G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objective: To evaluate the comprehensive intervention effect of lunch for primary and secondary school students in Minhang District, so as to provide a theoretical and practical basis for lunch intervention in school. Methods: From October to December 2023, a convenience sampling method was used to select 1 937 students from one primary and secondary school in Minhang District.A comprehensive intervention measure focusing on "reducing oil and salt" for lunch recipe optimization and nutrition education was carried out, and a questionnaire survey was conducted to evaluate the intervention effect three months later. Chi square test and Wilcoxon rank test were used to compare the data before and after the intervention. Results: After intervention, the use of cooking oil and salt, the supply of protein and fat in primary and secondary school lunches were reduced, and had no obvious impact on energy and other major nutrients. After intervention, compared to before intervention, the proportion of primary school students who felt that lunch was greasy decreased (8.9%, 6.2%, χ 2=4.35), and the proportion of primary and secondary school students who felt that lunch were delicious decreased significantly (33.2%, 23.2%; 63.9%, 53.5%, χ 2=26.39, 17.52) ( P < 0.05 ). Secondary school students also felt reduced variety of food ingredients (46.9%, 38.3%, χ 2=16.05, P <0.05). In addition, after intervention, the total surplus rate of primary school students meals decreased (7.4%, 4.4%, χ 2=5.73), mainly reflected in the decrease of the surplus rate of staple foods (7.1%, 2.4%, χ 2=17.39), while the surplus rate of vegetable dishes increased ( 16.0 %, 21.2%, χ 2=6.01) ( P <0.05). Although there was no significant change in the total surplus rate of meals for secondary school students, the surplus rate of staple foods decreased (12.9%, 5.4%, χ 2=33.52), while the surplus rates of meat and vegetable dishes increased (11.2%, 26.9%; 17.5%, 33.2%, χ 2=74.26, 61.88) ( P <0.05). After intervention, there was no statistically significant difference in the overweight and obesity rates of primary school students ( χ 2=0.11,0.43) and secondary school students ( χ 2=0.01,0.00) compared to before intervention( P >0.05). After intervention, the lung capacity of primary school students [1 564 (1 269,1 890) mL] and sitting forward flexion [11.3 (7.6, 15.2) cm] increased compared to before intervention [1 522 (1 259, 1 819 ) mL, 10.5 (6.3, 13.5) cm] ( Z =2.20, 4.68, P <0.01), but there was no statistically significant difference in lung capacity and sitting forward flexion of secondary school students before and after intervention ( Z =-0.46, -0.08, P >0.05). Conclusion The comprehensive intervention of school lunch has promoted a significant decrease in the use of oil and salt in lunch and improved the quality of recipes, and has a positive impact on the situation of leftover lunch and the health of students to a certain extent.

Background A large number of power supply workers are involved in live working and are exposed to multiple risk factors for long periods of time during outdoor work, which in turn causes occupational health problems. Objective To identify potential ergonomic factors related to work-related musculoskeletal disorders (WMSDs) and estimate the ergonomic risk of electricians. Methods A total of 31 workers were randomly selected from a training base under a power supply enterprise in Guangxi, and their operation processes were recorded by video. Using the Rapid Upper Limb Assessment (RULA) method, the workers were scored by the posture of their arms, neck, and torso during operation, and the final scores were summarized to assess their risk level. Two independent samples t-tests were used to compare the differences in RULA scores. Results A total of 31 videos for mounting/dismounting insulation mask and 29 videos for breaking/connecting contact terminal were collected. The RULA score for mounting/dismounting insulation mask was 6.6 ± 0.7 (left side) and 7.0 ± 0.2 (right side), most of the workers had a score of 7 (71.0% on the left side and 96.8% on the right side), and the upper limb and overall scores on the right side were higher than those on the left side (P < 0.05). The RULA score for breaking/connecting contact terminal was 6.9 ± 0.4 (both right and left sides), most of workers had a score of 7 (89.7% on the left side and 93.1% on the right side), and the difference of the overall scores between the right and left side for this operation were not statistically significant (P > 0.05). The ergonomic risk levels for both operations were level 3 or higher. Conclusion Mounting/dismounting insulation mask and breaking/connecting contact terminal are typical upper limb operations, and have a high level of ergonomics risk, requiring effective preventive and protective measures.

