FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Modular intercalary prosthetic reconstruction for malignant and metastatic tumours of the proximal femur.

To illustrate the surgical technique and explore clinical outcomes of the reconstruction for the malignant and metastatic bone tumour of proximal femur with metallic modular intercalary prosthesis. Sixteen patients who underwent modular intercalary prosthetic reconstruction after tumour resection were included from April 2012 and October 2020. Prosthesis and screws parameters, resected bone length and residual bone length, clinical outcomes and survivorship were analyzed. All patients were followed up for an average of 19 months (range 1-74). In our series, 12 patients died of the progression of the primary disease at the final follow-up. The cumulative survivorship since the treatment of proximal femoral metastasis was 78.6% (11 patients) at 6 months and 38.5% (5 patients) at 1 year. The mean MSTS score was 22.25 ± 4.55 among all patients. There were no cases of loosening or breakage of the prostheses, plates or screws, despite the various measurements of prostheses and residual bones. Modular intercalary prosthetic reconstruction was an effective method for malignant tumour of the proximal femur, including the advantages of providing early pain relief, quickly restoring postoperative function, required a short operation time, and preserving the adjacent joints.

Preparation and property analysis of antioxidant of carbazole derivatives.

Carbazole derivatives can be used as antioxidants in the lubricating oil industry. The alkylation of carbazole with 2-chloro-2-methylpropane and 2-bromopropane catalyzed by anhydrous aluminum chloride was studied. Initially, 3,6-di-iso-propylcarbazole and 3,6-di-tert-butylcarbazole were using dichloromethane and dibromomethane as solvents at room temperature, respectively. The synthesis conditions were optimized. Subsequently, the effects of reaction time, catalyst dosage, and molar ratio of carbazole to alkylating agent were investigated, and orthogonal experiments were performed. The structures of the carbazole derivatives were characterized by Fourier infrared spectroscopy (FT-IR), mass spectrum (MS) and nuclear magnetic resonance spectroscopy (NMR). The thermal stability of the synthesized carbazole derivatives was investigated by differential scanning calorimetry (DSC). The carbazole derivatives were added into the lubricating oil with a mass fraction of 0.8% and the miscibility, stability and oxidation resistance of the mixed system were evaluated by mechanical stirring and a rotary pressure vessel oxidation test (RPVOT). The DSC results showed that there was good thermal stability for the carbazole derivatives. The mechanical stirring method revealed good solubility and stability for the mixture of oil and carbazole derivatives. The RPVOT results showed that isopropyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.39 times, and tert-butyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.91 times. The antioxidant effect of tert-butyl carbazole derivatives was better than that of isopropyl carbazole derivatives.

Relationship between bedtime, nighttime sleep duration, and anxiety symptoms in preschoolers in China.

Background: Sleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms. Methods: A cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined. Results: The bedtimes of preschoolers were concentrated between 21:01-22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01-23:00 and 21:01-22:00 were 2.86 (2.21-3.69), 1.51 (1.27-1.79) and 1.48 (1.26-1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23-1.51). Conclusion: An association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children.

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.

[Clinical Efficacy of Hypomethylating Agent Therapy in Patients with Chronic Myelomonocytic Leukemia].

OBJECTIVE: To observe the clinical efficacy and safety of hypomethylating agent therapy in chronic myelomonocytic leukemia (CMML). METHODS: From February 2014 to June 2021, the clinical data, efficacy, survival time and safety of CMML patients diagnosed in the Second Hospital of Hebei Medical University and treated with hypomethylating agent therapy were retrospectively analyzed. RESULTS: A total of 25 CMML patients received hypomethylating agent therapy, including 18 cases treated with decitabine (DEC) and 7 cases treated with azacytidine (AZA) as the basic treatment. Among them, 20 patients responded, and 7 patients got complete remission (CR). All patients with CR were treated with DEC as the basic treatment. Five cases of CR occurred in the first 4 courses of treatment. After a median follow-up of 16.4 (9.4-20.5) months, 4 patients with CR progressed to acute myeloid leukemia (AML). The median overall survival (OS) time of 25 CMML patients was 17.4 months (95%CI: 12.437-22.363). According to MD Anderson prognostic scoring system (MDAPS), CMML-specific prognostic scoring system (CPSS), CPSS molecular (CPSS-mol), Mayo molecular model (MMM), risk stratification of patients was performed, and the difference only between different risk stratification of MDAPS and survival time was statistically significant. Common adverse reactions of hypomethylating agent therapy in CMML patients included infection, gastrointestinal reaction, hematological toxicity, skin allergy and liver function damage. All patients' symptoms were improved after corresponding treatment. CONCLUSION: Hypomethylating agent therapy is effective and safe for CMML patients. CR mostly occurs in the first 4 courses of treatment, and hypomethylating agent therapy combined with low-dose chemotherapy can be used for patients who do not respond. Hypomethylating agent therapy can delay the disease, but can't prevent progression.

