mean arterial pressure and ox-ygenation index were lower(P＜0.05).The increased mean arterial pressure and oxygenation index were pro-tective factors for poor prognosis in S-AKI patients(P＜0.05),and the increased age,SCr,CTSB and NOX4 levels were risk factors for poor prognosis in S-AKI patients(P＜0.05).ROC curve showed that the area un-der the curve(AUC)of CTSB combined with NOX4 was significantly higher than AUC of single detection of CTSB and NOX4(Z=4.066,P＜0.001,Z=3.801,P＜0.001).Conclusion The serum levels of CTSB and NOX4 in S-AKI patients are elevated,and can indirectly reflect kidney function.CTSB combined with NOX4 can significantly improve the prediction efficiency of poor prognosis in S-AKI patients,which has potential ap-plication value for clinical treatment and nursing.

Objective:To investigate the effects of dual vascularized tissue-engineered bone constructed by vascular bundles and endothelial progenitor cells (EPCs) on repair of large bone defects and vascular regeneration.Methods:EPCs were seeded on the demineralized bone matrix (DBM) scaffolds and cultured for 6 days. The attachment and morphology of EPCs on DBM scaffolds were observed by electron microscopy. Next, the radial artery was implanted into a vascular groove opened inside the DBM-EPCs composite scaffolds. Finally, models of a large segmental bone defect were constructed using the radii from 18 New Zealand white rabbits. The rabbits were randomly divided into 4 groups using a simple random sampling method: DBM group, DBM+EPCs group, DBM+vascular bundle group, and DBM+EPCs+vascular bundle group. The DBM group and DBM+EPCs group shared the same rabbits so that transplantations were conducted into the left and right forearms respectively; the DBM+vascular bundle group and DBM+EPCs+vascular bundle group also shared the same rabbits so that transplantations were conducted into the left and right forearms respectively. Consequently, there were 9 experimental sites in each group. X-ray examination and gross morphological observation were performed to evaluate the bone regeneration in the experimental rabbits in each group at 4, 8, and 12 weeks after surgery, and CD31 immunofluorescence staining was used to evaluate the vascular regeneration. Micro-CT was used to analyze bone tissue parameters and reconstruct the three-dimensional structures of the defects site at 12 weeks after surgery.Results:Compared with the DBM, DBM+EPCs and DBM+vascular bundle groups, the DBM+EPCs+vascular bundle group showed new bone tissue crawling on the scaffold surface at 4 weeks after surgery, almost complete healing of the bone defect area at 8 weeks, and forming of a complete and dense bone bridge and appearance of a bone marrow cavity at 12 weeks. Micro-CT data at 12 weeks after surgery showed regular arrangement of the trabeculae, significantly improved mineralization, and increased thickness of the bone cortex in the DBM+EPCs+vascular bundle group. Additionally, in the DBM+EPCs+vascular bundle group, the number of microvessels was significantly higher than that in the other groups at 4, 8, 12 weeks after surgery ( P<0.05), and the angiogenesis and bone tissue regeneration were particularly prominent at 12 weeks after surgery. The number of CD31 cells in the DBM+EPCs+vascular bundle group increased significantly more than that in the DBM, DBM+EPCs and DBM+vascular bundle groups ( P<0.05). Conclusion:As the dual vascularized tissue-engineered bone constructed by vascular bundles and EPCs can significantly promote bone tissue regeneration and angiogenesis, it may be a potential therapeutic strategy for repair of large bone defects.

Infections associated with orthopaedic implants are currently one of the major concerns of orthopaedic surgeons. Metallic antimicrobial nanocoatings have demonstrated great potential in preventing implant infections due to their excellent antimicrobial properties and biocompatibility. However, there are potential risks associated with these metal nanoparticles, such as cytotoxicity of silver and copper, and rapid dissolution of zinc and magnesium which affects implant stability. Therefore, the clinical application of nanometallic coatings still faces challenges in how to better enhance biosafety, regulate degradation rate, and enhance osseointegration. This paper reviews the progress and challenges in the application of antimicrobial nanometallic coatings on implants to provide a reference for related research.

Tissue engineering bone technology, grounded in seed cells, cytokines, and scaffold supports, provides an effective solution for addressing extensive bone defects, demonstrating significant potentials in the field of bone repair. However, this technology still faces numerous challenges. Focusing on vascularization in engineered bones, this article reviews various methods to enhance vascularization within tissue-engineered bones, including multicellular co-culture, application of angiogenic factors, advanced 3D printing, and aid of surgical interventions. This article also analyses the latest research developments and the limitations of the methods, and speculates future research directions for tissue engineered bone.

Objective:To analyze the clinical characteristics, muscle imaging and pathological features of patients with anti-signal recognition particle positive immune-mediated necrotizing myopathy (SRP-IMNM).Methods:Nine patients with SRP-IMNM were collected in the Neuromuscular Disease Center of Jiaozuo People′s Hospital from May 2018 to May 2023, who were confirmed by skeletal muscle pathology and myositis-specific autoantibodies detection, and their clinical manifestations, muscle imaging and muscle pathology characteristics were systematically summarized.Results:Among the 9 patients with SRP-IMNM, there were 7 females and 2 males. The age of onset ranged from 18 to 59 years. All the patients presented proximal muscle weakness. Seven patients experienced neck weakness, and dysphagia was present in 5 patients. Laboratory examinations showed elevated serum creatine kinase levels in all 9 patients (1 866-6 725 U/L). Eight patients were combined with other antibodies positivity, except for anti-SRP antibody. Among them, 7 patients were combined with anti-Ro-52 antibody positivity, 4 patients combined with anti-Ro-52 antibody positivity alone, and 3 patients combined with 3 or more positive antibodies simultaneously. Those patients who presented with interstitial lung disease and cardiac involvement were all combined with other antibodies positivity. Seven patients completed thigh muscle magnetic resonance imaging (MRI), which showed diffuse skeletal muscle oedema, partial muscle atrophy and fatty replacement, primarily affecting the posterior thigh muscle group. Two patients underwent shank muscle MRI. The soleus involvement was evident, while the tibialis anterior muscle and gastrocnemius muscles were involved in 1 patient. All 9 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies. In 1 patient, a small amount of inflammatory cell infiltration was observed. Pipestem capillaries were observed in 4 patients. Immunohistochemical staining revealed a small number of CD68-positive lymphocytes in 8 patients. Additionally, 5 patients showed upregulation of major histocompatibility complex Ⅰ expression on the muscle fiber membrane, while 6 patients showed deposition of membrane attack complex (C5b-9) on non-necrotic muscle fibers and capillaries. P62 staining showed homogeneous fine-granular in sarcoplasm in 6 patients.Conclusions:In addition to proximal muscle weakness, patients with SRP-IMNM often experience neck weakness and dysphagia. Those with multiple antibodies are more likely to develop interstitial lung disease and cardiac involvement. SRP-IMNM patients have diffuse oedema in the affected muscles, and the posterior thigh muscles are more prone to atrophy and fatty tissue formation. C5b-9 deposition and pipestem capillaries are significant pathological features of SRP-IMNM, which provide additional evidence for clinical diagnosis.

Objective:To investigate the clinical phenotypes, muscle magnetic resonance imaging (MRI) and pathological changes, and genetic characteristics of myfibrillar myopathies (MFMs) cuased by MYOT gene mutation. Methods:(1) The clinical data of a MFMs family caused by a de novo frameshift mutation in MYOT gene admitted to Department of Neurology, Jiaozuo People's Hospital Affiliated to Xinxiang Medical University in February 2021 were collected. Electromyography, muscle MRI, and pathological examination were used to confirm the changes of the muscle lesions. MYOT gene mutation in the proband and other patients was detected by next generation sequencing (NGS) and Sanger sequencing, respectively. The 3D structure models of myotilin protein before and after gene mutation were predicted by AlphaFold3 and pymol3. (2) Literature on MFMs caused by MYOT gene mutation was searched from Pubmed and China National Knowledge Infrastructure from the establishment of these databases to July 2024; clinical and genetic characteristics of MFMs caused by MYOT gene mutation were summarized. Results:(1) In the 9 patients from this family, 8 had onset in adolescence (16-20 years old). Unilateral or bilateral hand muscle weakness as the first symptoms appeared in most patients, and then, hand muscle atrophy gradually appeared and slowly progressed to the proximal limbs. Electromyography showed myogenic damage. Muscle MRI showed patchy long T1 and long T2 signal intensity in the bilateral anterior tibial muscles. Muscle pathological staining showed typical rimbed vacuoles, cytoplasm, smear-like muscle fibers and desmin abnormal deposition in some muscle fibers; electron microscopy revealed disorganized myofibril structures, focal myofibril lysis, Z-band streaming, and subsarcolemmal or myofibril mitochondrial accumulation. Heterozygous mutation in MYOT gene c.680_683del (p.Val227GlufsTer10) locus was noted in 8 patients and daughter of the proband. Bioinformatics analysis suggested that MYOT gene c.680_683del mutation could cause premature termination of myotilin translation, leading to the production of a truncated protein, thereby disrupting its normal structure and function. (2) Eighty-nine patients with MFMs caused by MYOT gene mutation in previous literature mainly manifested as chronic progressive weakness of the distal or proximal limbs, with some involving the myocardium, respiratory muscles, or peripheral nerves. A total of 12 MYOT gene mutations were identified, with p. Ser60phe being the most common mutation. Except for p.Tyr4_his9del, being an in-frame mutation, the others were missense mutations. Conclusion:MFMs caused by MYOT gene mutation exhibit obvious clinical heterogeneity, characterized by very slow progression of muscle weakness; MYOT gene locus c.680_683del (p.Val227GlufsTer10) is a de novo heterozygous mutation.

Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.