RESUMEN
OBJECTIVE The expression of cancerous inhibitor of protein phosphatase 2A(CIP2A)in hypopharyngeal carcinoma FaDu cells(FaDu cells)was reduced by shRNA to understand its role in the occurrence and development of hypopharyngeal carcinoma.METHODS Specific shRNA sequence was designed,lentivirus was packaged and transfected into hypopharyngeal carcinoma FaDu cells,and CIP2A expression was specifically knocked down.The expression of CIP2A was detected by RT-PCR and Western blot.RESULTS 1.After shRNA knocked down CIP2A in FaDu cells,the CIP2A mRNA expression in the experimental group(CIP2A knocked down group)was significantly lower than that in the blank group,and the CIP2A protein expression in the experimental group was also significantly lower than that in the blank group.2.Cell cloning and CCK8 experiments showed that the cell proliferation ability of the experimental group was significantly decreased compared with that of the blank group(t=50.86,P<0.01;t=12.406,P<0.001);The results of cell scratch test showed that the transverse migration ability of the experimental group was significantly decreased compared with the blank group,and the longitudinal migration ability of the experimental group was significantly decreased compared with the blank group by Transwell test(t=40.038,P<0.01;t=12.247,P<0.001).CONCLUSION After knockdown CIP2A expression in hypopharyngeal carcinoma FaDu cells,the proliferation and migration ability of hypopharyngeal cancer cells decreased,suggesting that CIP2A is involved in regulating the biological behavior of hypopharyngeal cancer cells and can be used as a potential anticancer target.
RESUMEN
OBJECTIVE@#To analyze the differentially phosphorylated proteins in DENV-2-infected human umbilical venous endothelial cells (HUVECs) and explore the possible pathogenic mechanism of DENV-2 infection.@*METHODS@#The total proteins were extracted from DENV-2-infected HUVECs and blank control HUVEC using SDT lysis method. The phosphorylated proteins were qualitatively and quantitatively analyzed using tandem mass spectrometry (TMT). The identified differentially phosphorylated proteins were analyzed by bioinformatics analyses such as subcellular localization analysis, GO enrichment analysis, KEGG pathway analysis and protein-protein interaction (PPI) analysis. Western blotting was used to detect the expressions of phosphorylated Jun, map2k2 and AKT1 proteins in DENV-2-infected HUVECs.@*RESULTS@#A total of 2918 modified peptides on 1385 different proteins were detected, and among them 1346 were significantly upregulated (FC > 1.2, P < 0.05) and 1572 were significantly downregulated (FC < 0.83, P < 0.05). A total of 49 phosphorylated conserved motifs were obtained by amino acid conservative motif analysis. The most abundant differentially phosphorylated peptides in protein domain analysis included RNA recognition motif, protein kinase domain and PH domain. Subcellular localization analysis showed that the differentially modified peptides were mainly localized in the nucleus and cytoplasm. GO enrichment and KEGG pathway analysis showed that the differential peptides were mainly enriched in the regulation of stimulation response, biosynthesis of small molecules containing nuclear bases, and migration of phagosomes and leukocytes across the endothelium. PPI and KEGG joint analysis showed that the up-regulated and down-regulated differentially phosphorylated proteins were enriched in 15 pathways. In DENV-2-infected HUVECs, Western blotting detected differential expressions of phosphorylated proteins related with the autophagy pathway, namely JUN, MAP2K2 and AKT1, and among them p-JUN was significantly down-regulated and p-AKT1 and p-MAP2K2 were significantly upregulated (P < 0.01).@*CONCLUSION@#DENV-2 infected HUVECs show numerous differentially expressed proteins. The downregulation of p-JUN and upregulation of p-MAP2K2 and p-AKT1 suggest their potential roles in regulating autophagy, which is probably involved in the mechanism of DENV-2 infection.
Asunto(s)
Humanos , Autofagia , Muerte Celular , Núcleo Celular , Células Endoteliales de la Vena Umbilical Humana/virología , Dengue , ProteomaRESUMEN
Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.