Cadinane sesquiterpenes from the stems and branches of Illicium ternstroemioides.

Three new cadinane sesquiterpenes (1-3) and three known sesquiterpenes were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and HRESIMS data. The structures of illiternins A-C (1-3) were confirmed by single crystal X-ray diffraction, allowing for the determination of their absolute configurations. Compounds 3 and 6 exhibited antiviral activity against Coxsackievirus B3 with IC50 values of 33.3 and 57.7 µM, respectively.

Bi-ligand-fabricated CdS quantum dots to photo-induce aqueous-phase aldol condensation for biomass-derived carbonyl compounds.

CdS QDs were fabricated using bi-ligands 11-sulfanylundecanoic acid and proline for photo-induced aqueous-phase aldol condensation of biomass-derived furfural compounds and ketones, and they displayed acceptable selectivity, activity and recycling properties for generation of a wide range of products with diverse applications. This work facilitates understanding the molecular-level design concepts of semiconductor photocatalysts.

A meta-analysis of the efficacy and safety of the traditional Chinese medicine formula Kaixinsan decoction for depression.

BACKGROUND: Kaixinsan (KXS) decoction is a traditional Chinese herbal formulation commonly used to treat depression. This study aimed to evaluate the efficacy and safety of KXS, which is widely used, alone and in combination with other therapies, for the treatment of depression. The main objective was to assess the efficacy and safety of KXS in the treatment of depression as a single agent or in combination with other methods. METHODS: Randomized controlled trials of KXS in the treatment of depression were systematically searched from several Chinese and English databases with no language restriction. Patients in these studies met the relevant diagnostic criteria for depression. Data on HAMD, SDS, practical situations, and occurrence of side effects in the studies were extracted. Finally, the methodological quality and risk of bias of the included studies were assessed using the Jadad scale and Cochrane bias evaluation tool. RESULTS: Twelve studies with 1034 patients were included after screening. The Jadad scale and Cochrane bias evaluation tool indicated that the quality of the studies ranged from fair to good, with 41.7% categorized as good and 58.3% as poor. Egger test and funnel plots showed that the publication bias remain low. CONCLUSION: The results showed that the frequency of side effects in the control group was higher than that in the treatment group, and there was a statistically significant difference. KXS was comparable or superior to antidepressants in treating depression and has fewer side effects. The data analysis showed that effectiveness and other indicators differed significantly by geographic area and dosage form, which has implications for future clinical work.

Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty.

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB.

Metadherin inhibits chemosensitivity of triple-negative breast cancer to paclitaxel via activation of AKT/GSK-3ß signaling pathway.

