BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.
Animals ; Neurons/physiology* ; Mice ; Prefrontal Cortex/cytology* ; Parvalbumins/metabolism* ; Brain Mapping/methods* ; Neural Pathways/physiology* ; Somatostatin/metabolism* ; Male ; Interneurons/physiology* ; Mice, Inbred C57BL ; Thalamus/physiology* ; Mice, Transgenic

Objective:To explore the feasibility of deep learning-based restoration of obscured thyroid ultrasound images.Methods:A total of 358 images of thyroid nodules were retropectively collected from January 2020 to October 2021 at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and the images were randomly masked and restored using DeepFillv2. The difference in grey values between the images before and after restoration was compared, and 6 sonographers (2 chief physicians, 2 attending physicians, 2 residents) were invited to compare the rate of correctness of judgement and detection of image discrepancies. The ultrasound features of thyroid nodules (solid composition, microcalcifications, markedly hypoechoic, ill-defined or irregular margins, or extrathyroidal extensions, vertical orientation and comet-tail artifact) were extracted according to the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). The consistency of ultrasound features of thyroid nodules before and after restoration were compared.Results:The mean squared error of the images before and after restoration ranged from 0.274 to 0.522, and there were significant differences in the rate of correctness of judgement and detection of image discrepancies between physicians of different groups(all P<0.001). The overall accuracy rate was 51.95%, the overall detection rate was 1.79%, there were significant differences also within the chief physicians and resident groups (all P<0.001). The agreement rate of all ultrasound features of the nodules before and after image restoration was higher than 70%, over 90% agreement rate for features such as solid composition and comet-tail artifact. Conclusions:The algorithm can effectively repair obscured thyroid ultrasound images while preserving image features, which is expected to expand the deep learning image database, and promote the development of deep learning in the field of ultrasound images.

OBJECTIVE: To evaluate the application of surgical strategies for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving the C ₂ segment. METHODS: The literature about the surgery for cervical OPLL involving C ₂ segment was reviewed, and the indications, advantages, and disadvantages of surgery were summarized. RESULTS: For cervical OPLL involving the C ₂ segments, laminectomy is suitable for patients with OPLL involving multiple segments, often combined with screw fixation, and has the advantages of adequate decompression and restoration of cervical curvature, with the disadvantages of loss of cervical fixed segmental mobility. Canal-expansive laminoplasty is suitable for patients with positive K-line and has the advantages of simple operation and preservation of cervical segmental mobility, and the disadvantages include progression of ossification, axial symptoms, and fracture of the portal axis. Dome-like laminoplasty is suitable for patients without kyphosis/cervical instability and with negative R-line, and can reduce the occurrence of axial symptoms, with the disadvantage of limited decompression. The Shelter technique is suitable for patients with single/double segments and canal encroachment >50% and allows for direct decompression, but is technically demanding and involves risk of dural tear and nerve injury. Double-dome laminoplasty is suitable for patients without kyphosis/cervical instability. Its advantages are the reduction of damage to the cervical semispinal muscles and attachment points and maintenance of cervical curvature, but there is progress in postoperative ossification. CONCLUSION OPLL involving the C ₂ segment is a complex subtype of cervical OPLL, which is mainly treated through posterior surgery. However, the degree of spinal cord floatation is limited, and with the progress of ossification, the long-term effectiveness is poor. More research is needed to address the etiology of OPLL and to establish a systematic treatment strategy for cervical OPLL involving the C ₂ segment.
Humans ; Longitudinal Ligaments/surgery* ; Ossification of Posterior Longitudinal Ligament/surgery* ; Treatment Outcome ; Osteogenesis ; Decompression, Surgical/methods* ; Cervical Vertebrae/surgery* ; Laminoplasty/methods* ; Kyphosis/surgery* ; Retrospective Studies

Interval timing is involved in a variety of cognitive behaviors such as associative learning and decision-making. While it has been shown that time estimation is adaptive to the temporal context, it remains unclear how interval timing behavior is influenced by recent trial history. Here we found that, in mice trained to perform a licking-based interval timing task, a decrease of inter-reinforcement interval in the previous trial rapidly shifted the time of anticipatory licking earlier. Optogenetic inactivation of the anterior lateral motor cortex (ALM), but not the medial prefrontal cortex, for a short time before reward delivery caused a decrease in the peak time of anticipatory licking in the next trial. Electrophysiological recordings from the ALM showed that the response profiles preceded by short and long inter-reinforcement intervals exhibited task-engagement-dependent temporal scaling. Thus, interval timing is adaptive to recent experience of the temporal interval, and ALM activity during time estimation reflects recent experience of interval.
Animals ; Mice ; Reward ; Time Factors ; Cognition ; Learning ; Decision Making ; Reinforcement, Psychology

