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1.
Front Microbiol ; 15: 1353015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638898

RESUMO

Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve constipation, however the specific mechanism is still unclear. This study investigates that hemp seed (HS) and its water-ethanol extract (HSE) attenuates loperamide-induced constipation in mice. The research results show that: the fecal water content and small intestinal transit rate of mice in the hemp seed group and hemp seed hydroalcoholic extract group were significantly increased compared with MC group, and the first red feces defecation time was significantly shortened; HS and HSE significantly influence serum levels of Gastrin (Gas), motilin (MTL), substance P (SP), and endothelin (ET), potentially mediating their effects on gastrointestinal motility. HS and HSE can improve colon inflammation in constipated mice with H&E staining. Compared with the model of constipation group, the content of short-chain fatty acids in the HS group and HSE group increased significantly. Gut microbiome studies have shown that the structure and abundance of intestinal flora are altered. HS and HSE changed the abundance of Odoribacter, Bacteroide, Lactobacillus and Prevotella. Together, these results suggest that HS have the potential to stimulate the proliferation of beneficial gut microbes and promote intestinal motility, thereby improving gut health and relieving symptoms of constipation.

2.
Hematol Oncol ; 41(1): 167-177, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36305496

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of hyperinflammatory statuses that are difficult to diagnose and can be life-threatening. Bone marrow (BM) hemophagocytosis is one of the diagnostic criteria according to HLH 2004 diagnostic criteria and HS score. Limited studies have focused on the prognostic factors of BM hemophagocytosis and its association with hematologic malignancies. We aimed to analyze the clinical significance of BM hemophagocytosis. Patients with BM hemophagocytosis, either by cytology or pathology, were enrolled at Taipei Veterans General Hospital from January 2002 to July 2021. Relevant clinical and laboratory data were extracted from medical records. Of 119 patients with BM hemophagocytosis, 57 were diagnosed with hematologic malignancies. The median age of the patients was 58, ranging from 21 to 90. Splenomegaly (adjusted odds ratio [aOR] 2.96; 95% confidence interval [CI] 1.13-7.79) was a risk factor for hematologic malignancies, while autoimmune disease (aOR 0.07; 95% CI 0.01-0.39) and increased D-dimer (aOR 0.25; 95% CI 0.07-0.92) were protective factors. Risk factors for mortality in patients with BM hemophagocytosis were hematologic malignancies (adjusted hazard ratio [aHR] 2.34; 95% CI 1.24-4.44), Eastern Cooperative Oncology Group score ≥3 (aHR 2.42; 95% CI 1.20-4.89) and thrombocytopenia (aHR 3.09; 95% CI 1.04-9.16). In conclusion, among patients with BM hemophagocytosis, splenomegaly was a predictor of hematologic malignancies. Patients with hematologic malignancies, poor performance status, or thrombocytopenia had a higher mortality risk. Further validation studies are warranted.


Assuntos
Neoplasias Hematológicas , Linfo-Histiocitose Hemofagocítica , Humanos , Prognóstico , Medula Óssea/patologia , Esplenomegalia/complicações , Esplenomegalia/patologia , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Estudos Retrospectivos
3.
Chinese Journal of Epidemiology ; (12): 445-451, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-969926

RESUMO

Objective: To investigate the association between physical exercise and non-alcoholic fatty liver disease (NAFLD) in people infected with HBV. Methods: The information about the 3 813 participants infected with HBV, including the prevalence of NAFLD, prevalence of physical exercise and other covariates, were collected from the National Science and Technology Major Project of China during 2016-2020. The logistic regression model was used to evaluate the association between physical exercise and NAFLD in HBV infected patients, and subgroup analysis was performed to identify the effect modifiers. Results: A total of 2 259 HBV infected participants were included in the final analysis and 454 (20.10%) had NAFLD. After adjusting for covariates, we found that moderate physical exercise was a protective factor for NAFLD (OR=0.66, 95%CI: 0.46-0.94). Subgroup analysis suggested that the protective effect of moderate physical exercise on NAFLD might be stronger in women (OR=0.61, 95%CI: 0.36-1.01), those <45 years old (OR=0.24, 95%CI: 0.06-0.80), those who had low education level (OR=0.16, 95%CI: 0.04-0.49), those who had low annual income (OR=0.39, 95%CI: 0.16-0.89 for <30 000 yuan RMB; OR=0.64, 95%CI: 0.40-1.00 for 30 000-80 000 yuan RMB), those who had hypertension (OR=0.45, 95%CI: 0.21-0.88), those with BMI ≥24.0 kg/m2 (OR=0.66, 95%CI: 0.43-1.01), those who had more daily fruit or vegetable intake (OR=0.61, 95%CI: 0.38-0.97), those who had more daily meat intake (OR=0.49, 95%CI: 0.23-0.97), and those who had no smoking history (OR=0.66, 95%CI: 0.45-0.95) or passive smoking exposure (OR=0.61, 95%CI: 0.37-0.97). Conclusions: Among HBV infected patients, moderate physical exercise was negatively associated with the prevalence of NAFLD. Women, young people, those who had low education level, those who had low annual income, those with hypertension, those with high BMI, those who had more daily fruit or vegetable and meat intakes, and those who had no smoking history or passive smoking exposure might be more sensitive to the protective effect.


