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.Safety analysis of Yttrium-90 resin microsphere selective internal radiation therapy on malignant liver tumors
Jia CAI ; Shiwei TANG ; Rongli LI ; Mingxin KONG ; Hongyan DING ; Xiaofeng YUAN ; Yuying HU ; Ruimei LIU ; Xiaoyan ZHU ; Wenjun LI ; Haibin ZHANG ; Guanwu WANG
Chinese Journal of Clinical Medicine 2025;32(1):24-29
Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (90Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent 90Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of 90Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (99mTc-MAA) perfusion test and received the 90Y-SIRT; one patient received 90Y-SIRT after the second 99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of 90Y-SIRT for treating malignant liver tumors are mild, indicating good safety.
3.Effect and mechanism of BYL-719 on Mycobacterium tuberculosis-induced differentiation of abnormal osteoclasts
Jun ZHANG ; Jian GUO ; Qiyu JIA ; Lili TANG ; Xi WANG ; Abudusalamu·Alimujiang ; Tong WU ; Maihemuti·Yakufu ; Chuang MA
Chinese Journal of Tissue Engineering Research 2025;29(2):355-362
BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.
4.Self-face Advantage Processing and Its Mechanisms
Xiao-Xia TANG ; Shu-Jia ZHANG ; Ying ZHANG ; Li WANG
Progress in Biochemistry and Biophysics 2025;52(7):1771-1791
Self-face is a unique and highly distinctive stimulus, not shared with others, and serves as a reliable marker of self-awareness. Compared to other faces, self-face processing exhibits several advantages, including the self-face recognition advantage, self-face attention advantage, and self-face positive processing advantage. The self-face recognition advantage manifests as faster and more accurate identification across different orientations and spatial frequency components, supported by enhanced early event-related potential (ERP) components, such as N170. Attentional biases toward self-face are evident in target detection during spatial tasks and the attentional blink effect in temporal paradigms. However, measurement sensitivity, perceptual load, and task demands contribute to some mixed findings. Positive biases further characterize the self-face processing advantage, with individuals perceiving their faces as more attractive or trustworthy than objective representations. These biases even extend to self-similar others, influencing social behaviors such as trust and voting preferences. Self-face processing advantages have been observed at an unconscious level and are regulated by several factors, including self-esteem, cultural differences, and multisensory integration. Cultural and individual differences play a crucial role in shaping self-face advantages. Individuals from Western cultures, which emphasize independent self-construal, exhibit stronger self-face biases compared to those from East Asian collectivist contexts. Self-esteem also modulates self-face advantages: high-self-esteem individuals generally maintain their self-face recognition advantage despite interference, exhibit attentional prioritization of self-faces, and demonstrate enhanced positive associations with subliminal self-faces. In contrast, low-self-esteem individuals display recognition vulnerabilities to social cues, show context-dependent attentional divergence (prioritizing others’ faces in task-oriented settings while prioritizing self-face in free-viewing tasks), and exhibit reversed positive associations with subliminal self-faces. Multisensory integration, such as synchronized visual-tactile cues, enhances self-face advantages and induces perceptual plasticity. This phenomenon is exemplified by the enfacement illusion, in which synchronous visual and tactile inputs update the mental representation of the self-face, leading to assimilation with another face. Neuroanatomically, self-face processing is predominantly lateralized to the right hemisphere and involves a network of brain regions, including the occipital lobe, temporal lobe, frontal lobe, insula, and cingulate gyrus. Disruptions in these networks are linked to self-face processing deficits in socio-cognitive disorders. For instance, autism spectrum disorder (ASD) and schizophrenia are associated with attenuated self-face advantages and abnormal neural activity in regions such as the right inferior frontal gyrus, insula, and posterior cingulate cortex. These findings suggest that self-face processing could serve as a potential biomarker for the early diagnosis and intervention of such disorders. In recent years, researchers have proposed various theoretical explanations for self-face processing and its advantage effects. However, some studies have reported no significant behavioral or neural advantages of self-faces over familiar faces, leaving the specificity of self-face a subject of debate. Further elucidation of self-face specificity requires the adoption of a face association paradigm, which controls for facial familiarity and helps determine whether qualitative differences exist between self-faces and familiar faces. Given the close relationship between self-face processing advantages and socio-cognitive disorders (e.g., ASD, schizophrenia), a deeper understanding of self-face specificity has the potential to provide critical insights into the early identification, classification, and intervention of these disorders. This research holds both theoretical significance and substantial social value.
