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 comprehensively analyze the clinical characteristics and risk factors of children with refractory mycoplasma pneumonia(RMPP),precisely identify the joint predictors in these children,and construct a prediction model.This aims to offer a scientific foundation for the early identification of RMPP and the formulation of accurate treatment and medication strategies.Methods A retrospective analysis was performed on the clinical data of 282 children diagnosed with mycoplasma pneumoniae pneumonia(MPP)who were admitted to the Pediatric Department of the Seventh Medical Center of the Chinese People's Liberation Army General Hospital between August 1,2023,and February 29,2024.Among these children,119 with RMPP were classified into the RMPP group,while the remaining 163 with general MPP(GMPP)were assigned to the GMPP group.The clinical data of both groups,encompassing age,gender,duration of fever,symptoms,laboratory test indices,chest imaging data,complications,etc.,were compared.A logistic probability model(LogP model)for joint application was constructed.The discriminatory ability of the model was evaluated using the area under the receiver operating characteristic(ROC)curve,and the calibration of the model was assessed by means of a calibration curve.Results In comparison with the GMPP group,children in the RMPP group exhibited a significantly longer duration of fever(P=0.002).Moreover,they had a higher incidence of complications,including myocardial damage and coagulation dysfunction(P<0.05).Regarding inflammatory markers,the levels of C-reactive protein(CRP),procalcitonin(PCT),and lactate dehydrogenase(LDH)were notably elevated in the RMPP group(P<0.05),whereas the level of albumin(Alb)was lower(P=0.001).In the RMPP group,the levels of interleukin-2(IL-2),interleukin-5(IL-5),interleukin-8(IL-8),interleukin-1β(IL-1β),and D-Dimer were increased,while the levels of interleukin-6(IL-6)and interleukin-17(IL-17)were decreased(P<0.05).Chest computed tomography(CT)scans revealed a higher proportion of lung consolidation,pleural effusion,and atelectasis in the RMPP group(P<0.05).Multivariate logistic regression analysis demonstrated that CRP,total bilirubin(T-BIL),LDH,IL-17,and prothrombin time(PT)were independent risk factors for RMPP(P<0.05).The receiver operating characteristic(ROC)predictive model established based on these factors had an area under the curve(AUC)of 0.787(95%confidence interval[CI]:0.693～0.880),with a cutoff value of 0.421,a sensitivity of 0.786,and a specificity of 0.660.The calibration curve indicated that the predicted probability matched well with the reference probability,and there was no statistical difference in the results of the Hosmer-Lemeshow test(P>0.05).Conclusions The clinical features of children with RMPP are predominantly characterized by prolonged fever,moderate lung lesions,other organ injuries,and high inflammatory markers.CRP,T-BIL,LDH,IL-17,and PT can act as independent risk factors for RMPP.

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

Objective To comprehensively analyze the clinical characteristics and risk factors of children with refractory mycoplasma pneumonia(RMPP),precisely identify the joint predictors in these children,and construct a prediction model.This aims to offer a scientific foundation for the early identification of RMPP and the formulation of accurate treatment and medication strategies.Methods A retrospective analysis was performed on the clinical data of 282 children diagnosed with mycoplasma pneumoniae pneumonia(MPP)who were admitted to the Pediatric Department of the Seventh Medical Center of the Chinese People's Liberation Army General Hospital between August 1,2023,and February 29,2024.Among these children,119 with RMPP were classified into the RMPP group,while the remaining 163 with general MPP(GMPP)were assigned to the GMPP group.The clinical data of both groups,encompassing age,gender,duration of fever,symptoms,laboratory test indices,chest imaging data,complications,etc.,were compared.A logistic probability model(LogP model)for joint application was constructed.The discriminatory ability of the model was evaluated using the area under the receiver operating characteristic(ROC)curve,and the calibration of the model was assessed by means of a calibration curve.Results In comparison with the GMPP group,children in the RMPP group exhibited a significantly longer duration of fever(P=0.002).Moreover,they had a higher incidence of complications,including myocardial damage and coagulation dysfunction(P<0.05).Regarding inflammatory markers,the levels of C-reactive protein(CRP),procalcitonin(PCT),and lactate dehydrogenase(LDH)were notably elevated in the RMPP group(P<0.05),whereas the level of albumin(Alb)was lower(P=0.001).In the RMPP group,the levels of interleukin-2(IL-2),interleukin-5(IL-5),interleukin-8(IL-8),interleukin-1β(IL-1β),and D-Dimer were increased,while the levels of interleukin-6(IL-6)and interleukin-17(IL-17)were decreased(P<0.05).Chest computed tomography(CT)scans revealed a higher proportion of lung consolidation,pleural effusion,and atelectasis in the RMPP group(P<0.05).Multivariate logistic regression analysis demonstrated that CRP,total bilirubin(T-BIL),LDH,IL-17,and prothrombin time(PT)were independent risk factors for RMPP(P<0.05).The receiver operating characteristic(ROC)predictive model established based on these factors had an area under the curve(AUC)of 0.787(95%confidence interval[CI]:0.693～0.880),with a cutoff value of 0.421,a sensitivity of 0.786,and a specificity of 0.660.The calibration curve indicated that the predicted probability matched well with the reference probability,and there was no statistical difference in the results of the Hosmer-Lemeshow test(P>0.05).Conclusions The clinical features of children with RMPP are predominantly characterized by prolonged fever,moderate lung lesions,other organ injuries,and high inflammatory markers.CRP,T-BIL,LDH,IL-17,and PT can act as independent risk factors for RMPP.

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.
Humans ; Anastomotic Leak/etiology* ; Rectal Neoplasms/complications* ; Drainage ; Anastomosis, Surgical/adverse effects* ; Reoperation/adverse effects* ; Hemorrhage ; Retrospective Studies

OBJECTIVE: To investigate the efficacy of posterior axillary approach internal fixation for Ideberg Ⅰa andⅡ glenoid fractures. METHODS: From December 2018 to September 2021, 9 patients with lower part of glenoid fractures were treated by posterior axillary approach, including 3 males and 6 females, aged from 50 to 78 years old. All the fractures were closed fractures. According to Ideberg type of scapular glenoid fracture was type Ⅰa in 6 cases and type Ⅱ in 3 cases. AP and lateral X-ray films of scapula were taken at 6, 12 weeks and 6 and 12 months postoperatively. Constant-Murley and disabilities of the arm shoulder and hand (DASH), and other complications were recorded at the latest follow-up. RESULTS: Nine patients were followed up, ranged from 6 to 15 months. And bone healing was achieved in all 9 patients at the final follow-up, the healing time 3 to 6 months, Constant-Murley score at the final follow-up ranged from 55 to 96, and DASH score ranged from 3.33 to 33.33. Both of them were better than preoperative. CONCLUSION The posterior axillary approach internal fixation for Ideberg Ⅰa and Ideberg Ⅱ Glenoid fractures scapular fracture is satisfactory and worthy of clinical application.
Male ; Female ; Humans ; Middle Aged ; Aged ; Fractures, Bone/surgery* ; Fracture Fixation, Internal ; Shoulder/surgery* ; Scapula/surgery* ; Shoulder Fractures ; Fractures, Closed ; Treatment Outcome ; Retrospective Studies