Triple-negative breast cancer (TNBC) has an aggressive clinical course, and paclitaxel (PTX)-based chemotherapy remains the main therapeutic drug. Metadherin (MTDH) acts as an oncogene that regulates proliferation, invasion, metastasis, and chemoresistance. This study aimed to investigate whether TNBC chemosensitivity to PTX was related to the MTDH/AKT/glycogen synthase kinase-3beta (GSK-3ß) pathway. Clinical baseline characteristics and immunohistochemistry (IHC) were used to evaluate the expression and prognosis of MTDH and AKT (protein kinase B, PKB) in TNBC patient samples. MTDH shRNA, MTDH overexpression vector, MK-2206, and PTX intervention were used in cell models and mouse tumor-bearing models. Afterwards, mRNA and protein levels were assessed using quantitative real-time polymerase chain reaction and Western blot. Evaluate the level of tumor cell apoptosis and cell cycle using flow cytometry. Cell viability was detected using Cell Count Kit 8. The in vivo imaging system is used to analyze the growth of tumors. We found that higher expression of MTDH or AKT resulted in poorer disease-free survival and a lower Miller-Payne grade. MTDH promotes cell proliferation and increases p-AKT and p-GSK-3ß expression in TNBC cells. Notably, suppression of AKT terminated MTDH overexpression-induced cell proliferation and apoptosis. MTDH knockdown or the AKT inhibitor MK2206 reduced the p-AKT and p-GSK-3ß ratio, reduced cell viability and proliferation, increased cell apoptosis, and increased chemosensitivity to PTX. In vivo, xenograft tumors of an MTDH knockdown+MK2206 group treated with PTX were the smallest compared to other groups. In short, MTDH inhibits TNBC chemosensitivity to PTX by activating the AKT/GSK-3ß signaling pathway.

Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial.

BACKGROUND: Despite the usefulness of white light endoscopy (WLE) and non-magnified narrow-band imaging (NBI) for screening for superficial oesophageal squamous cell carcinoma and precancerous lesions, these lesions might be missed due to their subtle features and interpretation variations among endoscopists. Our team has developed an artificial intelligence (AI) system to detect superficial oesophageal squamous cell carcinoma and precancerous lesions using WLE and non-magnified NBI. We aimed to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. METHODS: We did a multicentre, tandem, double-blind, randomised controlled trial at 12 hospitals in China. Eligible patients were aged 18 years or older and underwent sedated upper gastrointestinal endoscopy for screening, investigation of gastrointestinal symptoms, or surveillance. Patients were randomly assigned (1:1) to either the AI-first group or the routine-first group using a computerised random number generator. Patients, pathologists, and statistical analysts were masked to group assignment, whereas endoscopists and research assistants were not. The same endoscopist at each centre did tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-first group, the endoscopist did the first examination with the assistance of the AI system and the second examination without it. In the routine-first group, the order of examinations was reversed. The primary outcome was the miss rate of superficial oesophageal squamous cell carcinoma and precancerous lesions, calculated on a per-lesion and per-patient basis. All analyses were done on a per-protocol basis. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100052116) and is completed. FINDINGS: Between Oct 19, 2021, and June 8, 2022, 5934 patients were randomly assigned to the AI-first group and 5912 to the routine-first group, of whom 5865 and 5850 were eligible for analysis. Per-lesion miss rates were 1·7% (2/118; 95% CI 0·0-4·0) in the AI-first group versus 6·7% (6/90; 1·5-11·8) in the routine-first group (risk ratio 0·25, 95% CI 0·06-1·08; p=0·079). Per-patient miss rates were 1·9% (2/106; 0·0-4·5) in AI-first group versus 5·1% (4/79; 0·2-9·9) in the routine-first group (0·37, 0·08-1·71; p=0·40). Bleeding after biopsy of oesophageal lesions was observed in 13 (0·2%) patients in the AI-first group and 11 (0·2%) patients in the routine-first group. No serious adverse events were reported by patients in either group. INTERPRETATION: The observed effect of AI-assisted endoscopy on the per-lesion and per-patient miss rates of superficial oesophageal squamous cell carcinoma and precancerous lesions under WLE and non-magnified NBI was consistent with substantial benefit through to a neutral or small negative effect. The effectiveness and cost-benefit of this AI system in real-world clinical settings remain to be further assessed. FUNDING: National Natural Science Foundation of China, 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University, and Chengdu Science and Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

[Research progress on Rhododendron molle in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

Progress of research on organ protection of acupuncture and moxibustion in the prevention and treatment of sepsis. / é’ˆåˆºé˜²æ²»è„“æ¯’ç—‡çš„å™¨å®˜ä¿æŠ¤ä½œç”¨åŠæœºåˆ¶ç ”ç©¶è¿›å±•.

