Latest ArticlesObjective To investigate the effect of macrophage inflammatory protein-1α (MIP-1α) on proliferation, migration and osteo-differentiation of human periodontal stem cells (hPDLSCs) and its possible mechanism. Methods A total of 16 healthy teeth (orthodontic minus premolar or blocked third molar) extracted from patients aged 12 to 25 years attending the outpatient clinic of the Department of Stomatology, the Second Affiliated Hospital of Xinjiang Medical University from November 2020 to October 2021 were collected and primary stem cells were cultured by tissue block method combined with enzymatic digestion, and the cell phenotype was identified by flow cytometry. (1) Cell biological characteristics experiment: the 3rd generation hPDLSCs were divided into 0 (control group), 1 and 10 μg/ml MIP-1α groups, and each group was then added with α-MEM medium containing volume fraction of 10% fetal bovine serum, 100 U/ml penicillin, and 2 mmol/L glutamine, respectively, and the proliferation ability of each group was detected by CCK-8 method after 24, 48 and 72 h of intervention. The lateral migration ability of cells in each group was detected by scratch assay after 24 h of intervention. (2) Effect and possible mechanism of osteo-differentiation: 3rd generation hPDLSCs were divided into 0 (control group) 1 and 10 μg/ml MIP-1α groups, and osteogenic induction solution was added to each group, and osteogenic ability of cells was detected by alkaline phosphatase (ALP) staining and semi-quantitative analysis 7 d after intervention and by alizarin red staining and semi-quantitative analysis 14 d after intervention;osteogenic ability of cells was detected by qRT-PCR and Western blotting. The mRNA and protein expression of osteogenic genes Runt-related transcription factor 2 (Runx2), bone bridge protein (OPN) and transcription factor SP7 (Osterix) and Notch1 receptor,Jagged 1 ligand and downstream factor Hey1 were detected by qRT-PCR and Western blotting 7 d after intervention. Results Flow cytometry results showed that hPDLSCs STRO-1 and CD146 showed positive expression, and CD34 showed negative expression.(1) In the experiment of cell biological characteristics, the results of CCK-8 method showed that the differences in OD values of hPDLSCs were not statistically significant (P>0.05) in 1 μg/ml and 10 μg/ml MIP-1α groups at 24 h and 48 h compared with control group; at 72 h, the differences in OD values of hPDLSCs were not statistically significant (P>0.05) in 1 μg/ml MIP-1α group compared with control group, while the differences in OD values of hPDLSCs in 10 μg/ml MIP-1α group were significantly higher (P<0.05). The results of scratch assay showed that the difference of scratch healing rate of cells in 1 μg/ml MIP-1α group was not statistically significant compared with that in control group (P>0.05), while the scratch healing rate of 10 μg/ml MIP-1α group was significantly higher (P<0.05). (2) In the experiments of the effect of osteo-differentiation and possible mechanism, ALP staining and semi-quantitative results showed that the ALP activity was obviously lower in 1 μg/ml and 10 μg/ml MIP-1α groups than that in control group (P<0.05). The results of alizarin red staining and semi-quantification showed that the number of mineralized nodules in 1 μg/ml and 10 μg/ml MIP-1α groups were significantly less than that in control group (P<0.05). qRT-PCR and Western blotting results showed that the osteogenesis-related genes Runx2, OPN and Osterix mRNA and protein expression levels in 1 μg/ml MIP-1α group of hPDLSCs were not statistically significant compared with control group, while those in the 10 μg/ml MIP-1α group were significantly lower (P<0.05). Notch1 mRNA and protein expression levels in 1 μg/ml and 10 μg/ml MIP-1α groups were significantly lower than those in control group (P<0.05); Jagged1 and Hey1 mRNA and protein expression levels in 10 μg/ml MIP-1α group were lower than those in control group (P<0.05). while the differences were not statistically significant in the 1 μg/ml MIP-1α group (P>0.05). Conclusion MIP-1α can promote proliferation and inhibit the osteo-differentiation of hPDLSCs, and the mechanism may be related to the inhibition of Notch signaling pathway activation.
