C-Terminal Binding Protein: Regulator between Viral Infection and Tumorigenesis.

C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell proliferation, differentiation, apoptosis, and immune responses. The CtBP family comprises two highly conserved proteins, CtBP1 and CtBP2, which have been shown to play critical roles in both tumorigenesis and the regulation of viral infections. Elevated CtBP expression is noted in various tumor tissues, promoting tumorigenesis, invasiveness, and metastasis through multiple pathways. Additionally, CtBP's role in viral infections varies, exhibiting differing or even opposing effects depending on the virus. This review synthesizes the advances in CtBP's function research in viral infections and virus-associated tumorigenesis, offering new insights into potential antiviral and anticancer strategies.

Sonodynamic Therapy-Driven Immunotherapy: Constructing AIE Organic Sonosensitizers Using an Advanced Receptor-Regulated Strategy.

Benefit from the deeper penetration of mechanical wave, ultrasound (US)-based sonodynamic therapy (SDT) executes gratifying efficacy in treating deep-seated tumors. Nevertheless, the complicated mechanism of SDT undeniably hinders the exploration of ingenious sonosensitizers. Herein, a receptor engineering strategy of aggregation-induced emission (AIE) sonosensitizers (TPA-Tpy) with acceptor (A)-donor (D)-A' structure is proposed, which inspects the effect of increased cationizations on US sensitivity. Under US stimulation, enhanced cationization in TPA-Tpy improves intramolecular charge transfer (ICT) and accelerates charge separation, which possesses a non-negligible promotion in type I reactive oxygen species (ROS) production. Moreover, abundant ROS-mediated mitochondrial oxidative stress triggers satisfactory immunogenic cell death (ICD), which further promotes the combination of SDT and ICD. Subsequently, subacid pH-activated nanoparticles (TPA-Tpy NPs) are constructed with charge-converting layer (2,3-dimethylmaleic anhydride-poly (allylamine hydrochloride)-polyethylene glycol (DMMA-PAH-PEG)) and TPA-Tpy, achieving the controllable release of sonosensitizers. In vivo, TPA-Tpy-mediated SDT effectively initiates the surface-exposed of calreticulin (ecto-CRT), dendritic cells (DCs) maturation, and CD8+ T cell infiltration rate through enhanced ROS production, achieving suppression and ablation of primary and metastatic tumors. This study provides new opinions in regulating acceptors with eminent US sensitization, and brings a novel ICD sono-inducer based on SDT to realize superior antitumor effect.

Cu-Tremella fuciformis polysaccharide-based tumor microenvironment-responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy.

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.

In Vivo Effect of Single Intra-Articular Injection of Tranexamic Acid on Articular Cartilage and Meniscus: Study in a Rat Model.

BACKGROUND: Tranexamic acid (TXA) has been increasingly used in arthroscopic surgery to prevent hemarthrosis. Despite its effectiveness, safety concerns have been raised regarding its potential cytotoxicity to articular cartilage and meniscus following intra-articular injection. METHODS: To evaluate the impact of TXA on cartilage and meniscus, a rat model of knee instability was utilized wherein anterior cruciate ligament (ACL) transection surgery was followed by a single intra-articular injection of TXA at varying concentrations (0, 20, 50, 100, and 150 mg/mL) in saline solution. Cell viability assessment of the cartilage and meniscus (n = 6 per group) was conducted at 24 hours, and gross observation and histological analysis of the medial tibial plateau and medial meniscus were conducted at 2, 4, and 8 weeks (n = 6 per group and time point). RESULTS: The chondrocyte viability was significantly decreased in the 50, 100, and 150 mg/mL TXA groups compared with the specimens injected with saline solution only (saline group) (p = 0.001, p < 0.001, p < 0.001, respectively), as was meniscal cell viability (p = 0.042, p < 0.001, p < 0.001, respectively). At week 8, the saline and 20 and 50 mg/mL groups showed relatively normal appearances, whereas the 100 and 150 mg/mL groups exhibited increased and varying severity of cartilage and meniscal degeneration. In the 150 mg/mL group, the mean Osteoarthritis Research Society International score was significantly higher than that in the saline and 20 mg/mL groups (p = 0.010 and p = 0.007). Additionally, the mean meniscus score in the 150 mg/mL group was significantly higher than that in the saline, 20 mg/mL, and 50 mg/mL groups (p = 0.020, p = 0.021, p = 0.031, respectively). CONCLUSIONS: Our findings indicate that concentrations of TXA at or above 100 mg/mL can lead to decreased cell viability in both cartilage and meniscus, resulting in significant cartilage degeneration in rats with ACL transection. Furthermore, the use of 150 mg/mL of TXA led to significant meniscal degeneration. CLINICAL RELEVANCE: It is prudent to avoid using concentrations of TXA at or above 100 mg/mL for intra-articular injection, as such concentrations may result in adverse effects on the cartilage and meniscus.