RESUMEN
【Objective】 To establish a co-expression lncRNA-mRNA ceRNA network and explore the potential molecular mechanism of lncRNA in dengue fever. 【Methods】 DENV-2-infected and normal pHUVEC were sequenced and screened for differentially expressed lncRNA and mRNA by gene microarray technology. Differentially expressed mRNA was analyzed by protein-protein interaction (PPI), and significantly related co-expressed lncRNA-mRNA was screened by Pearson’s correlation coefficient. The microRNA (miRNA) that bound to co-expressed lncRNA-mRNA was predicted by the database. The ceRNA network of co-expressed lncRNA-mRNA was constructed by Cytoscape software. Finally differentially expressed mRNAs and co-expressed lncRNA-mRNA were analyzed by GO and KEGG enrichment, and co-expressed lncRNA-mRNA was verified by RT-qPCR. 【Results】 At 48 h and 72 h after infection, 105 and 51 differentially expressed mRNAs were obtained, respectively, while 59 and 29 differentially expressed lncRNAs were obtained, respectively. Furthermore, at the two time intervals, there were 10 differential mRNAs and 5 differential lncRNAs, respectively. PPI analysis of differential mRNAs showed that isocratic values of interleukin 6 (IL6), interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), and 2’-5’-oligoadenylate synthetase 2 (OAS2) were relatively high. The pairing results of lncRNA-mRNA co-expression analysis with the highest correlation coefficients at 48 h and 72 h after infection were XLOC_001966-SMTNL1 and XLOC_001966-ESR2, respectively. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the functions of differentially expressed mRNA and co-expressed lncRNA-mRNA were mainly involved in virus epidemic prevention response, immune response, and signal transduction, as well as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, type I interferon, and cytokine receptor interaction. RT-qPCR revealed that lncRNA XLOC-I2-8991 was upregulated in the co-expressed lncRNA-mRNA, whereas all the other lncRNA and mRNA were downregulated. 【Conclusion】 This study initially revealed the potential lncRNA-mRNA co-expression network during dengue virus infection, and found that co-expressed lncRNA-mRNA was mainly enriched in the immune regulation and signal transduction pathways during virus infection. The findings will help further exploration into the infection mechanism of DENV-2.
RESUMEN
Aim To establish a high-throughput screening cell model for GLP-1 receptor agonists. Methods A pEGFP-GLP-1R-3 C recombinant plasmid was constructed and transfected into HEK293T cells. The cells were screened with G418 and flow cytometry. The established stable cell line was named HEK293TGLP-lR-3C-eGFP cell line. The expression level of GLP-1 R-3C-eGFP protein was confirmed by Western blotting and laser confocal microscopy. Then cyclic adenosine monophosphate (cAMP) response element reporter gene was transfected into the HEK293T-GLP-lR-3C-eGFP cells. The luminescence values were detected by One-Step Luciferase Reporter Gene Assay Kit after stimulation with different concentrations of GLP-1 peptide. The luminescence values reflected the cellular cAMP level, which was verified using the cAMP kit (E L I S A). Results HEK293T-GLP-lR-3C-eGFP cell line was successfully constructed. The relative light unit change trend after stimulation with different concentrations of GLP-1 was similar to that of the cellular cAMP level change trend. The value of Z' in this experiment was 0.52. Conclusions A recombinant HEK293T cell line is established, which can be used for high-throughput screening of GLP-1 receptor agonists.
