Different doses of bevacizumab in combination with chemotherapy for advanced colorectal cancer: a meta-analysis and Bayesian analysis.

OBJECTIVE: The aim of the present study was to explore the incremental benefit of bevacizumab (Bev) in the treatment of advanced colorectal cancer (CRC) with different doses. METHODS: A literature search of eight electronic databases (China National Knowledge Infrastructure, Wanfang databases, Chinese Biomedical Database, VIP medicine information, Cochrane Library, MEDLINE, PubMed, and EMBASE) was conducted from database creation to December 2022. Randomized controlled trials (RCTs) that compared Bev at various dosages + chemotherapy (CT) versus placebo (or blank control) + CT were selected. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR; complete response [CR] + partial response [PR]), and grade ≥ 3 adverse events (AEs) were integrated first by pooled analysis. The likelihood of ideal dosage of Bev was then ranked using random effects within Bayesian analysis. RESULTS: Twenty-six RCTs involving 18,261 patients met the inclusion criteria. OS increased significantly after using 5 mg (HR: 0.87, 95% CI 0.75 to 1.00) and 10 mg dosages of Bev (HR: 0.75, 95% CI 0.66 to 0.85) with CT, but statistical significance was not attained for the 7.5 mg dose (HR: 0.95, 95% CI 0.83 to 1.08). A significantly increased in PFS with doses of 5 mg (HR: 0.69, 95% CI 0.58 to 0.83), 7.5 mg (HR: 0.81, 95% CI 0.66 to 1.00), and 10 mg (HR: 0.60, 95% CI 0.53 to 0.68). ORR distinctly increased after 5 mg (RR: 1.34, 95% CI 1.15 to 1.55), 7.5 mg (RR: 1.25, 95% CI 1.05 to 1.50), and10 mg (RR: 2.27, 95% CI 1.82 to 2.84) doses were administered. Grade ≥ 3 AEs increased clearly in 5 mg (RR: 1.11, 95% CI 1.04 to 1.20) compared to 7.5 mg (RR: 1.05, 95% CI 0.82 to 1.35) and 10 mg (RR: 1.15, 95% CI 0.98 to 1.36). Bayesian analysis demonstrated that 10 mg Bev obtained the maximum time of OS (HR: 0.75, 95% CrI 0.58 to 0.97; probability rank = 0.05) indirectly compared to 5 mg and 7.5 mg Bev. Compared with 5 mg and 7.5 mg Bev, 10 mg Bev also holds the longest duration for PFS (HR: 0.59, 95% CrI 0.43 to 0.82; probability rank = 0.00). In terms of ORR, 10 mg Bev holds the maximum frequency (RR: 2.02, 95% CrI 1.52 to 2.66; probability rank = 0.98) in comparison to 5 mg and 7.5 mg Bev clearly. For grade ≥ 3 AEs, 10 mg Bev has the maximum incidence (RR: 1.15, 95% CrI 0.95 to 1.40, probability rank = 0.67) in comparison to other doses of Bev. CONCLUSION: The study suggests that 10 mg dose Bev could be more effective in treating advanced CRC in efficacy, but 5 mg Bev could be more safer in terms of safety.

[Role of histone posttranslational modifications in the regulation of ovarian function].

The ovary is the reproductive organ of female mammals, which is responsible for producing mature eggs and secreting sex hormones. The regulation of ovarian function involves the ordered activation and repression of genes related to cell growth and differentiation. In recent years, it has been found that histone posttranslational modification can affect DNA replication, damage repair and gene transcriptional activity. Some regulatory enzymes mediating histone modification are co-activators or co-inhibitors associated with transcription factors, which play important roles in the regulation of ovarian function and the development of ovary-related diseases. Therefore, this review outlines the dynamic patterns of common histone modifications (mainly acetylation and methylation) during the reproductive cycle and their regulation of gene expression for important molecular events, focusing on the mechanisms of follicle development and sex hormone secretion and function. For example, the specific dynamics of histone acetylation are important for the arrest and resumption of meiosis in oocytes, while histone (especially H3K4) methylation affects the maturation of oocytes by regulating their chromatin transcriptional activity and meiotic progression. Besides, histone acetylation or methylation can also promote the synthesis and secretion of steroid hormones before ovulation. Finally, the abnormal histone posttranslational modifications in the development of two common ovarian diseases (premature ovarian insufficiency and polycystic ovary syndrome) are briefly described. It will provide a reference basis for understanding the complex regulation mechanism of ovarian function and further exploring the potential therapeutic targets of related diseases.