Low-Dose Staphylococcal Enterotoxin C2 Mutant Maintains Bone Homeostasis via Regulating Crosstalk between Bone Formation and Host T-Cell Effector Immunity.

Studies in recent years have highlighted an elaborate crosstalk between T cells and bone cells, suggesting that T cells may be alternative therapeutic targets for the maintenance of bone homeostasis. Here, it is reported that systemic administration of low-dose staphylococcal enterotoxin C2 (SEC2) 2M-118, a form of mutant superantigen, dramatically alleviates ovariectomy (OVX)-induced bone loss via modulating T cells. Specially, SEC2 2M-118 treatment increases trabecular bone mass significantly via promoting bone formation in OVX mice. These beneficial effects are largely diminished in T-cell-deficient nude mice and can be rescued by T-cell reconstruction. Neutralizing assays determine interferon gamma (IFN-γ) as the key factor that mediates the beneficial effects of SEC2 2M-118 on bone. Mechanistic studies demonstrate that IFN-γ stimulates Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling, leading to enhanced production of nitric oxide, which further activates p38 mitogen-activated protein kinase (MAPK) and Runt-related transcription factor 2 (Runx2) signaling and promotes osteogenic differentiation. IFN-γ also directly inhibits osteoclast differentiation, but this effect is counteracted by proabsorptive factors tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) secreted from IFN-γ-stimulated macrophages. Taken together, this work provides clues for developing innovative approaches which target T cells for the prevention and treatment of osteoporosis.

Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis.

Osteoporosis, a common systematic bone homeostasis disorder related disease, still urgently needs innovative treatment methods. Several natural small molecules were found to be effective therapeutics in osteoporosis. In the present study, quercetin was screened out from a library of natural small molecular compounds by a dual luciferase reporter system. Quercetin was found to upregulate Wnt/ß-catenin while inhibiting NF-κB signaling activities, and thereby rescuing osteoporosis-induced tumor necrosis factor alpha (TNFα) impaired BMSCs osteogenesis. Furthermore, a putative functional lncRNA, Malat1, was shown to be a key mediator in quercetin regulated signaling activities and TNFα-impaired BMSCs osteogenesis, as mentioned above. In an ovariectomy (OVX)-induced osteoporosis mouse model, quercetin administration could significantly rescue OVX-induced bone loss and structure deterioration. Serum levels of Malat1 were also obviously rescued in the OVX model after quercetin treatment. In conclusion, our study demonstrated that quercetin could rescue TNFα-impaired BMSCs osteogenesis in vitro and osteoporosis-induced bone loss in vivo, in a Malat1-dependent manner, suggesting that quercetin may serve as a therapeutic candidate for osteoporosis treatment.

Lattice Boltzmann Simulation of Coupling Heat Transfer between Solid and Gas Phases of Nanoporous Materials.