RESUMEN
Objective:To investigate the risk factors associated with the positive results of early postpartum depression screening.Methods:This study involved 2 889 women who were negative in prenatal depression screening and delivered in the Maternal and Child Health Hospital of Hubei Province from 1 March to 30 April 2021. The Edinburgh Postnatal Depression Scale (EPDS) score, Adaptation Partnership Growth Affection Resolve (APGAR) score, and related living habits of the enrolled subjects were investigated on the 5th to 7th day after delivery. All patients were divided into two groups with 2 354 in the negative group (EPDS score<13) and 535 in the positive group (EPDS score≥13), based on the EPDS scores at 5 to 7 days postpartum. Chi-square test, trend Chi-square test, and rank-sum test were used for univariate analysis. Risk factors associated with positive depression screening were analyzed using binary logistic regression. Results:Univariate analysis suggested that there were statistically significant differences between the two groups in maternal personality, marital relationship, family functioning, sleep quality during pregnancy, smoking and drinking habits during pregnancy, prenatal EPDS score, mode of delivery, whether or not to have intrapartum cesarean section and forceps delivery, duration of labor in vaginal delivery, the proportions of puerperae and neonates who were transferred to intensive care unit (ICU), twin pregnancy, placenta previa, abnormal fetal position, premature birth, postpartum hemorrhage, and having three or more complication (all P<0.05). Binary logistic regression analysis suggested that extravertion ( OR=0.483, 95% CI:0.369-0.632), good marital relations ( OR=0.540, 95% CI:0.422-0.691) and good sleep during pregnancy ( OR=0.340, 95% CI:0.245-0.471) were protective factors for early postpartum depression, while introversion ( OR=1.632, 95% CI:1.275-2.088), poor marital relations ( OR=3.495, 95% CI: 1.946-6.276), moderate family dysfuntion ( OR=4.038, 95% CI:2.667-6.114) and severe family dysfunction ( OR=20.234, 95% CI: 2.446-167.364), smoking ( OR=2.071, 95% CI:1.315-3.263) and drinking during pregnancy ( OR=1.924, 95% CI:1.142-3.243), twin pregnancy ( OR=2.680, 95% CI:1.435-5.005), placenta previa ( OR=2.567, 95% CI:1.316-5.009), having three or more complications ( OR=1.876, 95% CI: 1.316-2.674), forceps delivery ( OR=3.043, 95% CI:1.185-7.816), intrapartum cesarean section ( OR=1.917, 95% CI:1.232-2.982), postpartum hemorrhage ( OR=1.668, 95% CI:1.069-2.604), and postpartum ICU admission ( OR=2.601, 95% CI: 1.112-6.086) were risk factors for early postpartum depression. Conclusions:Healthy living habits, and good mood contribute to decreasing postpartum depression in pregnant women. Education for parturients with serious illness or complications should be strengthened to help develop a proper understanding of the disease.
RESUMEN
Objective@#To investigate the experience of child sexual abuse (CSA) and depressive symptoms among young men who sex with men (YMSM) in Guangzhou, and then to explore the impact of CSA on depressive symptoms.@*Methods@#A convenient sampling method was used to recruit MSM. YMSM who aged 18-24 and have lived in Guangzhou for more than 3 months were included in this study. Data on demographic characteristics, homosexual partners seeking behaviors, sexual orientation, CSA experience and depression were collected through an electronic questionnaire. χ 2 tests were used to compare the proportion of CSA and depressive symptoms among YMSM with different characteristics. Logistic regressions were preformed to assess the impact of CSA on depression.@*Results@#The proportion of CSA experience and depressive symptoms among participants were 31.51% (115/365) and 47.95% (175/365), respectively. Participants with junior high school education or lower and who sought homosexual partners offline reported(75.00%,62.22%) a higher proportion of depressive symptoms( χ 2=7.97,4.19, P <0.05). After adjusting for factors e.g. ethnicity, residence, resident duration in Guangzhou, studentship, education, monthly income, sexual orientation and homosexual partners seeking behaviors, the multivariable Logistic regression model showed that YMSM with CSA experience (a OR=1.81, 95%CI =1.12-2.93) were more likely to have depressive symptoms than those without CSA experience.@*Conclusion@#The prevalence of CSA experience and depressive symptom is relatively high among YMSM in Guangzhou, and CSA experience is associated with higher risk of depressive symptoms. More attention should be paid to strengthen the psychological intervention for YMSM, especially for those who experienced CSA, so as to reduce the risk of depression and improve mental health among YMSM.
