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.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Objective:To apply statistical process control (SPC) techniques to the quality assurance of non-normal radiotherapy plans through Johnson transformation, establishing patient-specific tolerance and action limits based on treatment sites and dose/distance assessment criteria, thereby enhancing the intensity-modulated radiation therapy (IMRT) verification accuracy and dose delivery precision.Methods:In this study, 951 gamma analysis data of patient-specific quality assurance (PSQA) executed on the Halcyon accelerator platform were selected and categorized into six groups based on treatment sites, including brain (102 cases), head and neck (100 cases), breast (229 cases), lung (154 cases), esophagus (223 cases), and pelvic (143 cases) groups. The six groups of data were statistically analyzed through Anderson-Darling normality tests ( α = 0.05) using Minitab 21 software. Non-normal data were transformed into normal data through Johnson transformation and then were used to establish treatment site-specific tolerance and action limits, which were compared with the Shewhart control charts based on normal distributions. Results:The PSQA result of the six groups all exhibited non-normal distributions ( P < 0.05). Through Johnson transformation, the tolerance and action limits for the head and neck, breast, lung, esophagus, and pelvic areas under the 3%/2 mm criterion ranged from 95.13% to 96.16% and 94.19% to 95.91%, respectively. In contrast, the tolerance and action limits ranged from 91.15% to 94.86% and 89.94% to 94.78% under the 2%/2 mm criterion. Directly applying Shewhart control charts without normality assumptions yielded higher tolerance limits compared to the application of Johnson transformation, increasing the false positive rate in the non-normal PSQA process. Conclusions:Applying the SPC techniques directly to a non-normal process can lead to an increased false alarm rate and wrong process interpretation. The SPC techniques combined with Johnson transformation enable more effective monitoring of a non-normal PSQA process, facilitating timely identification of potential factors that may lead to an out-of-control process based on the treatment site-specific limits.

Objective:Dubin-Johnson syndrome (DJS) is a hereditary liver disease caused by biallelic pathogenic variants in the ABCC2 gene. As a rare disease, the ABCC2 genotype and clinical phenotype characteristics of DJS patients still need to be summarized in depth. Methods:Nine cases diagnosed with DJS and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University were collected as the study subjects. Clinical and laboratory data, general information, symptoms, signs, pathological changes, treatment, and prognostic conditions were systematically analyzed. Targeted high-throughput sequencing was used to detect hereditary diseases. The positive results for the family lineage were verified by Sanger sequencing. The pathogenicity of the novel ABCC2 variants was evaluated according to the American College of Medical Genetics and Genomics guidelines and standards. One-way analysis of variance or Kruskal-Wallis test was used to compare the statistical differences between multiple groups of data. Results:Among the nine DJS cases, seven and two were males, and females. All of them had the initial symptom of jaundice (100%), with a median age of onset of 5 (2,15) days. During the course of the disease, seven (7/9) and two (2/9) cases had hepatomegaly and splenomegaly. All of the patients exhibited direct hyperbilirubinemia, concurrently with elevated total bile acids (TBA) and γ-glutamyl transferase (GGT). Serum transaminases (4/9) and alkaline phosphatase levels (3/9) were elevated in some patients. A total of twelve types of ABCC2 variants were detected in nine cases, of which c.2362_2363del (p.Leu788ValfsTer13), c.364C>T (p.Gln122Ter), c.338T>C (p.Leu113Pro) and c.419T>A (p.Ile140Lys) were novel pathogenic/likely pathogenic variants. Jaundice disappeared and alleviated in five cases (5/9) and four cases (4/9), while hepatomegaly improved in five cases (5/9) at the last follow-up at 7.79 (7.0,15.25) months following treatment with drugs such as liver protectives, choleretics, and jaundice-reducing agents. Among them, three cases (3/9) had a normal restored liver size. All patients had varying degrees of improvement in bilirubin, TBA, GGT, and ALP levels. Conclusions:The onset of high GGT cholestatic jaundice is the main clinical manifestation in patients with neonatal DJS. The genetic analysis results showed four novel types of variants, which expanded the ABCC2 gene variation spectrum, providing novel molecular markers for confirming a diagnosis of DJS. The patient's clinical manifestations and laboratory abnormalities improved or disappeared after internal medicine treatment, suggesting that DJS may be a type of genetic disease with a favorable long-term prognosis.