Objective To analyze the prognostic value of thrombin generation assay(TGA)and coagulation factor testing in postoperative deep venous thrombosis(DVT)of lower extremities in elderly patients with traumatic fracture.Methods A retrospective case-control study was conducted to collect traumatic patients older than 60 years old who underwent surgery in our department from March 2019 to March 2022.The number of patients was 104.According to the ultrasonic examination of DVT 5 days after operation,the patients were divided into DVT group and non-DVT group.The differences of general demographic data,previous chronic diseases,time from trauma to operation,related indexes of TGA and TF coagulation factors(F)between the two groups were analyzed.The indexes with statistical significance were analyzed by receiver operating curve(ROC);the indexes with statistically significant differences were analyzed by Logistic regression and the prediction probability was calculated by ROC curve analysis.Results The incidence of postoperative DVT was 21.12％.Compared with the non-DVT group,the time from trauma to operation was longer in the DVT group,and the peak value under 5 pmol/L TF activation was lower(258.13±40.88 vs 209.58±30.09).F V,F Ⅷ and Fib were higher(141.25(125.38,158.18)vs 176.12(150.65,186.34),145.49(133.36,147.48)vs 165.96(153.07,180.65),3.25± 0.55 vs 3.92±0.72,respectively).The differences were statistically significant(all P＜0.01).ROC curve analysis showed that the time from trauma to operation,the peak value of 5 pmol/L TF activation,F V,FⅧ and Fib combined had more predictive value for postoperative DVT,the AUC was 0.91(P＜0.01),the sensitivity was 0.82 and the specificity 0.92.Conclusion The time from trauma to operation,the peak value of TGA under the condition of 5 pmol/L TF activation,F V,F Ⅷ and Fib have excellent prognostic value for the postoperative DVT of lower extremities in elderly patients with traumatic fracture,and the combined detection is more significative.

Injection fear is widespread in the population, which can cause patients to tolerate or avoid injection, reduce treatment compliance, and increase the burden of healthcare. Choosing appropriate injection fear assessment tools in clinical practice is helpful to understand the degree, psychological characteristics and influencing factors of individual injection fear. In this paper, the contents, characteristics and application methods of fear of injection assessment tools at home and abroad are reviewed, in order to provide reference for the application and development of fear of injection assessment tools for medical staff.

Objective:To explore the mediating effect of nurse professional self-concept between autonomous learning ability and perceived professional benefit.Methods:From April to June 2019, 295 nurses from two hospitals in Yanbian were selected as the research subject by convenience sampling. A survey was conducted on nurses using the General Information Questionnaire, Questionnaire of Nurses' Perceived Professional Benefits, Rating Scale of Self-directed Learning Competence for Nurses, and Professional Self-concept Scale of Nurses. A total of 295 questionnaires were distributed, and 290 valid questionnaires were collected, with an effective response rate of 98.3% (290/295) .Results:290 nurses scored (133.49±21.75) on the Questionnaire of Nurses' Perceived Professional Benefits, (129.74±26.08) on the Rating Scale of Self-directed Learning Competence for Nurses, and (89.39±14.65) on the Professional Self-concept Scale of Nurses. Pearson correlation analysis results showed that there were positive correlations among nurses' perceived professional benefit, autonomous learning ability, and professional self-concept ( P<0.05). The stepwise regression analysis showed that nurse professional self-concept played a complete mediating effect between nurse autonomous learning ability and perceived professional benefit. Conclusions:Nurses' professional self-concept plays a complete mediating effect between autonomous learning ability and nurses' perceived professional benefit. Effective intervention in nurses' professional self-concept and autonomous learning ability is an important way to enhance their perceived professional benefit.

Nasal tip hypertrophy is one of the common nasal tip morphological abnormalities in clinical practice. A comprehensive treatment regimen is possible only when one can correctly understand the mechanism of nasal tip hypertrophy. In this paper, the mechanism and treatment of nasal tip hypertrophy were analyzed and summarized in order to provide some reference for rhinoplastic surgeons.