Objective: To investigate the distribution of GP (B-A-B) hybrid glycophorins in several Chinese minority populations from southern regions of China (Guangdong & Guizhou). Methods: Whole blood samples were collected from 536 blood donors representing 15 different Chinese ethnic minority groups, including She, Bouyei, Yi and Miao, as well as Chuanqing populations. Genomic DNA was extracted and GYP (B-A-B) genotyping was conducted by high resolution melting (HRM) minority method using the GYPB pseudoexon 3-specific primers. Direct sequencing of GYPB pseudoexon 3 was performed in the samples with variant curves. Results: Only one genotype of GP (B-A-B) hybrid glycophorins (GYP Mur/GYPB) was identified among these 536 samples. In total, 15 She (15/162, 9.26%), 18 Bouyei (18/113, 15.93%), 3 Yi (3/79, 3.80%), 3 Chuanqing (3/45, 6.67%), 2 Bai (2/42, 4.76%), 3 Miao (3/40, 7.50%), 1 Shui (1/12, 8.33%), 2 Gelao (2/12, 16.67%), 1 Tujia (1/8, 12.50%) and 1 Dong (1/6, 16.67%) blood donors with heterozygous GYP Mur allele were identified. Among 8 Hui, 5 Manchu, 2 Mongolian, 1 Yao and 1 Li donors, no GYP (B-A-B) hybrid gene carrier was found. In addition, four nucleotide polymorphisms (SNPs) were identified in 6 samples with a variant melting curve detected by HRM. Conclusion: GP. Mur is the most common type of GP (B-A-B) hybrid glycophorins among Chinese minority populations, with frequency varying across different populations. It is recommended to involve GP. Mur reagent cells in the antibody screening cells for populations with a high frequency of GYP Mur allele.

ObjectiveAlthough expression of the TEAD1 protein in preadipocytes has been established, its function remains unclear. In this study, we sought to detect transcripts of TEAD1 in chicken and to examine the effects of this protein on the proliferation, migration, apoptosis, and differentiation of immortalized chicken preadipocyte cell lines (ICP1). MethodsThe full-length sequence of the TEAD1 gene was cloned and the two transcripts were subjected to bioinformatics analysis. The subcellsular localization of TEAD1 transcripts was determined based on indirect immunofluorescence. The effects of TEAD1 transcripts overexpression on the proliferation of ICP1 cells were examined by RT-qPCR, CCK-8, and EdU assays; the effects of TEAD1 transcripts on ICP1 cells migration were examined based on the scratch test; and the effects of TEAD1 transcripts overexpression on ICP1 cells apoptosis were analyzed using apoptosis-Hoechst staining and RT-qPCR. The expression of TEAD1 transcripts in different tissues, cells lines, and ICP1 at different periods of differentiation was analyzed by RT-qPCR. The effects of TEAD1 transcripts overexpression on lipid droplet accumulation and adipogenic-related gene expression in ICP1 cells were analyzed based on Oil Red O and BODIPY staining, RT-qPCR, Western blot, and dual-luciferase reporter gene assays. Finally, the content of triglyceride (TG) was measured in TEAD1 overexpressed ICP1 cells. ResultsThe full-length TEAD1 was cloned and two TEAD1 transcripts were identified. The TEAD1-V1 protein was found to be localized primarily in the cell nucleus, whereas the TEAD1-V2 protein is localized in the cell cytoplasm and nucleus. The overexpression of both TEAD1-V1 and TEAD1-V2 significantly inhibited the proliferation of ICP1 cells. Whereas the overexpression of TEAD1-V1 promoted ICP1 cell migration, the overexpression of TEAD1-V2 had no significant effects on ICP1 migration; the overexpression of both TEAD1-V1 and TEAD1-V2 significantly promoted the apoptosis of ICP1 cells. We found that the different transcripts of TEAD1 have similar expression pattern in different tissues and cells lines. During induced preadipocyte differentiation, the expression of these genes initially declined, although subsequently increased. Overexpression of TEAD1-V1 promoted a significant reduction in lipid droplet formation and inhibited C/EBPα expression during the differentiation of ICP1 cells (P<0.05). However, the overexpression of TEAD1-V2 had no significant effect on lipid droplet accumulation or the expression of adipogenic-related proteins (P>0.05). Overexpression of TEAD1-V1 significantly decreased triglyceride content in ICP1 cells (P<0.05), while overexpression of TEAD1-V2 had no effect on triglyceride content in ICP1 cells (P>0.05). ConclusionIn this study, for the first time, identified two TEAD1 transcripts. Overexpressed transcripts TEAD1-V1 and TEAD1-V2 both inhibited the proliferation of chicken preadipocytes and promoted apoptosis of chicken preadipocytes. TEAD1-V1 inhibited the differentiation of preadipocytes and promoted the migration of preadipocytes, while TEAD1-V2 had no effect on the differentiation and migration of preadipocytes.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective:To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). Methods:A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c. 4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+ PS2_Moderate+ PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy for the fetus. Conclusion:The c. 4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

This article reported a case of neurodevelopmental disorder accompanied by spastic diplegia and visual impairment with the manifestation of small fetal head circumference. Prenatal ultrasonography performed at 33 +5 weeks of pregnancy revealed small fetal head circumference (-2.61SD) and oligohydramnios. Whole-exome sequencing identified a heterozygous frameshift variation of c.1623_1624insA (p.R542Tfs*30) in the CTNNB1 gene (NM_001904.4) of the fetus. No phenotypic abnormalities or corresponding gene variations were detected in the parents, suggesting it was a de novo variation. Based on the clinical manifestations, the fetus was diagnosed with a neurodevelopmental disorder accompanied by spastic diplegia and visual defects. Following genetic counseling, the pregnant woman chose to terminate the pregnancy.

Objective To investigate the therapeutic effect and mechanism of Yiqi Tongqiao Prescription on nasopharyngeal carcinoma in nude mice.Methods Thirty-two nude mice were randomly divided into normal group,model group,Yiqi Tongqiao Prescription low-and high-dose groups,with eight mice in each group.Except for the normal group,the other groups of nude mice were used to construct a nasopharyngeal carcinoma model.After treatment,the tumor volume of nude mice was measured,the levels of serum transforming growth factor β1(TGF-β1)and vascular endothelial growth factor(VEGF)were detected by enzyme-linked immunosorbent assay(ELISA),the pathological morphology of nasal mucosa was observed by hematoxylin-eosin(HE)staining,the mRNA expressions of tissue inhibitor of metalloproteinase 1(TIMP-1)and matrix metalloproteinase 9(MMP-9)in nasal mucosa were detected by quantitative polymerase chain reaction(PCR),the protein expressions of Wnt-1 andβ-catenin in nasal mucosa were detected by Western Blot.Results Compared with the normal group,the tumor volume of nude mice in the model group was increased,the levels of serum TGF-β1 and VEGF were increased,the mRNA expression level of TIMP-1 in nasal mucosa was decreased,the mRNA expression level of MMP-9 was increased,and the protein expression levels of Wnt-1 and β-catenin in nasal mucosa were increased(all P＜0.05).HE staining results showed structural defects of nasal mucosa,and a large number of eosinophils and other inflammatory cell infiltration.Compared with the model group,the tumor volume of nude mice in the low-and high-dose groups of Yiqi Tongqiao Prescription was reduced,the levels of serum TGF-β1 and VEGF were decreased,the mRNA expression level of TIMP-1 in nasal mucosa was increased,the mRNA expression level of MMP-9 was decreased,and the protein expression levels of Wnt-1 and β-catenin in nasal mucosa were decreased(all P＜0.05)in a dose-dependent manner.HE staining results showed that the morphology of nasal mucosa cells was significantly improved.Conclusion Yiqi Tongqiao Prescription inhibits the activity of MMP-9 through the endogenous regulation of TIMP-1 to maintain the homeostasis of extracellular matrix in nasopharyngeal carcinoma,and inhibits the abnormal activation of Wnt/β-catenin signaling pathway and reduces the release of TGF-β1 and VEGF to reduce tumor angiogenesis,thereby playing a role in tumor inhibition for nude mice with nasopharyngeal carcinoma.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

In the progression of end-stage liver disease,the incidence of sleep disorders in patients with liver cirrhosis is high.Currently,western medicine treatment has obvious liver and kidney damage and adverse reactions after discontinuation,which affects the therapeutic effect.Cirrhosis and sleep disorders can be separately attributed to the category of"abdominal mass"and"insomnia"in traditional Chinese medicine.The"abdominal mass"is caused by the disorder of liver and spleen qi movement,as well as the obstruction of phlegm-dampness and blood stasis.In the development of"abdominal mass",the liver failed in ensuring free movement of qi,the spleen failed in transportation and transformation,liver yin and liver blood became insufficiency and the imbalance of yin and yang in the zang-fu organs became imbalanced,and then the ethereal soul depart from the housing,which leads to"insomnia"as an outward manifestation.Professor ZHOU Xiao-Zhou focuses on the concept of qi and blood,and points out that the pathogenesis of sleep disorder in cirrhosis is characterized by liver stagnation and spleen deficiency.He proposed that the treatment principle is to regulate the liver and spleen simultaneously,as well as to nourish the heart and calm the mind.Professor ZHOU has developed Ganyinghua Anshen Formula for treating sleep disorders in cirrhosis,which is derived from the modification of Xiangsha Liujunzi Decoction,and is composed of 14 Chinese medicines of vinegar-prepared Cyperi Rhizoma,Amomi Fructus,Coicis Semen,Dioscoreae Rhizoma,bran-fried Atractylodis Macrocephalae Rhizoma,Galli Gigerii Endothelium Corneum,Gardeniae Fructus,Codonopsis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Citri Reticulatae Pericarpium,Sclerotium Poriae Pararadicis,Longan Arillus,Albiziae Cortex,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The formula has achieved remarkable clinical effect.The clinical experience of Professor ZHOU Xiao-Zhou for treating sleep disorders in cirrhosis through regulating the liver and spleen simultaneously will provide a reference for its clinical treatment with traditional Chinese medicine.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.