Assuntos
Humanos , Feminino , Adolescente , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Vírus da Hepatite B , Fatores de Risco , Poluição por Fumaça de Tabaco , Exercício Físico , Hipertensão
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986972

RESUMO

OBJECTIVE@#To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout.@*METHODS@#The Sidt2 knockout (Sidt2-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed.@*RESULTS@#Sidt2-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2-/- HL7702 cells.@*CONCLUSION@#Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.


Assuntos
Humanos , Proteínas de Membrana Lisossomal/metabolismo , Autofagia , Apoptose , Hepatócitos , Lisossomos/metabolismo , Cloroquina/farmacologia , Proteínas de Transporte de Nucleotídeos/metabolismo
5.
Chinese Journal of Epidemiology ; (12): 677-682, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985546

RESUMO

HIV cluster detection and response (CDR) is a critical strategy to end the HIV epidemic by offering information to identify prevention and care services gaps. The risk metrics for HIV clusters can be classified into three groups: growth-based metrics, characteristic-based metrics, and phylogeny-based metrics. When identifying HIV risk clusters, the public health response can reach people in the affected networks, including people with undiagnosed HIV, people with diagnosed HIV who might not be accessing HIV care or other services, and people without HIV who would benefit from prevention services. To provide references for HIV precise prevention in China, we summarized the risk metrics and the intervention measures for CDR.


Assuntos
Humanos , Infecções por HIV/prevenção & controle , Síndrome da Imunodeficiência Adquirida/epidemiologia , Saúde Pública , Epidemias/prevenção & controle , China/epidemiologia
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-990384

RESUMO

Objective:To explore the application effect of the intelligent ward combined with DMAIC in improving the procedure and shortening the time of operation, so as to provide a reasonable basis for optimizing and improving the operation process.Methods:This was a prospective study. A total of 240 patients with gynecological surgery hospitalized in Shengjing Hospital of China Medical University from August to November 2021 were selected as the research object. From August to September 2021, the routine management mode of staff in the operating room and ward was adopted as the control group, with a total of 120 cases. From October to November 2021, the intelligent ward combined with DMAIC mode of staff in the operating room and ward was adopted as the observation group, with a total of 120 cases. The time of receiving operation notice, preoperative preparation time, preparation time of transfer personnel, waiting time after the arrival of transfer personnel and the total time of receiving operation were compared between the two groups.Results:The time of receiving operation notice was (1.42 ± 0.61) min in the observation group, which was less than that in the control group (3.53 ± 1.12) min, the difference was statistically significant ( t=18.14, P<0.05). The preoperative preparation time was (8.43 ± 1.80) min in the observation group,which was less than that in the control group (11.36 ± 2.01) min, the difference was statistically significant ( t=11.89, P<0.05). There was no significant difference in the preparation time of transfer personnel between the two groups ( P>0.05). The waiting time after the arrival of transfer personnel was 2.33(1.75, 2.93) min in the observation group, which was less than that in the control group 5.19(3.46, 8.42) min, the difference was statistically significant ( t=-10.06, P<0.05). The total time of receiving operation was (23.90 ± 4.94) min in the observation group, which was less than that in the control group (28.84 ± 4.75) min, the difference was statistically significant ( t=7.90, P<0.05). Conclusions:The intelligent ward combined with DMAIC improves the operation receiving process of the ward, shortens the total time for receiving the operation, and effectively improves the work quality and efficiency of the medical staff.