RESUMEN
This study aims to explore the targets of ginsenosides in brain based on drug affinity responsive target stability(DARTS) technology. Specifically, DARTS technology was combined with label-free liquid chromatography tandem mass spectrometry(LC-MS) to screen out the proteins in the brain that might interact with ginsenosides. Based on the screening results, adenylate kinase 1(AK1) was selected for further confirmation. First, the His-AK1 fusion protein was yielded successively through the construction of recombinant prokaryotic expression vector, expression of target protein, and purification of the fusion protein. Biolayer interferometry(BLI) was employed to detect the direct interaction of Rg_1, Re, Rb_1, Rd, Rh_2, F1, Rh_1, compound K(CK), 25-OH-PPD, protopanaxa-diol(PPD), and protopanaxatriol(PPT) with AK1, thereby screening the ginsenoside monomer or sapogenin that had strong direct interaction with the suspected target protein AK1. Then, the BLI was used to further determine the kinetic parameters for the binding of PPD(strongest interaction with AK1) to His-AK1 fusion protein. Finally, molecular docking technology was applied to analyze the binding properties between the two. With DARTS and LC-MS, multiple differential proteins were screened out, and AK1 was selected based on previous research for target verification. Fusion protein His-AK1 was obtained by prokaryotic expression, and the response(nm) of Re, Rg_1, Rd, Rb_1, Rh_1, Rh_2, F1, PPT, PPD, 25-OH-PPD, and CK with His-AK1 was respectively 0.003 1, 0.001 9, 0.042 8, 0.022 2, 0.013 4, 0.037 3, 0.013 9, 0.030 7, 0.140 2, 0.016 0, and 0.040 8. The K_(on), K_(off), and K_D values of PPD and His-AK1 were determined by the BLI as 1.22×10~2 mol~(-1)·L·s~(-1), 1.04×10~(-2) s~(-1), 8.52×10~(-5) mol·L~(-1). According to the molecular docking result, PPD bound to AK1 with the absolute value of the docking score of 3.438, and hydrogen bonds mainly formed between the two. Thus, AK1 is one of the protein action sites of ginsenosides in the brain. The direct interaction between ginsenoside metabolite PPD and AK1 is the strongest.
Asunto(s)
Encéfalo/metabolismo , Cromatografía Liquida , Ginsenósidos , Simulación del Acoplamiento Molecular , TecnologíaRESUMEN
Aim To explore the mechanism of action of the active ingredients of Callerya nitida var.hirsutissima corresponding to the target gene in the treatment of triple-negative breast cancer(TNBC), using network pharmacology, molecular docking technology and in vitro experimental verification.Methods Based on literature research and combined with database screening, the main active components of Callerya nitida var.hirsutissima and the related targets of TNBC were obtained.Intersection genes were found to construct a protein interaction(PPI)network diagram, and core targets were screened according to the size of the correlation.A core target interaction network model of "Traditional Chinese Medicine-Ingredients-Targets-Disease" was constructed.The intersection targets were analyzed for gene GO function and KEGG pathway enrichment analysis.Finally, molecular docking and in vitro experimental verification of the selected components and the target were carried out.Results A total of 38 active components of Callerya nitida var.hirsutissima were collected, as well as 388 related potential targets, 3 919 TNBC targets, and 277 Callerya nitida var.hirsutissima therapeutic targets for TNBC.It mainly acted on multiple targets such as PIK3R1, PIK3CA, MAPK1, AKT1, SRC, etc.In in vitro experiments, it could be seen that the chloroform fraction of Callerya nitida var.hirsutissima and the monomer compounds luteolin and betulin had certain inhibitory effects on cell proliferation.All groups could inhibit the expression of VEGFA, AKT, PIK3CA, CDK1, CDK4 within the range of administration concentration.Conclusions Based on network pharmacology and molecular docking methods, this study explores the possible targets and signaling pathways of Callerya nitida var.hirsutissima in the treatment of TNBC, and conducts in vitro verification experiments to further verify the prediction of network pharmacology.
