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.

Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.

OBJECTIVE To study the pharmacodynamics and pharmacokinetics of semaglutide(Sem)capsules in type 2 diabetic model rats.METHODS Male SD rats were divided into the normal control group,type 2 diabetic model group and model+Sem capsules(0.839,1.678 and 2.517 mg·kg-1)groups.A type 2 diabetic rat model was induced by high sugar and high fat diet feeding combined with ip given streptozotocin(STZ)injection.Seven days after modeling,the model+Sem capsules group was ig given Sem capsules at the corresponding dose in a fasting state,once a day,for 14 d.Body mass,fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)levels were regularly mea-sured in each group of rats.Plasma from rats in the model+Sem capsules 0.839,1.678 and 2.517 mg·kg-1 groups at different time points was collected at the end of the continuous administration of Sem capsules,and the content of Sem in the plasma of rats was determined by liquid chromatography-tandem mass spectrometry.Concentration-time curves were plotted,and the main pharmacokinetic parameters were fitted by the WinNonlin non-atrial model method.RESULTS Compared with the model group,the body mass of rats in model+Sem capsules dosing groups decreased significantly after 7 and 14 d of Sem capsules intervention(P<0.05,P<0.01),so did FBG(P<0.01)and the HbA1c level(P<0.01).Meanwhile,FBG and HbA1c levels of rats in model+Sem capsules 1.678 and 2.517 mg·kg-1 groups were not significantly different from those of the normal control group after 14 d of Sem capsules intervention,suggesting that FBG and HbA1c levels were basically restored to normal.Phar-macokinetic results showed that the elimination half-life(t1/2)of Sem in plasma after ig administration of Sem capsules 0.839,1.678,and 2.517 mg·kg-1 for 14 d in rats was 7.40±1.34,7.48±0.33 and(8.23±0.90)h,respectively,the peak concentration(Cmax)was 18±9,81±23 and(256±53)μg·L-1,time to peak(Tmax)was 0.06±0.13,1.56±0.88,(1.50±1.00)h,respectively,the area under the curve(AUC0-t)was 158±76 μg·h·L-1,858±310 and(3795±1539)μg·h·L-1,and the accumulation index was 1.12±0.05,1.12±0.01 and 1.15±0.04,respectively.CONCLUSION Sem capsules ig administrated can effectively reduce body mass,FBG and HbA1c levels in type 2 diabetic model rats,and lead to glucose reduction and by mass loss.After 14 d of continuous administration of Sem capsules,there is no accu-mulation of semaglutide in rats in the dose range of 0.839-2.517 mg·kg-1,and the exposure increases with the dose.

Objective To explore the relationship between the status of infarct related artery(IRA)occlusion and thrombus types in patients with non-ST-segment elevation myocardial infarction(NSTEMI)using optical coherence tomography(OCT).Methods A total of 170 NSTEMI patients who underwent emergency percutaneous coronary intervention at Henan Provincial People1s Hospital from October 2021 to August 2023 and underwent OCT examination were included in the study.Among them,83 cases were in the total occlusion group and 87 cases were in the non-total occlusion group.The baseline characteristics,coronary angiography findings,and OCT results of the patients were compared and analyzed.Results Compared with the non-total occlusion group,the patients in the total occlusion group were more younger(P=0.013),the proportion of male was higher(P=0.026),and the proportion of patients with hypertension(P=0.010)and diabetes(P=0.033)was lower.In the total occlusion group,left circumflex artery(LCX)served as the main IRA,whereas in the non-total occlusion group,left anterior descending(LAD)was the predominant IRA(P=0.012);In addition,there was a significantly higher occurrence of rentrop grade Ⅱ～Ⅲ in the total occlusion group compared to the non-total occlusion group(P=0.022).The OCT results showed that in most cases,the total occlusion group was caused by plaque rupture events(P=0.014),mainly red/mixed thrombus(P＜0.001);The non-total occlusion group was more commonly associated with plaque erosion events(P=0.014),with white thrombus being the main cause(P＜0.001).Conclusions Total occlusion of infarct-related artery in NSTEMI patients often occurs in the LCX,and the patient is more younger,the thrombus type is mainly red/mixed thrombus,while non-total occlusion lesions are mainly white thrombus.

Objective:To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism.Methods:CCK-8 method was used to detect the killing effect of metformin,arsenic trioxide and combined application on KG1a cells.Annexin V-FITC/P1 Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1 a cells.Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein.Results:Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1 a cells and induce apoptosis of KG1 a cells,and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P＜0.05).The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P＜0.05).Conclusion:Metformin can synergize with arsenic trioxide to kill KG1a cells,and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

Objective:To study the serological characteristics of ABO*A2.08 subtype and explore its genetic molecular mechanism.Methods:ABO blood group identification was performed on proband and her family members by routine serological methods.ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specific primer(PCR-SSP),and direct sequencing of PCR products from exons 6 and 7 of ABO gene were directly sequenced and analyzed.The effect of gene mutation in A2.08 subtype on structural stability of GTA protein was investigated by homologous protein conserved analysis,3D molecular modeling and protein stability prediction.Results:The proband's serological test results showed subtype Ax,and ABO genotyping confirmed that the proband's genotype was ABO*A207/08.Gene sequencing of the proband's father confirmed the characteristic variation of c.539G＞C in the 7th exon of ABO gene,leading to the replacement of polypeptide chain p.Arg180Pro(R180P).3D protein molecular modeling and analysis suggested that the number of hydrogen bonds of local amino acids in the protein structure was changed after the mutation,and protein stability prediction showed that the mutation had a great influence on the protein structure stability.Conclusion:The mutation of the 7th exon c.539G＞C of ABO gene leads to the substitution of polypeptide chain amino acid,which affects the structural stability of GTA protein and leads to the change of enzyme activity,resulting in the A2.08 phenotype.The mutated gene can be stably inherited.