7.
Endocrinology ; 163(11)2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-35957590

RESUMO

Thioredoxin-interacting protein (TXNIP) has emerged as a key factor in pancreatic beta cell biology, and its upregulation by glucose and diabetes contributes to the impairment in functional beta cell mass and glucose homeostasis. In addition, beta cell deletion of TXNIP protects against diabetes in different mouse models. However, while TXNIP is ubiquitously expressed, its role in pancreatic alpha cells has remained elusive. We generated an alpha cell TXNIP knockout (aTKO) mouse and assessed the effects on glucose homeostasis. While no significant changes were observed on regular chow, after a 30-week high-fat diet, aTKO animals showed improvement in glucose tolerance and lower blood glucose levels compared to their control littermates. Moreover, in the context of streptozotocin (STZ)-induced diabetes, aTKO mice showed significantly lower blood glucose levels compared to controls. While serum insulin levels were reduced in both control and aTKO mice, STZ-induced diabetes significantly increased glucagon levels in control mice, but this effect was blunted in aTKO mice. Moreover, glucagon secretion from aTKO islets was >2-fold lower than from control islets, while insulin secretion was unchanged in aTKO islets. At the same time, no change in alpha cell or beta cell numbers or mass was observed, and glucagon and insulin expression and content were comparable in isolated islets from aTKO and control mice. Thus together the current studies suggest that downregulation of alpha cell TXNIP is associated with reduced glucagon secretion and that this may contribute to the glucose-lowering effects observed in diabetic aTKO mice.


Assuntos
Diabetes Mellitus Experimental , Células Secretoras de Glucagon , Hiperglicemia , Células Secretoras de Insulina , Pancreatopatias , Animais , Glicemia/metabolismo , Proteínas de Transporte , Diabetes Mellitus Experimental/metabolismo , Glucagon/metabolismo , Células Secretoras de Glucagon/metabolismo , Glucose/metabolismo , Hiperglicemia/genética , Hiperglicemia/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Camundongos , Estreptozocina , Tiorredoxinas
8.
Chinese Journal of School Health ; (12): 274-279, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-920632

RESUMO

Objective@#To investigate correlations between motor skills with focused and shifting attention among preschool children, and to provide basis for the overall development of preschool children aged 4-6 years.@*Methods@#During March to June 2020, a total of 165 preschool children aged 4-6 years were selected and investigated with subscales of the Bruininks Oseretsky Test of Motor Proficiency 2nd Edition (BOT-2) for agility and limb bilateral coordination assessment, and subscales of the Movement Assessment Battery for Children test 2nd Edition (MABC-2) for throwing and catching skill assessment, as well as balance subscale for the assessment of limb movement coordination, hand eye coordination, agility, and balance. The Kansas Reflection Impulsivity Scale for Preschoolers for Pre schoolers (KRISP) and Dimensional Change Card Sort (DCCS) were used to assess focused and shifting attention levels. Correlation and linear regression analyses were performed for statistical analysis.@*Results@#Except for one handed throwing skills and shifting attention, there were statistically significant gender differences between boys and girls in total score of body movement coordination, total score of hand to eye coordination, hand to hand connection, total score of agility of movement, total score of movement balance, static support, walking on tiptoe, foot to foot jump and focused attention( t =-6.86, -2.00 ,-3.15,-3.75,-3.00,-2.95,-2.18,-2.11,-3.21, P <0.05), and girls were better than boys; children s total score of body movement coordination, total score of hand to eye coordination, hand to hand connection, agility of movement, walking on tiptoe and focused attention improves with age( r =0.47,0.41,0.47,0.51,0.16,0.31, P <0.05); After excluding the interference of gender and age, total score of body movement coordination was significantly correlated with preschool children s focused attention( β=0.31,95%CI =0.08-0.39, P <0.01).@*Conclusion@#Limb movement coordination and focused attention are significantly and positively correlated among preschool children aged 4-6 years. Therefore, preschool education and family activities should focus on designing and developing limb movement coordination related games and courses to enhance the focused attention of and form favorable attention quality in preschool children aged 4-6 years.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-924054

