The thoracolumbar interfascial block with local anesthesia in osteoporotic vertebral compression fractures treated with percutaneous kyphoplasty provides better analgesia compared with local anesthesia alone: A randomized controlled study.

Objective: To evaluate the safety and efficacy of the thoracolumbar interfascial block (TLIPB) in percutaneous kyphoplasty (PKP), and to confirm that the TLIPB further minimizes perioperative pain and residual back pain on the basis of local anesthesia. Method: From April 2021 to May 2022, 60 patients with osteoporotic vertebral compression fractures were included in this prospective randomized controlled trial. Patients were randomly assigned to a local anesthesia group (A group) or a TLIPB on the basis of local anesthesia group (A + TLIPB group) before PKP. Pain level (visual analog scale, VAS), amount of analgesic rescue drugs (parecoxib), operative time, mean arterial pressure, heart rate, and complications were assessed and compared between the two groups. Results: Compared with the A group, VAS scores were lower in the A + TLIPB group, respectively, when the trocar punctured the vertebral body (7.4 ± 0.7 vs. 4.5 ± 0.9; P < 0.01), during balloon dilatation (6.6 ± 0.9 vs. 4.6 ± 0.9; P < 0.01), during bone cement injection (6.3 ± 0.6 vs. 4.3 ± 0.8; P < 0.01), 1 h after surgery (3.5 ± 0.7 vs. 2.9 ± 0.7; P < 0.01), and 24 h after surgery (2.5 ± 0.8 vs. 1.9 ± 0.4; P < 0.01). Residual back pain (VAS: 1.9 ± 0.9 vs. 0.9 ± 0.8; P < 0.01) and the incidence of rescue analgesic use (P = 0.02) in the A + TLIPB group were lower compared with the A group. Compared with the A group, mean arterial pressure and heart rate were lower in the A + TLIPB group when the trocar punctured the vertebral body, and with balloon dilatation and bone cement injection; however, there were no statistical differences between the groups 1 and 24 h after surgery. The incidences of bone cement leakage, constipation, and nausea were similar between the two groups. No patient developed infection, neurological injuries, constipation in either group. Conclusion: The addition of the TLIPB to local anesthesia can further minimize perioperative pain and residual back pain, and reduce perioperative rescue analgesic use. When added to local anesthesia, the TLIPB is an effective and safe anesthetic method for PKP. Clinical trial registration: This study has been registered in the Clinical Trial registration: ChiCTR-2100044236.

BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism.

Bromodomain-containing protein 9 (BRD9), a component of non-canonical BAF chromatin remodeling complex, has been identified as a critical therapeutic target in hematological diseases. Despite the hematopoietic origin of osteoclasts, the role of BRD9 in osteoclastogenesis and bone diseases remains unresolved. Here, we show Brd9 deficiency in myeloid lineage enhances osteoclast lineage commitment and bone resorption through downregulating interferon-beta (IFN-ß) signaling with released constraint on osteoclastogenesis. Notably, we show that BRD9 interacts with transcription factor FOXP1 activating Stat1 transcription and IFN-ß signaling thereafter. Besides, function specificity of BRD9 distinguished from BRD4 during osteoclastogenesis has been evaluated. Leveraging advantages of pharmacological modulation of BRD9 and flexible injectable silk fibroin hydrogel, we design a local deliver system for effectively mitigating zoledronate related osteonecrosis of the jaw and alleviating acute bone loss in lipopolysaccharide-induced localized aggressive periodontitis. Overall, these results demonstrate the function of BRD9 in osteoclastogenesis and its therapeutic potential for bone diseases.

Pyroptosis-related gene-based prognostic signature for predicting the overall survival of oral squamous cell carcinoma patients.

Purpose: Oral squamous cell carcinoma (OSCC) is the most common oral cancer worldwide. Pyroptosis is a type of programmed cell death mediated by caspase, accompanied by an inflammatory response, and plays an important role in cancer progression. The purpose of this study was to explore and identify potential biomarkers and further elucidate the potential role of cell pyroptosis in OSCC. Methods: We regarded the samples from The Cancer Genome Atlas database as a training dataset, screened differentially expressed genes (DEGs), and further screened out OSCC phenotypic characteristic genes by using weighted gene co-expression network analysis. The analysis of 42 known pyroptosis-related genes showed that Psuch genes were widely expressed, mutated, and methylated in OSCC samples. Results: Through correlation analysis, we identified our OSCC pyroptosis-related DEGs. To further evaluate the prognostic value of pyroptosis-related regulators, we constructed a seven gene-based prognostic signature using Cox univariate analysis and least absolute shrinkage and selection operator Cox regression analysis. Meanwhile, we found that patients in the low-risk group had higher immune infiltration. Moreover, our results also indicated significant differences in sensitivity to cisplatin and gefitinib between the high-risk and low-risk groups. Conclusion: Our study successfully constructed the pyroptosis-related prognostic signature, which might play a potential prediction role in OSCC prognosis. Our findings also suggested that pyroptosis-related regulators might be novel biomarkers for tumor diagnosis and treatment in OSCC.