RESUMEN
Purpose@#Both primary and revisional bariatric surgery are on the rise due to global obesity pandemic. This study aimed to assess the indications for revision after one-anastomosis gastric bypass (OAGB) and the outcomes after laparoscopic conversion of OAGB to roux-en-y gastric bypass (RYGB). @*Materials and Methods@#Retrospective review on patients that had undergone conversion of OAGB to RYGB between June 2007-June 2019 in a tertiary bariatric center, followed by literature review. @*Results@#Out of 386 revisional bariatric surgery, a total of 14 patients underwent laparoscopic conversion of OAGB to RYGB. The mean age was 44.7 with 71% female. The mean pre-revision BMI was 29.2 kg/m2 . The primary indications for revision were bile reflux (n=7), marginal ulcer (n=3), inadequate weight loss or weight regain (IWL/WR) (n=3) and protein-calorie malnutrition (n=1). Conversion of OAGB to RYGB was completed laparoscopically in all cases.The mean length of stay was 4.1 days. There was no intraoperative or early post-operative complication. The mean total weight loss (rTWL%) after revision at year one, year three and year five post-revision were 11.5%, 18.1% and 29.1%, respectively. All patients achieved resolution of bile reflux and marginal ulcer. There was no mortality in this cohort. @*Conclusion@#Bile reflux, marginal ulcer, IWL/WR and malnutrition were the main indications for revision after OAGB in this study. In concordance with the available evidence, laparoscopic conversion of OAGB to RYGB was safe and effective in dealing with late complications of OAGB.
RESUMEN
The Leguminosae perennial vines of Callerya and Millettia have many species and wide distribution, not only can be used for medicines, but also they have ornamental and insecticidal effects. With increasing demand for Spatholobi Caulis, and the reserves of wild medicinal materials are on the verge of exhaustion, resulting in the increasing number of mixtures and substitutes in the market, which makes it urgent to study the origin of Spatholobi Caulis. By referring to related literature, there are three major origins of Spatholobi Caulis, including Callerya, Millettia and Spatholobus. Callerya is separated from Millettia, they are divided and united for many times, now the official website of Flora of China has accepted the revision of them as two genera. This paper intends to compare the chemical components and pharmacodynamic effects of Callerya and Millettia, aiming to explore the similarities and differences between the two genera, so as to determine the rationality and necessity of separating Callerya from Millettia. After comparing, it was found that the chemical composition and pharmacodynamic effects of the two genera were different, which supported the separation of Callerya from Millettia, and it was not recommended to mix use of them.
RESUMEN
Purpose@#Both primary and revisional bariatric surgery are on the rise due to global obesity pandemic. This study aimed to assess the indications for revision after one-anastomosis gastric bypass (OAGB) and the outcomes after laparoscopic conversion of OAGB to roux-en-y gastric bypass (RYGB). @*Materials and Methods@#Retrospective review on patients that had undergone conversion of OAGB to RYGB between June 2007-June 2019 in a tertiary bariatric center, followed by literature review. @*Results@#Out of 386 revisional bariatric surgery, a total of 14 patients underwent laparoscopic conversion of OAGB to RYGB. The mean age was 44.7 with 71% female. The mean pre-revision BMI was 29.2 kg/m2 . The primary indications for revision were bile reflux (n=7), marginal ulcer (n=3), inadequate weight loss or weight regain (IWL/WR) (n=3) and protein-calorie malnutrition (n=1). Conversion of OAGB to RYGB was completed laparoscopically in all cases.The mean length of stay was 4.1 days. There was no intraoperative or early post-operative complication. The mean total weight loss (rTWL%) after revision at year one, year three and year five post-revision were 11.5%, 18.1% and 29.1%, respectively. All patients achieved resolution of bile reflux and marginal ulcer. There was no mortality in this cohort. @*Conclusion@#Bile reflux, marginal ulcer, IWL/WR and malnutrition were the main indications for revision after OAGB in this study. In concordance with the available evidence, laparoscopic conversion of OAGB to RYGB was safe and effective in dealing with late complications of OAGB.