RESUMO

Objective To provide the reference resource for the safe clinical use of the compound of diphenhydramine hydrochloride and caffeine by observing its effects on the nervous system, cardiovascular system and respiratory system in experimental animals. Methods Single dose of the compound of diphenhydramine hydrochloride and caffeine was given to animals orally. The effects on climbing ability of mice and blood pressure, electrocardiogram, respiration rate and amplitude in beagle dogs were observed and recorded. Results With the dosage of the compound of diphenhydramine hydrochloride and caffeine (diphenhydramine hydrochloride / caffeine ratio is 1/2.4) at 51, 102, 204 mg/kg, there was no significant effect on the climbing ability in mice. With the dosages of 14.2, 28.3, 56.6 mg/kg for male Beagle dogs and 5.66, 14.2, 28.3 mg/kg for female Beagle dogs, no significant effects were observed in systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, ECG(P wave, R wave , T wave, QRS time, PR interval, QT interval), respiratory rate and amplitude. Conclusion Under the experimental conditions, single oral dose of the compound of diphenhydramine hydrochloride and caffeine has no significant effect on the nervous system, cardiovascular system and respiratory system in experimental animals. Those results suggest that the compound of diphenhydramine hydrochloride and caffeine is a safe agent for clinical use.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-927866

RESUMO

Objective To assess the psychological status of staff at the centers for disease control and prevention(CDC) in Sichuan during the outbreak of coronavirus disease 2019(COVID-19) and explore the influencing factors. Methods The staff at Sichuan provincial,municipal,and county(district)-level CDC were selected by convenience sampling.Their basic information,work status,training status,work difficulties,and support from the work group were collected from the self-filled questionnaires online.The Generalized Anxiety Disorder Scale and the 9-question Patient Health Questionnaire were respectively employed to measure the anxiety and depression of the staff.The stepwise Logistic regression was carried out to analyze the influencing factors of anxiety and depression in CDC staff. Results Among the 653 staff,58.35% and 50.06% presented anxiety and depression,respectively.The regression results showed that age(OR=0.95,95%CI=0.92-0.97) and mental support from the work group(OR=0.61,95%CI=0.45-0.82) were the protective factors while physical fatigue(OR=1.82,95%CI=1.20-2.74),work pressure(OR=1.61,95%CI=1.21-2.12),and insufficient protective equipment(OR=1.92,95%CI=1.06-3.49) were the risk factors for depression of CDC staff.Age(OR=0.97,95%CI=0.94-0.99),length of sleep per day(OR=0.74,95%CI=0.56-0.96),and participation in technical training(OR=0.33,95%CI=0.12-0.95) were the protective factors while mental fatigue(OR=1.68,95%CI=1.18-2.41),work pressure(OR=2.94,95%CI=2.08-4.17),and unclear incentive system for overtime(OR=1.99,95%CI=1.23-3.23) were the risk factors for the anxiety of CDC staff. Conclusion The anxiety and depression status of CDC staff during the COVID-19 outbreak were worrying,which were mainly affected by age,sleep,supply of protective equipment,incentive system,fatigue,and work pressure.


Assuntos
Humanos , Ansiedade/epidemiologia , COVID-19 , China/epidemiologia , Estudos Transversais , Surtos de Doenças , SARS-CoV-2 , Inquéritos e Questionários , Estados Unidos
11.
Journal of Clinical Hepatology ; (12): 1774-1779, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-941535

