Prolonged efficacy of cefazolin in intraosseous regional prophylaxis for total knee arthroplasty: a rabbit model study.

BACKGROUND: A novel approach known as intraosseous regional administration (IORA) has emerged as a technique for delivering prophylactic antibiotics, and it results in higher tissue concentrations around the knee. It is hypothesized that IORA of cefazolin for antibiotic prophylaxis during total knee arthroplasty will result in sustained effective levels for a longer duration. The aim of the current study was to investigate temporal changes in peri-knee cefazolin blood concentrations after IORA of cefazolin. METHODS: Twelve rabbits were randomly divided into two groups, with six rabbits in each group. In control group a single intravenous bolus injection of cefazolin (10 mL, 100 mg) was administered into the marginal ear vein. In experimental groupexperimental group the same dose of cefazolin was injected into the left tibial marrow cavity after tourniquet inflation at the base of the left thigh. Blood samples were collected periodically at different timepoints, and cefazolin concentrations were determined. RESULTS: The intraosseous treatment resulted in significant differences in plasma cefazolin concentrations at all timepoints. Experimental group exhibited higher plasma cefazolin concentrations than control group. CONCLUSIONS: Cefazolin in intraosseous regional prophylaxis exhibits effectiveness in intraoperative antibiotic prophylaxis by maintaining concentrations above the minimum inhibitory concentration for extended durations, rather than relying solely on high concentrations.

Telomerase Reverse Transcriptase and p53 Regulate Mammalian Peripheral Nervous System and CNS Axon Regeneration Downstream of c-Myc.

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.

c-Myc controls the fate of neural progenitor cells during cerebral cortex development.

The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex.

Calcium/calmodulin-dependent protein kinase II regulates mammalian axon growth by affecting F-actin length in growth cone.

While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+ ) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.

Regulation of adult mammalian intrinsic axonal regeneration by NF-κB/STAT3 signaling cascade.

The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.

Effects of erythropoietin for precaution of steroid-induced femoral head necrosis in rats.

BACKGROUND: Steroids such as glucocorticoid have been widely used for their excellent anti-inflammatory, anti-immune, and anti-shock properties. However, the long-term use in high doses has been found to cause necrosis of femoral head and other serious adverse reactions. Thus, it is of great importance to safely use these medications on patients without inducing bone necrosis. METHODS: In this preclinical study, we examined the effects of erythropoietin (EPO) to attenuate the induction of steroid-induced femoral bone necrosis using rats to build up the in-vivo models. Rats were randomly divided into three groups: negative control group (group A), disease group (group B), and EPO group (group C). 20 mg/kg methylprednisolone was administrated into group B and group C for 6 weeks with two intramuscular injections per week per rat. Group C was further given daily intraperitoneal injections of rHuEPO during this period. Group A received only injection of saline at the same schedule. 12 weeks after the initial drug administration, the rats' femoral tissues were harvested for HE staining, immunohistochemistry studies for PECAM-1(also CD31) expression and Western Blotting for VEGF expression. RESULTS: Histology studies showed that compared with the disease group, EPO group had significant improvement and bone morphology being much closer to the negative control group. Immunohistochemical studies revealed that EPO group had statistically much more expression of PECAM-1 than the other groups did. Western Blot demonstrated that the EPO group had significantly higher VEGF expression than the disease group. CONCLUSION: Results suggested that simultaneous injection of EPO could partially prevent steroid-induced ANFH.

Devosia honganensis sp. nov., isolated from the soil of a chemical factory.

A Gram-negative, strictly aerobic, yellow-pigmented and rod-shaped bacterium, designated strain NSL10(T), was isolated from the waste surface soil of a chemical factory in Hongan, China. Strain NSL10(T) was found to grow optimally at pH 7.0, 30 °C and in the absence of NaCl in modified LB medium. Cells were found to be positive for catalase and oxidase. The G+C content of the total DNA was determined to be 66.8 mol%. The 16S rRNA gene sequence of strain NSL10(T) showed the highest similarity to that of Devosia albogilva IPL15(T) (96.80 %), followed by Devosia geojensis BD-c194(T) (96.46 %) and Devosia chinhatensis IPL18(T) (96.27 %). The major cellular fatty acids of strain NSL10(T) were identified as C18:1 ω7c/C18:1 ω6c (48.2 %) and C16:0 (17.7 %). The major polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and an unidentified compound. Minor amounts of unidentified glycolipids and unidentified polar lipids were also detected. These chemotaxonomic data supported the affiliation of strain NSL10(T) to the genus Devosia. In conclusion, on the basis of biochemical, physiological characteristics and molecular properties, strain NSL10(T) represents a novel species within the genus Devosia, for which the name Devosia honganensis sp. nov., is proposed. The type strain is NSL10(T) (=KCTC 42281(T) = ACCC 19737(T)).