Gastric cancer is the third leading cause of death from malignancy and the fifth most common malignancy in the world. The development and progression of intestinal-type gastric cancer is in accordance with the "Correa model", in which gastric mucosal intestinal metaplasia (GIM) is the key link in the transformation of the gastric mucosa from benign to malignant and is also one of the most common precancerous lesions of gastric cancer, therefore, it is the key to investigate the pathogenesis of GIM and intervene it at an early stage for the prevention and treatment of gastric cancer. Helicobacter pylori (HP) infection is considered as one of the recognized risk factors for GIM. However, GIM cannot be reversed by eradication of HP alone, considering that there may be other factors that continue to play a role in the development and progression of GIM. In recent years, it has been confirmed in several studies that bile reflux can induce GIM, but the specific molecular mechanism by which bile reflux induces GIM is not clear.The mechanism of bile reflux induced gastric mucosal injury, the relationship between GIM and gastric cancer, the research status of bile reflux induced GIM, and the molecular mechanisms of bile acid induced GIM are discussed in this article, aiming to improve clinicians' understanding of GIM induced by bile reflux and provide a basis for the early intervention of GIM and prevention of gastric cancer.
Objective To evaluate the application value of extended non-invasive prenatal genetic testing (NIPT-plus) in prenatal screening. Methods All the NIPT-plus data were collected from Zhujiang Hospital of Southern Medical University and the Seventh Affiliated Hospital of Southern Medical University from January 2018 to June 2021. The abnormal results of NIPT-plus were validated by fetal chromosome examination through amniocentesis. The positive predictive value and negative predictive value of NIPT-plus were analyzed, and the fetal prognosis was followed up. Results A total of 2191 cases were detected, and 38 cases were abnormal (positive rate was 1.7%), among which 6 cases were chromosomal copy number variation. A total of 31 cases were confirmed by amniocentesis, of which 18 cases were consistent with the results of NIPT-plus. The total positive predictive value of NIPT-plus was 58.1%, and the negative predictive value was 100.0%. There were 5 cases of chromosome copy number variation for prenatal diagnosis, of which 3 cases were consistent with the results of NIPT-plus test and the positive predictive value was 60.0%. Conclusion The use of NIPT-plus in prenatal screening has a certain warning value for pregnant women with risk of fetal chromosomal abnormalities.
With the burgeoning development of glycobiology, a growing body of research shows a significant relationship between the development of various diseases and polysaccharides. Glycocalyx, an important component of the vascular endothelium, has a villi-like structure and plays a highly crucial role in maintaining vascular homeostasis. In-depth multidisciplinary studies have further revealed that the biological functions of glycocalyx are not only limited to vascular homeostasis, but are also closely related to various diseases in vivo. Foundations of glycocalyx composition and biological function, this paper reviews the latest research of glycocalyx biodegradation mechanism from the perspective of biological relevance of glycocalyx main components [heparan sulfate (HS), chondroitin sulfate (CS), hyaluronic acid (HA) and core protein] to cancer, corona virus disease 2019 (COVID-19), trauma surgery and other diseases by visualization and molecular biology experimental methods, and intends to provide new thoughts for clinical development of novel diagnostic methods and therapeutic targets.
