Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.
Infant, Newborn ; Female ; Pregnancy ; Humans ; Premature Birth ; Diabetes, Gestational ; Obstetric Labor, Premature ; Hospitals ; Iatrogenic Disease

Myopia is considered to be a disease occurred under the influence of genetic and environmental factors, and it can only be restored by corrective surgeries. The current surgical methods include laser surgeries and phakic intraocular lens(PIOL)implantation, and PIOL has the advantages of wide range of correction, repeatable procession and small damage to corneal tissue. Furthermore, good visual acuity can be achieved after implantation of intraocular lens. Implantable collamer lens(ICL)is the most common surgical method in this group. The vertical distance between the highest point of the posterior central surface of the implanted lens and the anterior surface of the crystalline lens is called vault. It will cause serious complications if the vault turns out to be abnormal. Up to now, there is no optimal prediction method. This research focuses on vault, discusses the ideal range of postoperative vault, the safety and effectiveness of this surgery, and analyzes the existing prediction methods to provide directions for future clinical research.

Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.
Non-alcoholic Fatty Liver Disease ; Schisandra ; Insulin Resistance ; Lignans

Abstract:Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Long-term alcoholism causes a series of pathological changes in the liver, which eventually leads to the occurrence of liver diseases with an increasing incidence. At present, significant progress has been made in the pathogenesis and pathological development of alcoholic liver disease, but the relevant mechanism of ALD has not been thoroughly studied. It is necessary to improve the existing animal model or establish a new, more comprehensive animal ALD model to simulate human ALD. Experimental animal models of ALD, especially rodents, are often used to simulate human ALD, and the ideal rodent ALD model can effectively simulate all aspects of alcohol in human liver. But so far, the commonly used animal models all have certain defects, and there is no complete animal model that can simulate human ALD. This paper reviewed the pathogenesis of ALD, related methods and influencing factors of ALD model, and provided a theoretical basis for relevant researchers to establish the ALD rodent model. 

Humans ; Encephalitis

OBJECTIVE: To explore the effect of inhibiting polyribonucleotide nucleotidyl-transferase 1 (PNPT1) on oxygen-glucose deprivation (OGD)-induced apoptosis of mouse atrial myocytes. METHODS: Cultured mouse atrial myocytes (HL-1 cells) with or without OGD were transfected with PNPT1-siRNA or a negative control siRNA (NC-siRNA group), and the cell survival rate was detected using CCK-8 assay. The expression levels of ACTB and TUBA mRNA were detected with qPCR, and the protein expression of PNPT1 was detected with Western blotting. The apoptosis rate of the treated cells was determined with flow cytometry, the mitochondrial membrane potential was detected using JC-1 kit, and the mitochondrial morphology was observed using transmission electron microscope. RESULTS: With the extension of OGD time, the protein expression levels of PNPT1 increased progressively in the cytoplasm of HL-1 cells (P < 0.05). Transfection with PNPT1-siRNA significantly reduced PNPT1 expression in HL-1 cells (P < 0.05). Exposure to OGD significantly enhanced degradation of ACTB and TUBA mRNA (P < 0.05) and markedly increased the apoptosis rate of HL-1 cells (P < 0.05), and these changes were significantly inhibited by transfection with PNPT1-siRNA (P < 0.05), which obviously increased mitochondrial membrane potential and improved mitochondrial morphology of HL-1 cells exposed to OGD. CONCLUSION Inhibition of PNPT1 improves mitochondrial damage and reduces degradation of apoptotic-associated mRNAs to alleviate OGD-induced apoptosis of mouse atrial myocyte.
Animals ; Apoptosis ; Cell Survival ; Glucose/pharmacology* ; Mice ; Myocytes, Cardiac ; Oxygen/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering/metabolism*

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 μmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.
Chromatography, Liquid ; Chrysanthemum ; Flavonoids ; Kinetics ; Pharmaceutical Preparations ; Tandem Mass Spectrometry ; Xanthine Oxidase/metabolism*

Objective:To simulate the occupancy rates of baicalein， quercetin and galangin on the target sites of xanthine oxidase in vivo. Method:In this experiment， the half inhibitory concentration （IC₅₀） of febuxostat， baicalein， quercetin and galangin against xanthine oxidase were determined by in vitro enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant （k_on） and dissociation rate constant （k_off） were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters （k_on and k_off） and extracted pharmacokinetic data， the target occupancy model in vivo was established. Result:The IC₅₀ values of febuxostat， baicalein， quercetin and galangin were 0.002 7， 1.63， 0.38， 1.59 µmol·L^-1， respectively. The IC₅₀ of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate in vivo of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg^-1 in rats， the time of target occupancy rate >70% in vivo lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg^-1， the time of target occupancy rate >50% in vivo lasted for about 10 h and 1.7 h， respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and in vivo pharmacokinetic curves can effectively evaluate the in vivo inhibitory activity of compounds against the target.

IMM0306 is a recombinant human signal regulatory protein α-anti-CD20 mouse chimeric antibody fusion protein, intended to treat refractory or recurrent CD20 positive B-cell non-Hodgkin lymphoma (B-NHL) in clinical. In this study, an ELISA method was established to evaluate the pharmacokinetics of IMM0306 in human serum. The experiment was approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences (No. CTR20192612). Recombinant human CD47 protein was coated with the plate overnight, blocking the plate with 5% skin milk for 2 h. After washing, 100 μL per well standard and unknown samples were added, and incubated for 1.5 h. After washing, the detection antibody Anti-IMM0306-Biotin was added and incubated for 1 h, and then HRP-labeled streptavidin was added for 1 h, and the color was detected. The optimal concentration of coating reagent was 2 μg·mL^-1 by ELISA method, and the optimal dilution of anti-IMM0306-biotin and SA-HRP were 1∶500 and 1∶5 000, respectively. The lower limit of quantitation was 4 ng·mL^-1, and the standard curve range was 4-100 ng·mL^-1. The verification results of the method meets the corresponding acceptance criteria, and can be used in IMM0306 clinical pharmacokinetic studies.

Development of thoracolumbar vertebra (TLV) and rib primordium (RP) is a common evolutionary feature across vertebrates, although whole-organism analysis of the expression dynamics of TLV- and RP-related genes has been lacking. Here, we investigated the single-cell transcriptome landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene expression signatures. In-depth dissection of the gene expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and RP development. Further analysis of cell type-specific and strand-specific expression uncovered the extremely high level of HOXA10 3'-UTR sequence specific to osteoblasts of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.