RESUMEN
In this paper, the molecular mechanism of Spatholobi Caulis in the treatment of non-small cell lung cancer(NSCLC) was studied through network pharmacology and molecular docking analysis. With traditional Chinese medicine(TCM) Spatholobi Caulis as the study object, active ingredients of Spatholobi Caulis and corresponding potential drug targets were obtained from Traditio-nal Chinese Medicine Pharmacology Platform(TCMSP) database; GeneCards database was used to collect cancer-related genes; Cytoscape software was used to build Spatholobi Caulis active ingredient-target-pathway relationship network. DAVID database was used for GO and KEGG enrichment analysis of targets, KEGG signaling pathway was visualized, and compounds were screened out for molecular docking. Finally, in vitro experiments on human lung cancer cells, A549 treated with luteolin and licochalcone A were used to preliminarily verify the core targets and pathways, cell proliferation was detected by CCK-8 method, and expressions of caspase-3 and Bax protein were detected by Western blot. A total of 23 active components and 170 potential drug targets were selected from Spatholobi Caulis, involving 127 pathways in total. Molecular docking results showed that licochalcone A,(Z)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-phenyl) ethyl] acrylamide, consumeclose grain successfully docked with the key target EGFR, and binding energy of the three compounds was less than-5 kcal·mol~(-1). CCK-8 results showed that luteolin, licochalcone A, and Spatholobi Caulis extract had the inhibitory effect on human lung cancer A549 cells. Western blot showed that luteolin, licochalcone A and Spatholobi Caulis extract could induce cell apoptosis by increasing the expressions of pro-apoptotic factors caspase-3 and Bax. In this study, the anti-lung cancer effect of Spatholobi Caulis was studied through network pharmacology and molecular docking, in order to provide ideas for the molecular mechanism of Spatholobi Caulis in the treatment of lung cancer.
Asunto(s)
Humanos , Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos/farmacología , Neoplasias Pulmonares/genética , Medicina Tradicional China , Simulación del Acoplamiento MolecularRESUMEN
Conformation dynamics attributes to the biological functions of active proteins and conformation ensembles. The conformation ensembles include protein stable states (PSS) that can be measured by conventional structural biology approaches and the invisible protein states (IPS) that cannot be measured by conventional structural biology ones. The conformational exchange between IPS and PSS plays an important role in the biological functions of proteins. In this review, we briefly describe the basic properties of IPS and discuss its contribution to the development of the classical molecular recognition mechanism of “keylock hypothesis” and "induced fit hypothesis" into "conformational selection hypothesis". Furthermore, this review compares the advantages and disadvantages of the current structural biology approaches for investigating the conformational properties of IPS. Because of advanced NMR technology, the exploration of the conformational properties of IPS in experimental manner has become feasible. It is expected that the study of IPS and its function will not only help clarify the molecule recognition mechanism of proteins, but also provide a basis for guiding the design of targeted drugs.
RESUMEN
OBJECTIVE@#To construct and validate an individualized nomogram to predict the probability of occurrence of portal vein thrombosis (PVT) after splenectomy in patients with hepatitis B cirrhosis.@*METHODS@#We retrospectively collected the clinical data from 180 patients with hepatitis B cirrhosis undergoing splenectomy with postoperative anticoagulation therapy during the period from January, 2014 to January, 2020 in our hospital. The patients were randomized into modeling group (= 120) and validation group (=60), and the former group was further divided into PVT group (=49) and non-PVT group (=71) according to the occurrence of PVT occurred within 1 month after splenectomy. The independent risk factors of PVT after splenectomy were screened in the modeling group using univariate and multivariate binary logistic regression analyses and were used for construction of the nomogram prediction model. The area under the receiver-operating characteristic (AUROC) curve (C-index), GiViTI calibration belt and Hosmer-Lemeshow test, and the DCA curve were used to estimate the discrimination power, calibration and clinical efficiency of the prediction model in both the model construction group and validation group.@*RESULTS@#Univariate and multivariate logistic regression analyses showed that a history of hemorrhage, portal vein diameter, spleen vein diameter, spleen volume, varicose, postoperative platelet change, and postoperative D-dimer differed significantly between PVT group and non-PVT group ( < 0.05), and portal vein diameter, spleen vein diameter, and postoperative platelet change were independent risk factors of PVT after splenectomy ( < 0.05). The prediction model had a good discrimination power with AUROC (C-index) of 0.880 (95% : 0.818-0.942) in the modeling group and 0.873 (95% : 0.785-0.960) in the validation group. The 80% and 95% region of GiViTI calibration belt did not cover the 45-degree diagonal bisector line (=0.965 and 0.632, respectively), and the P-values of the Hosmer-Lemeshow test were 0.624 and 0.911, respectively, suggesting a high reliability of the predicted probability by the model. DCA curve analysis showed a threshold probability of 30.5%, with a net benefit of 30% in the modeling group and 34% in the validation group, indicating a good clinical efficiency of the model.@*CONCLUSIONS@#The model for predicting the risk of PVT after splenectomy in patients with hepatitis B cirrhosis can help in early identification of patients having high risks of PVT.
