OBJECTIVE To observe the effect of Codonopsis and Glycyrrhiza glycoconjugates on migration and membrane potential of small intestinal epithelial cells(IEC-6),and to explore the promoting effects of Yiqi jianpi herb Codonopsis and Glycyrrhiza on gastrointestinal mucosal injury repair and the underlying mechanisms. METHODS Under normal conditions or loaded with the inhibitor of potassium channel 4-aminopyridine(4-AP),IEC-6 cells were treated with Codonopsis and Glycyrrhiza glycoconjugates (25-200 mg · L-1) for 24 h,respectively. IEC-6 cell migration was observed by the phase contrast microscope and cell membrane potential was detected by flow cytometry. RESULTS Codonopsis and Glycyrrhiza glycoconjugates (50 and 100 mg · L-1) increased the number of migrated IEC-6 cell compared with normal control group(P<0.01,P<0.05). Compared with normal control group,4-AP reduced the number of migrated IEC-6 cell(P<0.01). Codonopsis and Glycyrrhiza glycoconjugates (50-200 mg · L-1)reversed cell migration inhibited by 4-AP significantly when compared with 4-AP model group(P<0.01). The results of flow cyometry analysis showed that the cell membrane poten?tial was increased after treatment with Codonopsis and Glycyrrhiza glycoconjugates(50 mg · L-1)compared with normal control group and resulted in an increase in cell membrane hyperpolarization(P<0.01). Compared with normal control group,4-AP decreased the cell membrane potential(P<0.01)and resulted in cell membrane depolarization. Also,compared with 4-AP model group,cell membrane depolarization induced by 4-AP was reversed by treatment with Codonopsis and Glycyrrhiza glycoconjugates(100 and 200 mg·L-1). CONCLUSION Codonopsis and Glycyrrhiza glycoconjugates may promote gastrointestinal mucosal injury repair and the mechanisms may involve the activation of signaling pathways by affecting polyamine-dependent intestinal epithelial cell migration voltage-gated K+channels.

Objective To explore the effects of microRNA(miRNA)- 30c knockdown on proliferation,diffe-rentiation of P19 cells. Methods miRNA - 30c knockdown plasmid(miRNA - 30c knockdown group)or no - load vector(negative control group)was transfected into P19 cells by lipo2000 and stable cell lines were selected by Blastici-din;Dual luciferase reporter gene system was used to confirm miRNA - 30c knockdown. Cell counting kit - 8(CCK - 8) assay was adopted to detect cell proliferation activity. An inverted microscope was used to observe morphological chan-ges of P19 cell differentiation. Cells were induced to differentiated to myocardiocyte with dimethyl sulfoxide(DMSO). Differentiation marker genes including cTnT,NKX2. 5,GATA4 relative mRNA expression levels were detected with real - time quantitative polymerase chain reaction,respectively. Results Observation of green fluorescent protein ex-pression under a fluorescence microscope indicated similar transfection efficiencies,and miRNA - 30c knockdown re-leased the activity of target gene Gli2. As a result,miRNA - 30c knockdown vector was constructed successfully(P ﹤0. 001). During differentiation of mouse P19 cells into myocardial cells,the beating cell clusters in miRNA - 30c knockdown cells were much lower than those in the control cells,and cTnT,NKX2. 5,GATA4 in miRNA - 30c knock-down cells showed significantly lower expression than those in the control cells( all P ﹤ 0. 05). Conclusions miRNA - 30c inhibits the P19 cell proliferation and differentiation. This study gives us a new insight of heart develop-ment and we need more efforts on exploring the deep function of heart diseases.

Berberine(BBR),an isoquinoline alkaloid,has been found in many plants,such as Coptis chinensis Franch and Phellodendron chinense Schneid.Although BBR has a wide spectrum of pharmacological effects,its oral bioavailability is extremely low.In recent years,gut microbiota has emerged as a cynosure to un-derstand the mechanisms of action of herbal compounds.Numerous studies have demonstrated that due to its low bioavailability,BBR can interact with the gut microbiota,thereby exhibiting altered pharma-cological effects.However,no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects.Here,we describe the direct interactive relationships between BBR and gut microbiota,including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota.In addition,the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed.Furthermore,we provide our viewpoint on future research directions regarding BBR and gut microbiota.This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.

