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.

This study aimed to investigate the therapeutic effect of Yindan Pinggan capsules (YDPG) on intrahepatic cholestasis (IHC) through animal experiments, while utilizing network pharmacology and molecular docking techniques to explore its potential mechanisms. Initially, the therapeutic effect of YDPG on an α-naphthylisothiocyanate (ANIT)-induced IHC mouse model was assessed through liver function tests, routine blood tests, and liver pathology analysis. Subsequently, network pharmacology tools were employed to predict the active components, core targets, and signaling pathways of YDPG. Molecular docking technology was employed to verify the binding activity of key active components of YDPG with core targets, followed by protein immunoblotting to validate the key targets. Results showed that YDPG significantly improved liver function abnormalities and hepatocyte damage in IHC mice. Network pharmacology analysis revealed that 94 active components in YDPG were associated with 396 targets for the treatment of IHC, and were significantly enriched in pathways such as the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, lipid metabolism, and bile secretion. Molecular docking results showed good binding activity between key active components of YDPG and core targets of the PI3K-AKT signaling pathway. Further protein immunoblotting confirmed that YDPG could reduce the phosphorylation levels of PI3K and AKT proteins, core targets of the PI3K-AKT pathway in liver tissue. These findings suggest that YDPG may alleviate biological processes such as oxidative stress and inflammatory responses by regulating the PI3K-AKT signaling pathway, thereby improving liver damage in IHC mice and exerting a therapeutic effect on IHC. This experiment has been approved by the Animal Experiment Ethics Committee of Jinan University (ethical approval number: IACUC-20241011-09).

OBJECTIVE To compare the predictive accuracy and clinical applicability of four vancomycin individualized dosing tools （SmartDose， ClinCalc， Gulou， Pharmado） and provide a basis for rational clinical medication use. METHODS A retrospective cohort study was conducted， enrolling 479 adult patients who received vancomycin therapy and underwent steady-state trough concentration monitoring in Zhongshan Hospital， Fudan University （Xiamen Branch） from January 1， 2022， to June 30， 2024. The predictive accuracy of each tool was evaluated using indicators， such as mean error （ME）, mean absolute error （MAE）， mean percentage error （MPE）， mean absolute percentage error （MAPE）， the proportion of patients with an absolute percentage error （APE） of less than 30%， the 95% limits of agreement， and the overall relative percentage difference between predicted and measured values. Using indicators such as accessibility， patient management， and recommendation of multiple treatment options， the clinical panxso@163.com applicability of the tools for all patients was evaluated； using the discrepancy in accuracy between the predicted and actual measured blood drug concentrations as an indicator， the clinical applicability was assessed for patients in different renal function subgroups （hyperfunction， normal， mild impairment， moderate impairment， and severe impairment）. RESULTS In terms of accuracy， SmartDose demonstrated the best overall performance with an MAPE of 46.40% and a proportion of APE ＜30% （46.56%）. Bland-Altman analysis indicated that SmartDose had the smallest overall relative percentage difference （－7.25%）， although the 95% limits of agreement were broad for all tools， with differences between the upper and lower limits exceeding 200%. In terms of applicability， all four dosing tools were freely accessible and demonstrated good availability； SmartDose and Pharmado provided the most comprehensive solutions， offering features such as patient management， multiple regimen recommendations， and drug concentration-time curve plotting. Stratified analysis based on renal function revealed that Pharmado showed optimal prediction for hyperfiltration patients （mean difference： 0.11 mg/L）. SmartDose and ClinCalc showed relatively better performance in normal and mild renal impaiment （mean difference： 0.37， 0.51 mg/L and －1.13， －1.33 mg/L，respectively）. SmartDose performed best in moderate renal impairment （mean difference： －2.60 mg/L）. Pharmado and Gulou had smaller prediction biases in severe renal impairment （mean differences： 1.52 mg/L and －0.23 mg/L， respectively）. CONCLUSIONS The four individualized dosing tools demonstrated limited accuracy in the initial prediction of vancomycin concentrations. Among them， SmartDose demonstrates the highest overall prediction accuracy and possesses comprehensive clinical management features. It is recommended that Pharmado be preferred for patients with renal hyperfiltration； SmartDose or ClinCalc can be used for patients with normal or mildly impaired renal function； SmartDose is recommended for patients with moderately impaired renal function； Pharmado or Gulou may be considered for patients with severely impaired renal function.

