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 observe the regulatory mechanism of drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method on the expression of growth and differentiation factor 9(GDF9)and apoptosis of ovarian granulosa cells in rats with controlled ovarian hyperstimulation(COH).Methods Serum of COH rats(blank serum)and serum of COH rats gavaged by the Jinghou Zengzhi Prescription were prepared.A COH rat model was established and ovarian granulosa cells were collected.The experiment was divided into 5 groups:blank serum group,drug-containing serum group,drug-containing serum+SB203580[p38 mitogen-activated protein kinase(p38MAPK)inhibitor]group,drug-containing serum + PDTC[nuclear transcription factor κB(NF-κB)inhibitor]group,drug-containing serum + SB203580 + PDTC group.The mRNA expression levels of p38MAPK,casein kinase 2(CK2),nuclear transcription factor κB inhibitor α(IκBα),NF-κB and GDF9 were detected by real-time quantitative polymerase chain reaction(qRT-PCR),and GDF9 protein expression level was detected by Western Blot,and ovarian granulosa cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Results The drug-containing serum of Jinghou Zengzhi Prescription decreased the mRNA expressions of p38MAPK and NF-κB,elevated the mRNA expressions of CK2 and IκBα,increased the mRNA and protein expression levels of GDF9,and decreased the apoptosis rate of ovarian granulosa cells in COH rats.The addition of p38MAPK inhibitor SB203580 alone and the addition of NF-κB inhibitor PDTC alone both promoted the mRNA and protein expressions of GDF9 and reduced the apoptosis rate of granulosa cells.Conclusion The drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method can promote the expression of GDF9 and inhibit the apoptosis of ovarian granulosa cells in rats with COH,and its mechanism may be related to the regulation of the expression of genes of the dual signaling pathways of p38MAPK and NF-κB.

Objective To investigate the feasibility of constructing a preeclampsia(PE)risk model based on multiple exosomal micrornas(miRNA)expression levels and to verify its efficacy in predicting PE.Methods A total of 1037 pregnant women who were archived in our hospital from June 2019 to December 2021 and whose gestational weeks were less than or equal to 20 weeks were selected as the research subjects.The expression of exosomal miRNA(including miR-155-5p,miR-215-5p,miR-203a-3p,miR-199a-5p and miR-125a-3p)in all samples was detected by qRT-PCR.Then,all patients were followed up to the end of pregnancy.The occurrence of PE during the follow-up period was counted,and all samples were divided into the PE group and the control group according to results.Cox regression was used to analyze the influencing factors of PE.The multi-miRNA risk model was constructed with ggrisk package,and the predictive effect of the model on PE was evaluated by receiver operating characteristic(ROC)curve.Results By the end of follow-up on October 31,2022,974 cases were finally followed up,and the follow-up completion rate was 93.92%.Among all the 974 patients who completed the follow-up,65 patients developed PE,so they were finally divided into the PE group,and 909 cases were used as the control group.The age,pre-pregnancy BMI and waist circumference at 12 weeks of gestation were higher in the PE group than those in the control group(P＜0.05).The proportions of smoking history and drinking history were higher in the PE group than those of the control group(P＜0.05).The contents of triglyceride(TG),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),alanyl aminotransferase(ALT),aspartate aminotransferase(AST),platelet distribution width(PDW),mean platelet volume(MPV),miR-155-5p,miR-199a-5p and miR-215-5p were higher in the PE group than those in the control group,while contents of thyroid stimulating hormone(TSH),miR-125a-3p and miR-203a-3p were lower in the PE group than those in the control group(P＜0.05).The expression levels of miR-125a-3p,miR-155-5p,miR-199a-5p and miR-215-5p were independent predictors of PE(P＜0.05).The predictive risk model constructed from the above miRNAs had good predictive value in the occurrence of PE(AUC=0.998),with a sensitivity of 98.46%(63/65)and a specificity of 93.94%(854/909).Conclusion miR-125a-3p,miR-155-5p,miR-199a-5p,miR-203a-3p and miR-215-5p are significantly related to the occurrence of PE,and the PE prediction model constructed with the above five miRNAs has better effect.