Guidelines for management of pediatric acute hyperextension spinal cord injury.

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.

Assessment of acute traumatic cervical spinal cord injury using conventional magnetic resonance imaging in combination with diffusion tensor imaging-tractography: a retrospective comparative study.

PURPOSE: The application of conventional magnetic resonance imaging (MRI) in combination with diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) to diagnose acute traumatic cervical SCI has not been studied. This study explores the role of MRI with DTI-DTT in the diagnosis of acute traumatic cervical spinal cord injury (SCI). METHODS: Thirty patients with acute traumatic cervical SCI underwent conventional MRI and DTI-DTT. Conventional MRI was used to detect the intramedullary lesion length (IMLL) and intramedullary hemorrhage length (IMHL). DTI was used to detect the spinal cord's fractional anisotropy (FA) and apparent diffusion coefficient value, and DTT detected the imaginary white matter fiber volume and the connection rates of fiber tractography (CRFT). Patients' neurological outcome was determined using the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades. RESULTS: Patients were divided into group A (without AIS grade conversion) and group B (with AIS grade conversion). The IMLL and IMHL of group A were significantly higher than those of group B. The FA and CRFT of group A were significantly lower than those of group B. The final AIS grade was negatively correlated with the IMLL and IMHL, and positively correlated with the FA and CRFT. According to imaging features based on conventional MRI and DTI-DTT, we propose a novel classification and diagnostic procedure. CONCLUSIONS: The combination of conventional MRI with DTI-DTT is a valid diagnostic approach for SCI. Lower IMLL and IMHL, and higher FA value and CRFT are linked to better neurological outcomes.

Acute hyperextension myelopathy in children: Radiographic predictors of clinical improvement.

STUDY DESIGN: Retrospective case series SETTING: Three hospitals in China. OBJECTIVE: Previous research indicates that only neurological status on admission determines prognosis of acute hyperextension myelopathy (AHM). The object of this study is to analyze other unfavorable predictors of AHM in children. METHODS: The clinical data of children with AHM were retrospectively analyzed. The ASIA impairment scale (AIS) grade was recorded upon admission and at last follow-up. Intramedullary lesion length (IMLL) was measured in the sagittal T2-weighted imaging (T2WI) within two weeks after onset; gadolinium enhancement in the cord was recorded for each patient. Relationships among AIS grade, IMLL, gadolinium enhancement in the cord, and clinical improvement were assessed. RESULTS: A total of 33 patients were included in this retrospective study. IMLL between complete and incomplete injury was significantly different (p < 0.01) in the subacute stage, and no difference was observed in the acute stage. Correlation analysis revealed that AIS grade on admission (r = 0.906, p < 0.001) was significantly positively correlated with clinical improvement. IMLL (r = -0.608, p < 0.001) and abnormal gadolinium enhancement (r = -0.816, p < 0.001) in the cord in the subacute stage were significantly negatively correlated with clinical improvement. There were no associations between IMLL in the acute stage and clinical improvement (r = -0.248, p = 0.242). The statistically significant predictors of clinical improvement were AIS grade on admission, IMLL in the subacute stage, and abnormal gadolinium enhancement. CONCLUSION: IMLL in the subacute stage and abnormal gadolinium enhancement in the cord are two other prognostic predictors of AHM in children.

Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis.

BACKGROUND: This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR). METHODS: Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR). RESULTS: The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs. CONCLUSIONS: The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.