RESUMO

Objective To investigate the value of interleukin-6 (IL-6) combined with Model for End-stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 86 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to their survival status after follow-up for 90 days, they were divided into death group with 50 patients and survival group with 36 patients. ELISA was used to measure the serum level of IL-6, and a statistical analysis was performed for general information. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was performed for IL-6 and other variables; a binary logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients with HBV-ACLF; the receiver operating characteristic (ROC) curve was used to assess the value of IL-6 combined with MELD score in predicting the prognosis of HBV-ACLF. Results There were significant differences between the death group and the survival group in hematocrit ( t =2.413), platelet count ( t =6.584), total bilirubin (TBil) ( t =-8.070), prothrombin time (PT) ( U =77.500), international standardized ratio ( U =102.000), HBV DNA ( t =-2.767), IL-6 ( t =-16.543), and MELD score ( t =-8.192), and the death group had a significantly higher level of IL-6 than the survival group (27.13±12.18 pg/mL vs 9.72±5.56 pg/mL, P < 0.001). The Pearson correlation analysis showed that IL-6 was positively correlated with TBil and PT ( r =0.579 and 0.681, both P < 0.001). The binary logistic regression analysis showed that IL-6 (odds ratio[ OR ]=1.480, 95% confidence interval [ CI ]: 1.196~1.833, P =0.007) and MELD score ( OR =1.128, 95% CI : 1.033~1.231, P < 0.001) were independent risk factors for the death of HBV-ACLF patients within 90 days. IL-6 combined with MELD score had an area under the ROC curve (AUC) of 0.891 (95% CI : 0.778~0.999), with a higher AUC than IL-6 (AUC=0.838, 95% CI : 0.687~0.989) or MELD score (AUC=0.783, 95% CI : 0.634~0.933). IL-6 combined with MELD score had a significantly higher value than IL-6 alone in predicting the prognosis of patients with HBV-ACLF ( Z =-2.257, P =0.024). Conclusion IL-6 combined with MELD score can be used as a good model for predicting the short-term prognosis of patients with HBV-ACLF.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-931679

RESUMO

Objective:To investigate the change in serum epidermal growth factor (EGF) level in patients with Parkinson's disease (PD) and correlate it with cognitive impairment.Methods:A total of 154 patients with early PD who received treatment in Hangzhou Third People's Hospital between July 2017 and June 2018 were included in this study. They were randomly divided into mild cognitive impairment (observation group) and no cognitive impairment (control group) according to the severity of cognitive impairment. Cognitive impairment was graded using Montreal cognitive assessment scale. Motor function was assessed using Unified Parkinson's Disease Rating Scale Part III formulated by International Parkinson and Movement Disorder Society. All these assessments were performed at enrollment and at the end of 2-year follow-up. Serum EGF level was measured by double antibody sandwich enzyme-linked immunosorbent assays. Patients without cognitive impairment were divided into four groups according to quartiles of serum EGF levels. The conversion rate of PD-MCI was calculated at 2 years of follow-up and compared between groups.Results:Among 154 patients, 68 (44.16%) patients developed PD-MCI, and 86 (55.84%) patients had no cognitive impairment. Montreal cognitive assessment scale score and serum EGF level in the observation group were (20.01 ± 3.15) points and (267.79 ± 63.18) ng/L, respectively, which were significantly lower than those in the control group [(28.21 ± 2.84) points, (491.53 ± 67.38) ng/L, t = 8.11, 9.03, both P < 0.001]. Unified Parkinson's Disease Rating Scale Part III score in the observation group was significantly higher than that in the control group [(23.47 ± 5.33) points vs. (18.69 ± 4.37) points, t = 5.18, P < 0.001]. Among the first quartile group, 14 (63.64%) patients converted to PD-MCI; while among the fourth quartile group, 2 (9.52%) patients converted to PD-MCI. The conversion rate of PD-MCI in the second, third and fourth quartile groups was significantly lower than that in the first quartile group (χ 2 = 9.73, 14.48, 33.47, all P < 0.05). Conclusion:Cognitive impairment in patients with PD is closely related to serum EGF level. Serum EGF level is a hematological index to predict cognitive impairment in patients with PD. This study is innovative and scientific.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-955343