In order to deeply study the heat conduction of nanoporous aerogel, a model of gas-solid heat conduction was established based on the microstructure of aerogel. The model was divided into two subdomains with uniform mesh because of the different gas-solid characteristics, and simulation was performed on each domain using the lattice Boltzmann method. The value of temperature on the boundaries of subdomains was determined by interpolation. Finally, the temperature distribution and the thermal conductivity were maintained. It can be concluded that when the gas-phase scale was fixed, the temperature distribution of the solid phase became more uniform when the scale increased; when the solid-phase scale was fixed, the temperature jump on the gas-solid interface decreased with the increase in the gas-phase scale; and the thermal conductivity of gas-solid coupling varied with the scale of the gas phase or solid phase, showing a scale effect in varying degrees.

One-stop molecular classification of endometrial carcinoma using comprehensive next-generation sequencing.

This study aims to investigate the feasibility of molecular classification using only comprehensive next-generation sequencing-based techniques and its relationship with survival outcomes in patients with endometrial cancer. Paired tumor-normal sequencing data of 1021 cancer-related genes using tumor tissues or peripheral blood samples and clinical data were retrospectively collected from a cohort of endometrial cancers. The microsatellite instability status was inferred using the MSIsensor (v0.5) with a cut-off of 8%. Sixty patients were classified into four groups: POLEMUT group (13.3%), MSI-H group (20%), TP53WT group (45%) and TP53MUT group (21.7%). Patients within TP53MUT group were more common in serous carcinoma compared to endometrioid carcinoma (P = .0098). TP53WT was significantly correlated with early stage and low grade. TP53MUT group was associated with significantly worse DFS compared to MSI-H group and TP53WT group (P = .014 and .004, respectively). Comprehensive next-generation sequencing is a reliable and simple method to stratify the prognosis of endometrial carcinoma. It can be potentially used to guide treatment of patients with endometrial cancer in routine practice.

Malat1 attenuated the rescuing effects of docosahexaenoic acid on osteoarthritis treatment via repressing its chondroprotective and chondrogenesis activities.

Osteoarthritis (OA) is a degenerative disease associated with joint inflammation, articular cartilage degeneration and subchondral hypertrophy. Small molecules which both ameliorate chondrocyte OA phenotype and activate bone marrow-derived mesenchymal stem cells (BMSCs) chondrogenesis under inflammatory conditions have the therapeutical potential for OA treatment. In this study, we characterized a novel small molecule which could ameliorate OA progression via novel regulating mechanisms. Docosahexaenoic acid (DHA), a bioactive molecule, was screened from a small molecule library and showed anti-inflammatory and chondroprotective effects in OA chondrocytes, as well as ameliorated IL-1ß impaired BMSCs chondrogenesis in Wnt/ß-catenin and NF-κB signaling dependent manners. Furthermore, Malat1 was found to be the key mediator of DHA-mediating anti-inflammation chondroprotection and chondrogenesis. DHA also rescued cartilage loss and damage in a surgery-induced OA mice model. The elevation of serum Malat1 levels caused by OA was also downregulated by DHA treatment. Taken together, our findings demonstrated that DHA, with a dual-signaling repression property, exerted its anti-inflammation, chondroprotection and chondrogenesis function possibly via regulating Malat1 level, suggesting that it may be a possible drug candidate for OA patients with elevated MALAT1 expression levels.

Pulsed Electromagnetic Field Enhances Healing of a Meniscal Tear and Mitigates Posttraumatic Osteoarthritis in a Rat Model.