Objective:To analyze the current research status and hot spots of metabolic syndrome after renal transplantation, and provide reference for domestic research in this field.Methods:Computer retrieval of the literature related to renal transplantation metabolic syndrome in the Chinese Biomedical Literature Service System and the Web of Science core collection database was conducted from January First, 2002 to December 31, 2022. The retrieval results were analyzed using Citespace.6.1.R3c software.Results:After screening, a total of 1024 papers related to metabolic syndrome of renal transplantation were included, including 409 Chinese papers and 615 English papers. In the past 20 years, the number of papers related to metabolic syndrome of renal transplantation in foreign countries has increased progressively, and the overall domestic literature has not increased significantly. Domestic and international research focuses mainly on the epidemiology, pathogenesis, risk factors and related hazards of metabolic syndrome in renal transplantation.Conclusions:The research on metabolic syndrome in renal transplantation has received more and more attention, and still has great research prospects. The risk factors and intervention methods of metabolic syndrome in renal transplantation have been the research focus of scholars at home and abroad in recent years. Chinese scholars can further explore on the basis of previous research, strengthen the exchange and cooperation between different fields, institutions and countries, so as to optimize and improve the related research of metabolic syndrome in kidney transplantation.

MicroRNAs (miRNAs) are small, non-coding single-stranded RNAs that suppress protein expression by binding to the 3′ untranslated regions of their target genes. Many studies have shown that miRNAs have important roles in congenital heart diseases (CHDs) by regulating gene expression and signaling pathways. We previously found that miR-30c was highly expressed in the heart tissues of aborted embryos with ventricular septal defects. Therefore, this study aimed to explore the effects of miR-30c in CHDs. miR-30c was overexpressed or knocked down in P19 cells, a myocardial cell model that is widely used to study cardiogenesis. We found that miR-30c overexpression not only increased cell proliferation by promoting cell entry into S phase but also suppressed cell apoptosis. In addition, we found that miR-30c inhibited dimethyl sulfoxide-induced differentiation of P19 cells. miR-30c knockdown, in contrast, inhibited cell proliferation and increased apoptosis and differentiation. The Sonic hedgehog (Shh) signaling pathway is essential for normal embryonic development. Western blotting and luciferase assays revealed that Gli2, a transcriptional factor that has essential roles in the Shh signaling pathway, was a potential target gene of miR-30c. Ptch1, another important player in the Shh signaling pathway and a transcriptional target of Gli2, was downregulated by miR-30c overexpression and upregulated by miR-30c knockdown. Collectively, our study revealed that miR-30c suppressed P19 cell differentiation by inhibiting the Shh signaling pathway and altered the balance between cell proliferation and apoptosis, which may result in embryonic cardiac malfunctions.
Aborted Fetus ; Apoptosis* ; Blotting, Western ; Cell Differentiation ; Cell Proliferation ; Embryonic Development ; Female ; Gene Expression ; Heart ; Heart Diseases ; Heart Septal Defects, Ventricular ; Hedgehogs ; Luciferases ; MicroRNAs ; Pregnancy ; RNA ; S Phase ; Untranslated Regions

Objective:To investigate the risk factors of systolic dysfunction early complicated in patients with isolated traumatic brain injury (iTBI) and to evaluate the influence of complicated systolic dysfunction on the prognosis of iTBI patients.Methods:From January 2017 to October 2018, 123 patients with moderate or severe iTBI admitted to Trauma Centre in our hospital were included in the study, and patients with previous cardiovascular diseases were excluded. Left ventricular systolic function was assessed by transthoracic echocardiography within 24 h after admission. The patients were divided into normal systolic function group ( n=100) and systolic dysfunction group ( n=23) according to the results of echocardiography. Data were collected from all patients on admission, including GCS score, systolic blood pressure, heart rate, high-sensitivity cardiac troponin T (hs-cTnT), clinical treatment variables (use of sedative drugs, vasoactive drugs, etc.), craniotomy or not and clinical outcomes (survival or death) during hospitalization. Logistic regression analysis was used to analyze the related factors for iTBI patients complicated with systolic dysfunction, and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of each index for iTBI patients complicated with cardiac insufficiency. Results:The systolic blood pressure (147.3±23.3) mmHg, the heart rate (96.1±26.3) beats/min and the hs-cTnT level (16.48±8.17) pg/mL in the systolic dysfunction group were higher than those in the normal systolic function group on admission (all P<0.05); and the GCS score in the systolic dysfunction group was lower than that in the normal systolic function group ( P<0.05). Logistic regression analysis showed that the heart rate ( OR=1.129, 95% CI: 1.001-1.516; P=0.038), the GCS score ( OR=0.640, 95% CI: 0.445-0.920; P=0.016) and the hs-cTnT level ( OR=1.054, 95% CI: 1.009-1.101; P=0.002) on admission were independent risk factors for iTBI patients complicated with systolic dysfunction. The area under the ROC curve (AUC) of the hs-cTnT levelon admission was the largest (AUC=0.863, P<0.01). The in-hospital mortality of patients in the systolic dysfunction group was higher than that of patients in the normal systolic function group (52.5% vs 22%, P=0.004). Conclusions:The heart rate, the GCS score and the serum hs-cTnT level on admission were independent risk factors for iTBI patients complicated with systolic dysfunction. The hs-cTnT level could better predict the occurrence of cardiac systolic dysfuncion, and higher in-hospital mortality was found in iTBI patients complicated with systolic dysfunction. Therefore, early detection and timely intervention may improve the prognosis of these patients.