Internal fixation of anterior acetabular fractures with a limited pararectus approach and the anatomical plates: preliminary results.

BACKGROUND: The surgical treatment of acetabular fracture has adverse outcomes and high risk, and minimally invasive method is a good way to reduce complications and improve hip joint function. This study is to investigate the treatment of certain acetabular fractures primarily involving the anterior column and quadrilateral plate using a limited pararectus approach and the anatomical plates. METHODS: A consecutive cohort of 17 patients with anterior displaced acetabular fractures were managed operatively with a limited approach and the anatomical plates. Ten patients had anterior column fractures, 1 patient had anterior wall fracture, 4 patients had transverse fractures and 2 patients had anterior column with posterior hemi-transverse fractures. The inferior half of the pararectus approach was adopted to open the medial window and to access the anterior column and the quadrilateral plate. The anatomical plates were used for internal fixation. Residual displacements were assessed on the postoperative CT scans using a standardized digital method. The surgical details, hip functional outcomes, and complications were noted. RESULTS: All of the patients were operated using the limited pararectus approach and the anatomical plates successfully. The mean operative time and blood loss were 90.9 min and 334.1 ml, respectively. The average postoperative residual gap and step displacement on CT were 2.9 mm and 0.7 mm, respectively. The radiological outcome was estimated according to the Matta score, ten of the cases were graded anatomical, six were graded imperfect, and one was graded poor. Follow up averaged 15 months. Functional outcomes were excellent for nine, good for six, and fair for two. It was noted that one case of peritoneal injury was repaired intraoperatively. CONCLUSIONS: The limited pararectus approach with the advantages of less trauma, direct exposure to the anterior column and quadrilateral plate. The anatomical plates can fit with the surface of the acetabulum, which saves the time of remodeling plates during operation and facilitate fracture reduction. The combination approach can be a good choice for limited surgery of displaced anterior acetabular fractures especially involving the quadrilateral plate.

Preparation of Boronic Acid-Functionalized Silica Nanocomposites for Selective Enrichment of Glycoproteins.

A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO2 -BA) by 'thiol-ene' click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γ-mercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO2 -BA were characterized by transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and Brunner-Emmet-Teller measurements (BET). The adsorption behavior of the SiO2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, 7.64 µmol/g) than non-glycoproteins (bovine serum albumin, BSA, 0.83 µmol/g). In addition, the practicality of the SiO2 -BA was further assessed by selective enrichment of glycoproteins from egg white samples.

Recommendations of protective measures for orthopedic surgeons during COVID-19 pandemic.

PURPOSE: It was the primary purpose of the present systematic review to identify the optimal protection measures during COVID-19 pandemic and provide guidance of protective measures for orthopedic surgeons. The secondary purpose was to report the protection experience of an orthopedic trauma center in Wuhan, China during the pandemic. METHODS: A systematic search of the PubMed, Cochrane, Web of Science, Google Scholar was performed for studies about COVID-19, fracture, trauma, orthopedic, healthcare workers, protection, telemedicine. The appropriate protective measures for orthopedic surgeons and patients were reviewed (on-site first aid, emergency room, operating room, isolation wards, general ward, etc.) during the entire diagnosis and treatment process of traumatic patients. RESULTS: Eighteen studies were included, and most studies (13/18) emphasized that orthopedic surgeons should pay attention to prevent cross-infection. Only four studies have reported in detail how orthopedic surgeons should be protected during surgery in the operating room. No detailed studies on multidisciplinary cooperation, strict protection, protection training, indications of emergency surgery, first aid on-site and protection in orthopedic wards were found. CONCLUSION: Strict protection at every step in the patient pathway is important to reduce the risk of cross-infection. Lessons learnt from our experience provide some recommendations of protective measures during the entire diagnosis and treatment process of traumatic patients and help others to manage orthopedic patients with COVID-19, to reduce the risk of cross-infection between patients and to protect healthcare workers during work. LEVEL OF EVIDENCE: IV.