BACKGROUND: Meniscal tears in the avascular region are thought to rarely heal and are a considerable challenge to treat. Although the therapeutic effects of a pulsed electromagnetic field (PEMF) have been extensively studied in a variety of orthopaedic disorders, the effect of a PEMF on meniscal healing has not been reported. HYPOTHESIS: PEMF treatment would promote meniscal healing and prevent osteoarthritis progression. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 72 twelve-week-old male Sprague-Dawley rats with full-thickness longitudinal medial meniscal tears in the avascular region were divided into 3 groups: control (Gcon), treatment with a classic signal PEMF (Gclassic), and treatment with a high-slew rate signal PEMF (GHSR). Macroscopic observation and histological analysis of the meniscus and articular cartilage were performed to evaluate the meniscal healing and progression of osteoarthritis. The synovium was harvested for histological and immunofluorescent analysis to evaluate the intra-articular inflammation. Meniscal healing, articular cartilage degeneration, and synovitis were quantitatively evaluated according to their scoring systems. RESULTS: Dramatic degenerative changes of the meniscus and articular cartilage were noticed during gross observation and histological evaluation in Gcon at 8 weeks. However, the menisci in the 2 treatment groups were restored to normal morphology, with a smooth surface and shiny white color. Particularly, the HSR signal remarkably enhanced the fibrochondrogenesis and accelerated the remodeling process of the regenerated tissue. The meniscal healing scores of the PEMF treatment groups were significantly higher than those in Gcon at 8 weeks. Specifically, the HSR signal showed a significantly higher meniscal repair score than did the classic signal at week 8 (P < .01). Additionally, the HSR signal significantly downregulated the secretion levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) in the meniscus and synovium as compared with the control group. When compared with the 2 treatment groups, Gcon had significantly higher degeneration scores (Gcon vs Gclassic, P < .0001; Gcon vs GHSR, P < .0001). The HSR signal also exhibited significantly lower synovitis scores compared with the other two groups (Gcon vs Gclassic, P < .0001; Gclassic vs GHSR, P = .0002). CONCLUSION: A PEMF promoted the healing of meniscal tears in the avascular region and restored the injured meniscus to its structural integrity in a rat model. As compared with the classic signal, the HSR signal showed increased capability to promote fibrocartilaginous tissue formation and modulate the inflammatory environment, therefore protecting the knee joint from posttraumatic osteoarthritis development. CLINICAL RELEVANCE: Adjuvant PEMF therapy may offer a new approach for the treatment of meniscal tears attributed to the enhanced meniscal repair and ameliorated osteoarthritis progression.

MicroRNA-744-5p suppresses tumorigenesis and metastasis of osteosarcoma through the p38 mitogen-activated protein kinases pathway by targeting transforming growth factor-beta 1.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Accumulating evidence has revealed that microRNAs (miRNAs) play a crucial role in the progression of OS. In this study, we found that miR-744-5p was the least expressed miRNA in patients with OS by analyzing GSE65071 from the GENE EXPRESSION OMNIBUS (GEO) database. Through real-time quantitative PCR (qRT-PCR), western blotting, colony formation assay, 5-Ethynyl-2-Deoxyuridine (EdU) incorporation assay, transwell migration, and invasion assays, we demonstrated its ability to inhibit the proliferation, migration, and invasion of OS cells in vitro. According to the luciferase reporter assay, transforming growth factor-ß1 (TGFB1) was negatively regulated by miR-744-5p and reversed the effects of miR-744-5p on OS. Subcutaneous tumor-forming animal models and tail vein injection lung metastatic models were used in animal experiments, and it was found that miR-744-5p negatively regulated tumor growth and metastasis in vivo. Furthermore, rescue assays verified that miR-744-5p regulates TGFB1 expression in OS. Further experiments revealed that the p38 MAPK signaling pathway is involved in the miR-744-5p/TGFB1 axis. Generally, this study suggests that miR-744-5p is a negative regulator of TGFB1 and suppresses OS progression and metastasis via the p38 MAPK signaling pathway.

MicroRNA-378 contributes to osteoarthritis by regulating chondrocyte autophagy and bone marrow mesenchymal stem cell chondrogenesis.