RESUMO

Objective:To identify the pathogenic gene and inheritance pattern in a pedigree of congenital iris coloboma with congenital cataract.Methods:The method of pedigree investigation was adopted.A pedigree of congenital iris coloboma with congenital cataract was collected by Yunnan Disabled Rehabilitation Center and the 2nd Afliated Hospital of Kunming Medical University in February 2020.Ophthalmic examinations were carried out on the female proband, her parents, her children and her husband, and the clinical diagnosis was made.Genomic DNA was extracted from peripheral blood samples collected from the family members.The suspected pathogenic gene in the proband and her husband was screened by whole exome sequencing and was identified by bioinformatics analysis.The amino acid conservation was analyzed by UGENE software.The impact of the mutation on protein translation was predicted using MutationTaster software.The pathogenicity of the mutation was assessed according to the American College of Medical Genetics (ACMG) Standards and Guidelines.Pathogenic gene and mutations were verified by Sanger sequencing.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the 2nd Afliated Hospital of Kunming Medical University (No.PJ-2020-61).Written informed consent was obtained from each subject or custodian.Results:The proband showed large iris defects in both eyes with only a small amount of observable iris tissue in the periphery, lens cortical opacity and posterior capsule opacification, accompanied by nystagmus.A novel heterozygous frameshift variation c. 415dupA (p.R139fs) was located in exon 8 of PAX6 gene, and the variation was conservative across multiple species.The variation was in the highly conserved region of PAX6 gene and caused the dysfunction of PAX6 protein.The variation was graded as PVS1+ PM2+ PP1, a pathogenic variation, based on ACMG guidelines.The pedigree was consistent with co-segregation, indicating that the novel variation was pathogenic.The proband and her children were diagnosed, but her parents were phenotypically normal, in accordance with autosomal dominant inheritance. Conclusions:The novel frameshift variation c.415dupA (p.R139fs) on the exon 8 of PAX6 gene is responsible for congenital iris coloboma with congenital cataract in the pedigree.This is the first report of this novel variation in PAX6 gene.

14.
Endocrinology ; 162(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33367814

RESUMO

Increased glucagon is a hallmark of diabetes and leads to worsening of the hyperglycemia, but the molecular mechanisms causing it are still unknown. We therefore investigated the possibility that microRNAs might be involved in the regulation of glucagon. Indeed, analysis of the glucagon 3' untranslated region (UTR) revealed potential binding sites for miR-320a, and using luciferase reporter assays we found that miR-320a directly targets the 3' UTRs of human and rodent glucagon. In addition, endogenous glucagon mRNA and protein expression as well as glucagon secretion were reduced in response to miR-320a overexpression, whereas inhibition of miR-320a upregulated glucagon expression. Interestingly, miR-320a expression was decreased by high glucose, and this was associated with an increase in glucagon expression in human islets and mouse αTC1-6 cells. Moreover, miR-320a overexpression completely blunted these effects. Importantly, miR-320a was also significantly downregulated in human islets of subjects with type 2 diabetes and this was accompanied by increased glucagon expression. Thus, our data suggest that glucose-induced downregulation of miR-320a may contribute to the paradoxical increase in glucagon observed in type 2 diabetes and reveal for the first time that glucagon expression is under the control by a microRNA providing novel insight into the abnormal regulation of glucagon in diabetes.


Assuntos
Glucagon/genética , MicroRNAs/fisiologia , Regiões 3' não Traduzidas/efeitos dos fármacos , Regiões 3' não Traduzidas/genética , Adolescente , Adulto , Idoso , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucagon/metabolismo , Células Secretoras de Glucagon/efeitos dos fármacos , Células Secretoras de Glucagon/metabolismo , Glucose/farmacologia , Células HEK293 , Humanos , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-910408

RESUMO

Radiation-induced bystander effect (RIBE) refers to that irradiated cells release signaling factors and induce responses in nonirradiated cells.In other words, it is the communication between irradiated and nonirradiated cells by intracellular signals. RIBE could influence the efficacy of tumor radiotherapy, but also has potential risk to the normal tissues outside of radiation field. Studies have found that ionizing radiation can induce the alteration of miRNA expression not only in the irradiated cells but also in adjacent nonirradiated tissues, and miRNAs may play an important role in the regulation of signaling pathways between irradiated and nonirradiated bystander cells. This article reviewed the roles of miRNAs in RIBE.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-909154