Guideline for diagnosis and treatment of spine trauma in the epidemic of COVID-19.

Outbreak of COVID-19 is ongoing all over the world. Spine trauma is one of the most common types of trauma and will probably be encountered during the fight against COVID-19 and resumption of work and production. Patients with unstable spine fractures or continuous deterioration of neurological function require emergency surgery. The COVID-19 epidemic has brought tremendous challenges to the diagnosis and treatment of such patients. To coordinate the diagnosis and treatment of infectious disease prevention and spine trauma so as to formulate a rigorous diagnosis and treatment plan and to reduce the disability and mortality of the disease, multidisciplinary collaboration is needed. This expert consensus is formulated in order to (1) prevent and control the epidemic, (2) diagnose and treat patients with spine trauma reasonably, and (3) reduce the risk of cross-infection between patients and medical personnel during the treatment.

Early durotomy with duroplasty for severe adult spinal cord injury without radiographic abnormality: a novel concept and method of surgical decompression.

PURPOSE: Treatment options for adult spinal cord injury without radiographic abnormality (ASCIWORA) varied. Compression of ASCIWORA may more likely result from spinal cord lesions such as edema and hemorrhage or contusion. This study aimed to explore the clinical effect of early durotomy with duroplasty decompression in the treatment of severe ASCIWORA. METHODS: Data of 16 patients with ASCIWORA who underwent early ( < 72 h) posterior laminectomy followed by durotomy with duroplasty decompression from June 2015 to January 2017 were retrospectively analyzed. Patients' prognosis was analyzed by American Spinal Injury Association Impairment Scale (AIS) grades and scores. In 3 patients, intraspinal pressure (ISP) was continuously monitored for 1 week. RESULTS: Cervical magnetic resonance imaging (MRI) revealed spinal cord edema in 9 patients and suspected hemorrhage or contusion in 7 cases. Pathological manifestations of spinal cord injury found during the operation were consistent with preoperative MRI findings. Of the 16 cases, AIS grade was improved by 1 grade in 3 cases, 2 grades in 11 cases, and 3 grades in 1 case. The AIS scores at the last follow-up were significantly higher than preoperative scores. There was a high level of ISP after laminectomy, whereas ISP continued to decrease steadily after durotomy. CONCLUSIONS: Durotomy helps thoroughly decompress the spinal cord and improve cerebrospinal fluid circulation in severe ASCIWORA cases. Cervical MRI and pathological investigation of the spinal cord can be used to evaluate and predict the prognosis of ASCIWORA patients. ISP monitoring is an effective method for evaluating intramedullary pressure and decompression. These slides can be retrieved under Electronic Supplementary Material.

[Simultaneous determination of 9 major components of dachengqi tang in rat plasma by UPLC-MS/MS].

The study established a UPLC-MS/MS method that is used for simultaneous determination nine major bioactive compounds of Dachengqi Tang in rat plasma. Using Aglient C18 column (2.1 mm x 50 mm,1.7 microm) was chromatographed, using methanol-5 mmol x L(-1) ammonium formate mobile phase gradient, elution 0.3 mL x min(-1). In the plasma pre-treatment process, not only the method of methanol and acetonitrile protein precipitation was investigated, and different factors extraction solvent, the type of the scroll time, the number and the type of extraction solvent, the extraction volume of the extraction solution of liquid-liquid extraction is investigated. Finally, with ibuprofen as an internal standard, using ethyl acetate liquid-liquid extraction method pretreatment blood, N2 dry reconstituted supernatant after centrifugation UPLC-MS/MS analysis, in electrospray ionization (ESI) negative mode, using multiple reaction monitoring mode for testing. The linear range of emodin, rhein, aloe-emodin, chrysophanol, magnolol, honokiol, hesperidin and hesperitin is 0.33-660, 0.40-792, 0.41-827, 0.34-680, 0.45-907, 0.46-927, 0.43-867, 0.34-683, 0.39-787 microg x L(-1) respectively, good linear relationship; and extraction recovery were greater than 69.39%, days after the day of the RSD is less than 15%. This method can be used to study the rat gastric large bearing gas after Dachengqi Tang, the simultaneous determination of nine components in plasma for its pharmacokinetics and efficacy material base to provide a theoretical basis.