RESUMEN
Objective:To evaluate the insulin resistance of patients with polycystic ovary syndrome (PCOS) by hyperinsulin-euglycemic clamp test, and to explore the characteristics of glycolipid metabolism and sex hormone levels in PCOS patients with insulin resistance.Methods:Seventy-three patients with PCOS and 27 healthy women with body mass index and age matched with PCOS patients who were admitted to the Department of Endocrinology of Affiliated Hospital of Zunyi Medical University from July 2017 to February 2019 were underwent hyperinsulin-euglycemic clamp test. All subjects were grouped according to glucose metabolic rate, body mass index, and homeostasis model assessment for insulin resistance (HOMA-IR), the changes and differences of glucose and lipid metabolism and sex hormone indexes in PCOS patients were analyzed.Results:In the PCOS group, impaired glucose regulation accounted for 3.23% (1/31), and abnormal lipid metabolism for 9.68% (3/31). In the PCOS with insulin resistance group, impaired glucose regulation accounted for 7.14% (3/42). Abnormal blood lipid metabolism reached 47.62% (20/42), and 5 patients were diagnosed with metabolic syndrome, accounting for 11.90%. Correlation analysis showed glucose metabolic rate and body mass index, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, cortisol, triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), free androgen index (FAI), and glutamyl transpeptidase (GGT) were negatively correlated(all P<0.05), while positively correlated with high density lipoprotein-cholesterol (HDL-C; P=0.028). HOMA-IR was positively correlated with body mass index, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HbA 1C, LDL-C ( P<0.05), and negatively correlated with glucose metabolic rate and HDL-C ( P<0.05). Body mass index and waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, triglyceride, and LDL-C ( P<0.05) were positively correlated, and negatively correlated with glucose metabolic rate, HDL-C, and sex hormone binding globulin (SHBG; P<0.01). Multivariate linear stepwise regression analysis showed that body mass index, total cholesterol, triglyceride, and cortisol were principal factors affecting glucose metabolic rate. Fasting plasma glucose, fasting insulin, and systolic blood pressure were important factors influencing HOMA-IR. Glucose metabolic rate, HOMA-IR, HDL-C, while SHBG were still vital to body mass index. Conclusion:FAI, SHBG, and cortisol may be involved in the insulin resistance development of PCOS patients, and PCOS patients with insulin resistance were more susceptible to metabolic disorders.
RESUMEN
Objective::To analyze and identify the metabolites of major components of Shaoyao Gancaotang in urine and feces of normal and polycystic ovary syndrome (PCOS) rats, and to explore the effect of PCOS on the metabolism of Shaoyao Gancaotang. Method::Female SD rats were randomly divided into normal group and PCOS group. PCOS rat model was prepared by administration of letrozole solution for 21 days, and the estrous cycle of rats was observed. UHPLC-QTRAP-MS/MS technique and LightSight 2.3 software were used to analyze and identify the metabolites of major components of Shaoyao Gancaotang in urine and feces of normal and PCOS rats. The mobile phase was water-methanol for gradient elution, the flow rate was 0.3 mL·min-1, electrospray ion source was employed under negative ion mode. Result::Phase Ⅰ and phase Ⅱ reactions mainly occurred in drug metabolism. A total of 27 metabolites were detected in urine of normal rats, and 34 metabolites were detected in urine of PCOS rats. A total of 29 metabolites were detected in feces of normal rats, and 27 metabolites were detected in feces of PCOS rats. Conclusion::The metabolites in the urine of PCOS rats are more diverse than those of normal rats, and the disease status of PCOS may affect the in vivo metabolic pathway of active ingredients in Shaoyao Gancaotang.