RESUMO

Objective:To evaluate the stability of newly formed blood vessels in the carotid plaque using qualitative and quantitative analysis of contrast-enhanced ultrasound images and to investigate its correction with the occurrence of ischemic stroke.Methods:A total of 100 patients with carotid artery plaques diagnosed by routine ultrasound who received treatment between August 2017 and December 2019 in Haiyan People's Hospital, China were included in this study. They were divided into an ischemic stroke group ( n = 60) and a non-ischemic stroke group ( n = 40) according to the occurrence of stroke. Two groups of patients underwent contrast-enhanced ultrasound examination of the carotid artery. The correlation between the stability of the newly formed vessels in the carotid plaque and the occurrence of ischemic stroke was quantitatively analyzed. Results:Contrast-enhanced ultrasound results revealed low or medium intensity of echoes. The proportion of patients exhibiting grade 3-4 intensity of echoes in the ischemic stroke group was significantly higher than that in the non-ischemic stroke group ( P < 0.05). Time to peak in the ischemic stroke group was significantly shorter than that in the non-ischemic stroke group [(25.46 ± 3.25) seconds vs. (32.77 ± 4.28) seconds, t = 3.783, P = 0.000]. In the ischemic stroke group, peak intensity [(59.62 ± 10.18) dB vs. (47.53 ± 14.36) dB, t = 3.263, P = 0.000] and the area under the receiver operating characteristic curve [(2 365.37 ± 346.03) cm 2vs. (1 695.42 ± 525.44) cm 2, t = 4.981, P = 0.000] were significantly higher than those in the non-ischemic stroke group (both P < 0.05). Conclusion:Contrast-enhanced ultrasound visual scoring combined with quantitative ultrasonography technology can be used to assess the stability and possible development process of carotid plaques, which provide practical and reliable evidence for selecting a rational opportunity for clinical treatment of ischemic cerebrovascular disease and developing a reasonable treatment plan.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-908740

RESUMO

Objective:To explore the characteristics of cerebral blood flow changes in MRI perfusion imaging in patients with Parkinson disease (PD) cognition disorders and its correlation with serum epidermal growth factor (EGF) level.Methods:One hundred and twenty PD patients diagnosed and treated from September 2017 to September 2020 in Hangzhou Third People′s Hospital were selected. According to the presence of mild cognitive impairment (MCI), they were divided into PD-MCI group (60 cases) and PD without cognition impairment (PD-NCI) group (60 cases). Another 60 cases of healthy physical examination during the same period were selected as the normal control group. MRI perfusion imaging was used to evaluate the cerebral vascular perfusion in each group, and the EGF level of each group was determined by enzyme-linked immunosorbent assay and compared.Results:The CBF and CBV in the PD-MCI group and PD-NCI group were lower than those in the normal control group, while the MTT was longer than that in the normal control group:(14.78 ± 2.49), (18.21 ± 2.84) ml/(100 g·min) vs. (18.21 ± 2.84) ml/(100g·min); (1.42 ± 0.29), (1.83 ± 0.31) ml/100 g vs. (2.87 ± 0.54) ml/100 g; (10.53 ± 2.18), (7.85 ± 1.39) s vs. (4.29 ± 1.05) s, and the differences were statistically significant ( P<0.05). The CBF and CBV in the PD-MCI group were lower than those in the PD-NCI group, while MTT was longer than that in the PD-NCI group, and the differences were statistically significant ( P<0.05). The level of serum EGF in the PD-MCI group and PD-NCI group were lower than those in the normal control group: (146.25 ± 30.12), (208.17 ± 21.25) ng/L vs. (242.38 ± 25.46) ng/L; the level of serum EGF in the PD-MCI group was lower than that in the PD-NCI group, and the differences were statistically significant ( P<0.05). CBF, CBV and EGF were linearly positively correlated with Montreal Cognitive Assessment Scale (MoCA) scores ( r1 = 0.810, r2 = 0.732, r3 = 0.825, P<0.05), while MTT was linearly negatively correlated with MoCA scores ( r4 = -0.756, P<0.05). Conclusions:PD-MCI patients have abnormal cerebral blood flow, and serum EGF level decrease. In PD-MCI patients, CBF, CBV and EGF are linearly positively correlated with MoCA scores, while MTT is linearly negatively correlated with MoCA scores.

