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.

The UK screening and treatment of retinopathy of prematurity(ROP)updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists,following the standards of the National Institute for Health and Care Excellence.They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022,and formally published in Early Human Development in March 2023.The guidelines provide evidence-based recommendations for the screening and treatment of ROP.The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks.The treatment section covers treatment indications,timing,methods,and follow-up visits of ROP.This article interprets the guidelines and compares them with ROP guidelines/consensus in China,providing a reference for domestic peers.

The"Guidelines for parenteral nutrition in preterm infants:the American Society for parenteral and enteral nutrition"were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023.The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition(PN)for preterm infants.In comparison to similar guidelines,this set offers more detailed perspectives on PN for preterm infants.It presents evidence-based recommendations for the commencement time,nutrient dosage,and composition of PN,considering primary outcomes such as growth and development,as well as secondary outcomes like sepsis,retinopathy of prematurity,parenteral nutrition-related liver disease,and jaundice.This article aims to interpret the guidelines to provide a reference for colleagues in the field.

Objective To observe the sedative and analgesic effects of bupivacaine hydrochloride injection combined with neostigmine methylsulfate injection in critically ill patients after general anesthesia operation.Methods Acute and critical patients who were to undergo general anesthesia were randomly divided into control group and treatment group.Two groups received general anesthesia combined with epidural block anesthesia.After operation,the control group was continuously pumped 0.75％bupivacaine hydrochloride injection 45 mL through the epidural catheter,the treatment group was given 2 μg·kg-1 neostigmine methylsulfate injection on the basis of continuous pumping of bupivacaine injection through epidural catheter in the control group.Comparing the pain numerical rating scale(NRS)for 12 h,24 h,48 h,and 72 h of postoperative analgesia and the Ramsay sedation scores(Ramsay),hemodynamic index and safety in the two groups.Results Treatment group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.Control group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.The 12-hour Ramsay in the control group and the treatment group were(2.62±0.46)and(2.58±0.51)points;the 24-hour Ramsay were(2.32±0.45)and(2.27±0.39)points;the 48-hour Ramsay were(2.12±0.36)and(2.04±0.32)points;and the 72-hour Ramsay were(1.68±0.34)and(1.57±0.29)points,respectively;the 12-hour NRS were(1.64±0.26)and(1.53±0.28)points;the 24-hour NRS were(2.14±0.37)and(2.23±0.34)points;the 48-hour NRS were(2.57±0.39)and(2.44±0.42)points;the 72-hour NRS were(2.89±0.46)and(2.61±0.51)points,respectively.The NRS score at 72 h after operation in the treatment group was significantly lower than that in the control group(P＜0.05).The 12 h heart rate(HR)in the control group and treatment group were(75.90±6.45)and(75.42±6.24)time·min-1;24 h HR were(76.37±6.28)and(76.43±5.34)times·min-1,48 h HR(78.57±5.14)and(76.95±5.27)time·min-1;72 h HR were(76.49±4.41)and(78.17±4.64)time·min-1,respectively.The 12 h mean arterial pressure(MAP)in the control group and treatment group were(94.34±7.86)and(95.24±7.45)mmHg;24 h MAP were(95.71±7.55)and(96.56±7.29)mmHg;48 h MAP were(96.58±7.36)and(97.64±7.69)mmHg;72 h MAP were(97.63±8.15)and(96.77±8.53)mmHg,respectively the differences of the above indexes between the control group and the treatment group were not statistically significant(all P＞0.05).The extubation time of control group and treatment group were(63.42±16.34)and(59.56±17.27)h,respectively,with no statistical significance(P＞0.05).The adverse drug reactions of two groups were nausea and vomiting,use of rescue analgesics 12 h after surgery,and wound infection.The incidences of postoperative adverse drug reactions in the control group and the treatment group were 26.67％and 23.33％,respectively,with no statistical significance(P＞0.05).Conclusion Bupivacaine hydrochloride injection combined with neostigmine methylsulforte injection can significantly enhance the epidural analgesia effect in acute and critical patients undergoing general anesthesia,and the safety is better.