Apoptosis is a process of programmed cell death,which has the function of maintaining skin balance.In psoriasis,the disturbance of apoptosis is characterized by abnormal prolif-eration of keratinocytes.Traditional Chinese medicine(TCM)has a regulatory effect on keratinocyte apoptosis,which can in-hibit the excessive proliferation of psoriasis epidermis,promote normal epidermal differentiation,and maintain epidermal homeo-stasis.It has the advantages of fewer adverse reactions and multi-targets.Therefore,this article summarizes and analyzes the specific mechanism of various active ingredients of TCM to in-duce the apoptosis of psoriasis keratinocytes by interfering with related factors and signaling pathways,hoping to provide a refer-ence for the treatment of psoriasis with TCM.

Cardiac cephalalgia is a rare disease caused by underlying coronary artery disease that presents as headache with or without chest symptoms.Headache symptoms are often caused by referred pain,increased intracranial pressure and release of large amounts of pain-causing neurochemicals due to myocardial ischemia,and cortical hypoperfusion.Due to the low overall prevalence of the disease,the lack of chest pain typical of coronary heart disease,and the fact that it may be difficult to distinguish from headaches caused by neurological diseases,accurate diagnosis and treatment of the disease are often delayed.We report a case of acute coronary syndrome with headache only.Revascularization was achieved through percutaneous coronary intervention therapy,followed by standard secondary prevention pharmacotherapy.Follow-up six months postoperatively showed a significant improvement in exercise tolerance,with no further headache episodes.The purpose is to improve the understanding of patients with cardiac cephalalgia,with a view to early identification and timely intervention,and ultimately improve the symptoms and prognosis.

MicroRNAs(miRNAs)are small non-coding RNAs that are closely associated with the occur-rence and progression of tumors and other diseases.However,miRNAs require high-sensitivity and high-specificity detection due to their low abundance,high sequence homology,and rapid degradation.The RNA-cleaving deoxyribozyme(RCD)is a functional single-stranded DNA molecule that enables specific cleavage of substrates to release miRNAs that can be recycled with the assistance of metal ions,prompting cyclic signal amplification.Recently,developing new methods based on RCD catalytic amplification for miRNA high-sensitivity detection has become the focus of researchers.Based on combing with the various new technologies and materials in miRNA biosensors,this study classifies and reviews the new methods for detecting miRNAs based on deoxyribozyme catalytic amplification developed in recent years.We sepa-rate these miRNA detection strategies into three categories:RCDs combined with DNA self-assembly,i-sothermal amplification,and nanomaterials.We explore the basic principles of each approach,the latest research advancements,and application scenarios in biomedical sensors and medical detection.This re-view provides a foundation and reference for further research of highly sensitive and accurate miRNA de-tection strategies.

In order to understand the characteristics of avian leukosis virus(ALV)infection and the polymorphisms of receptor genes Tva,Tvb and NHE1 sequences in different Qingyuan Ma chick-en breeding farms,the isolation and identification of exogenous ALV virus,receptor gene amplifi-cation and sequencing analysis were carried out in five Qingyuan Ma chicken breeding farms.The results of virus isolation and subtype identification showed that the positive rate of exogenous ALV virus isolation in farms A,B and C was less than 5％,among which there was ALV-J infection alone in farm A,mixed infection with ALV-J and ALV-K in farm B,ALV-K infection a-lone in farm C,and no exogenous ALV infection was detected in farm D and E.Polymorphism anal-ysis of recipient genes showed that there were different frequencies of Tvar3,Tvar4 and Tvbr3 re-sistance alleles in A-E farms,and the distribution frequency of Tvar3 was 0.2-0.6,the distribution frequency of Tvar4 was 0.3-0.7,and the distribution frequency of Tvbr3 was 0.1-0.7.In addition,there were Tvar5 resistance alleles in both B and D farms,with a distribution frequency of 0.2.A to-tal of 18 SNP mutations occurred in the NHE1 receptor gene sequence,and further analysis showed that positions 1 279,1 361,1 369,1 406,1 442,and 1 912 were non-synonymous mutations,which could cause changes in amino acids.The study suggested that there were differences in the exogenous ALV and its subtypes among the five Qingyuan Ma chicken breeders,and each farm should have a more targeted and unique purification strategy.The distribution of Tva and Tvb re-sistance alleles at different frequencies,along with the occurrence of 6 non-synonymous mutations in the NHE1 gene,indicate that Qingyuan Ma chicken have the potential of genetic resistance breeding.