Sepsis is a major disease that threatens human life and health. Clinically, it is mainly based on supportive treatment and lacks specific treatment methods. Acupuncture has important clinical significance in the prevention and treatment of sepsis. In the present paper, we systematically searched CNKI and PubMed databases, included the clinical trials and animal experiments on the prevention and treatment of sepsis with acupuncture, summarized the clinical efficacy and the mechanism of acupuncture. Results indicate that the role of acupuncture therapies in improving sepsis involves inhibiting systemic inflammatory response, alleviating oxidative stress, regulating immune system, and resisting cell apoptosis, thus having a protective effect on multiple organs. The mechanism involves multiple signaling pathways and related factors.

Prenylated C6-C3 derivatives from the root of Illicium ternstroemioides with antiviral activity.

Six previously undescribed prenylated C6-C3 derivatives (1-6) were isolated from the root of Illicium ternstroemioides A. C. Smith. Their structures were elucidated based on extensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of 1-3 were determined using electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD). Compound 3 exhibited weak activity against Coxsackievirus B3 with an IC50 value of 33.3 µM, and compound 5 exhibited more potent activity against Coxsackievirus B3 with an IC50 value of 6.4 µM.

Postoperative Functional Assessment in Patients with Tumors Around the Knee Treated with Endoprosthetic Reconstruction: A Multicenter Retrospective Cohort Study.

OBJECTIVES: The restoration of as much normal function as possible has become an important goal following the endoprosthetic reconstruction. The objective of this study was to assess the functional outcome after endoprosthetic reconstruction for tumors around the knee and to explore prognostic factors of functional outcome. METHODS: We retrospectively collected data on patients who underwent tumor prosthetic replacements consecutively. Musculoskeletal Tumour Society score and Toronto Extremity Salvage Score were used to assess the functional outcome at 1, 3, 6, 12, and 24 months after surgery. The logistic model was used to select factors that had potential predictive value for postoperative function. Potential prognostic factors included age, gender, tumor site, type of tumor, length of bone resection, type of prosthesis, length of prosthetic stem, chemotherapy, pathological fracture, and body mass index. RESULTS: At the 24 months after surgery, the mean musculoskeletal tumor society (MSTS) score was 81.4% and the mean Toronto extremity salvage score (TESS) was 83.6%. At the last follow-up, 68% of patients and 73% of patients received perfect or good MSTS score and TESS score, respectively. The multivariate analysis according to ordered-logit model showed that age < 35 years, distal femoral prosthesis, and length of bone resection < 14 cm were independent prognostic factors of better functional outcome. CONCLUSIONS: Endoprosthetic reconstruction may provide good functional results for most patients. Younger patients with distal femoral prosthesis and shorter resection of bone (on the premise of complete resection of tumor) are more likely to obtain satisfactory functional results after surgery.

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.

Comparison of demineralized bone matrix with different cycling crushing times in posterolateral fusion model of athymic rats.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.

A biphasic calcium phosphate/acylated methacrylate gelatin composite hydrogel promotes osteogenesis and bone repair.

PURPOSE/AIM: Bone defects caused by trauma, tumors, congenital malformation, or inflammation are very common in orthopedics. In recent years, mimicking the composition and structure of natural bone tissue has become a hot topic in biomaterial research, with the aim of developing an ideal biomaterial for bone defect transplantation. Here, the feasibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel to repair bone defects was evaluated in vitro and in rats. MATERIALS AND METHODS: The biocompatibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel was evaluated by cytoskeleton staining, live/dead cell staining and cell proliferation assays. The in vitro osteogenic activities of the composite hydrogel were evaluated by alkaline phosphatase and alizarin red staining, as well as osteogenic gene expression analysis at both transcript and protein levels. The in vivo bone repair activities were evaluated using the rat skull defect model. RESULTS: The BCP/GelMA composite hydrogel displayed excellent biocompatibility and promoted osteogenesis of bone marrow mesenchymal stem cells in vitro. In addition, the BCP/GelMA composite hydrogel markedly promoted new bone formation in the rat skull-defect model. CONCLUSIONS: BCP/GelMA composite hydrogel may be an effective artificial material for bone tissue engineering.