Objective To observe the sedative and analgesic effects of bupivacaine hydrochloride injection combined with neostigmine methylsulfate injection in critically ill patients after general anesthesia operation.Methods Acute and critical patients who were to undergo general anesthesia were randomly divided into control group and treatment group.Two groups received general anesthesia combined with epidural block anesthesia.After operation,the control group was continuously pumped 0.75％bupivacaine hydrochloride injection 45 mL through the epidural catheter,the treatment group was given 2 μg·kg-1 neostigmine methylsulfate injection on the basis of continuous pumping of bupivacaine injection through epidural catheter in the control group.Comparing the pain numerical rating scale(NRS)for 12 h,24 h,48 h,and 72 h of postoperative analgesia and the Ramsay sedation scores(Ramsay),hemodynamic index and safety in the two groups.Results Treatment group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.Control group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.The 12-hour Ramsay in the control group and the treatment group were(2.62±0.46)and(2.58±0.51)points;the 24-hour Ramsay were(2.32±0.45)and(2.27±0.39)points;the 48-hour Ramsay were(2.12±0.36)and(2.04±0.32)points;and the 72-hour Ramsay were(1.68±0.34)and(1.57±0.29)points,respectively;the 12-hour NRS were(1.64±0.26)and(1.53±0.28)points;the 24-hour NRS were(2.14±0.37)and(2.23±0.34)points;the 48-hour NRS were(2.57±0.39)and(2.44±0.42)points;the 72-hour NRS were(2.89±0.46)and(2.61±0.51)points,respectively.The NRS score at 72 h after operation in the treatment group was significantly lower than that in the control group(P＜0.05).The 12 h heart rate(HR)in the control group and treatment group were(75.90±6.45)and(75.42±6.24)time·min-1;24 h HR were(76.37±6.28)and(76.43±5.34)times·min-1,48 h HR(78.57±5.14)and(76.95±5.27)time·min-1;72 h HR were(76.49±4.41)and(78.17±4.64)time·min-1,respectively.The 12 h mean arterial pressure(MAP)in the control group and treatment group were(94.34±7.86)and(95.24±7.45)mmHg;24 h MAP were(95.71±7.55)and(96.56±7.29)mmHg;48 h MAP were(96.58±7.36)and(97.64±7.69)mmHg;72 h MAP were(97.63±8.15)and(96.77±8.53)mmHg,respectively the differences of the above indexes between the control group and the treatment group were not statistically significant(all P＞0.05).The extubation time of control group and treatment group were(63.42±16.34)and(59.56±17.27)h,respectively,with no statistical significance(P＞0.05).The adverse drug reactions of two groups were nausea and vomiting,use of rescue analgesics 12 h after surgery,and wound infection.The incidences of postoperative adverse drug reactions in the control group and the treatment group were 26.67％and 23.33％,respectively,with no statistical significance(P＞0.05).Conclusion Bupivacaine hydrochloride injection combined with neostigmine methylsulforte injection can significantly enhance the epidural analgesia effect in acute and critical patients undergoing general anesthesia,and the safety is better.

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.
Animals ; Rats ; Interleukin-6 ; Network Pharmacology ; Animal Experimentation ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Liver Cirrhosis/genetics* ; Medicine, Chinese Traditional ; Capsules ; Class I Phosphatidylinositol 3-Kinases ; Collagen ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To explore the risk factors of hidden blood loss in osteoporosis vertebral compression fractures during percutaneous vertebral augmentation. METHODS: From October 2018 to December 2019, 360 patients with osteoporosis vertebral compression fractures who received percutaneous vertebral augmentation were enrolled in this study. The factors analyzed included gender, age, surgical methods, disease course, height, weight, the operative segment, bone mineral density, amount of bone cement, operative time, percentage of height loss, percentage of vertebral height restoration, cement leakage, blood clotting function, preoperative and postoperative hemoglobin and hematocrit and other internal diseases. Total blood loss was calculated by Gross's formula, influential factors of the hidden blood loss were further analyzed by t-test, multivariate linear regression and one-way ANOVA analysis. RESULTS: Surgical methods, the operative segment, disease course, cement leakage, preoperative hemoglobin, cement leakage via the basivertebral and segmental vein were significantly correlated with hidden blood loss(P<0.05). CONCLUSION Patients with percutaneous kyphoplasty, two-level and multi-level surgery, the course of the disease beyond 6 weeks, cement leakage via the basivertebral and segmental vein, and lower preoperative hemoglobin had more perioperative hidden blood loss.
Bone Cements/adverse effects* ; Fractures, Compression/etiology* ; Humans ; Kyphoplasty/methods* ; Osteoporosis/complications* ; Osteoporotic Fractures/surgery* ; Retrospective Studies ; Risk Factors ; Spinal Fractures/etiology* ; Treatment Outcome ; Vertebroplasty/adverse effects*