Objective:To evaluate the relationship between sevoflurane preconditioning-induced reduction of cognitive impairment and hippocampal necroptosis after cardiopulmonary bypass (CPB) in rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 6 months, weighing 400-450 g, were divided into 4 groups ( n=15 each) using the random number table method: control group (group C), sevoflurane group (Sev group), CPB group and CPB+ sevoflurane preconditioning group (CPB+ Sev group). The rats were exposed to 0.4% sevoflurane for 2 h in CPB+ Sev group and Sev group. The CPB model was established at 30 min after the end of sevoflurane preconditioning in CPB+ Sev group. The open field test was performed to assess the autonomic movement ability on the 2nd day after CPB. The Morris water maze test was used to assess the cognitive function on the 3rd day after CPB. The hippocampal tissues were removed after the end of the Morris water maze test for determination of the necroptosis rate and cytosolic calcium concentration of hippocampal neuron ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated receptor-interacting protein kinase 1 (p-RIPK1), phosphorylated RIPK3 and phosphorylated mixed-lineage kinase-like domain (p-MLKL) (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (by transmission electron microscopy). Results:There was no statistically significant difference in the parameters of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, the time of staying at the original platform quadrant was shortened, the hippocampal necroptosis rate and [Ca 2+ ] i were increased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was up-regulated ( P<0.05), the organelles of hippocampal neurons swelled, lysosomes broke, and some chromatin in nuclei dissoluted in CPB group. Compared with CPB group, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, the hippocampal necroptosis rate and [Ca 2+ ] i were decreased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was down-regulated ( P<0.05), and the damage to the ultrastructure of hippocampal neurons was sinificantly reduced in CPB+ Sev group ( P<0.05). Conclusions:The mechanism by which sevoflurane preconditioning attenuates cognitive impairment may be related to the inhibition of calcium overload-mediated hippocampal necroptosis in a rat model of CPB.

Objective:To evaluate the relationship between sevoflurane preconditioning-induced reduction of cognitive impairment and hippocampal necroptosis after cardiopulmonary bypass (CPB) in rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 6 months, weighing 400-450 g, were divided into 4 groups ( n=15 each) using the random number table method: control group (group C), sevoflurane group (Sev group), CPB group and CPB+ sevoflurane preconditioning group (CPB+ Sev group). The rats were exposed to 0.4% sevoflurane for 2 h in CPB+ Sev group and Sev group. The CPB model was established at 30 min after the end of sevoflurane preconditioning in CPB+ Sev group. The open field test was performed to assess the autonomic movement ability on the 2nd day after CPB. The Morris water maze test was used to assess the cognitive function on the 3rd day after CPB. The hippocampal tissues were removed after the end of the Morris water maze test for determination of the necroptosis rate and cytosolic calcium concentration of hippocampal neuron ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated receptor-interacting protein kinase 1 (p-RIPK1), phosphorylated RIPK3 and phosphorylated mixed-lineage kinase-like domain (p-MLKL) (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (by transmission electron microscopy). Results:There was no statistically significant difference in the parameters of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, the time of staying at the original platform quadrant was shortened, the hippocampal necroptosis rate and [Ca 2+ ] i were increased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was up-regulated ( P<0.05), the organelles of hippocampal neurons swelled, lysosomes broke, and some chromatin in nuclei dissoluted in CPB group. Compared with CPB group, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, the hippocampal necroptosis rate and [Ca 2+ ] i were decreased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was down-regulated ( P<0.05), and the damage to the ultrastructure of hippocampal neurons was sinificantly reduced in CPB+ Sev group ( P<0.05). Conclusions:The mechanism by which sevoflurane preconditioning attenuates cognitive impairment may be related to the inhibition of calcium overload-mediated hippocampal necroptosis in a rat model of CPB.