A method of percutaneous vertebroplasty under the guidance of two C-arm fluoroscopes.

OBJECTIVE: To compare the clinical application in the percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. METHODS: One hundred forty three elderly patients with Osteoporotic vertebral compression fractures (OVCFs) underwent percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. The number of pulsed imagings, the time of operation and the incidence of cement leakage were recorded. RESULTS: The average number of pulsed imagings was 16.00±1.58 vs 13.07±2.00 per patient under the guidance of one vs two C-arm fluoroscopes. The average time of operation was 48.42±5.00 minutes vs 39.70±7.42 minutes per patient under the guidance of one vs two C-arm fluoroscopes. The incidence of cement leakage was 20% vs 15.7% of the patients under the guidance of one vs two C-arm fluoroscopes. The differences in the number of pulsed imagings and the time of operation were statistically significant. The difference in incidence of cement leakage was not statistically significant. CONCLUSION: The two-fluoroscopic technique reduce the labor cost, the radiation, the time of operation and the operation risk.

The top 100 most cited articles on axon regeneration from 2003 to 2023: a bibliometric analysis.

Objective: In this study, we used a bibliometric and visual analysis to evaluate the characteristics of the 100 most cited articles on axon regeneration. Methods: The 100 most cited papers on axon regeneration published between 2003 and 2023 were identified by searching the Web of Science Core Collection database. The extracted data included the title, author, keywords, journal, publication year, country, and institution. A bibliometric analysis was subsequently undertaken. Results: The examined set of 100 papers collectively accumulated a total of 39,548 citations. The number of citations for each of the top 100 articles ranged from 215 to 1,604, with a median value of 326. The author with the most contributions to this collection was He, Zhigang, having authored eight papers. Most articles originated in the United States (n = 72), while Harvard University was the institution with the most cited manuscripts (n = 19). Keyword analysis unveiled several research hotspots, such as chondroitin sulfate proteoglycan, alternative activation, exosome, Schwann cells, axonal protein synthesis, electrical stimulation, therapeutic factors, and remyelination. Examination of keywords in the articles indicated that the most recent prominent keyword was "local delivery." Conclusion: This study offers bibliometric insights into axon regeneration, underscoring that the United States is a prominent leader in this field. Our analysis highlights the growing relevance of local delivery systems in axon regeneration. Although these systems have shown promise in preclinical models, challenges associated with long-term optimization, agent selection, and clinical translation remain. Nevertheless, the continued development of local delivery technologies represents a promising pathway for achieving axon regeneration; however, additional research is essential to fully realize their potential and thereby enhance patient outcomes.

A Bibliometric study of the top 100 most-cited papers in high tibial osteotomy.

Background: High tibial osteotomy (HTO) is a well-established surgical procedure employed to treat medial compartment knee osteoarthritis by modifying the mechanical axis of the lower limb, thereby reducing the load on the affected joint. It has gained increased attention in recent years, resulting in numerous research advancements in this field. Methods: The top 100 most-cited papers on HTO, published between 1970 and 2023, were identified by searching the Web of Science Core Collection database. Data, including the title, author, keywords, journal, publication year, country, and institution, were extracted. Subsequently, a bibliometric analysis was performed. Results: The 100 papers collectively garnered a total of 15 833 citations, with a median of 122 and an average of 158.33 citations per article. Since the onset of the 21st century, there has been a significant increase in the number of publications and citations. Lobenhoffer authored the most published papers. The majority of papers originated from the USA. Hannover Medical School produced the most papers. Analysis of keywords in the articles revealed several research hotspots, including open-wedge osteotomy, biomechanical study, tibial slope, patellar height, Puddu plate, TomoFix plate, stability, complications, and accuracy. Conclusion: This study offers bibliometric insights into HTO, underscoring that the USA is a prominent leader in this field. HTO has garnered increasing attention since the onset of the 21st century and is expected to remain a significant research area in the future. Concurrently, the authors advise focusing on potential research hotspots, such as the navigation system, to augment the accuracy of the correction.