Macrophage migration inhibitor factor (MIF): Potential role in cognitive impairment disorders.

Macrophage migration inhibitory factor (MIF) is a cytokine in the immune system, participated in both innate and adaptive immune responses. Except from immune cells, MIF is also secreted by a variety of non-immune cells, including hematopoietic cells, endothelial cells (ECs), and neurons. MIF plays a crucial role in various diseases, such as sepsis, rheumatoid arthritis, acute kidney injury, and neurodegenerative diseases. The role of MIF in the neuropathogenesis of cognitive impairment disorders is emphasized, as it recruits multiple inflammatory mediators, leading to activating microglia or astrocyte-derived neuroinflammation. Furthermore, it contributes to the cell death of neurons and ECs with the binding of apoptosis-inducing factor (AIF) through parthanatos-associated apoptosis-inducing factor nuclease (PAAN) / MIF pathway. This review comprehensively delves into the relationship between MIF and the neuropathogenesis of cognitive impairment disorders, providing a series of emerging MIF-targeted pharmaceuticals as potential treatments for cognitive impairment disorders.

Botulinum toxin A attenuates osteoarthritis development via inhibiting chondrocyte ferroptosis through SLC7Al1/GPX4 axis.

Osteoarthritis (OA) is a prevalent joint degenerative disease, resulting in a significant societal burden. However, there is currently a lack of effective treatment option available. Previous studies have suggested that Botulinum toxin A (BONT/A), a macromolecular protein extracted from Clostridium Botulinum, may improve the pain and joint function in OA patients, but the mechanism remains elusive. This study was to investigate the impact and potential mechanism of BONT/A on OA in vivo and in vitro experiment. LPS increased the levels of ROS, Fe2+and Fe3+, as well as decreased GSH levels, the ratio of GSH / GSSH and mitochondrial membrane potential. It also enhanced the degeneration of extracellular matrix (ECM) and altered the ferroptosis-related protein expression in chondrocytes. BONT/A rescued LPS-induced decrease in collagen type II (Collagen II) expression and increase in matrix metalloproteinase 13 (MMP13), mitigated LPS-induced cytotoxicity in chondrocytes, abolished the accumulation of ROS and iron, upregulated GSH and the ratio of GSH/ GSSH, improved mitochondrial function, and promoted SLC7A11/GPX4 anti-ferroptosis system activation. Additionally, intra-articular injection of BONT/A inhibited the degradation of cartilage in OA model rats. This chondroprotective effect of BONT/A was reversed by erastin (a classical ferroptosis agonist) and enhanced by liproxstatin-1 (a classic ferroptosis inhibitor). Our research confirms that BONT/A alleviates the OA development by inhibiting the ferroptosis of chondrocytes, which revealed to be a potential therapeutic mechanism for BONT/A treating the OA.

[Effects of selective phosphodiesterase 4 inhibitor on expression of aquaporin 5 in airway mucus hypersecretion model of rats].