Objective To investigate the effects and possible mechanism of electret and 5-fluorouracil(5-FU)on the growth of scar fibroblasts.Methods The effect of+5000 V electret combined with different concentrations of 5-FU on the proliferation of scar fibroblasts was detected by automatic enzyme labeling instrument.The apoptosis of scar fibroblasts and the mRNA expression of p53 and other apoptotic genes were studied by fluorescence microscopy and RT-PCR technology under the action of electrostatic field.Results ① After the treatment of positive electret and different concentrations of 5-FU for 72 h,the cell proliferation rate decreased,and the inhibition rate of scar cells in the+5000 V electret+160 μg/ml 5-FU group was(0.15±0.051)%.②+5000 V electret group could promote the apoptosis of scar fibroblasts;The number of apoptotic cells in+5000 V electret and 5-FU group was higher than that in 5-FU group.③The mRNA expression levels of four apoptotic genes in the+5000 V electret group were increased,and the expression levels of four signature genes in the+5000 V electret and 5-FU group were increased compared with those in the 5-FU group.Conclusion The combination of positive electret and 5-FU had a synergistic effect on inhibiting cell growth.The mechanism of positive electret inhibiting scar cell growth may be through promoting the expression of apoptosis gene,and then affecting the growth state of cells to inhibit cell growth.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Background Operation and maintenance work in the power grid industry often involving climbing, manual handling, and poor postures causing serious problems like work-related musculoskeletal disorders (WMSDs). The influencing factors of WMSDs are not very clear, but the problem has been widely concerned in this industry. Objective To understand the prevalence and influencing factors of WMSDs among climbing task-involved workers in power supply enterprises. Methods Using a cross-sectional design, a total of 702 workers involving climbing task from 10 power supply enterprises in Jilin Province, Tianjin Municipality, and Shandong province were selected as study subjects using cluster sampling. The Musculoskeletal Disorders Questionnaire which was revised by Lei Yang was used to estimate the prevalence and identify related factors of WMSDs. \begin{document}$ {\chi ^2} $\end{document} test and multiple logistic regression were used to analyze the data. Results A total of 702 subjects were approached, 649 valid questionnaires were recovered, and the effective recovery rate was 92.45%. The prevalence of WMSDs was 81.2%, and neck (65.0%), low back (59.0%), and shoulders (54.4%) were areas of high prevalence of WMSDs. The multiple logistic regression analysis results showed that sometimes and often/very often holding awkward postures were the risk factors of neck, shoulders, low back, knees, upper back, hands/wrists, ankles/feet, elbows, and hips/thighs WMSDs; the OR (95%CI) values were 1.931 (1.260-2.959) and 3.145 (1.810-15.465), 2.700 (1.694-4.305) and 3.888 (2.224-6.798), 1.860 (1.213-2.852) and 3.150 (1.833-5.414), 2.348 (1.456-3.785) and 3.689 (2.130-6.388), 1.782 (1.128-2.815) and 3.274 (1.935-5.538), 1.710 (1.014-2.884) and 2.595 (1.455-4.630), 1.836 (1.019-3.305) and 2.860 (1.526-5.358), 2.250 (1.185-4.275) and 3.032 (1.505-6.108), 2.080 (1.048-4.128) and 3.127 (1.501-6.516), respectively. Department staff shortage was the risk factor of neck, shoulders, low back, upper back, hands/wrists, and ankles/feet WMSDs; the OR (95%CI) values were 1.791 (1.038-3.093), 2.000 (1.119-3.573), 2.506 (1.429-4.394), 2.063 (1.113-3.822), 2.256 (1.069-4.762), and 2.699 (1.103-6.601), respectively. Frequent knee bending was the risk factor of knees, upper back, and hands/wrists WMSDs; the OR (95%CI) values were 1.895 (1.327-2.704), 1.586 (1.131-2.224), and 2.026 (1.390-2.951), respectively. Often pushing/pulling heavy objects