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:This study aims to discuss the diagnosis and treatment of pediatric appendicovesical fistula (AVF).Methods:A retrospective analysis was conducted on the clinical data of a pediatric patient with AVF admitted to our hospital in March 2023. The patient was a 6-year and 11-month old male who was hospitalized on March 21, 2023, due to difficulty urinating accompanied by diarrhea for two weeks. Computed tomography (CT) revealed bladder stones. The preoperative diagnosis was bladder stones. Transurethral cystoscopic lithotripsy with laser was performed under general anesthesia. Two weeks postoperatively, the child presented with recurrent symptoms of frequent urination, urinary pain, and diarrhea. Urine routine examination indicated a urinary tract infection. Over a month of antibiotic treatment was ineffective, and symptoms such as pneumaturia and fecaluria emerged, with exacerbation of diarrhea, suggesting the possibility of a fistulous tract between the child's intestine and bladder. Further bladder ultrasonography with contrast showed microbubbles of contrast medium leaking from the right posterior bladder wall into the intestinal tract. Enhanced magnetic resonance imaging (MRI) demonstrated a small, sharp tube-like shadow at the upper edge of the right posterior bladder, with a strip-like, significantly enhanced shadow within the lumen. The preoperative diagnosis was revised to appendicovesical fistula. During cystoscopic examination, a papillary-like protrusion was identified on the right lateral wall of the bladder, with no evident orificium fistulae or foreign body discharge noted at the protrusion site. Consequently, robot-assisted laparoscopic partial cystectomy, appendectomy, and lysis of adhesions were performed.Results:The patient was administered antibiotic for a 10-day course of anti-infection and a urinary catheter was maintained for 13 days. The patient recovered entirely and had been discharged after the removal of the urinary catheter. At an 11-month follow-up, there were no reported specific discomforts.Conclusions:Pediatric AVF is rare, and bladder contrast-enhanced ultrasonography and MRI are preferred for initial diagnostic evaluation. The diagnosis can be confirmed by specific clinical presentations such as intermittent pneumaturia and fecaluria, diarrhea with bladder stones. Laparoscopic surgery or robot-assisted laparoscopic surgery could be a feasible treatment option.

Objective To explore the therapeutic effect of transumbilical single-port laparoscopic high uterosacral ligament suspension(HUS)and iliacpubic ligament fixation(ILF)in the treatment of pelvic organ prolapse(POP)mainly caused by middle pelvic defects.Methods Clinical data of 15 cases of POP with middle pelvic defects from June 2017 to June 2023 were analyzed retrospectively.The HUS and ILF were performed by transumbilical single-port laparoscopy.At one year after operation,gynecological examination(POP-Q system)and maximum straining pelvic MRI examination were performed for objective evaluation.The Pelvic Floor Distress Inventory Short Form(PFDI-20)and Pelvic Organ Prolapse-Urinary Incontinence Sexual Questionnaire(PISQ-12)were used for subjectiveevaluation.Results Theoperationtimewas 65-135 min(mean,102.9±16.3 min),thebleedingvolumewas 20-50 ml,and the postoperative hospital stay was 6-9 d.Follow-up time ranged from 6 to 72 months(mean,42.8±22.3 months),among which 14 cases were≥12 months.No pelvic pain,lumbosacral pain,urinary retention and thread exposure occurred.Stress urinary incontinence(SUI)occurred in 1 case at 1 year after operation.Surgical failure was noted in 1 case(degree Ⅱ),the objective success rate being 93.3%(14/15).At 1 year after operation,the distance from the anatomical landmarks of pelvic MRI to the pubococcygeal line(PCL)was significantly higher than that before operation(P<0.01),and the PFDI-20 and PISQ-12 scores were significantly better than those before operation(P<0.01).Conclusions Transumbilical single-port laparoscopic HUS and ILF is a safe and effective mutual aid procedure for the treatment of POP mainly caused by middle pelvic defects with surgical indications,which can improve pelvic floor function and quality of life.It is simple and easy to perform with low cost of consumables,which is suitable for primary hospitals.