Objective To investigate the effect and mechanism of up-regulating calcium-sensing receptor (CaSR) on osteogenic differentiation of complex culture with porous tantalum-bone marrow mesenchymal stem cells (BMSCs). Methods BMSCs were extracted from SD rats and cultured to the third passage, and identified by alizarin red staining and toluidine blue staining after osteogenic and chondrogenic induction. The growth and adhesion of BMSCs on porous tantalum surface were observed by fluorescence microscope. CCK-8 assay was used to detect the proliferation of BMSCs cultured at different concentrations (200, 250, 300, 350, 400 μmol/L) of GdCl3 for 1-5 d, and the optimal concentration was selected. Confocal laser scanning microscopy was used to observe the intracellular calcium distribution after activation of CaSR. The third-generation of BMSCs were divided into control group (with osteogenic induction medium), GdCl3 group (with osteogenic induction medium containing 300 μmol/L GdCl3), porous tantalum group (with domestic porous tantalum material, with osteogenic induction medium) and GdCl3+porous tantalum group (with domestic porous tantalum material, with osteogenic induction medium containing 300 μmol/L GdCl3). At the 7th day of culturing, alkaline phosphatase (ALP) activity was measured in each group. On the 7th, 14th and 21st day of culturing, the protein secretion levels of type I collagen (ColⅠ) and osteopontin (OPN) were detected by ELISA, and the protein expression levels of ColⅠ, OPN, Runt-related transcription factor 2 (Runx2) and Homer 1 were detected by Western blotting. Results Alizarin red and toluidine blue staining showed that the isolated and extracted cells were BMSCs; CCK-8 assay showed that 300 μmol/L GdCl3-treated cells had the highest activity (P<0.05); confocal laser scanning microscopy showed that the intracellular calcium content was significantly increased after activation of CaSR (P<0.05). ALP activity on day 7 and relative expression levels of ColⅠ, OPN, Runx2 and Homer1 protein on days 7, 14 and 21 in GdCl3 group, porous tantalum group and GdCl3+porous tantalum group were higher than those in control group (P<0.05). ALP activity and relative expression levels of ColⅠ, Runx2 and Homer1 protein on day 7 were higher in GdCl3+porous tantalum group than those in GdCl3 group and porous tantalum group; relative expression levels of ColⅠ, OPN, Runx2 and Homer1 protein on day 14 were higher than those in GdCl3 group; relative expression levels of ColⅠ, OPN, Runx2 and Homer1 protein on day 21 were higher than those in porous tantalum group, the secretion levels of ColⅠ on days 7, 14, and 21, and OPN on days 7 and 21 were higher than those in GdCl3 group, porous tantalum group and GdCl3 + porous tantalum group (P<0.01). The secretion levels of ColⅠ on day 21 and OPN on day 14 in GdCl3 group were higher than those in control group (P<0.05). The secretion of OPN protein was higher in GdCl3 group than in control group on the 21st and 14th day of culture (P<0.05). Conclusions After co-culture of porous tantalum with BMSCs, up-regulation of CaSR may promote osteogenic differentiation of BMSCs by activating the expression of Col I, Runx2 and OPN.
Objective To analyze the correlation between inflammatory index and respiratory failure (RF) in patients with idiopathic pulmonary fibrosis (IPF). Methods The clinical data of 169 patients with IPF admitted in the First Hospital of Lanzhou University from January 2019 to October 2021 were collected, and then divided into the group with respiratory failure (RF group, n=84) and the group without respiratory failure (non-RF group, n=85) according to the arterial blood gas analysis. The clinical data such as blood routine and biochemical data were collected for comparison between the two groups. Logistic regression analysis was performed to screen the possible risk factors of RF in IPF patients; Spearman correlation analysis was used to explore the correlation between multiple inflammatory indicators and between PaO2 level and inflammatory indicators; The diagnostic value of inflammatory indicators was analyzed in IPF patients complicated with RF by using the ROC curve. Results NLR (neutrophil to lymphocyte ratio) and PLR (platelet to lymphocyte ratio) were significantly higher in RF group than in non-RF group, while LMR(lymphocyte to monocyte ratio) were significantly lower than those in non-RF group, the differences were statistically significant (P<0.05). Spearman correlation analysis was conducted on NLR, PLR, LMR and CRP, PCT and PaO2 levels in all patients, it was indicated that NLR, PLR were positively correlated with CRP and PCT (P<0.05), while LMR was negatively correlated with CRP and PCT (P<0.05), moreover, there was a negative correlation between NLR and PaO2 level (P<0.05), and a positive correlation between LMR and PaO2 level (P<0.05). Logistic multifactor regression analysis suggested that smoking and increased NLR were independent risk factors for RF in IPF patients. ROC analysis indicated that NLR and LMR could be effectively used in diagnosis of IPF complicated with RF, and the area under the curve was 0.738(95%CI 0.663-0.812) and 0.736(95%CI 0.660-0.812), respectively.PLR had limited diagnostic value for IPF complicated with RF, and the area under the curve was only 0.629(95%CI 0.545-0.714), while the combined diagnostic ability of NLR, PLR and LMR was higher than the three single indexes, and the area under the curve was 0.760(95%CI 0.689-0.832). Conclusions Elevated NLR is an independent risk factor for RF in IPF patients. NLR, PLR, LMR and their combination have certain diagnostic value for IPF patients complicated with RF, and the combined diagnostic ability of the three is better than the three single indicators alone.