Osteoarthritis (OA) is the most common joint disease; thus, understanding the pathological mechanisms of OA initiation and progression is critical for OA treatment. MicroRNAs (miRNAs) have been shown to be involved in the progression of osteoarthritis, one candidate is microRNA-378 (miR-378), which is highly expressed in the synovium of OA patients during late-stage disease, but its function and the underlying mechanisms of how it contributes to disease progression remain poorly understood. In this study, miR-378 transgenic (TG) mice were used to study the role of miR-378 in OA development. miR-378 TG mice developed spontaneous OA and also exaggerated surgery-induced disease progression. Upon in vitro OA induction, miR-378 expression was upregulated and correlated with elevated inflammation and chondrocyte hypertrophy. Chondrocytes isolated from articular cartilage from miR-378 TG mice showed impaired chondrogenic differentiation. The bone marrow mesenchymal stem cells (BMSCs) collected from miR-378 TG mice also showed repressed chondrogenesis compared with the control group. The autophagy-related protein Atg2a, as well as chondrogenesis regulator Sox6, were identified as downstream targets of miR-378. Ectopic expression of Atg2a and Sox6 rescued miR-378-repressed chondrocyte autophagy and BMSC chondrogenesis, respectively. Anti-miR-378 lentivirus intra-articular injection in an established OA mouse model was shown to ameliorate OA progression, promote articular regeneration, and repress hypertrophy. Atg2a and Sox6 were again confirmed to be the target of miR-378 in vivo. In conclusion, miR-378 amplified OA development via repressing chondrocyte autophagy and by inhibiting BMSCs chondrogenesis, thus indicating miR-378 may be a potential therapeutic target for OA treatments.

Tibial cortex transverse transport accelerates wound healing via enhanced angiogenesis and immunomodulation.

AIMS: Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named 'tibial cortex transverse transport' (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model. METHODS: A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes. RESULTS: Gross and histological examinations showed that TTT technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In the TTT group, haematoxylin and eosin (H&E) staining demonstrated a better epidermis and dermis recovery, while immunohistochemical staining showed that TTT technique promoted local collagen deposition. The TTT technique also benefited to angiogenesis and immunomodulation. In the TTT group, blood flow in the wound area was higher than that of other groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the TTT group with double immune-labelling of CD31 and α-Smooth Muscle Actin (α-SMA). The number of M2 macrophages at the wound site in the TTT group was also increased. CONCLUSION: The TTT technique accelerated wound healing through enhanced angiogenesis and immunomodulation. Cite this article: Bone Joint Res 2022;11(4):189-199.

The Performance of Artificial Intelligence in Cervical Colposcopy: A Retrospective Data Analysis.

OBJECTIVE: We aimed to evaluate the performance of artificial intelligence (AI) system in detecting high-grade precancerous lesions. METHODS: A retrospective and diagnostic study was conducted in Chongqing Cancer Hospital. Anonymized medical records with cytology, HPV testing, colposcopy findings with images, and the histopathological results were selected. The sensitivity, specificity, and areas under the curve (AUC) in detecting CIN2+ and CIN3+ were evaluated for the AI system, the AI-assisted colposcopy, and the human colposcopists, respectively. RESULTS: Anonymized medical records from 346 women were obtained. The images captured under colposcopy of 194 women were found positive by the AI system; 245 women were found positive either by human colposcopists or the AI system. In detecting CIN2+, the AI-assisted colposcopy significantly increased the sensitivity (96.6% vs. 88.8%, p=0.016). The specificity was significantly lower for AI-assisted colposcopy (38.1%), compared with human colposcopists (59.5%, p < 0.001) or the AI system (57.6%, p < 0.001). The AUCs for the human colposcopists, AI system, and AI-assisted colposcopy were 0.741, 0.765, and 0.674, respectively. In detecting CIN3+, the sensitivities of the AI system and AI-assisted colposcopy were not significantly higher than human colposcopists (97.5% vs. 92.6%, p=0.13). The specificity was significantly lower for AI-assisted colposcopy (37.4%) compared with human colposcopists (59.2%, p < 0.001) or compared with the AI system (56.6%, p < 0.001). The AUCs for the human colposcopists, AI system, and AI-assisted colposcopy were 0.759, 0.674, and 0.771, respectively. CONCLUSIONS: The AI system provided equally matched sensitivity to human colposcopists in detecting CIN2+ and CIN3+. The AI-assisted colposcopy significantly improved the sensitivity in detecting CIN2+.

Knowledge of HPV, its vaccines, and attitudes toward HPV vaccines among obstetrician-gynecologists, pediatricians and immunization services providers in Western China.