5.Contrast-Enhanced Ultrasound in the Differential Diagnosis of Gallbladder Polypoid Lesions:A Multicenter Study
Ligang JIA ; Xiang FEI ; Xiang JING ; Mingxing LI ; Fang NIE ; Dong JIANG ; Shaoshan TANG ; Wei ZHANG ; Hong DING ; Tao SONG ; Qi ZHOU ; Bei ZHANG ; Zhixia SUN ; Xiaojuan MA ; Nianan HE ; Fang LI ; Yingqiao ZHU ; Wen CHENG ; Yukun LUO
Chinese Journal of Medical Imaging 2024;32(11):1147-1154
Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.
6.Construction and verification of risk management model of ultrasonic scalpel use based on logistic regression analysis
Jie TANG ; Haoming HUANG ; Ziyu ZHANG ; Jia ZHOU
China Medical Equipment 2024;21(8):142-146
Objective:To construct the risk management model of ultrasonic scalpel based on logistic regression(LR)algorithm,and to improve the quality of ultrasonic risk management.Methods:Based on the LR algorithm,the risk management model of ultrasonic scalpel use was constructed and the model was verified.A total of 28 ultrasonic scalpels in clinical use in Shanghai Pulmonary Hospital from January 2022 to December 2023 were selected.Based on the time,the conventional management model was adopted during the use of the equipment in 2022,and the LR risk management model(referred to as risk management)was applied during the use of the equipment in 2023.The risk management quality score,risk warning score and experience score of the management personnel involved in the use of the equipment between the two management modes were compare by using the self-made evaluation scale.Results:The average scores of ultrasonic scalpel maintenance record,usage record,data filing,maintenance card hanging and scrapping treatment using risk management were(9.54±0.37),(9.67±0.34),(9.73±0.21),(9.18±0.35)and(9.92±0.31),respectively,which were higher than those of the conventional management,the difference was statistically significant(t=55.666,32.235,49.511,40.311,23.122,P<0.05).The average scores of ultrasonic scalpel risk identification accuracy,early warning timeliness and comprehensive prevention and control using risk management were(9.66±1.20),(9.92±1.48),and(9.87±1.04),respectively,which were higher than those of the conventional management mode,the difference was statistically significant(t=11.840,8.371,8.032,P<0.05).The average scores of ultrasonic scalpel preventive maintenance personnel,maintenance personnel and operators on the use experience of ultrasonic scalpel in risk management mode were(96.61±6.08),(95.07±5.19)and(97.73±5.93),respectively,which were higher than those in the conventional management mode,the difference was statistically significant(t=4.991,4.156,4.870,P<0.05).Conclusion:The application of ultrasonic scalpel risk management model based on LR algorithm to the use management of ultrasonic scalpel can improve the quality of ultrasonic scalpel risk management,avoid risk hazards,and enhance the safety and stability of clinical use of ultrasonic scalpel.
7.Research progress on myeloid-derived suppressor cells in multiple myeloma
Tang BIN ; Peng XIAOHUAN ; Xiong HAO ; Liu JIA ; Zhu XIAOFENG ; Li LIJUAN ; Zhang LIANSHENG
Chinese Journal of Clinical Oncology 2024;51(6):308-312
Multiple myeloma(MM)is a malignant proliferative disease of plasma cells,ranking as the second most common hematologic tu-mor.Although the use of proteasome inhibitors and immunotherapeutic regimens has improved the prognosis of patients with MM,it re-mains incurable in most patients,mainly because of the eventual development of drug resistance in MM cells.Myeloid-derived suppressor cells(MDSCs)are a heterogeneous group of cells causing significant suppression of the T-cell immune response.They arise from bone mar-row myeloid progenitor cells that are blocked from differentiation and promote MM development by resisting immune destruction.Recent studies indicate that MDSCs stimulate MM cell proliferation,inducing drug resistance and metastasis.In this paper,we review multiple mechanisms exhibited by MDSCs in MM pathogenesis and discuss the feasibility and challenges of current therapeutic strategies targeting MDSCs,aiming to provide pertinent references regarding MM treatment.
8.Effects of facial emotion recognition on prosocial behavior of medical students in mask-obscured scenes:mediating effect of state empathy
Zhenming ZHANG ; Yingcan ZHENG ; Yingdan TANG ; Xinjie TAN ; Feifei WANG ; Jia WANG ; Mengyin ZHU ; Yitong XUE ; Guoyu YANG
Journal of Army Medical University 2024;46(13):1585-1592
Objective To explore the mediating effect of facial emotion recognition on prosocial behavior of medical students in mask-obscured scenes.Methods Fifty-three medical students from a medical university in Chongqing were enrolled from July to September 2023 to complete the facial emotion recognition task,the dictator gaming task and the state empathy test.Spearman correlation analysis was used to examine the correlation between mask wearing and state empathy,trait empathy and prosocial behaviours,and the PROCESS procedure was used to test the mediation of state empathy and the moderating effect of mask wearing or not.Results ①mask wearing,state empathy and prosocial behaviour were significantly correlated(P<0.01);② State empathy exerted mediated effect between facial emotion recognition and prosocial behavior,with the largest effect size(47%)for the relative mediating effect of sadness;③The interaction terms of facial emotion recognition and mask wearing had a significant effect on state empathy(P<0.05).Conclusion Facial emotion recognition can influence prosocial behavior directly and also exert indirect effect on prosocial behavior through state empathy.Compared to the condition without mask wearing,mask wearing can significantly facilitate the effect of happy,sad and neutral emotions on state empathy.
9.Predictive value of platelet distribution width/platelet count for retinopathy in patients with type 2 diabetes mellitus
Jia LU ; Tong ZHANG ; Chaochao YANG ; Chunmeng TANG
International Journal of Laboratory Medicine 2024;45(10):1207-1211
Objective To explore the predictive efficacy of platelet distribution width/platelet count(PDW/PLT)in retinopathy in patients with type 2 diabetes mellitus(T2DM).Methods A total of 120 pa-tients with T2DM admitted to Ma'anshan 17th Metallurgical Hospital from January 2020 to January 2023 were selected as the study group and were divided into the non-retinopathy group(n=69)and the retinopathy group(n=51).Another 80 healthy people who came to the hospital for physical examination during the same period were selected as the control group.The PDW and PLT were detected in all subjects after admission,and the PDW/PLT was calculated.The general data and biochemical indexes of each group were analyzed and compared.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of PDW/PLT in patients with T2DM complicated with retinopathy,and multivariate Logistic regression was used to analyze the related factors affecting patients with T2DM complicated with retinopathy.Results PDW and PDW/PLT in the study group were higher than those in the control group,and PLT was lower than that in the control group,and the differences were statistically significant(P<0.05).PDW and PDW/PLT in the ret-inopathy group were higher than those in the non-retinopathy group,and PLT was lower than that in the non-retinopathy group,and the differences were statistically significant(P<0.05).The ROC curve analysis re-sults showed that the area under the curve(AUC)of PDW for predicting retinopathy in T2DM patients was 0.840(95%CI:0.790-0.890),and the AUC of PLT for predicting retinopathy in T2DM patients was 0.765(95%CI:0.715-0.815),and the AUC of PDW/PLT for predicting retinopathy in T2DM patients was 0.906(95%CI:0.876-0.936).Multivariate Logistic stepwise regression analysis results showed that disease dura-tion(OR=3.047,95%CI:1.863-4.983),glycosylated hemoglobin(OR=3.963,95%CI:1.976-7.947),PDW/PLT(OR=4.191,95%CI:1.833-9.584)were risk factors for retinopathy in patients with T2DM(P<0.05).Conclusion PDW/PLT is increased in T2DM patients with retinopathy,which could be used as an inde-pendent risk factor for T2DM patients with retinopathy,and has a high predictive value for retinopathy.
10.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

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