In the process of maintaining the steady state of bone tissue, the transcription network and signal pathway of the body play a vital role. These complex regulatory mechanisms need precise coordination to ensure the balance between bone formation and bone absorption. Once this balance is broken, it may lead to pathological changes of bone and cartilage, and then lead to various bone diseases. Therefore, it is of great significance to understand these regulatory mechanisms for the prevention and treatment of bone diseases. In recent years, with the deepening of research, more and more lncRNA has been found to be closely related to bone health. Among them, nuclear paraspeckle assembly transcript 1 (NEAT1), as an extremely abundant RNA molecule in mammalian nuclei, has attracted extensive attention. NEAT1 is mainly transcribed from a specific site in human chromosome 11 by RNA polymerase II (RNaseP), which can form two different subtypes NEAT1_1 and NEAT1_2. These two subtypes are different in intracellular distribution and function, but they participate in many biological processes together. Studies have shown that NEAT1 plays a specific role in the process of cell growth and stress response. For example, it can regulate the development of osteoblasts (OB), osteoclasts (OC) and chondrocytes by balancing the differentiation of bone marrow mesenchymal stem cells (BMSCs), thus maintaining the steady state of bone metabolism. This discovery reveals the important role of NEAT1 in bone development and remodeling. In addition, NEAT1 is closely related to a variety of bone diseases. In patients with bone diseases such as osteoporosis (OP), osteoarthritis (OA) and osteosarcoma (OS), the expression level of NEAT1 is different. These differential expressions may be closely related to the pathogenesis and progression of bone diseases. By regulating the level of NEAT1, it can affect a variety of signal transduction pathways, and then affect the development of bone diseases. For example, some studies show that by regulating the expression level of NEAT1, the activity of osteoclasts can be inhibited, and the proliferation and differentiation of osteoblasts can be promoted, thus improving the symptoms of osteoporosis. It is worth noting that NEAT1 can also be used as a key sensor for the prevention and treatment of bone diseases. When exercising or receiving some natural products, the expression level of NEAT1 will change, thus reflecting the response of bones to external stimuli. This feature makes NEAT1 an important target for studying the prevention and treatment strategies of bone diseases. However, although the role of NEAT1 in bone biology and bone diseases has been initially recognized, its specific mechanism and regulatory relationship are still controversial. For example, the expression level, mode of action and interaction with other molecules of NEAT1 in different bone diseases still need further in-depth study. This paper reviews the role of NEAT1 in maintaining bone and cartilage metabolism, and discusses its expression and function in various bone diseases. By combing the existing research results and controversial points, this paper aims to provide new perspectives and ideas for the prevention and treatment of bone diseases, and provide useful reference and enlightenment for future research.

ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Objective: To investigate the status of overweight and obesity and associated factors among primary and middle school students in Huzhou City, Zhejiang Province, so as to provide insights into formulating the prevention and control strategies for overweight and obesity in students. Methods: Primary and middle school students from 5 counties (cities, districts) of Huzhou City were selected by using stratified cluster random sampling method from September to November, 2023. The general information, dietary habits and exercise behaviors were collected using the Student Health Status and Influencing Factors Questionnaire. Height and weight were measured, and body mass index was used to analyze overweight and obesity in primary and middle school students. A multivariable logistic regression model was used to analyze the influencing factors of overweight and obesity. Results: A total of 7 573 students were surveyed, including 3 791 males (50.06%) and 3 782 females (49.94%). There were 2 754 primary school students (36.37%), 2 744 junior high school students (36.23%) and 2 075 senior high school students (27.40%). There were 2 166 students with overweight and obesity (28.60%), 1 186 students with overweight (15.66%), and 980 students with obesity (12.94%). Multivariable logistic regression analysis showed that gender (female, OR=0.546, 95%CI: 0.493-0.604), frequency of sweetened beverage consumption (once and more per day, OR=1.349, 95%CI: 1.102-1.650), and frequency of milk and milk products consumption (less than once per day, OR=0.742, 95%CI: 0.577-0.954) were the influencing factors for overweight and obesity in primary and middle school students. Conclusion The prevalence of overweight and obesity among primary and middle school students in Huzhou City is 28.60%, and is associated with gender, frequency of sweetened beverages and milk and milk products consumption.