OBJECTIVE: To explore the mechanism of selective phosphodiesterase 4 (PDE4) inhibitor and observe its effects on the in vitro expression of aquaporin 5 (AQP5) in a rat model of airway mucus hypersecretion. METHODS: Forty healthy male rats were randomized into 4 groups (n = 10 each). The normal control and drug control groups underwent normal saline aerosol inhalation or YM976 lavage respectively for 12 days while the model and treatment groups acrolein atomization inhalation or acrolein atomization inhalation plus YM976 lavage respectively for 12 days. The middle lobe of right lung were fixed, embedded and stained by hematoxylin and eosin to observe the histological changes of small airway. The mucin secretion by goblet cells in lung tissue was tested by alcian blue staining. And the effects of selective PDE4 inhibitor on the expression of AQP5 were detected by immunohistochemical stain. Reverse transcription-polymerase chain reaction and Western blot were used to determine the levels of AQP5 mRNA and protein. RESULTS: In the treatment group, mucus gland hyperplasia and airway mucus hypersecretion and positive staining area ratio of alcian blue staining decreased significantly compared with the model group (10.23% ± 0.94% vs 14.74% ± 1.06%, P < 0.05). And the expression of AQP5 mRNA (1.26 ± 0.19) and protein (0.56 ± 0.13) also declined significantly versus the model group ((0.96 ± 0.17), (0.43 ± 0.15), P < 0.05). CONCLUSION: Selective PDE4 inhibitors alleviate the pathological damage of lung tissue and enhance the expression of AQP-5 in airway mucus hypersecretion.

Photocatalytic oxygen evolution and antibacterial biomimetic repair membrane for diabetes wound repair via HIF1-α pathway.

Diabetic wounds always have puzzled patients and caused serious social problems. Due to the lack of local blood vessels, severe hypoxia is generated in the defect area, which is an essential reason for the difficulty of wound healing. We have constructed a photocatalytic oxygen evolution and antibacterial biomimetic repair membrane to solve the problems of wound repair. A scanning electron microscope and transmission electron microscope characterized the biomimetic repair membrane. The oxygen evolution of the biomimetic membrane was tested by an oxygen meter. The excellent antibacterial performance of the biomimetic repair membrane was also verified by co-culture with Staphylococcus aureus and Escherichia coli. It was confirmed that the expression of collagen and HIF1-α in fibroblasts was significantly increased in vitro. And the mitochondrial activity of the vascular and nerve was increased considerably. In vivo, the healing time of diabetes wounds treated with the biomimetic repair membrane was significantly reduced, the collagen and the number of pores were increased considerably, and vascular regeneration was enhanced. The biomimetic repair membrane has an excellent performance in photocatalytic oxygen evolution and antibacterial and can significantly promote the repair of diabetes wounds. This will provide a promising treatment for diabetes wound repair.

Corrigendum to "Photocatalytic oxygen evolution and antibacterial biomimetic repair membrane for diabetes wound repair via HIF1-α pathway" [Mater. Today Bio 20 (2023) 100616].

[This corrects the article DOI: 10.1016/j.mtbio.2023.100616.].

Neuro-bone tissue engineering: emerging mechanisms, potential strategies, and current challenges.

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve-bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.

Photosensitive and Conductive Hydrogel Induced Innerved Bone Regeneration for Infected Bone Defect Repair.

Repairing infected bone defects is a challenge in the field of orthopedics because of the limited self-healing capacity of bone tissue and the susceptibility of refractory materials to bacterial activity. Innervation is the initiating factor for bone regeneration and plays a key regulatory role in subsequent vascularization, ossification, and mineralization processes. Infection leads to necrosis of local nerve fibers, impeding the repair of infected bone defects. Herein, a biomaterial that can induce skeletal-associated neural network reconstruction and bone regeneration with high antibacterial activity is proposed for the treatment of infected bone defects. A photosensitive conductive hydrogel is prepared by incorporating magnesium-modified black phosphorus (BP@Mg) into gelatin methacrylate (GelMA). The near-infrared irradiation-based photothermal and photodynamic treatment of black phosphorus endows it with strong antibacterial activity, improving the inflammatory microenvironment and reducing bacteria-induced bone tissue damage. The conductive nanosheets and bioactive ions released from BP@Mg synergistically improve the migration and secretion of Schwann cells, promote neurite outgrowth, and facilitate innerved bone regeneration. In an infected skull defect model, the GelMA-BP@Mg hydrogel shows efficient antibacterial activity and promotes bone and CGRP+ nerve fiber regeneration. The phototherapy conductive hydrogel provides a novel strategy based on skeletal-associated innervation for infected bone defect repair.