1.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
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.
2.Emergency medical response strategy for the 2025 Dingri, Tibet Earthquake
Chenggong HU ; Xiaoyang DONG ; Hai HU ; Hui YAN ; Yaowen JIANG ; Qian HE ; Chang ZOU ; Si ZHANG ; Wei DONG ; Yan LIU ; Huanhuan ZHONG ; Ji DE ; Duoji MIMA ; Jin YANG ; Qiongda DAWA ; Lü ; JI ; La ZHA ; Qiongda JIBA ; Lunxu LIU ; Lei CHEN ; Dong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(04):421-426
This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.
3.Correlation of MET Status with Clinicopathological Features and Prognosis of Advanced Prostatic Acinar Adenocarcinoma
Weiying HE ; Wenjia SUN ; Huiyu LI ; Yanggeling ZHANG ; De WU ; Chunxia AO ; Jincheng WANG ; Yanan YANG ; Xuexue XIAO ; Luyao ZHANG ; Xiyuan WANG ; Junqiu YUE
Cancer Research on Prevention and Treatment 2025;52(8):698-704
Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=
4.Analysis of risk factors for bile leakage after laparoscopic common bile duct exploration with primary closure
Wu GUO ; Jun-Jian LIU ; Hai-Tao SHANG ; De-Lin ZHANG ; Xi-Bo ZHANG ; Zhong-Lian LI
Journal of Regional Anatomy and Operative Surgery 2024;33(10):844-848
Objective To explore the risk factors for bile leakage after laparoscopic common bile duct exploration(LCBDE)with primary closure.Methods The clinical data of 560 patients with choledocholithiasis who underwent LCBDE with primary closure in Tianjin Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to September 2023 were retrospectively analyzed,and the patients were divided into the bile leak group and the non-bile leak group according to the occurrence of postoperative bile leakage.The risk factors affecting the occurrence of postoperative bile leakage were analyzed by multivariate analysis.Results A total of 64 cases(11.4% )experienced varying degrees of bile leakage,including 55 cases of grade A bile leakage,7 cases of grade B,and 2 cases of grade C.The thin common bile duct(OR=0.07,P<0.001),history of hypertension(OR=4.56,P<0.001),and high BMI(OR=1.17,P=0.002)were the risk factors for postoperative bile leakage in patients with choledocholithiasis.Conclusion Patients with thin common bile duct,hypertension and obesity are more likely to occur postoperative bile leakage.Patients with choledocholithiasis who have the above high-risk factors should be cautious in choosing LCBDE with primary closure.
5.Design of automatic urine volume detection and collection device
Yan CHEN ; De-Zhao ZHAI ; Xiao-Quan ZHANG ; Fu-Long LIU ; Xiao-Tao ZHANG ; Yong-Mei ZHANG ; Wei CEHN ; Fang ZHANG ; Guo-Hui WU ; Jun DENG ; Dan LI
Chinese Medical Equipment Journal 2024;45(4):66-69
Objective To develop an automatic urine volume detection and collection device to solve the problems of routine urine test.Methods An automatic urine volume detection and collection device was developed with the components of a main control system,a detection system,a prompting system and a grasping and moving system.The main control system consisted of two STM32 microcontrollers and a reset switch;the detection system was made up of a weighing module,an infrared module and indicator lights,which had its urine volume automatic detection algorithm developed based on the Keil5 platform;the prompting system realized voice broadcasting through the voice module fixed on the back panel of the box;the grasping and moving system was composed of a rail drive motor(86CM stepper motor),a photoelectric switch and a motorized gripper.Results The device developed tested urine samples with an accuracy of 99.44%,and could collect qualified samples automatically and quickly.Conclusion The device developed detects urine volume and collects samples automatically,and enhances the accuracy and efficiency of urine examination.[Chinese Medical Equipment Journal,2024,45(4):66-69]
6.Effects of antenatal corticosteroids on outcomes of very premature infants and neurodevelopment during infancy
Zhi CHEN ; Ming LI ; Li-Li ZHANG ; De WU
Chinese Journal of Contemporary Pediatrics 2024;26(10):1040-1045