Chronic graft-versus-host disease(cGVHD)is one of a major complication that affecting the long-term survival and living quality of patients after allogeneic hematopoietic stem cell transplantation,with the incidence of 30％-70％.Unlike acute GVHD,cGVHD involves a large number of immune cells and cytokines in addition to T cell,which is activated abnormally by the donor,and cytokine storms,which characterized by infiltration of donor lymphocytes and damage to host target organ.Recent studies have further made progress in targeting related immune cells and cytokines.In this review,the pathogenesis and therapeutic prospects of cGVHD were summarized from the perspectives of classical innate and adaptive immunity.

Objective:To investigate which indicator is more advantageous when using arterial oxygen saturation(SaO2)and fingertip pulse oxygen saturation(SpO2)for blood oxygen detection in patients with hyperleukocytic acute leukemia(HAL).Methods:In this prospective research,the difference between SaO2 and SpO2 of 18 HAL patients(observation group)and 14 patients(control group),as well as the relationship between the difference and white blood cell(WBC)counts were analyzed.Results:SaO2 was lower than SpO2 in the observation group(P＜0.05),and SpO2-SaO2 difference was positively correlated with WBC counts(r=0.47).However,there was no statistical difference between SaO2 and SpO2 in the control group.SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group,but there was no statistical difference.There was no downward trend of SaO2 and PO2 in the control group.Conclusion:HAL patients have a phenomenon where SaO2 is lower than SpO2,that is pseudohypoxemia,and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro.SpO2 can be monitored bedside in real time and is non-invasive,it is a better way to detect the blood oxygen status of HAL patients.

Objective:To explore the causes of platelet aggregation in version 6.4 Trima Accel automated blood collection system and the effect of 2 intervention measures.Methods:The data on platelet aggregation(n=61)and non-aggregation(n=323)of 61 donors in 2020 were collected and the causes of aggregation were analyzed.Then the 72 donors with platelet aggregation in 2021 were randomized into intervention group A(increasing the anticoagulant-to-blood ratio)and intervention group B(wrapping the donor's arm with an electric blanket to keep warm and improve the blood flow speed).The collection time,average blood flow speed,number of machine alarms,anticoagulant usage,deaggregation and citrate reaction of the two groups were compared.Results:Platelet aggregation was negatively correlated with the average blood flow speed(r=-0.394)and positively correlated with the collection time(r=0.458).The equations for predicting aggregation and non-aggregation were constructed based on Bayesian and Fisher discriminant analysis,and the predicted accuracy was 77.1％.The comparison of the effects of two intervention measures showed that the average blood flow speed in group B was higher than that in group A;the collection time,number of machine alarms,anticoagulant usage and proportion of citrate reaction in blood donors in group B were all lower than those in Group A,all these differences were significant(P＜0.05).In the entire cohort in 2021,90.28％of the products were immediately deaggregated after collection,and 9.72％of the products were deaggregated within 4 hours.There was no statistically significant difference in deaggregation between the two intervention groups(P＞0.05).Conclusion:During apheresis platelet collection,the predictive equations for aggregation and non-aggregation can be used to predict the occurrence probability of aggregation,and the intervention can be made in advance.Both intervention measures are effective in reducing platelet aggregation,however,measure B has the advantages of improving the speed of blood collection,shortening the collection time,reducing the alarm frequency and the anticoagulant usage,and reducing the incidence of citrate reaction in blood donors.

Objective:To analyze the gene mutation types and composition characteristics of patients with thalassemia in Chengdu Region,Sichuan Province.Methods:6 649 suspected thalassemia patients with positive screening results who visited Chengdu Women's and Children's Center Hospital from January 2017 to December 2020 were selected as the study subjects.Among them,there were 2 273 males and 4 376 females.The frequency and distribution of α and β genotypes of thalassemia in this cohort was analyzed by Luminex liquid-phase microarray method.Results:Among the 6 649 samples,3 787 were genetically diagnosed as thalassemia,with a total positive rate of 56.96％;in which,2 063(31.03％)cases were β-thalassemia,1 629(24.50％)cases were α-thalassemia,and 95(1.43％)cases were α combined with β thalassemia.The types of β-thalassemia gene mutation were mainly CD17/N(36.45％,752/2 063),CD41-42/N(25.30％,522/2 063),and IVS-Ⅱ-654/N(24.72％,510/2 063);and 2 037 cases of simple heterozygous mutations were identified,accounting for 98.74％of β-thalassemia patients.The types of α-thalassemia gene mutation were mainly--SEA/α α(79.01％,1 287/1 629),-α37/α α(10.62％,173/1 629),-α37/--SEA(2.95％,48/1 629),and-α42/α α(2.15％,35/1 629).The αcombined with β thalassemia was dominated by-α 3 7/α α;CD17/N and-α3 7/α α;IVS-Ⅱ-654/N,both accounting for 14.74％(14/95)of patients with α combined with β thalassemia.Conclusion:In Chengdu region,Sichuan province,βthalassemia is more common than α thalassemia,the main type of β thalassemia mutation is CD17/N,and the main type of α thalassemia mutation is--SEA/α α,with regional characteristics.