BACKGROUND: In mainland China, HPV vaccines have been available to the public. However, only a few related studies among health care providers, as the key information providers, were reported although public concerns on HPV vaccines still exist. In this study, we aim to assess the knowledge of HPV, its vaccines, and attitudes toward HPV vaccines among the three most important groups of health care providers in Western China. METHOD: This was a cross-sectional questionnaire-based study. Health care providers including obstetrician-gynecologists (OB-GYNs), pediatricians, and immunization service providers in Western China were investigated regarding their knowledge of HPV and its vaccines and their attitudes toward HPV vaccines. RESULTS: Of 1079 health care providers completing the survey, 1015 (94.1%) knew HPV infection is the primary cause of cervical cancer. However, lower knowledge levels of other HPV-related diseases were also found (43.2%). About three-quarters (74.1%) of practitioners interviewed would be willing to recommend HPV vaccination, which was found to be lower among the OB-GYNs (69.6%) and the pediatricians (73.2%). "Lack of relevant knowledge," "concerns on safety and efficacy" and price were the three most important concerns surrounding HPV vaccination. CONCLUSION: The interviewed practitioners did not have adequate knowledge of HPV and its vaccines in depth. Education interventions are highly recommended to the health care providers, especially for OB-GYNs and pediatricians, to increase the coverage of HPV vaccination among the population. For the currently high price of vaccines, a future co-sharing mechanism between the government, the providers, and the individuals might be a solution.

DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis.

As one of the leading causes of bone fracture in postmenopausal women and in older men, osteoporosis worldwide is attracting more attention in recent decades. Osteoporosis is a common disease mainly resulting from an imbalance of bone formation and bone resorption. Pharmaceutically active compounds that both activate osteogenesis, while repressing osteoclastogenesis hold the potential of being therapeutic medications for osteoporosis treatment. In the present study, sesamin, a bioactive ingredient derived from the seed of Sesamum Indicum, was screened out from a bioactive compound library and shown to exhibit dual-regulating functions on these two processes. Sesamin was demonstrated to promote osteogenesis by upregulating Wnt/ß-catenin, while repressing osteoclastogenesis via downregulating NF-κB signaling . Furthermore, DANCR was found to be the key regulator in sesamin-mediated bone formation and resorption . In an ovariectomy (OVX)-induced osteoporotic mouse model, sesamin could rescue OVX-induced bone loss and impairment. The increased serum level of DANCR caused by OVX was also downregulated upon sesamin treatment. In conclusion, our results demonstrate that sesamin plays a dual-functional role in both osteogenesis activation and osteoclastogenesis de-activation in a DANCR-dependent manner, suggesting that it may be a possible medication candidate for osteoporotic patients with elevated DNACR expression levels.

Sox11 Modified Tendon-Derived Stem Cells Promote the Repair of Osteonecrosis of Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a leading cause of mobility impairment which may lead to a total hip replacement. Recent studies have found tendon derived stem cells (TDSCs) might be an ideal cell source for musculoskeletal tissue regeneration. And our previous study has shown Sox11 could promote osteogenesis of bone marrow-derived MSCs. However, the effect of TDSCs or Sox11 over-expressing TDSCs (TDSCs-Sox11) on bone regeneration in ONFH has not been investigated. In the present study, TDSCs were infected with AAV carrying Sox11 or empty vector. We showed that Sox11 could promote the proliferation and osteogenic differentiation of TDSCs, as well as angiogenesis in vitro. The western blot analysis showed that Sox11 could activate the PI3K/Akt signaling pathway to promote osteogenesis of TDSCs. Finally, using a rabbit model of hormone-induced ONFH, our result demonstrated that local administration of TDSCs or TDSCs overexpressing Sox11 could accelerate bone regeneration in necrotic femoral heads, and TDSCs overexpressing Sox11 showed better effects. TDSCs over-expressing Sox11 might be a promising cell source for stem cell therapy to promote bone regeneration, such as ONFH, fracture, bone defect, and so on.

Local administration of allogeneic or autologous bone marrow-derived mesenchymal stromal cells enhances bone formation similarly in distraction osteogenesis.

BACKGROUND AIMS: Distraction osteogenesis (DO) is a surgical technique to promote bone regeneration that requires a long time for bone healing. Bone marrow-derived mesenchymal stromal cells (MSCs) have been applied to accelerate bone formation in DO. Allogeneic MSCs are attractive, as they could be ready to use in clinics. Whether allogeneic MSCs would have an effect similar to autologous MSCs with regard to promoting bone formation in DO is still unknown. This study compares the effect of autologous MSCs versus allogeneic MSCs on bone formation in a rat DO model. METHODS: Rat bone marrow-derived MSCs were isolated, characterized and expanded in vitro. Adult rats were subjected to right tibia transverse osteotomy. On the third day of distraction, each rat received one injection of phosphate-buffered saline (PBS), autologous MSCs or allogeneic MSCs at the distraction site. Tibiae were harvested after 28 days of consolidation for micro-computed tomography examination, mechanical test and histological analysis. RESULTS: Results showed that treatment with both allogeneic and autologous MSCs promoted bone formation, with significantly higher bone mass, mechanical properties and mineral apposition rate as well as expression of angiogenic and bone formation markers at the regeneration sites compared with the PBS-treated group. No statistical difference in bone formation was found between the allogeneic and autologous MSC treatment groups. CONCLUSIONS: This study indicates that allogeneic and autologous MSCs have a similar effect on promoting bone consolidation in DO. MSCs from an allogeneic source could be used off-the-shelf with DO to achieve early bone healing.

Effect of an educational intervention on human papillomavirus (HPV) knowledge and attitudes towards HPV vaccines among healthcare workers (HCWs) in Western China.

BACKGROUND: Healthcare workers (HCWs) play a key role in the recommendation of HPV vaccination. Our study aimed to understand to what extent a structured health intervention could change the knowledge and attitudes toward HPV and its vaccines among HCWs in Western China. METHODS: This was a multi-center, questionnaire-based interventional study conducted across 12 cities of seven provinces in Western China, from November 2018 to July 2019. Participants were recruited from local health systems by e-invitation. Questionnaires were administered to participants before and after the intervention. RESULTS: A total of 1448 HCWs attended the educational lectures and 1354 participants completed both pre- and post-study questionnaires. In general, HCWs had satisfactory baseline knowledge regarding HPV and its vaccines compared with other populations, and a significantly higher knowledge level was observed after the intervention. However, some more specific knowledge on the vaccination procedures, other HPV-related diseases and whether HPV testing was required before vaccination was relatively poor. Following the educational intervention, the correct responses to the above questions increased (P < .001). However, it was still lower compared with answers to other questions. Change was also detected regarding HCWs' willingness to recommend HPV vaccines to the appropriate population (P < .001). CONCLUSION: Educational intervention on HPV and its vaccines is effective in improving HCWs' knowledge levels and willingness to recommend HPV vaccines. Future educational interventions should focus more on knowledge regarding HPV-related diseases and HPV vaccination. Education campaigns targeting rural HCWs are urgently needed in the near future.

Development and validation of an artificial intelligence system for grading colposcopic impressions and guiding biopsies.

BACKGROUND: Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies. METHODS: Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance. RESULTS: The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516, p < 0.001). For detecting pathological high-grade squamous intraepithelial lesion or worse (HSIL+), CAIADS showed higher sensitivity than the use of colposcopies interpreted by colposcopists at either biopsy threshold (low-grade or worse 90.5%, 95% CI 88.9-91.4% versus 83.5%, 81.5-85.3%; high-grade or worse 71.9%, 69.5-74.2% versus 60.4%, 57.9-62.9%; all p < 0.001), whereas the specificities were similar (low-grade or worse 51.8%, 49.8-53.8% versus 52.0%, 50.0-54.1%; high-grade or worse 93.9%, 92.9-94.9% versus 94.9%, 93.9-95.7%; all p > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758. CONCLUSIONS: The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.