GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Background::Computer-aided detection (CAD) software has been introduced to automatically interpret digital chest X-rays. This study aimed to evaluate the performance of CAD software (JF CXR-1 v3.0, which was developed by a domestic Hi-tech enterprise) in tuberculosis (TB) case finding in China.Methods::In 2019, we conducted an internal evaluation of the performance of JF CXR-1 v3.0 by reading standard images annotated by a panel of experts. In 2020, using the reading results of chest X-rays by a panel of experts as the reference standard, we conducted an on-site prospective study to evaluate the performance of JF CXR-1 v3.0 and local radiologists in TB case finding in 13 township health centers in Zhongmu County, Henan Province.Results::Internal assessment results based on 277 standard images showed that JF CXR-1 v3.0 had a sensitivity of 85.94% (95% confidence interval [CI]: 77.42%, 94.45%) and a specificity of 74.65% (95% CI: 68.81%, 80.49%) to distinguish active TB from other imaging conditions. In the on-site evaluation phase, images from 3705 outpatients who underwent chest X-ray detection were read by JF CXR-1 v3.0 and local radiologists in parallel. The imaging diagnosis of local radiologists for active TB had a sensitivity of 32.89% (95% CI: 22.33%, 43.46%) and a specificity of 99.28% (95% CI: 99.01%, 99.56%), while JF CXR-1 v3.0 showed a significantly higher sensitivity of 92.11% (95% CI: 86.04%, 98.17%) ( p < 0.05) and maintained high specificity at 94.54% (95% CI: 93.81%, 95.28%). Conclusions::CAD software could play a positive role in improving the TB case finding capability of township health centers.

Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To propose a novel radiotherapy marking method-the"#"-character method,which aimed at improving the accuracy and repeatability of positioning during radiotherapy.Methods:A specially"cross-shaped"stamp was designed by this study,which consisted of a handheld square base with a"cross-shaped"protrusion.Using this stamp,the extreme positions of end-expiration and end-inspiration were marked respectively at the laser-guided regions on the directly above and bilateral sides of the patient's body,and each position was printed a"+"character.Finally,a"#-shaped"signal was formed,which represented the full range of respiratory motion of patients.The study included two parts:surface displacement caused by respiration was simulated through a three-dimensional(3D)motion platform,which was used to conduct a phantom experiment for anthropomorphic dummy,A randomized controlled study involving 40 patients,who were treated between January and June 2024 at the Department of Radiotherapy,Cancer Hospital,Chinese Academy of Medical Sciences,were conducted.The cohort included 20 patients with breast tumor(Positioning the outer contour by exposing the chest)and 20 patients with thoracic tumor(fixed position of using thermoplastic film).These patients were divided into two groups for comparison,which received respectively the"#-shaped"method and the conventional"+-shaped"method.The cone-beam computed tomography(CBCT)images before treatment were used to compare the influences of the two kinds of marking methods on the positioning errors of patients with breast tumor and patients with thoracic tumor.Then,the statistical analysis was used to assess precision and accuracy of positioning.Results:The result of phantom experiment indicated that the positioning error of the"#-shaped"method was significantly better than that of the"+-shaped"method under various parameters of respiratory movement.Under three kinds of different respiratory cycles(3,4,and 5 seconds)and amplitudes(8,12,and 15 mm),the positioning errors of the"#-shaped"method were respectively(0.15±0.04)cm,(0.19±0.05)cm and(0.35±0.14)cm,while the"+-shaped"method were respectively(0.42±0.16)cm,(0.64±0.28)cm and(0.88±0.37)cm,and the differences were statistically significant(t=8.347,3.416,2.901,P<0.05).The results of actual patients indicated the positioning error[(0.97±0.32)cm]of the"#-shaped"method was significantly lower than[(1.62±0.47)cm]of the"+-shaped"method for patients with breast tumor(Positioning the outer contour by exposing the chest),and the difference was significant(t=3.615,P<0.05).On the other hand,the positioning error[(0.69±0.24)cm]of the"#-shaped"method was significantly lower than[(0.97±0.39)cm]of the"+-shaped"method for patients with thoracic tumor(fixed position of using thermoplastic film),and the difference also was significant(t=1.934,P<0.05).Conclusion:Compared to the conventional"+-shaped"method,the"#-shaped"method appears higher accuracy and repeatability during the positioning process of radiotherapy,which especially is suitable to the treatment for breast tumor and thoracic tumor that need accurately control the influences of respiratory motion.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To assess the effects of various leisure hobbies on the ability of daily living(ADL)and the quality of life among older adults in China.Methods:A cross-sectional study was conducted using data from the 4th Chinese Urban and Rural Elderly Living Conditions Sample Survey.We categorized community recreation hobbies into two types: dynamic hobbies, which include walking, playing ball games, dancing, and other physical activities, and static hobbies, which encompass activities that do not require physical exertion, such as reading, watching TV, and drawing.The EuroQol five-dimension scale(EQ-5D)-3L was employed to evaluate the quality of life.Older adults who maintained either dynamic or static hobbies for three consecutive years from 2017 to 2019 were initially screened.The relationship between different types of leisure hobbies and ADL scores, as well as quality of life at various time points, was analyzed using