was the risk factor of shoulders, low back, and hips/thighs WMSDs; the OR (95%CI) values were 1.485 (1.066-2.192), 1.547 (1.064-2.749), and 1.822 (1.160-2.862), respectively. Long-time heavily neck tilting forward was the risk factor of elbows and hips/thighs WMSDs; the OR (95%CI) values were 1.649 (1.068-2.546) and 2.005 (1.285-3.129) respectively. Long-time ankle or foot bending was the risk factor of ankles/feet and elbows WMSDs; the OR (95%CI) values were 2.481 (1.685-3.655) and 1.655 (1.065-2.571) respectively. Cold or changes in temperature was the risk factor of neck and shoulders WMSDs; the OR (95%CI) values were 2.182 (1.072-4.443) and 2.116 (1.010-4.431) respectively. Exercise was the protective factor of neck, shoulders, low back, upper back, and ankles/feet WMSDs; the OR (95%CI) values were 0.493 (0.363-0.666), 0.625 (0.438-0.888), 0.404 (0.283-0.576), 0.570 (0.408-0.797), and 0.639 (0.436-0.937), respectively. Conclusion The prevalence of WMSDs is high among workers involving climbing task in power supply enterprises, and neck, low back, and shoulders are the most commonly affected body parts. The influencing factors involve awkward postures, repetitive movements, repetitive tasks, pushing/pulling heavy objects, staff shortage, poor working environment, and exercise.

Background Power grid is a basic industry of national economy. The occupational health problems among operation and maintenance workers in this industry have become increasingly prominent in recent years, and they should receive enough attention. Objective To estimate the prevalence of work-related musculoskeletal disorders (WMSDs) of neck and shoulder among operation and maintenance workers of power supply enterprises, and analyze related influencing factors. Methods From March to June 2021, a total of 1433 operation and maintenance worker from 10 power supply enterprises in three provinces of North China were selected as research subjects using cluster sampling method. A revised Musculoskeletal Disorders Questionnaire was used to investigate the prevalence and ergonomic factors of neck and shoulder pain in the past year. χ² test and logistic regression model were used to explore influencing factors of neck and shoulder pain among operation and maintenance workers. Results A total of 1343 valid questionnaires were recovered and the effective recovery rate was 93.72%. The neck pain prevalence was 66.0% (886 cases) and the shoulder pain prevalence was 54.1% (727 cases). The multiple logistic regression analysis results showed that often/very often long-time sitting (OR=1.864, 95%CI: 1.236-2.811; OR=1.659, 95%CI: 1.091-2.524), sometimes holding awkward postures (OR=1.695, 95%CI: 1.294-2.219; OR=1.596, 95%CI: 1.218-2.092), often/very often holding awkward postures (OR=2.416, 95%CI: 1.618-3.607; OR=2.058, 95%CI: 1.405-3.015), long-time slight neck tilting forward (OR=1.327, 95%CI: 1.023-1.722; OR=1.571, 95%CI: 1.221-2.022), long-time elbows bending (OR=1.327, 95%CI: 1.023-1.722; OR=1.506, 95%CI: 1.112-2.040) and department or team staff shortages (OR=1.578, 95%CI: 1.153-2.161; OR=1.831, 95%CI: 1.320-2.539) were associated with higher neck and shoulder pain prevalence rates. While exercise (OR=0.630, 95%CI: 0.492-0.809; OR=0.707, 95%CI: 0.557-0.899) was associated with lower neck and shoulder pain prevalence rates. Doing same work every day (OR=1.704, 95%CI: 1.305-2.225) was associated with a higher neck pain prevalence rate. Awkward postures with ineffectual force (OR=1.808, 95%CI: 1.226-2.665) and often keeping arms above shoulders (OR=1.424, 95%CI: 1.017-1.992) were associated with a higher shoulder pain prevalence rate. Conclusion The prevalence rates of neck and shoulder pian are high among operation and maintenance workers of power supply enterprises in selected three provinces of North China, and the main associated factors include individual factors, awkward work postures, and labor organization.