Objective To investigate the clinical application value of chromosome karyotype combined with chromosome microarray analysis (CMA) on genetic diagnosis of embryo termination in early pregnancy. Methods The clinical information and embryo termination tissues were collected of 194 patients treated in the Prenatal Diagnosis Center of the Fourth Hospital of Shijiazhuang due to early embryo abortion from June 2019 to June 2020. Traditional chromosome karyotype analysis and CMA analysis were used for chromosome analysis of the enrolled embryos, and carry out genetic traceability test, summarize and analyze chromosome karyotype/CMA results in combination with embryo chromosome test results. Results (1) The average age of all enrolled patients was 34.1 (22-45) years, of them 120 cases (61.9%) were older than 35 years; The average gestational age was 9.75(7-14) weeks, of which 144 cases (74.2%) were with gestational age less than 10 weeks. Among 101 pregnant women (52.1%, 101/194) with adverse pregnancy and childbirth history, 79 cases (78.2%) had a history of embryo termination, and 22 cases had a history of spontaneous abortion (21.8%). (2) Among 124 cases with abnormal karyotype (63.9%, 124/194), 89 cases (71.8%)had trisomy, 15 cases (12.1%) had monosomy, 11 cases (8.9%) had triploidy, 8 cases (6.4%) had chimera, and 1 case (0.8%) had abnormal structure. (3) Among 33 cases of CMA test results, 9 cases of pathogenic, 2 cases of suspected pathogenic, 1 case of benign, and 21 cases of unknown clinical significance (VUS). The combination of CMA increased the detection rate of chromosomal variants by 4.6%. Among 124 cases of abnormal karyotype, 17 cases were associated with abnormal chromosome microstructure (3 cases were pathogenic, 1 case might be benign, and 13 cases were VUS). (4) The results of parental chromosome test showed that 4 cases of polymorphic chromosome changes and 4 cases of abnormal karyotype; Verification and comparison results in 33 couples with chromosome microstructure variation displayed that 1 case of benign and 1 case of VUS were inherited from the mother, and no chromosomal microstructural variation was detected from the other cases. Conclusion Traditional chromosome karyotype technology combined with CMA can effectively improve the detection rate of chromosome variation, and has certain reference value for guiding the future pregnancy.
Cognition is a process in which the human brain receives external information, processes it, and transforms it into internal psychological activities to obtain or apply knowledge. Cognitive impairment is the impairment of one or more functions in memory, language, visual space, execution, calculation, and understanding, affecting an individual's daily or social ability. With the aging of the population, the incidence rate of cognitive impairment is increasing. Currently, biomarkers related to the cognitive impairment have become a research focus. Gut microbiota has emerged as a potential player in pathophysiology of cognitive impairment. Trimethylamine N-oxide (TMAO), the metabolite produced by gut microbiota, has mechanistic relevance to cognitive impairment. Therefore, the main goal of the present review is to provide the reader with potential mechanisms of TMAO and cognitive impairment. Although a link between TMAO and cognitive impairment is far from definitive, this review will serve as a call for research into this new area.