Objective To explore the effects of antenatal corticosteroids(ACS)on the outcomes of very premature infants(VPIs)and neurodevelopment during infancy.Methods A retrospective study was conducted on 190 VPIs admitted to the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University from January 2020 to December 2022.The infants were categorized into four groups based on ACS usage and dosage:no ACS group(n=18),single-course group(n=88),multi-course group(n=40),and partial-course group(n=44).The clinical outcomes,Neonatal Behavioral and Neurological Assessment(NBNA)scores at 40 weeks of corrected age,and Gesell Developmental Schedule(Gesell)scores at 1 year of corrected age were compared among the four groups.The impact of timing of ACS use on the Gesell scores of infants at 1 year of corrected age in VPIs with specific gestational ages was analyzed.Results The incidence rates of neonatal respiratory distress syndrome,bronchopulmonary dysplasia,transient tachypnea of the newborn,and neonatal pneumonia were significantly lower in the partial-course,single-course,and multiple-course groups compared with the no ACS group(P<0.008).However,there was no significant difference among the partial-course,single-course,and multiple-course groups(P>0.008).The NBNA scores(behavioral ability,active muscle tone,primitive reflexes,and general assessment)at 40 weeks of corrected age were significantly higher in the no ACS,partial-course,and single-course groups than in the multiple-course group(P<0.008).The proportion of VPIs with normal neurodevelopment at 1 year of corrected age was significantly higher in the no ACS,partial-course,and single-course groups than in the multiple-course group(P<0.008).The timing of ACS use had no significant effect on neurodevelopment at a corrected age of 1 year in infants with various gestational ages(P>0.05).Conclusions ACS is crucial for the development of the respiratory system in VPIs,but multiple courses of ACS may cause neurodevelopmental abnormalities.The impact of ACS use on neurodevelopment is independent of gestational age and the timing of ACS use.
7.Clinical characteristics and nutritional status of children with Crohn's disease and risk factors for malnutrition
Dong-Dan LI ; Xiao-Lin YE ; Mei-Chen WANG ; Hong-Mei HUANG ; Jie YAN ; Tian-Zhuo ZHANG ; Fei-Hong YU ; De-Xiu GUAN ; Wen-Li YANG ; Lu-Lu XIA ; Jie WU
Chinese Journal of Contemporary Pediatrics 2024;26(11):1194-1201
Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6%) and 50 girls (42.4%),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7%,87/118),diarrhea (37.3%,44/118),and hematochezia (32.2%,38/118),and 63.6% (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6% (75/118),and the children with moderate or severe malnutrition accounted for 67% (50/75). There were 50 children (42.4%) with emaciation,8 (6.8%) with growth retardation,and 9 (7.6%) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3%),anemia in 74 children (62.7%),and a reduction in 25 hydroxyvitamin D in 15 children (60%,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.
8. Down-regulation of METTL5 inhibits proliferation, migration and invasion of triple-negative breast cancer cells through Wnt/6-catenin signaling pathway
Kun-Lin WU ; Hui-Hao ZHANG ; Kun-Lin WU ; Xiu-Ying LIAO ; Hui-Hao ZHANG ; Qian-Yi YAN ; De-Xing WANG
Chinese Pharmacological Bulletin 2024;40(2):285-291
Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.
9.Research status on the mechanism of traditional Chinese medicine regulating TGF-β1/Smads signaling pathway to intervene liver fibrosis
Yong-Biao TAO ; Shi-Rui YANG ; Long-De WANG ; Ya-Na WU ; Zhi-Ming ZHANG ; Fu LI
The Chinese Journal of Clinical Pharmacology 2024;40(6):918-922
Hepatic fibrosis(HF)is a pathophysiological outcome of chronic liver injury and is characterized by excessive accumulation of extracellular matrix protein.A number of studies have confirmed that the signaling pathways formed by transforming growth factor-β1(TGF-β1)and its downstream Smad family play an important role in the occurrence and development of HF,and the traditional Chinese medicine(TCM)research targeting this pathway is currently a hot spot in the reversal of HF.Therefore,taking TGF-β1/Smads signaling pathway as the entry point,this paper reviewed the mechanism of action of TCM compound formula and single drug extract in intervening TGF-β1/Smad pathway and related factors upstream and downstream of the pathway to reverse HF in recent years,revealed the targeted therapeutic effect of TCM,and provided new strategies for clarifying the mechanism of TCM.
10.Effect of low-concentration benzene, toluene, and xylene exposure on blood pressure of workers in a petroleum refining enterprise
Bingxian ZHOU ; Qisheng WU ; Shiheng FAN ; Zhuna SU ; Jianye PENG ; Chunyun LU ; Nengde ZHANG ; Lei JIN ; De´e YU ; Jing ZHANG
Journal of Environmental and Occupational Medicine 2024;41(9):1012-1019
Background Workers engaged in benzene-exposed or benzene-containing solvent-exposed operations in China are predominantly subjected to a low concentration of benzene series compounds, and prolonged exposure to low concentrations of benzene, toluene, and xylene (BTX) may have implications for blood pressure. Objective To investigate the influence of low-concentration BTX exposure on the blood pressure of workers, aiming to provide a basis for enterprises to devise associated health management strategies to mitigate the occurrence of hypertension among workers exposed to low concentrations of BTX. Methods Using a cross-sectional design, 884 workers from a petroleum refining enterprise in Hainan who participated in an occupational health examination in 2022 were selected as the study population, and were divided into an exposure group of 649 workers and a control group of 235 workers based on their reporting of BTX exposure or not. Data on workplace BTX concentrations and health examinations of the study subjects were collected and questionnaires were administered. In addition, S-phenylmercapturic acid (S-PMA), hippuric acid (HA), and methyl hippuric acid (MHA, including the three isomers 2-MHA, 3-MHA, and 4-MHA) were measured in the urine of the workers using high-performance liquid chromatography-tandem triple quadrupole mass spectrometry to assess internal BTX burden. The effects of low-concentration BTX exposure on blood pressure were analyzed. Results In 2022, the concentrations of benzene, toluene, and xylene of all monitoring points did not exceeded the national limits by either time-weighted average (TWA) or short-term exposure limit (STEL), indicating low-concentration BTX exposure. Regarding the internal burden of BTX, the concentrations of benzene metabolite S-PMA, toluene metabolite HA, and xylene metabolites 3-MHA and 4-MHA in the urine samples in the exposure group were higher than those in the control group (P < 0.05). The correlation analysis showed a positive correlation between urinary S-PMA concentration and diastolic blood pressure in the workers (r=0.265, P < 0.05). Differences in systolic and diastolic blood pressure distributions were statistically significant among workers grouped by sex, age, work years, educational levels, monthly income, body mass index (BMI), alcohol use, dietary oil, and types of residential address (P < 0.05). Significant differences in systolic blood pressure distribution were observed among workers by smoking status and levels of labor intensity (P < 0.05). Compared with the control group, the workers in the exposure group exhibited a significant increase in diastolic blood pressure (P < 0.05). The results of multiple linear regression showed that age, sex, and BMI had statistically significant effects on systolic blood pressure (P < 0.05), while age, work years, and BMI had statistically significant effects on diastolic blood pressure (P < 0.05). The systolic blood pressure of age > 35 years, male, overweight and obese workers was significantly higher than that of age ≤ 35 years, female, and underweight workers, and the diastolic blood pressure of age > 35 years, work years > 5 years, and obese workers was higher than age ≤35 years, ≤5 years of service, and underweight workers. Low-concentration BTX exposure was one of the main influencing factors for elevated diastolic blood pressure, and the exposed workers showed a 1.337 mmHg increase in diastolic blood pressure compared to the control group (P < 0.05). Conclusion Low-concentration BTX exposure, work years > 5 years, and obesity may elevate blood pressure among petroleum refininig workers. Regular blood pressure monitoring and enhanced health interventions for this occupational group are warranted.

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