Objective To investigate the effects of synovial fluid from patients with rheumatoid arthritis(RA)on the polarization of normal neutrophils and the MEK/ERK signaling pathway,thereby providing experimental evidence to elucidate the pathological mechanisms of RA and offering novel insights into its treatment.Methods Synovial fluid samples were collected from 20 RA patients and 20 osteoarthritis(OA)patients.ELISA was used to measure the levels of interferon-gamma(IFN-γ),tumor necrosis factor-alpha(TNF-α),transforming growth factor-beta(TGF-β)and interleukin-8(IL-8)in the synovial fluid.Neutrophils were isolated from the peripheral blood of healthy donors,and their purity was confirmed by flow cytometry.Neutrophils were then treated with synovial fluid and divided into four groups:Control(untreated),RA(treated with 10％RA synovial fluid),OA(treated with 10％OA synovial fluid),and anti-IFN-β(treated with 20 μg anti-IFN-β antibody as an N2-type control).Western blot was used to assess the changes in the expression of IFN-γ,TNF-α,TGF-β,MEK,p-MEK,ERK and p-ERK.Additionally,the MEK inhibitor PD0325901 was used to block the MEK/ERK pathway,and subsequent changes in IFN-γ and TGF-β expression in neutrophils were evaluated.Results The levels of IFN-γ,TNF-α,TGF-β and IL-8 in the synovial fluid of RA patients were significantly higher than those in OA patients.After intervention with RA synovial fluid,the relative expression of IFN-γ and TNF-α in neutrophils were significantly increased compared to those in the untreated control group and the OA group.While,TGF-β expression in the RA group was lower than that in both the control and anti-IFN-β groups.The relative expression of p-MEK and p-ERK in the RA group were significantly higher than those in the control,OA and Anti-IFN-β groups.Upon addition of the MEK inhibitor,the relative expression of p-MEK and p-ERK were reduced.Furthermore,in both the RA and OA groups,the relative expression levels of IFN-γ decreased,while the expression of TGF-β increased.Conclusion Synovial fluid from RA patients contains higher of IFN-γ,TNF-αand TGF-β,which activate neutrophils through phosphorylation of the MEK/ERK signaling pathway,promoting their polarization toward the pro-inflammatory N1 phenotype.

Objective:To develop an intelligent surveillance system for identifying upper gastrointestinal high-risk patients and assigning surveillance intervals, and to verify its efficacy.Methods:The endoscopic and pathological reports of 23 035 patients undergoing endoscopy at Renmin Hospital of Wuhan University from January to October 2021 were collected retrospectively. A training set of 17 934 patients (January to August) and a test set of 5 101 patients (September to October) were established. Keywords in the endoscopic and pathological reports were extracted by the intelligent surveillance system, and high-risk patients were automatically identified and classified into 7 risk levels. Then the standardized surveillance intervals were assigned based on the guideline. Guideline-based surveillance intervals assigned by expert endoscopists based on endoscopic and pathological reports were used as the golden standard. The accuracy of the intelligent surveillance system was calculated. Of the patients within the test set, 189 were hospitalized and the surveillance intervals given by physicians could be obtained from the electronic health records. The accuracy of the intelligent surveillance system with that of physicians from different departments was compared. Then 67 patients were randomly selected from 189 patients by simple random sampling to evaluate the adjunctive effect of the system in assigning surveillance intervals among 3 endoscopists.Results:The overall accuracy of the intelligent surveillance system in identifying upper gastrointestinal high-risk patients was 99.94% (5 098/5 101), and that of assigning surveillance intervals to correctly included patients was 100.00% (534/534). The intelligent surveillance system achieved significantly higher accuracy compared with all physicians from different departments [98.94% (187/189) VS 35.45% (67/189), χ2=118.01, P<0.001] as well as physicians from department of gastroenterology [100.00% (117/117) VS 24.79% (29/117), χ2=86.01, P<0.001]. With the assistance of the intelligent surveillance system, the endoscopists' accuracy of assigning surveillance intervals to 67 patients was significantly improved [55.22% (111/201) VS 22.39% (45/201), χ2=58.68, P<0.001]. Conclusion:The intelligent surveillance system can accurately identify upper gastrointestinal high-risk patients and assign surveillance intervals according to risk levels, which can alleviate the workload of doctors and improve the follow-up rate of patients.

Objective:To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. Methods:Four patients diagnosed with PMS at Guangzhou Women and Children′s Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Guangzhou Women′s and Children′s Medical Center Liuzhou Hospital (Ethics No. 2025-007).Results:All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 kb to 112.64 kb, primarily involving the SHANK3 gene. Conclusion:PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

Objective To summarize the magnetic resonance imaging(MRI)features of spinal adnexal tuberculosis in order to improve its early diagnosis.Methods Totally 21 spinal adnexal tuberculosis patients confirmed at some hospital from January 2019 to October 2023 had their clinical data and MRI images analyzed retrospectively to determine the basic clinical characteristics and MRI features.Results Of the 21 patients,8 ones had sudden lower extremity weakness and pyramidal tract signs,and the remaining 13 ones had no significant symptoms of neurologic deficit.The lesion involvement ranged from C4 to L5 vertebrae,with the involvement of lumbar segments in 13 cases,thoracic segments in 6 cases and cervical segments in 2 cases.There were 15 cases that had tuberculosis involving in only a single spinal adnexa and peripheral soft tissue,4 cases in 2 vertebrae and 2 cases in 3 vertebrae.There were 9 cases involving in pedicles,8 cases in vertebral plates and some cases involving in sphenoid process,transverse process or facet joints.The MRI features of spinal adnexal tuberculosis included the tuberculosis-infected bone showing slightly low signals on T1WI while slightly high signals on T2WI,edge enhancement by enhanced scan and edema and abscess of paravertebral soft tissue and intra-and extradural tuberculous abscess displayed clearly by the fat suppression and diffusion weighted imaging sequences of T2WI.Conclusion MRI effectively detects the abnormal signs of bone and soft tissue of spinal adnexal tuberculosis.The MRI findings of spinal adnexal tuberculosis are of characteristics,and MRI can be used as the first choice for imaging examination and differential diagnosis to realize early detection of spinal adnexal tuberculosis.[Chinese Medical Equipment Journal,2025,46(1):55-59]