Objective To investigate the effects of anti-HLA donor-specific antibodies(DSA)and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies,15(21.4％)patients were DSA positive,including 7(46.7％)cases of strong positive,3(20.0％)cases of moderate positive,and 5(33.3％)cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients(P=0.027).For the 6 patients developed graft failure(GF),4 were DSA+which was statistically higher than the DSA-patients(P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF(HR=9.273,95％CI:1.505～57.124,P=0.016).Among the 10 patients(7 strong positive and 3 moderate positive DSA)received desensitization therapy,4 patients received combination desensitization,with a 100％rate of successful transplantation,and 6 received single desensitization,with 4(66.7％)experiencing GF,so the GF rate was obviously lower in the combination than the single desensitization(P=0.008).Conclusion In haplo-HSCT patients,DSA is an important factor leading to implantation delay and GF.While,single desensitization treatment has limited efficacy.In combined DSA desensitization therapy,the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

Objective To investigate the impact of influence of personality traits of nurses as second victim and negative experience of nurses in adverse event and explore the intermediary roles of stress perception in influencing mechanism of negative experience.Methods Between March and April 2023,a convenience sampling method was employed to select 560 nurses from 3 general hospitals in Taiyuan City to conduct the study.The selected nurse all had experienced adverse events within last 3 months.The survey employed a general information questionnaire,Chinese big five personality questionnaire,second victim experience and support scale and Chinese version of stress perception scale.Pearson's correlation analysis was conducted to explore the correlation between the personality traits of nurses as second victim(specifically neuroticism),negative experiences and stress perception.The mediating role of stress perception between the neuroticism of nurses as second victim and negative experiences of nurses was analysed using PROCESS plug-in with the Bootstrap method.Results All of 560 distributed questionnaires were recovered,with a 100.00%of response rate.Personality traits of nurses as second victim were ranked in descending order with rigor,agreeableness,openness,neuroticism and extroversion.Both negative experiences and stress perception had higher scores(40.25±10.64 and 30.25±5.98,respectively).Neurotic personality in nurses as second victim was positively correlated with negative experience(r=0.528,P＜0.01)and stress perception(r=0.594,P＜0.01).Negative experiences showed a positive correlation with stress perception(r=0.339,P＜0.01).Neurotic personality of nurses as second victim had a significant direct impact on negative experiences[β=0.519,95%CI:0.318-0.720].As one of the stress perception dimensions,tension played a partial mediating role between neurotic personality in nurses as second victim and negative experience[β=0.148,95%CI:0.006-0.300],and a mediating effect percentage of 22.70%.Conclusions The neurotic personality of nurses as second victim can directly affect the negative experiences,either independently or in conjunction with tension.Nursing managers and nurses as second victims can reduce the negative experiences in adverse events by addressing higher neurotic personality and alleviating tension.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Reducing the consumption of attentional resources and improving human performance in dynamic visual sustained attention tasks is a key issue in sustained attention research. The multiple object tracking (MOT) task is a widely used paradigm for studying individual sustained attention. In a classic MOT paradigm, observers need to maintain their attention on specific targets among a set of distractors and track their movement. To further utilize attentional resources and improve tracking performance, researchers have proposed studying the additivity problem of grouping effects in attention tracking. Grouping effects during MOT is the phenomenon that moving items can be perceived into larger moving units based on featural cues of themselves or task requirements. This article reviewed previous studies about attention resources, classification, additivity, and neural mechanisms of grouping effects in MOT. Based on previous research, we concluded that grouping effects in MOT can be classified into three categories, i.e., spatiotemporal-based grouping, object-based grouping, and feature-based grouping, according to different grouping cues (spatiotemporal continuity, global perception and organization of objects, and surface featural similarity). Grouping based on multiple cues will produce greater effects compared with one cue, this is the additive effect. The study of additivity is important for understanding the cognitive mechanisms of different grouping effects, the attentional mechanisms, and resource allocation in individual dynamic visual tracking. This study summarized previous behavioral and neuroimaging research and systematically explored the non-additivity based on different surface features and the additivity based on surface features and specific spatiotemporal features. Exploring the mechanism of additivity effects provides us with new insight into understanding grouping effects. For future studies, researchers need to thoroughly investigate the neural mechanisms of different kinds of groupings. This can not only provide explanations for the additivity of groupings but also provide substantial evidence for the classification of groupings.

Glomerulocystic kidney disease(GCKD),a rare nephrocystic disorder,was the focus of this study.The FAT1 gene,comprising 27 exons,encoded a single-pass transmembrane protein with multiple biological functions.The extracellular portion of this protein consisted of 33 cadherin repeat sequences,5 epidermal growth factor-like domains,and a G-layer associated domain.This report detailed a case of glomerular cystic disease caused by a mutation in the FAT1 gene,which was treated with the traditional Chinese medicine formula'Shen Jiu Fang Modified'.This formula included Astragalus,Atractylodes,Poria,Angelica,Clematis,Silkworm,Hedyotis diffusa,Hibiscus leaf,among other ingredients,and aimed to invigorate the spleen and promote diuresis,as well as to nourish the kidneys and promote blood circulation.This case demonstrated the potential of traditional Chinese medicine in addressing rare kidney diseases,offering new insights for the diagnosis and treatment of similar complex cases.