Diagnostic accuracy of procalcitonin on POD3 for the early diagnosis of anastomotic leakage after colorectal surgery: A meta-analysis and systematic review.

OBJECTIVE: Anastomotic leakage is one of the most serious complications after colorectal surgery, and a reliable method for early diagnosis is urgently needed. Procalcitonin (PCT) is recently considered a potential biomarker by many studies, but their conclusions in detail are controversial. This meta-analysis was conducted to further explore and verify the diagnostic value of the procalcitonin level on postoperative day 3 (POD3) in patients undergoing colorectal surgery. METHODS: This review was performed using the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy (PRISMA-DTA) statement. Studies were searched in PubMed, EMBASE, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) until August 2021. Quality of the studies was scored based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and a summary receiver operating characteristics (SROC) curve were used to estimate the diagnostic value. Meta-regression and subgroup analyses were performed to further explore the primary source of heterogeneity and the influence of various factors on diagnostic accuracy. RESULTS: Eleven studies and 3393 patients were included in our meta-analysis. The derived cutoff value of PCT was 1.12 ng/ml by geometric mean and the pooled sensitivity, specificity, PLR, NLR and DOR were 0.768 (0.704-0.825), 0.788 (0.774-0.802), 4.600 (3.129-6.763), 0.339 (0.267-0.431) and 18.114 (9.872-33.239), respectively. The computed AUC from the SROC curve was 0.8714, and the Q* index was 0.8019. The results of meta-regression and subgroup analyses showed that the usage of laparoscopic surgery was the major factor in improving the reliability of PCT data, and 0.7-1.3 ng/ml may be the appropriate interval for PCT with the DOR (38.610 (16.324-91.321)) well above the average. CONCLUSIONS: The PCT level on POD3 has potential clinical value in the early diagnosis of AL and exhibits a better diagnostic accuracy in patients undergoing laparoscopic surgery. Cut-off values are recommended at the interval range of 0.7-1.3 ng/ml to ensure accurate diagnosis and safe discharge. Research Registry Registration Number: reviewregistry 1282.

[Effect of electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) on presurgical anxiety in patients with gynecological laparoscopic surgery].

OBJECTIVE: To observe the anti-anxiety effect of electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) in patients with gynecological laparoscopic surgery, and to explore its effect on the anesthetic dosage during anesthesia induction. METHODS: A total of 270 patients with gynecological laparoscopic surgery were randomized into an electroacupuncture group, a medication group and a control group, 90 cases in each group. At 24 h and 2 h before anesthesia induction, electroacupuncture was applied at Baihui (GV 20) and Sishencong (EX-HN 1) in the electroacupuncture group, with continuous wave, 100 Hz in frequency. At 30 min before anesthesia induction, midazolam of 0.02 mg/kg was given by intravenous drip in the medication group, while 0.9% sodium chloride solution was given by intravenous drip in the control group. At 10 min before anesthesia induction and 6 h after surgery, the scores of 6 item short form of state-trait anxiety inventory (STAI-S6) and visual analogue scale-anxiety (VAS-A) were observed; at 10 min before anesthesia induction (T1) and observer's assessment of alertness/sedation scale (OAA/S) grade 4 (T2), mean artery pressure (MAP), heart rate (HR) and value of bispectral index (BIS) were recorded; the dosage of propofol at T2 was recorded and the surgery related adverse reactions were compared among the 3 groups. RESULTS: At 10 min before anesthesia induction and 6 h after surgery, the STAI-S6 and VAS-A scores in the electroacupuncture group and the medication group were lower than those in the control group (P<0.05). Values of BIS at T1 and dosage of propofol at T2 in the electroacupuncture group and the medication group were lower than those in the control group (P<0.05). There were no statistical differences in MAP, HR and surgery related adverse reactions among the 3 groups (P>0.05). CONCLUSION: Electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) can effectively relieve the presurgical anxiety in patients with gynecological laparoscopic surgery, and reduce the dosage of propofol, its effect is similar to traditional anti-anxiety drug.

Osteogenic Induction of Low-dose Ipriflavone on Bone Marrow Mesenchymal Stem Cells Extracted from Osteoporosis Rats.