RESUMEN
Objective@#To analyze the epidemiological and spatial-temporal distribution of Brucellosis, epidemic encephalitis B and hemorrhagic fever with renal syndrome (HFRS) in Gansu province during 2014-2018 so as to provide evidence for the prevention and control of those diseases.@*Methods@#A database was established in Gansu province from 2014 to 2018, using the geographical information system. A spatial distribution map was drawn, with trend analysis and space-time clustering used to study the 3-dimention of the diseases, by using both ArcGIS 10.5 and SaTScan 9.6 softwares.@*Results@#Results from the trend surface analysis showed that the incidence of Brucellosis decreased gradually from north to south parts while the U type curve could reflect the distribution from the east to the west areas. Incidence of epidemic encephalitis B decreased significantly from south to north areas in the province, with incidence higher in the eastern than in the mid-west region. Difference on the incidence of HFRS was not significantly visible in the eastern and western regions, while the incidence was slightly higher in the southern than the northern parts of the province. Spatial and space-time clustering did exist among the 3 diseases in Gansu from 2014 to 2018. The areas with clusters of Brucellosis appeared in the eastern parts during 2014-2015, including 19 counties. The areas with secondary clusters of Brucellosis were seen in the Hexi district, including 4 counties, during 2017-2018. The areas with high incidence of epidemic encephalitis B were clustered in the middle and southeast areas, including 32 counties, during 2017-2018. Areas with most clusters of HFRS appeared in Min county of Dingxi city in 2018, with the areas of secondary clusters in 8 counties of the eastern areas in 2018.@*Conclusions@#The overall incidence rates of the 3 natural focus diseases were in a upward trend and showing obvious characteristics on spatial clustering. According to the distributive characteristics, effective measures should be developed accordingly.
RESUMEN
Objective@#To analyze the spatial distribution and both hot and cold spots of incidence on Brucellosis in Gansu province from 2013 to 2018.@*Methods@#Based on data from the Infectious Disease Reporting Information System in China, data related to space-time distribution and both hot and cold spots of Brucellosis in Gansu province from 2013 to 2018 were analyzed, by using the ArcGIS 10.5 software and GeoDa 1.6 software.@*Results@#The trend surface analysis showed that the incidence of Brucellosis decreased gradually from the northern to southern parts with slightly higher in the west than in the east of Gansu. Global spatial autocorrelation analysis showed that the Moran’s I of Brucellosis in Gansu province from 2013 to 2018 were 0.242, 0.487, 0.424, 0.460, 0.427 and 0.468 (P<0.01), suggesting that the incidence of Brucellosis had spatial clustering features in Gansu province. Local global spatial autocorrelation analysis showed that the number of hot spots were declining in the eastern and north-central regions while the hot spots were increasing in the Hexi area (Wuwei, Zhangye, Jinchang and Jiuquan cities). The cold spots areas were mainly seen in the eastern, southeastern and south of central regions in Gansu province.@*Conclusions@#The incidence of Brucellosis showed obviously spatial clustering characteristics in Gansu province. The number of hot spots were decreasing in the eastern and north of central regions while the hot spots were increasing in the Hexi area, suggesting that the prevention and control measures for Brucellosis should be further strengthened in these areas.
RESUMEN
Hepatolithiasis is a common benign biliary disease in China. It is a challenge to treat hepatolithiasis. Some patients with complicated hepatolithiasis fail to achieve satisfactory outcomes after several biliary operations, and therefore, how to improve the treatment outcome of hepatolithiasis is a major problem for biliary surgeons. At present, surgery is still the main treatment method for hepatolithiasis. Percutaneous transhepatic choledochoscopic lithotripsy (PTCSL), as a minimally invasive surgical treatment for hepatolithiasis, has been accepted by many biliary surgeons and patients with hepatolithiasis and gradually gains a place in the treatment of hepatolithiasis. This article reviews the research advances in PTCSL in the treatment of hepatolithiasis.