Objective:To preliminarily analyze the relationship between peripheral blood CD19 +CD27 +B cells, CD4 -CD8 -double-negative T cells, related cytokines and recurrence in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods:A retrospective analysis was performed on the clinical data of 72 patients with NMOSD admitted to Henan Provincial People′s Hospital between January 2019 and January 2021. According to presence or absence of recurrence within 1 year after treatment, they were divided into non-recurrence group ( n=30) and recurrence group ( n=42). The data such as gender, age and score of Extended Disability Status Scale (EDSS) at admission were collected. The levels of serum triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA) 1 and apolipoprotein B (ApoB) were detected by full-automatic biochemical analyzer. The level of total protein in cerebrospinal fluid was detected by full-automatic programmed protein analyzer. The levels of immunoglobulin (Ig) G and IgM in cerebrospinal fluid were detected by immunoturbidimetry. The counts of peripheral blood CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells were detected by flow cytometry. The levels of serum interleukin (IL)-6, IL-10 and IL-2 were detected by enzyme-linked immunosorbent assay. Results:EDSS score, neutrophils, proportions of cases with positive aquaporin 4 (AQP4) antibody and autoimmune antibody in the recurrence group were significantly higher than those in the non-recurrence group (all P<0.05). There was no statistically significant difference in serum TG, HDL-C, LDH-C, ApoB, ApoA1, total protein in cerebrospinal fluid, IgG or IgM between the non-recurrence group and the recurrence group (all P>0.05). The proportions of CD19 +B cells, CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells in the recurrence group were (1.21±0.12)%, (1.61±0.17)% and (1.39±0.25)%, significantly higher than those in the non-recurrence group [(0.85±0.07)%, (1.25±0.12)%, (0.89±0.22)%, t=15.51, 3.89, 12.06, all P<0.05]. The counts of CD19 +B cells, CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells in the recurrence group were (289.50±17.64) ×10 6/L, (4.67±0.03) ×10 6/L and (64.78±6.53) ×10 6/L, significantly higher than those in the non-recurrence group [(254.56±15.34) ×10 6/L, (3.18±0.03) ×10 6/L, (47.82±4.83) ×10 6/L, t=14.27, 4.26, 12.06, all P<0.05]. The level of serum IL-10 in the recurrence group was lower than that in the non-recurrence group [(18.56±1.97) ng/ml vs (24.72±2.52) ng/ml, t=11.64, P<0.05], while levels of IL-6 and IL-2 were significantly higher than those in the non-recurrence group [(15.12±1.54) pg/ml vs (11.47±1.23) pg/ml, (28.34±2.94) pg/ml vs (22.57±2.36) pg/ml, t=10.75, 8.89, both P<0.05]. Conclusion:The levels of peripheral blood CD19 +CD27 +B cells, CD4 -CD8 -double-negative T cells and related cytokines are abnormal in NMOSD patients, which may be related to the recurrence of NMOSD.

The new oral anticoagulants (NOAC) dabigatran, rivaroxaban, apixaban, and edoxaban are widely used in clinical anticoagulation because of their fixed doses and superior safety. Studies have pointed out that there are large inter-individual differences in the pharmacokinetic parameters and response of NOAC, which may be related to the genetic polymorphisms of transporters and metabolic enzymes involved in in-vivo processes. This article reviews the influence of gene polymorphism on the pharmacokinetics and adverse reactions of NOAC, and provides directions for future research.