OBJECTIVE: To investigate the effects of ipriflavone (IPF), a synthetic isoflavone plant oestrogen with a structure similar to that of oestradiol, on the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). METHODS: BMSCs were derived from ovariectomised rats (rBMSCs-OVX) and then induced with or without IPF. Cell cytotoxicity, mineralisation in vitro and osteoblast-specific gene expression of BMSCs were studied. RESULTS: IPF at a concentration of 10-8, 10-7 and 10-6 mol/l exhibited no cytotoxic effect on the proliferation of BMSCs but increased alkaline phosphatase activity and osteoblast-specific gene expression. CONCLUSION: IPF enhances osteogenic differentiation of rBMSCs-OVX partly in vitro, thus its use offers a potential strategy for the treatment of osteoporosis.

Synergistic effect between 2-N,6-O-sulfonated chitosan and bone morphogenetic protein-2.

The molecular structure of sulfonated chitosan is similar to heparin, and it has been proved to have some heparin functions. Studies have shown that heparin and bone morphogenetic protein-2 (BMP-2) have synergistic effects, but heparin has limitations in clinical application. In this paper, the synergistic effect of 2-N,6-O-sulfonated chitosan (26SCS) and BMP-2 was studied. The preparation of 26SCS was explored and 26SCS was co-cultured with bone marrow mesenchymal stem cells (BMSCs) to study the effects of 26SCS on the proliferation, adhesion behavior and osteogenic differentiation of BMSCs. The synergistic mechanism of 26SCS and BMP-2 was explored by circular dichroism and isothermal calorimetric titration. The results showed that 26SCS affected the secondary structure of BMP-2 protein, mainly caused the significant change of antiparallel conformation in ß-fold, and then improved the biological activity of BMP-2 and showed a dose-dependent manner. 26SCS was expected to be a synergistic factor of BMP-2.

Enhanced bone regeneration of the silk fibroin electrospun scaffolds through the modification of the graphene oxide functionalized by BMP-2 peptide.

INTRODUCTION: Bone tissue engineering has become one of the most effective methods to treat bone defects. Silk fibroin (SF) is a natural protein with no physiological activities, which has features such as good biocompatibility and easy processing and causes minimal inflammatory reactions in the body. Scaffolds prepared by electrospinning SF can be used in bone tissue regeneration and repair. Graphene oxide (GO) is rich in functional groups, has good biocompatibility, and promotes osteogenic differentiation of stem cells, while bone morphogenetic protein-2 (BMP-2) polypeptide has an advantage in promoting osteogenesis induction. In this study, we attempted to graft BMP-2 polypeptide onto GO and then bonded the functionalized GO onto SF electrospun scaffolds through electrostatic interactions. The main purpose of this study was to further improve the biocompatibility of SF electrospun scaffolds, which could promote the osteogenic differentiation of bone marrow mesenchymal stem cells and the repair of bone tissue defects. MATERIALS AND METHODS: The successful synthesis of GO and functionalized GO was confirmed by transmission electron microscope, X-ray photoelectron spectroscopy, and thermogravimetric analysis. Scanning electron microscopy, atomic force microscopy, mechanical test, and degradation experiment confirmed the preparation of SF electrospun scaffolds and the immobilization of GO on the fibers. In vitro experiment was used to verify the biocompatibility of the composite scaffolds, and in vivo experiment was used to prove the repairing ability of the composite scaffolds for bone defects. RESULTS: We successfully fabricated the composite scaffolds, which enhanced biocompatibility, not only promoting cell adhesion and proliferation but also greatly enhancing in vitro osteogenic differentiation of bone marrow stromal cells using either an osteogenic or non-osteogenic medium. Furthermore, transplantation of the composite scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. CONCLUSION: These findings suggested that the incorporation of BMP-2 polypeptide-functionalized GO into chitosan-coated SF electrospun scaffolds was a viable strategy for fabricating excellent scaffolds that enhance the regeneration of bone defects.

Functionalization of Silk Fibroin Electrospun Scaffolds via BMSC Affinity Peptide Grafting through Oxidative Self-Polymerization of Dopamine for Bone Regeneration.