Arthritis of the hip caused by arteriovenous malformations: A case report.

BACKGROUND Arthritis of the hip caused by arteriovenous malformations (AVMs) has been rarely reported. Therefore, total hip replacement (THR) in patients with AVM-induced arthritis of the hip is challenging. CASE SUMMARY We report a 44-year-old woman with aggravated right hip pain during the past decade. The patient presented with severe pain and a functional disorder of the right hip. X-ray examination revealed severely narrowed right hip joint space and abnormal trabecular bone loss in the femoral neck and trochanter area. Doppler ultrasound, magnetic resonance imaging and computed tomography angiography revealed AVMs surrounding the right hip, along with erosion. To ensure the safety of THR, we performed vascular embolization and temporary balloon occlusion of the iliac artery three times during the operation. However, serious hemorrhage occurred, which was rescued by the multimodality blood conservation strategy. THR was successfully performed, and the patient was discharged 8 d later for rehabilitation. Postoperative pathological examination showed osteonecrosis of the femoral head with malformed thick-walled vessels and focal granulomatous inflammation of the surrounding soft tissues. The Harris Hip Scale score increased from 31 to 82 at 3 mo of follow-up. The patient was followed up for 1 year, and all her clinical symptoms were significantly alleviated. CONCLUSION Arthritis of the hip caused by AVMs is rare in clinical practice. The activity and function of the involved hip joint can be effectively treated with THR after comprehensive imaging and multidisciplinary consultation.

Heel pain caused by os subcalcis: A case report.

BACKGROUND: The accessory bones are common bone variations around the feet and ankles, which usually originate from nonunion of the secondary ossification center adjacent to the main bone mass, and most of them remain asymptomatic. Os subcalcis is an accessory bone at the plantar aspect of the calcaneus, which is located just posterior to the insertion of the plantar fascia. Focal bone formation at the calcaneal plantar pole with heel pain has rarely been reported. CASE SUMMARY: A 55-year-old man presented to our clinic with left plantar heel pain and a progressive swelling for 8 years. X-ray, computer tomography and magnetic resonance imaging showed a large os subcalcison the plantar side of the calcaneus, located at the insertion of the plantar fascia. He underwent surgical excision of the lesion. Microscopically the bony trabeculae were intermingled with fat and covered with cartilage. CONCLUSION: This is a rare case with accessory os subcalcis leading to heel pain. It highlights the awareness of os subcalcis and helps avoid future misdiagnosis of heel pain.

Proteomics and bioinformatics analysis of cardiovascular related proteins in offspring exposed to gestational diabetes mellitus.

Introduction: Previous studies have demonstrated that exposed to the initial suboptimal intrauterine environment of gestational diabetes mellitus (GDM) may increase risk of cardiovascular disease in adulthood. Methods: In order to investigate the underlying mechanisms involved in the increased risk of cardiovascular diseases (CVDs) in the offspring of GDM, we applied a high-throughput proteomics approach to compare the proteomic expression profile of human umbilical vessels of normal and GDM offspring. Results: A total of significantly different 100 proteins were identified in umbilical vessels from GDM group compared with normal controls, among which 31 proteins were up-regulated, while 69 proteins were down-regulated. Differentially expressed proteins (DEPs) are validated using Western blotting analysis. The analysis of these differently expressed proteins (DEPs) related diseases and functions results, performed by Ingenuity Pathway Analysis (IPA) software. Based on "Diseases and Disorders" analysis, 17 proteins (ACTA2, ADAR, CBFB, DDAH1, FBN1, FGA, FGB, FGG, GLS, GSTM1, HBB, PGM3, PPP1R13L, S100A8, SLC12A4, TPP2, VCAN) were described to be associated with CVD, especially in Anemia, Thrombus and Myocardial infarction. Functional analysis indicated that DEPs involved in many cardiovascular functions, especially in "vasoconstriction of blood vessel" (related DEPs: ACTA2, DDAH1, FBN1, FGA, FGB, and FGG). Upstream regulator analyses of DEPs identifies STAT3 as inhibitor of ACTA2, FGA, FGB, and FGG. Conclusion: The results of this study indicate that intrauterine hyperglycemia is associated with an elevated risk of cardiovascular risk in the offspring.

Comparison of Early Clinical Results for Femoral Neck System and Cannulated Screws in the Treatment of Unstable Femoral Neck Fractures.

OBJECTIVE: To compare early clinical effects of the femoral neck system (FNS) and three cannulated screws for the treatment of patients with unstable femoral neck fractures. METHODS: A retrospective analysis with pair matching of 81 patients who received FNS or cannulated screw internal fixation for Pauwels type-3 femoral neck fracture in our hospital from January 2019 to December 2019 was conducted. Patients who received FNS were the test group, and those who received cannulated screws comprised the control group. Matching requirements were as follows: same sex, similar age, and similar body mass index (BMI). A total of 30 pairs were successfully matched at a 1:1 ratio, including 12 males and 18 females. The average age of the patients in the FNS group was 54.53 ± 6.71 years. In the cannulated screw group, the average age of the patients was 53.14 ± 7.19 years. The operation time, intraoperative blood loss, hospital stay, hospitalization cost, postoperative visual analog scale (VAS) score, time to walking without crutches, Harris score, femoral head necrosis rate, and complication rate were compared between the groups. RESULTS: Postoperative re-examination of radiographs showed satisfactory reduction in all patients, and all patients were followed up for 10-22 months. Those in the FNS group had lower postoperative VAS scores, earlier times to walking without crutches, higher Harris scores at the last follow-up, and lower complication rates (P < 0.05). VAS scores were lower in the FNS group (3.13 ± 1.07 scores) than in the cannulated screw group (3.77 ± 1.04 scores) (P = 0.018). Patients in the FNS group (5.23 ± 1.33 months) recovered to walking without crutches earlier than did those in the cannulated screw group (6.03 ± 1.45 months) (P<0.001). In addition, a statistically higher postoperative Harris score was detected in the FNS group (86.16 ± 7.26) than in the cannulated screw group (82.37 ± 7.52) (P = 0.039). Overall, a higher incidence of complications was observed in the cannulated screw group (9/30) than in the FNS group (2/30) (P = 0.042). However, intraoperative blood loss and hospitalization costs were greater in the FNS group (P < 0.05). Intraoperative blood loss was greater in the FNS group (99.73 ± 4.69) than in the cannulated screw group (30.27 ± 9.04) (P<0.001). In addition, patients in the FNS group (46976 ± 2270 ¥) spent more on hospitalization costs than did those in the cannulated screw group (15626 ± 1732 ¥) (P<0.001). No statistically significant difference in operation time, hospital stay, or femoral head necrosis rate was observed between the two groups (P > 0.05). CONCLUSION: For patients with unstable femoral neck fractures, FNS has better clinical efficacy than cannulated screws, though it is also more expensive.

Hydrophilic interaction chromatography combined with ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction for determination of underivatized neurotransmitters in dementia patients' urine samples.

A sensitive, rapid, precise and specific analytical method of hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC-QTRAP®/MS2) combined with a high-efficiency and easy sample preparation technology of ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction (UA-IL-DLLME) was developed to investigate neurotransmitters (NTs) in mild cognitive impairment, mild dementia and moderate dementia patients' urine samples. Firstly, the UA-IL-DLLME parameters were optimized using Plackett-Burman screening and rotatable central composite design, and the main optimal conditions were obtained: ultrasound power of 307 W, ultrasound time of 4.3 min and agitation time of 4.8 min. Secondly, HILIC-UHPLC-QTRAP®/MS2 method was developed to simultaneously determine 15 underivatized NTs in urine samples. The analysis results of clinical samples showed that some NTs such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamic acid (Glu) presented significant differences in different dementia stages. Finally, multivariate analysis based on the combination of principal component analysis and supervised counter propagation artificial neural network was developed for comprehensive analysis of the obtained clinical data sets. As a result, GABA and Glu were simultaneously presented meaningful contribution for classification of samples, and might be considered as potential differential compounds to the urine samples from cluster patients with different dementia stages. In summary, the presented strategy of preparation, analysis and statistics might be used to investigate NTs in different clinical biological fluids.