Total anomalous pulmonary venous connection (TAPVC) is a relatively rare but complex congenital heart disease characterized by the anomalous drainage of the pulmonary veins. Rather than connecting to the left atrium, the pulmonary veins drain either directly or indirectly into the systemic venous circulation or the right atrium via abnormal pathways. While there is broad consensus on the diagnostic criteria for TAPVC, significant debate persists regarding the optimal timing of surgical intervention, preferred surgical techniques, and postoperative management including re-intervention strategies. This article formulates a Chinese consensus based on evidence-based data from the literature and opinions from domestic experts, with the goal of further standardizing the surgical treatment of TAPVC in China.

In this study, we investigated the anti-inflammatory effect and mechanism of tilianin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The cell viability was detected by cell counting kit-8 (CCK-8) assay. The content of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immuno sorbent assay (ELISA) kits. The content of nitric oxide (NO) was assayed by Griess reagent method. The level of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The protein levels of Toll like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88), nuclear factors κB p65 (NF-κB p65), phosphorylated nuclear factor κB p65 (p-NF-κB p65), nuclear factor κB inhibitory protein α (IκBα) and phosphorylation nuclear factor κB inhibitory protein α (p-IκBα) were detected by Western blot. The mRNA and protein levels of NLRP3, pro-IL-1β, pro-IL-18 and pro-caspase-1 were detected by qRT-PCR and Western blot. Immunofluorescence staining was used to detect the nuclear translocation of NF-κB p65. The effect of tilianin on the TLR4/Myd88/NF-κB signaling pathway was further validated by using the TLR4 signaling inhibitor restatorvid (TAK242). The results showed that tilianin significantly reduced the levels of TNF-α, IL-6 and NO in the supernatant of RAW264.7 cells and decreased the content of intracellular ROS. Tilianin reduced the levels of TLR4, Myd88, p-NF-κB p65 and p-IκBα protein and nuclear translocation of NF-κB p65. Tilianin could reduce the protein levels of NLRP3, pro-IL-1β, pro-IL-18 and pro-caspase-1. Tilianin significantly inhibited the mRNA levels of NLRP3 and pro-IL-1β. The above research results indicated that tilianin could significantly alleviate the LPS-induced inflammatory response in RAW264.7 cells and its mechanism might be related to downregulate the TLR4/Myd88/NF-κB signaling pathway to inhibit NLRP3 inflammasome.