Electrospun scaffolds have been broadly studied to enhance bone regeneration because of the ability to simulate the structure and biological functions of the extracellular matrix. Polydopamine (PDA) is used to coat various surfaces at a slightly basic pH (8-8.5) and spontaneously reacts with nucleophilic functional groups. It is suitable for surface modifications of scaffolds correlated with bone formation. E7 is a newly discovered peptide with specific affinity for bone marrow mesenchymal stem cells (BMSCs). It can be useful for recruiting stem cells. Here, electrospun silk fibroin (SF) scaffolds were fabricated, and PDA was used for surface modification followed by grafting E7 (SF-PDA-E7). These composite SF-PDA-E7 electrospun scaffolds improved hydrophilicity, facilitated cell proliferation and adhesion, and boosted the osteogenic differentiation of BMSCs by creating osteoinduction conditions under the synergistic effects of PDA and E7. Moreover, the scaffolds showed high efficiency for recruiting BMSCs induced by E7 both in vitro and in vivo, which was associated with the SDF-1α/CXCR4 axis and the p38, extracellular signal-related kinase, and Akt signal transduction pathways. These functionalized electrospun scaffolds promoted regeneration of bone in the rat calvarial bone defect model. In general, this study verified that PDA could be a simple and efficient method for surface modification, and E7-grafted PDA-modified SF electrospun scaffolds were suitable for bone tissue engineering.

Biocompatible silk/calcium silicate/sodium alginate composite scaffolds for bone tissue engineering.

Scaffolds are crucial for bone tissue engineering since their compositions and properties could significantly affect the seeded cells' behavior. In this study, we developed an interpenetrating network hydrogel by utilizing Ca2+ from calcium silicate (CS) to simultaneously crosslink silk fibroin (SF) and sodium alginate (SA). Afterwards, the hydrogels were lyophilized to obtain scaffolds and systematically evaluated by physical characterizations, in vitro cytocompatibility and alkaline phosphatase (ALP) assay. We found that CS inside the porous structure of SF/CS/SA scaffolds could remarkably enhance hydrophilicity, degradation, compression resistance, bioactivity and pH of SF/CS/SA scaffolds. Scaffolds with CS concentrations of 25% and 12% (25/CS and 12/CS) could dominantly stimulate proliferation of bone marrow stromal cells (BMSCs). Besides, BMSCs cultured with 25/CS and 12/CS scaffolds showed high ALP activity, respectively. Consequently, this study suggested SF/CS/SA scaffolds possess potential in non-loading bone tissue engineering application.

Evaluation of synergistic osteogenesis between icariin and BMP2 through a micro/meso hierarchical porous delivery system.

BMP2 is well known as an outstanding growth factor for inducing new bone formation. However, improvements are still required to use BMP2 effectively and expand its clinical application due to the potential side effects at high doses. In this study, icariin (IC), a type of traditional Chinese medicine, was originally proposed to be a cooperative factor for BMP2. An alkaline phosphatase (ALP) activity assay showed that IC promoted BMP2 osteogenesis in a concentration-dependent manner with significant enhancement at 38.4 µM versus that for BMP2 at 0.8 µg/mL. Furthermore, we developed a composite hierarchical porous scaffold (SF/SBA15; composed of micropores of silk fibroin [SF] scaffold and mesopores of SBA15) for the controlled delivery of BMP2 and IC. This composite scaffold was investigated by a series of physical characterizations and displayed good in vitro cell biocompatibility. In addition, the composite scaffold also showed the degradation rate of 12% dry weight loss and a slight change in the microstructures within 10 days. Moreover, BMP2 and IC were loaded into the SF and SBA15 structures, respectively, of the SF/SBA15 scaffold. This protein/drug loading system (SFBMP2/SBA15IC) provided delivery of BMP2 with an initial burst release of 60.9%±0.9% in the first 24 hours and a gradual release over the subsequent 6 days to 97.9%±0.8%, whereas IC exhibited a burst release of 64.2%±0.7% in the first 24 hours, followed by a sustained release to 92.4%±0.8% over 10 days. With the prolonged local retention and interaction duration of BMP2 and IC, the SFBMP2/SBA15IC scaffold provided better osteogenic differentiation than other groups with different loading modes of BMP2 or IC, as determined by ALP staining and quantitation and Alizarin red staining. Finally, the results of quantitative real-time polymerase chain reaction analysis indicated that the SFBMP2/SBA15IC scaffold induced a significantly higher increase in the RUNX2, ALP, COL I, and OCN expression levels of cocultured bone marrow mesenchymal stem cells than other payload composite scaffolds. This study suggests that a micro/meso hierarchical porous delivery system of BMP2 and IC ensures osteogenic synergy and demonstrates promise for bone tissue engineering.

Celastrol inhibits lung infiltration in differential syndrome animal models by reducing TNF-α and ICAM-1 levels while preserving differentiation in ATRA-induced acute promyelocytic leukemia cells.

All-trans retinoic acid (ATRA) is a revolutionary agent for acute promyelocytic leukemia (APL) treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1) expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS) which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF-α and IL-1ß secretion, though treatment showed no effects on IL-8 and MCP-1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy.