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.The role of human umbilical cord-derived mesenchymal stem cells transplantation in alleviating radiation-induced ovarian injury
Mei ZHANG ; Chao YANG ; Bo CHENG ; Jianan WANG ; Yinghao MA ; Zheng ZHANG ; Qingxiang HOU ; Li MA
Chinese Journal of Radiological Health 2025;34(4):584-589
Objective Using female mice to investigate the reparative effects of human umbilical cord mesenchymal stem cells on radiation-induced ovarian injury. Methods Mice were randomly divided into three groups: a blank control group, a radiation model group, and a cell therapy group. Mice in the radiation model group and the cell therapy group received a single whole-body irradiation of 5 Gy X-rays. Within 2 hours post-irradiation, mice in the cell therapy group underwent ovarian transplantation of UC-MSCs. On days 1, 7, and 14 post-irradiation, body weight was measured, ovarian index was calculated, histopathological changes in ovarian tissue were examined, serum levels of reproductive hormones (follicle-stimulating hormone, anti-Müllerian hormone, and estradiol) were determined, and the colonization of implanted UC-MSCs in the mice was observed. Results On days 1, 7, and 14 post-irradiation, both the cell therapy group and the radiation model group showed decreased body weight compared to the blank control group (P < 0.05). On day 1 post-irradiation compared to day 1 pre-irradiation within the same group, the radiation model group exhibited a greater decrease in body weight than the cell therapy group (P < 0.05). On days 1, 7, and 14 post-irradiation, the ovarian index decreased in both the radiation model group and the cell therapy group compared to the blank control group (P < 0.05). On days 7 and 14 post-irradiation, the ovarian index in the cell therapy group was significantly higher than that in the radiation model group (P < 0.05). Ovarian tissue in the radiation model group exhibited atrophy and a reduction in the number of follicles at all stages. In contrast, follicles in the cell therapy group were large and abundant. On days 1, 7, and 14 post-irradiation, serum follicle-stimulating hormone levels in the cell therapy group were lower than those in the radiation model group, while anti-Müllerian hormone and estradiol levels were higher than those in the radiation model group (P < 0.01). In vivo fluorescence imaging demonstrated that UC-MSCs successfully colonized the ovarian tissue on days 1, 7, and 14 after transplantation. Conclusion UC-MSCs exert a repair effect on radiation-induced ovarian injury in mice.
3.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Threatened Abortion
Xinchun YANG ; Shuyu WANG ; Huilan DU ; Songping LUO ; Zhe JIN ; Rong LI ; Xiangyan RUAN ; Qin ZHANG ; Xiaoling FENG ; Shicai CHEN ; Fengjie HE ; Shaobin WEI ; Qun LU ; Yanqin WANG ; Yang LIU ; Qingwei MENG ; Zengping HAO ; Ying LI ; Mei MO ; Xiaoxiao ZHANG ; Ruihua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):241-246
Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine (TCM). The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology, Western medicine obstetrics and gynecology, and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion, the experts concluded that chromosome, endocrine, and immune abnormalities were the key factors for the occurrence of threatened abortion, and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion, TCM has advantages in preventing miscarriages, alleviating clinical symptoms and TCM syndromes, relieving anxiety, regulating reproductive endocrine and immune abnormalities, personalized and diversified treatment, enhancing efficiency and reducing toxicity, and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.
4.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Pulmonary Nodules
Mingwei YU ; Huairui ZHANG ; Xinghan ZHANG ; Xiao LI ; Rengui WANG ; Zhiqiang LONG ; Zhen WANG ; Bo PANG ; Jianwei HUO ; Wei CHEN ; Yong ZHU ; Baoli LIU ; Yanni LOU ; Ganlin ZHANG ; Jiayun NIAN ; Mei MO ; Xiaoxiao ZHANG ; Guowang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):238-245
In recent years, the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine (TCM) in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine, the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances, TCM theories of etiology and pathogenesis, the role and advantages of TCM in the whole course management of pulmonary nodules, contents and methods of research on pulmonary nodules, and science popularization work, aiming to provide a reference for clinical practice and scientific research. After discussion, the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness, blood stasis, and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules, improving physical constitution, ameliorating multi-system nodular diseases, reducing anxiety and avoiding excessive diagnosis and treatment, and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present, the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed, which needs to be further studied from multiple perspectives such as clinical epidemiology, biology, and evidence-based medicine. The primary task of current research is to find out the advantages, effective prescriptions, and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time, basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized, scientific, and accurate effective diagnosis and treatment.
5.Toxicokinetics of MDMA and Its Metabolite MDA in Rats
Wei-Guang YU ; Qiang HE ; Zheng-Di WANG ; Cheng-Jun TIAN ; Jin-Kai WANG ; Qian ZHENG ; Fei REN ; Chao ZHANG ; You-Mei WANG ; Peng XU ; Zhi-Wen WEI ; Ke-Ming YUN
Journal of Forensic Medicine 2024;40(1):37-42
Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.
6.Establishment and evaluation of a nomogram model for predicting postoperative frailty in elderly patients with gastrointestinal tumors
Jiajia LI ; Mei ZHAO ; Mei WANG ; Chao ZHANG
Chinese Journal of Practical Nursing 2024;40(3):181-188
Objective:To analyze the influencing factors of postoperative frailty in elderly patients with gastrointestinal tumors, establish a nomogram model for predicting postoperative frailty and evaluate its efficacy, so as to provide reference basis for formulating perioperative frailty management plans for elderly gastrointestinal tumor patients in the later stage.Methods:Convenience sampling method was used to select 376 elderly patients with gastrointestinal tumors who underwent surgical treatment in the First Affiliated Hospital of Anhui Medical University from December 2021 to August 2022 as the study objects. On the 5th day after surgery according to Tilburg Frailty Indicator, the patients were diagnosed whether they developed postoperative frailty and were divided into postoperative frailty group and postoperative non-frailty group. General data, laboratory indicators and clinical data of patients were collected. Univariate analysis and multivariate Logistic regression analysis were used to screen the independent influencing factors of postoperative frailty in elderly patients with gastrointestinal tumors. R software was used to establish a nomogram prediction model and conduct internal validation to evaluate the differentiation, calibration and clinical applicability of the model.Results:A total of 265 males and 111 females included aged (70.04 ± 5.89) years old, with 222 (59.0%) patients experienced postoperative frailty in this study. Multivariate analysis showed that low Barthel Index score ( OR=0.941, 95% CI 0.903-0.980), low hemoglobin ( OR=0.976, 95% CI 0.963-0.989), high Charison Comorbid Index score ( OR=1.457, 95% CI 1.128-1.882), preoperative frailty ( OR=4.369, 95% CI 1.486-12.841), and pathological stage Ⅲ-Ⅳ ( OR=2.053, 95% CI 1.253-3.364) were independent influencing factors for postoperative frailty of elderly gastrointestinal tumors (all P<0.05). The AUC before and after internal validation of the nomogram model was 0.811 (95% CI 0.768-0.854) and 0.803 (95% CI 0.762-0.856) respectively. The results of Hosmer-Lemeshow test showed good goodness of fit ( χ2=4.09, P>0.05). Decision curve analysis showed that the model had certain clinical applicability. Conclusions:Based on the risk factors of postoperative frailty in elderly patients with gastrointestinal tumors, the nomogram prediction model was established, which has good differentiation, consistency and clinical applicability, and can provide reference for clinical staff to make perioperative frailty management plan.
7.Comparison of Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT in evaluating patients with initial gastric cancer
Fangfang CHAO ; Xinli XIE ; Yanmei ZHANG ; Yanpeng LI ; Yanxia YU ; Xiaoli MEI ; Jianbo GAO ; Xingmin HAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(4):225-229
Objective:To compare Al 18F-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04 PET/CT with 18F-FDG PET/CT in the evaluation of patients with initial gastric cancer. Methods:Twenty patients (13 males, 7 females, age: 27-77 years) with histologically proven gastric cancer were recruited prospectively between March 2021 and July 2022 in the First Affiliated Hospital of Zhengzhou University. Each patient underwent both 18F-FDG and Al 18F-NOTA-FAPI-04 PET/CT within one week. SUV max, tumor background ratio (TBR) and positive detection rate of the two methods were compared (Wilcoxon signed rank sum test, McNemar χ2 test). Results:Al 18F-NOTA-FAPI-04 showed higher SUV max and TBR than those of 18F-FDG in primary tumors (10.2(8.0, 13.7) vs 5.2(3.3, 7.7), z=-3.47, P=0.001; 7.6(5.6, 10.3) vs 2.4(1.8, 3.0), z=-3.85, P<0.001). For the detection of primary gastric cancer, the positive detection rate of Al 18F-NOTA-FAPI-04 PET/CT showed the trend of being higher than that of 18F-FDG PET/CT (95%(19/20) and 75%(15/20); χ2=2.25, P=0.125). For assessing lymph node metastasis, the detection rate of Al 18F-NOTA-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT (78.9%(101/128) vs 64.8%(83/128); χ2=13.47, P<0.001). The SUV max and TBR of Al 18F-NOTA-FAPI-04 in lymph node were higher than those of 18F-FDG (5.3(3.5, 9.2) vs 2.8(1.8, 4.7), z=-7.31, P<0.001; 4.6(2.6, 6.5) vs 1.7(1.0, 3.0), z=-8.44, P<0.001). For the detection of peritoneal carcinomatosis, Al 18F-NOTA-FAPI-04 PET/CT showed higher peritoneal cancer index (PCI), SUV max, and TBR compared to 18F-FDG PET/CT (PCI: 12.0(3.0, 29.8) vs 5.5(0.5, 17.5), z=-2.22, P=0.026; SUV max: 8.2(4.4, 12.5) vs 2.7(1.9, 4.0); z=-2.52, P=0.012; TBR: 5.1(2.9, 13.3) vs 1.1(0.9, 2.0); z=-2.52, P=0.012). Conclusion:Al 18F-NOTA-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in primary and metastatic lesions of gastric cancer and might be a potential novel modality for imaging patients with gastric cancer.
8.Construction and Application of Characteristic Intelligent Pharmacy Service Platform in Ethnic Areas
Deyan WAGN ; Bin LIANG ; Xu ZHANG ; Yuan LIU ; Bin WU ; Chao MO ; Mei YUAN ; Yu LIU
Herald of Medicine 2024;43(1):64-67
Objective To construct a characteristic intelligent pharmacy service platform in ethnic areas,to optimize pharmacist resources,and to improve the quality of pharmacy services.Methods Taking Liangshan Yi autonomous prefecture of Sichuan Province as an example,the pharmaceutical care software was improved and innovated by adding various forms of medication guidance in Yi language.Results The platform was initially operated and 150 Yi language medication guidance was established.The platform pushes 461 medication guidance content daily,including 276 Yi and Han medication guidance.Patients can receive them through WeChat's official account or short message service(SMS),and the medication guidance rate has been significantly improved.Conclusion The characteristic pharmaceutical service platform in the Yi region can substantially improve the quality of pharmaceutical service,meet the individual demands of Yi patients and provide new ideas and methods for pharmaceutical service in other ethnic areas.
9.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
10.Mechanism of Guilingji to prevent the mild cognitive impairment in rats based on kidney metabonomics
Jing-chao SHI ; Yu-kun WANG ; Shu-ting YU ; Ai-rong ZHANG ; Xiao-xia GAO ; Xue-mei QIN
Acta Pharmaceutica Sinica 2024;59(4):1017-1027
This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (

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