Objective To investigate the effect of laryngeal and endotracheal surface anesthesia on cough reflex during extubation after excision of supratentorial tumors, and observe its safety. Methods Forty patients were recruited in present study who underwent supratentorial tumor resection under general anesthesia in the Department of Neurosurgery, Peking University International Hospital from March 2021 to March 2022. The patients were randomly divided into tetracaine group (n=20) and control group (n=20). Patients in tetracaine group were uniformly sprayed 2 ml of 2% tetracaine on the bilateral vocal cords, epiglottis and trachea with an atomized laryngeal anesthetic tube before intubation, and patients in control group received no such treatment Anesthesia management was the same in the both groups. Cough score during extubation, NRS score for throat pain after extubation, NRS score for incision pain, mean arterial pressure (MAP) and heart rate were recorded at 3 min after arterial intubation (T0), before tracheal intubation (T1), 30 s after pulling the cuff after intubation (T2), and when the patient is conscious enough to pull out the tracheal intubation (T3), and the occurrence of hoarseness, swallowing and coughing after extubation. Results Five patients in each group were excluded. The cough score was significantly lower in tetracaine group than in control group (0.4±0.6 vs. 2.6±0.5). Their difference was –2.2 (95%CI –2.5, –1.9), lower than the valid assumed value –1.8. NRS score of throat pain in tetracaine group was significantly lower than control group after extubation [2(0, 2) vs. 4(3, 4.5), P<0.001]. However, no statistically significant difference existed between the two groups in NRS scores of incision pain [3(2, 3) vs. 3(2.5, 3.5), P=0.705]. The MAP was significantly lower in tetracaine group than in control group at T3 [(90.87±13.37) mmHg vs. (102.8±11.52) mmHg, P=0.014]; At T0-T3, there was no significant difference in heart rate between the two groups (P>0.05). No side effects such as hoarseness, swallowing and coughing occurred in both groups after operation. Conclusion Before tracheal intubation in patients undergoing supratentorial tumor resection, laryngeal and endotracheal surface anesthesia with 2% tetracaine could reduce the degree of choking during extubation, relieve pharyngeal pain after extubation, the blood pressure was more stable and no serious adverse reaction was found.
Objective To investigate the clinical application value of chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in fetuses with increased nuchal translucency (NT). Methods From January 2020 to April 2022, clinical data of 1013 fetuses were collected who underwent invasive prenatal diagnosis due to NT thickening [defined as NT ≥95th centile for the crown-rump length (CRL)] in the Third Affiliated Hospital of Zhengzhou University. All fetuses were undergone CMA detection, 49 fetuses with negative CMA results underwent further prenatal WES. According to NT value, fetuses were divided into the following four groups: <3.5 mm group (529 cases, 21 cases underwent WES), 3.5-4.5 mm group (273 cases, 8 cases underwent WES), 4.5-5.5 mm group (98 cases, 7 cases underwent WES), and ≥5.5 mm group (113 cases, 13 cases underwent WES). According to the results of ultrasound examination, all fetuses were divided into structural malformation group (88 cases, 23 cases underwent WES) and isolated increased NT group (925 cases, 26 cases underwent WES). The possible chromosomal anomalies were analyzed by CMA first. Furthermore, 49 cases with increased NT but negative CMA results were investigated by WES, and the outcomes were followed up. Results CMA showed that, among the 1013 cases of NT thickened fetus, 224 cases (22.1%) of causative genetic defects were detected, including 182 (18.0%) cases with chromosomal aneuploidy and 42 (4.1%) cases with pathogenic copy number variation (pCNVs). Among different NT value groups, the positive rate of CMA in NT ≥5.5 mm group was the highest (47.8%). In addition, the positive rate of CMA in fetuses with increased NT and structural malformations was higher than in isolated increased NT (45.5% vs. 19.9%). WES detected monogenic disease in 5 of 49 fetuses (10.2%) with increased NT and negative CMA results, including 3 cases of autosomal dominant disease, 1 case of autosomal recessive hereditary disease and 1 case of X-linked recessive hereditary disease. All the five fetuses had structural malformations, two of them with increased NT <3.5 mm, and only one of them was born alive. Conclusion WES can detect out monogenic disease in fetuses with increased NT combined structural malformations with negative CMA results. Fetuses with increased NT should also be alert for the possibility of monogenic disease even if the NT value less than 3.5 mm.