repeated-measures ANOVA.Subsequently, propensity scores were matched based on gender, age, ethnicity, marital status, literacy, and chronic diseases, and five machine learning algorithms were utilized to identify the optimal model for predicting fully independent ADL and EQ-5D effect values.Based on the optimal predictive model, we conducted Shapley Additive Explanations(SHAP)and global analysis.Results:The total number of older adults who participated in the survey over the three consecutive years from 2017 to 2019 was 4 912.Among these, 2 594 individuals maintained the same hobby habits throughout this period, comprising 1 362 males and 1 232 females, with an average age of(70.81±6.71)years.Statistically significant differences in ADL scores and EQ-5D scores were observed between the dynamic and static leisure hobby groups(all P<0.05)across various time points, hobby group classifications, and interaction levels.Older adults engaged in dynamic hobbies exhibited superior ADL functioning and higher EQ-5D scores in comparison to those in the static hobby group, with these differences remaining statistically significant following propensity score matching(all P<0.05).In predicting full ADL independence, the SHAP value for dynamic hobbies ranked second, while for predicting an EQ-5D weighted value of 1, the SHAP value for dynamic hobbies ranked ninth.Overall, the type of dynamic hobby demonstrated a positive trend in its effect on the ability to perform daily activities independently and in achieving an EQ-5D weighted value of 1. Conclusions:In comparison to static hobbies, Chinese older adults who engage in dynamic hobbies exhibit improved daily mobility and a higher quality of life.Furthermore, dynamic hobbies positively influence the capacity for full independence in daily activities, as evidenced by an EQ-5D weighted value of 1.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the value of neutrophil extracellular traps (NETs) and interleukin (IL)-33 in the early diagnosis of contrast-induced acute kidney injury (CIAKI).Methods:It was a prospective cohort study. The clinical data of patients who underwent coronary angiography (CAG) in Sir Run Run Hospital, Nanjing Medical University from December 2022 to December 2023 were collected. The main indicators of NETs included myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone H3 (H3Cit) and antimicrobial peptide LL-37 amide (LL-37). Serum samples were collected before CAG, and 2 hours and 12 hours after CAG, and the levels of MPO, NE, H3Cit, LL-37, IL-33 and neutrophil gelatinase-associated lipocalin (NGAL) were detected. The differences of clinical data between CIAKI group and non-CIAKI group were compared. Multivariate logistic regression model was applied to analyze the risk factors of CIAKI. The receiver- operating characteristic curve was used to evaluate the predictive performance of biomarkers. Spearman correlation analysis was used to analyze the correlations among those biomarkers.Results:A total of 280 eligible patients with CAG were included in this study, with age of (65±13) years and 203 males (72.5%). The incidence rate of CIAKI was 11.8% (33/280). Compared with non-CIAKI group, the proportions of diabetes ( χ2=5.302, P=0.021), preoperative positive urine protein ( χ2=6.871, P=0.009), taking beta-blockers ( χ2=4.580, P=0.032), diuretics ( χ2=21.987, P<0.001) and calcium channel blocker ( χ2=10.424, P=0.001), preoperative blood glucose ( Z=2.807, P=0.005), preoperative blood urea nitrogen ( Z=2.504, P=0.012), neutrophil at 24 hours after CAG ( Z=2.173, P=0.030), serum creatinine at 24 hours after CAG ( Z=4.000, P<0.001), and blood urea nitrogen at 24 hours after CAG ( Z=4.459, P<0.001) were higher, while the preoperative hemoglobin ( Z=-2.380, P=0.017) and serum albumin ( Z=-2.556, P=0.011) were lower in CIAKI group. Multivariate logistic regression analysis showed that increasing neutrophil at 24 hours after CAG ( OR=1.180，95% CI 1.037-1.341), diuretics ( OR=5.615，95% CI 2.294-13.745) and calcium channel blockers ( OR=3.141，95% CI 1.374-7.182) were independent influencing factors of CIAKI. There were statistically significant differences in the levels of serum NE, MPO, H3Cit, LL-37, NGAL and IL-33 among before CAG, 2 hours after CAG and 12 hours after CAG in the overall population, CIAKI group and non-CIAKI group (all P<0.05). In addition, the changes of IL-33 before CAG and 12 hours after CAG was positively correlated with the changes of MPO, NE, H3Cit, LL-37, NGAL, serum creatinine and blood urea nitrogen before CAG and 12 hours after CAG (all P<0.05). The levels of NE ( Z=3.435, P=0.001; Z=6.164， P<0.001), MPO ( Z=3.627, P<0.001; Z=4.729, P<0.001), H3Cit ( Z=5.174, P<0.001; Z=6.241, P<0.001), LL-37 ( Z=4.986, P<0.001; Z=6.346, P<0.001), NGAL ( Z=2.956, P=0.003; Z=4.263, P<0.001) and IL-33 ( Z=5.056, P<0.001; Z=6.240, P<0.001) in CIAKI group at 2 h and 12 h after CAG were significantly higher than those in non-CIAKI group. The receiver-operating characteristic curve indicated that the combined AUC of neutrophil 24 hours after CAG, diuretics and calcium channel blockers in predicting CIAKI was 0.791. NE ( AUC=0.701), MPO ( AUC=0.712), H3Cit ( AUC=0.777), LL-37 ( AUC=0.767) and IL-33 ( AUC=0.795) at 2 hours after CAG predicted CIAKI relatively well. NE ( AUC=0.865), MPO ( AUC=0.758), H3Cit ( AUC=0.834), LL-37 ( AUC=0.840) and IL-33 ( AUC=0.867) at 12 hours after CAG had better prediction effect for CIAKI. The AUC of NETs combined with IL-33 in predicting CIAKI at 2 hours and 12 hours after CAG was 0.874 and 0.956, respectively. Conclusions:CIAKI patients exhibit elevated levels of NETs and IL-33. Serum MPO, NE, H3Cit, LL-37 and IL-33 at 12 hours after CAG can predict the occurrence of CIAKI. The combination of NETs and IL-33 is more effective in predicting CIAKI.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child