Objective: To analyze the effects of outdoor activities, sedentary behaviors and sleep duration on the risk of poor vision among primary and secondary school students after replacing them with each other, so as to provide a reference for precise intervention in the prevention and control of myopia among children and adolescents. Methods: From March to May 2023, a stratified cluster random sampling method was used to select 6 132 students in grades 4 to 12 in Hefei, Wuhu, Suzhou and Chizhou cities in Anhui Province. A questionnaire survey was conducted to collect the basic information, outdoor activities, sedentary behavior, and sleep duration, and a visual inspection was carried out by 5 m standard logarithmic visual acuity chart. The single activity model, segmentation model and isotemporal substitution model were used to analyze the relationship between outdoor activities, sedentary behaviors, sleep, and poor vision, and stratified analysis was performed by gender. Results: The detection rate of poor vision among the 6 132 primary and secondary school students was 76.9%, and the detection rate of poor vision was higher for girls ( 81.1 %) than for boys (72.6%), and the difference was statistically significant ( χ 2=61.37, P <0.01). The results of the single activity model and segmentation model showed that outdoor activity and sleep duration were correlated with a reduced risk of poor vision in primary and secondary school students ( OR =0.87, 0.88; 0.88, 0.91), while sedentary behavior was correlated with an increased risk of poor vision ( OR =1.05, 1.03) ( P <0.05). The results of the isotemporal substitution model showed that replacing the same amount of sedentary behavior with 1 h/d of outdoor activity was associated with 15% reduction in the risk of poor vision ( OR = 0.85), and replacing the same amount of sedentary behavior with 1 h/d of sleep was associated with a 12% reduction in the risk of poor vision ( OR =0.88) ( P <0.05). The results of the isotemporal substitution model stratified by gender showed that replacing the same amount of sedentary behavior with 1 h/d of outdoor activity and 1 h/d of sleep were associated with 22% and 8% reduction in the risk of poor vision in male students ( OR =0.78, 0.92), and replacing the same amount of sedentary behavior with 1 h/d of sleep was associated with 18% reduction in the risk of poor vision in female students ( OR =0.82) ( P <0.05). Conclusion Replacing sedentary behavior with 1 h/d of outdoor activity for boys and 1 h/d of sleep for girls and boys could reduce the risk of poor vision.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Purpose To explore the clinicopathological characteristics of tonsil squamous cell carcinoma(TSCC),and to explore the whole exome mutations and tumor mutational bur-den(TMB)in TSCC cases.Methods Ten patients with clini-cally and histopathologically confirmed TSCC and their clinico-pathological characteristics were collected,The expression of CK(AE1/AE3),CK5/6,p63,p40,p16 and Ki67 were meas-ured by two steps of EnVision,and the whole exome sequencing(WES)and TMB were conducted in 3 of them.Results A-mong the 10 patients,there were 6 females and 4 males which aged from 43 to 76 years old.Microscopically,the cancer cells infiltrated into the subdermis of crypts in the form ofnests and irregular cord,accompanied by comedo like necrosis,intercellu-lar bridges,and varying degrees of keratinization.Obvious atyp-ia and mitotic figures were easily seen.Follow-up was available in all cases,ranging from 6 to 45 months.Nine cases had sur-vived.Immunohistochemistry staining showed that all cases were positive for CK(AE1/AE3),CK5/6,p63,p40,and p16 was positively expressed in three cases,and the proliferation index Ki67 ranged from 40％to 90％.The WES of three cases showed that ARID1B and LRP6 were common cancer susceptibility genes,and WDFY4,ZFHX4 exhibited higher mutation rates,which were both 3/3.The TMB analysis showed that one out of three cases was＞9 mut/Mb.Conclusion The early symptoms of TSCC are not obvious that lead to easily missed and misdiag-nosed.The WES analyses suggest that WDFY4 and ZFHX4 had a higher mutation rate.The TMB analysis suggests that some TSCC patients may benefit from immunotherapy.

Objective: To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) and influencing factors among vegetable greenhouse workers, so as to provide insights into relevant intervention measurements. Methods: Workers from 4 vegetable greenhouse villages were sampled in the suburbs of Xining City using a cluster sampling method from March to April 2023. Participants' demographic information, characteristics of greenhouse operation and prevalence of WMSDs were collected using questionnaire surveys. Factors affecting the prevalence of WMSDs among vegetable greenhouse workers were identified using a multivariable logistic regression model. Results: A total of 550 questionnaires were distributed, and 518 valid questionnaires were recovered, with an effective response rate of 94.18%. There were 264 males (50.97%) and 254 females (49.03%), and 269 participants (51.93%) aged 50 years and older. The prevalence of WMSDs among vegetable greenhouse workers was 40.93% (212 cases). Waist, neck and back were mainly affected, with 185 (35.71%), 157 (30.31%), and 153 (29.54%) cases, respectively. Multivariable logistic regression analysis showed that workers who smoke (OR=2.406, 95%CI: 1.133-5.110), worked 8 hours and longer per day (OR=6.618, 95%CI: 3.492-12.542) and lift heavy loads of about 20 kg (OR=1.770, 95%CI: 1.013-3.092) had a higher risk of WMSDs. Conclusions WMSDs occurred in 40.93% of vegetable greenhouse workers in Xining City, and waist, neck and back were mainly affected. Smoking, working duration and lifting heavy loads may influence the prevalence of WMSDs among vegetable greenhouse workers in Xining City.