18.
Journal of Clinical Hepatology ; (12): 304-308, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-873396

RESUMO

ObjectiveTo investigate the value of interleukin-32 (IL-32) combined with Model for End-Stage Liver Disease (MELD) in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). MethodsA total of 92 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to the follow-up results at 3 months after diagnosis, the patients were divided into survival group with 40 patients and death group with 52 patients. ELISA was used to measure the serum level of IL-32. Clinical data of the patients were collected, including age, sex, underlying diseases, major complications, white blood cell count (WBC), platelet count (PLT), hematocrit (HCT), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), serum creatinine (SCr), prothrombin time (PT), international normalized ratio (INR), and HBV DNA. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a Pearson correlation analysis was performed for IL-32 and other variables; a binary logistic regression analysis was performed to investigate the independent risk factors for the prognosis of patients with HBV-ACLF. The receiver operating characteristic(ROC) curve(AUC) was used to evaluate the value of IL-32 combined with MELD score in predicting the prognosis of patients with HBV-ACLF. The normal Z test was used for comparison of AUC. ResultsThere were significant differences between the two groups in HCT, PLT, TBil, SCr, PT, INR, HBV DNA, IL-32, and MELD score (all P<0.05). IL-32 was positively correlated with TBil (r=0.952, P<0.001) and MELD score (r=0850, P<0.001). IL-32 (odds ratio [OR]=1.137, 95% confidence interval [CI]: 1040-1243, P=0.005) and MELD score (OR=1.055, 95% CI: 1.001-1.109, P=0.025) were independent risk factors for the death of HBV-ACLF patients. IL-32 combined with MELD score had the highest value in predicting the prognosis of patients with HBV-ACLF (AUC=0.992, 95% CI: 0.981-1000), with a significantly higher AUC than IL-32 (0.992 vs 0.984, Z=2.265, P<0.05) and MELD score (0.992 vs 0877, Z=3182, P<0.05). ConclusionBoth IL-32 and MELD score can predict the prognosis of patients with HBV-ACLF, and the combination of these two indicators has a better predictive value.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-911371

RESUMO

Objective:To investigate the effects of doxorubicin(DOX) on osteoblast differentiation of rat bone marrow mesenchymal stem cells(BMSCs) and osteoclast differentiation of bone marrow monocytes(BMMs) in vitro.Methods:Rat BMSCs were treated with various concentrations of DOX in osteogenic medium. The cell viability was detected by CCK-8 assay. Alizarin red staining and alkaline phosphatase(ALP) activity were used to detect the effect of DOX on osteogenic differentiation. Expressions of osteogenic differentiation-related genes were detected by real-time quantitative PCR, Western blot, and immunofluorescence. Similarly, BMMs were treated with various concentrations of DOX and its effects on cell viability and osteoclast differentiation were measured. Finally, the expressions of osteoclast-related genes were detected.Results:DOX treatment inhibited the ALP activity during BMSCs differentiation into osteoblasts and reduced the number of calcium nodules, along with decreased expressions of osteogenic-related genes(ALP, collagen-Ⅰ, and osteocalcin, P<0.05). DOX suppressed the expressions of Smad 1/5/9, bone morphogenetic protein 2(BMP-2), Osterix, and core binding factor α1(Runx2). BMP-2 supplement antagonized the effect of DOX on ALP activity. DOX promoted receptor activator of NF-κB ligand(RANKL) expression and inhibited osteoprotegerin expression. DOX promoted the osteoclast formation and expressions of osteoclast-related genes such as tartrate-resistant acid phosphatase, nuclear factor of activated T cells c1(NFATc1), and c-Fos in a direct and indirect manner. Conclusion:DOX inhibits BMSCs differentiation into osteoblasts through BMP-2/Smads signaling pathway while promotes RANKL-induced BMMs differentiation into osteoclasts in vitro.

20.
Cell Metab ; 32(3): 353-365.e8, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726606

RESUMO

Diabetes is characterized by hyperglycemia, loss of functional islet beta cell mass, deficiency of glucose-lowering insulin, and persistent alpha cell secretion of gluconeogenic glucagon. Still, no therapies that target these underlying processes are available. We therefore performed high-throughput screening of 300,000 compounds and extensive medicinal chemistry optimization and here report the discovery of SRI-37330, an orally bioavailable, non-toxic small molecule, which effectively rescued mice from streptozotocin- and obesity-induced (db/db) diabetes. Interestingly, in rat cells and in mouse and human islets, SRI-37330 inhibited expression and signaling of thioredoxin-interacting protein, which we have previously found to be elevated in diabetes and to have detrimental effects on islet function. In addition, SRI-37330 treatment inhibited glucagon secretion and function, reduced hepatic glucose production, and reversed hepatic steatosis. Thus, these studies describe a newly designed chemical compound that, compared to currently available therapies, may provide a distinct and effective approach to treating diabetes.


Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus Experimental/tratamento farmacológico , Glucagon/metabolismo , Hipoglicemiantes/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Administração Oral , Animais , Proteínas de Transporte/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Bibliotecas de Moléculas Pequenas/administração & dosagem , Estreptozocina
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