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.

Objective: To assess the awareness and associated factors of wild mushroom poisoning among students in Guizhou Province, so as to provide a scientific foundation for wild mushroom poisoning prevention and control among students. Methods: By a multi stage stratified cluster random sampling method, 1 162 students from Guizhou Province were selected in May 2024. The questionnaire survey was administered to evaluate knowledge regarding wild mushroom poisoning. Data were analyzed employing the χ 2 test and Logistic regression model. Results: Among the nine questions assessing awareness of wild mushroom poisoning, only three had the awareness rate exceeding 70%. Binary Logistic regression analysis revealed that students who "actively learn about the prevention of wild mushroom poisoning" ( OR=0.48, 95%CI =0.26-0.92) and "spread knowledge about wild mushroom poisoning to others" ( OR=0.47, 95%CI =0.33-0.69) scored higher on the wild mushroom poisoning knowledge questions ( P <0.05). Conversely, students with a habit of consuming wild mushrooms ( OR=1.52, 95%CI =1.15-2.02) scored lower ( P < 0.05 ). 42.3% of the students suggested that scientific dissemination and publicity about wild mushrooms should be intensified. Conclusions The awareness rate of wild mushroom poisoning knowledge among students in Guizhou Province requires further attention. Comprehensive knowledge should be disseminated systematically through various channels to further improve students awareness of the prevention and control of wild mushroom poisoning.

Objective: To develop a health literacy evaluation scale for Chinese high school students, providing a tool for dynamic monitoring of health literacy among high school students and evaluating the effectiveness of health school construction. Methods: Through theoretical research, an evaluation index system for health literacy of Chinese high school students was constructed. Two rounds of Delphi expert consultations were conducted to quantitatively screen the items, and the item pool was revised based on expert opinions to compile the health literacy evaluation scale for Chinese students. Two focus group interviews were held to collect suggestions from health educators, high school teachers, and high school students regarding optimized scale length, question types, difficulty and wording of the scale. The scale was revised accordingly. A pilot survey was conducted in Beijing and Tianjin in November 2024, and the reliability and validity of the scale were evaluated based on the pilot survey data. Results: The response rate in both rounds of Delphi expert consultations was over 80%, and the expert authority coefficient was over 0.70. The expert opinions were highly concentrated, and the dispersion was small. The revised item pool based on expert opinions contained 39 items. The revised scale based on the suggestions and opinions collected from the focus group interviews had a moderate number of questions and difficulty level. The pilot survey obtained 800 valid responses, with the response rate of 89.39%. The Cronbach α coefficient of the scale was 0.911, χ 2/df =3.321, the root mean square error of approximation was 0.054, the adjusted goodness-of-fit index was 0.991 , and the factor loadings of some items were less than 0.40. Conclusion The health literacy evaluation scale for Chinese high school students demonstrates scientific rigor and practical applicability, with good internal consistency and structural validity.

ObjectiveTo evaluate the clinical efficacy and safety of acupuncture combined with levodopa in the treatment of Parkinson's disease（PD）. MethodsA total of 60 patients with PD were enrolled and randomly assigned to test group or control group， with 30 patients in each group. The control group received levodopa only， starting at 100 mg per dose， three times daily， with gradual increases not exceeding a maximum daily dose of 800 mg. The test group received acupuncture three times per week in addition to levodopa. Both groups were treated for 12 weeks. Assessments were conducted before treatment， after 6 and 12 weeks treatment， using the Unified Parkinson's Disease Rating Scale（UPDRS）， Wearing-Off Questionnaire-9（WOQ-9）， Montreal Cognitive Assessment（MoCA）， Mini-Mental State Examination（MMSE）， Depression Rating Scale（DRS）， Hamilton Depression Scale（HAMD）， Hamilton Anxiety Scale（HAMA）， PD Questionnaire-39（PDQ-39）， and Pittsburgh Sleep Quality Index（PSQI）. Repeated measures ANOVA was utilized to evaluate the effects of time， group， and their interaction on each index. Spearman correlation analysis was conducted to examine the relationships between combined treatment and outcome scores. Adverse events in both groups were recorded throughout the study. ResultsBoth groups showed significant improvements after 6 and 12 weeks treatment， with decreases in UPDRS total score， WOQ-9 total score， DRS score， HAMD score， HAMA score， PDQ-39 score， and PSQI score， and increases in MoCA and MMSE scores（P＜0.05）. Compared with the control group， the test group demonstrated significantly greater improvements in all the above indicators after 6 and 12 weeks （P＜0.05）. Repeated measures ANOVA showed significant time main effects， group main effects， and their interaction across all outcome measures（P＜0.01）. Spearman correlation analysis revealed that combined therapy was significantly negatively correlated with UPDRS， WOQ-9， DRS， HAMD， HAMA， PDQ-39， and PSQI scores， while positively correlated with MoCA and MMSE scores after 12 weeks of treatment（P＜0.05）. Both groups did not experience any serious adverse events and did not affect treatment. ConclusionAcupuncture combined with levodopa is more effective than levodopa alone in improving motor function， non-motor symptoms， cognitive function， depression and anxiety， quality of life， and sleep quality in patients with PD， with good safety.

Objective: To develop and validate a health literacy assessment scale for junior high school students, providing an effective tool for evaluating and monitoring health literacy among Chinese adolescents. Methods: Based on school health education policy documents, a health literacy assessment framework was constructed, comprising five horizontal and four vertical dimensions. From May to June and August to September in 2024, the framework was refined through Delphi expert consultations and focus group discussions, leading to the development of the Health Literacy Assessment Scale for Junior High School Students. In September 2024, a convenience sample of 625 students from three junior high schools in Beijing and Tianjin completed the questionnaire. Item analysis, reliability, and validity tests were conducted to evaluate the scale. Results: The recovery rate for two rounds of expert consultation questionnaires was 100%. The expert authority coefficients ( Cr ) were 0.86 and 0.87 respectively (both >0.70), with Kendall W values of 0.34 and 0.27 ( P <0.05). The focus group discussions followed a rigorous structure, and after multiple rounds of item screening and revision, the version 3.0 of the junior high school students health literacy assessment scale was developed, comprising 57 items. Three items that failed to meet the comprehensive screening criteria were preliminarily removed, and the final scale contained 54 items. The scale demonstrated excellent reliability, with an overall Cronbach s α coefficient of 0.92 and split half reliability of 0.93. Confirmatory factor analysis [ χ 2/df =2.094, root mean square error of approximation ( RMSEA )=0.042, comparative fit index ( CFI )=0.911, Tucker Lewis index ( TLI )=0.907] indicated good model fit indices. Conclusions The preliminary development of the health literacy assessment scale for junior high school students follows a rigorous item screening process with well designed dimensions, demonstrating good reliability and validity, thus serving as an appropriate evaluation tool for adolescent health literacy.

Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans