Objective:To study the application effect of psychological nursing in pediatric clinical nursing.Method:100 pediatric patients who underwent treatment in our hospital from January 2019 to December 2020 were selected a...Objective:To study the application effect of psychological nursing in pediatric clinical nursing.Method:100 pediatric patients who underwent treatment in our hospital from January 2019 to December 2020 were selected as the research subjects.They were randomly divided into a control group and an observation group,with 50 cases in each group.The control group received routine nursing care,while the observation group received psychological care based on routine nursing care.The nursing compliance,incidence of adverse events,and parental satisfaction of the two groups of pediatric patients were compared and analyzed.Result:Through psychological nursing intervention,it was found that the observation group had better nursing compliance,incidence of adverse events,and parental satisfaction than the control group,P<0.05,the differences are statistically significant.Conclusion:The application of psychological nursing in pediatric clinical nursing can improve the compliance of pediatric care,reduce the incidence of adverse events,enhance parental satisfaction,and have clinical promotion and application value.展开更多
The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and impro...The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.展开更多
Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is uncle...Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.展开更多
AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), a...AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.展开更多
Contusion spinal cord injury(SCI)is a major medical and socio-economic problem globally.The incidence of SCI is highest among young adults due to motor vehicle accidents,military or sports injuries,and violence(Selvar...Contusion spinal cord injury(SCI)is a major medical and socio-economic problem globally.The incidence of SCI is highest among young adults due to motor vehicle accidents,military or sports injuries,and violence(Selvarajah et al.,2014).The elderly and children are also at risk due to falls and accidents.SCI causes neurodegeneration,with profound loss of locomotor and sensory functions(Siddiqui et al.,2015).Pain and depression are also prevalent in a majority of SCI patients.Expenses for severe SCI are high:initial hospitalization,rehabilitation,and most likely the continuing need for a caregiver and medical care.SCI survivors with less severe injuries usually face lower but still hefty medical bills.However,people≥50 years old with severe SCI may face medical expenses of over$1.8 million during their lifetimes.These injuries also affect spouses and family members,emotionally and financially,and most injuries jeopardize employment for those affected.展开更多
Robust and efficient AUV path planning is a key element for persistence AUV maneuvering in variable underwater environments. To develop such a path planning system, in this study, differential evolution(DE) algorithm ...Robust and efficient AUV path planning is a key element for persistence AUV maneuvering in variable underwater environments. To develop such a path planning system, in this study, differential evolution(DE) algorithm is employed. The performance of the DE-based planner in generating time-efficient paths to direct the AUV from its initial conditions to the target of interest is investigated within a complexed 3D underwater environment incorporated with turbulent current vector fields, coastal area,islands, and static/dynamic obstacles. The results of simulations indicate the inherent efficiency of the DE-based path planner as it is capable of extracting feasible areas of a real map to determine the allowed spaces for the vehicle deployment while coping undesired current disturbances, exploiting desirable currents, and avoiding collision boundaries in directing the vehicle to its destination. The results are implementable for a realistic scenario and on-board real AUV as the DE planner satisfies all vehicular and environmental constraints while minimizing the travel time/distance, in a computationally efficient manner.展开更多
Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index,and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer p...Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index,and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer patients achieve complete remission after chemotherapy,death still occurs due to relapse of persistent minimal residual disease(MRD) which remaining after initial cytotoxic chemotherapy. Advanced neuroblastoma(NB) is a leading cause of cancer deaths in young children. Retinoids are an important component of advanced NB therapy at the stage of MRD,yet half of all patients treated with 13-cis-retinoic acid still relapse and die. More effective combination therapies,with a lower side-effect profile,are required to improve outcomes for NB. Fenretinide or N-4-hydroxyphenyl retinamide is a synthetic derivative of retinoic acid which works on cancer cells through nuclear receptor-dependent and-independent signalling mechanisms. Moreover,several histone deacetylase inhibitors have entered early phase trials,and,suberoylanilide hydroxamic acid has been approved for use in adult cutaneous T cell lymphoma. A number of studies suggest that retinoid signal activation is necessary for histone deacetylase inhibitor activity. A better understanding of their mechanism of actions will lead to more evidence-based retinoid combination therapies.展开更多
AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined re...AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction(PCR),quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA,precancerous bile duct dysplasia and from disease-free controls.The functional impact of recombinant human(rh) TFF2 peptide treatment on proliferation and epidermal growth factor receptor(EGFR) /mitogenactivated protein kinase(MAPK) signaling was assessed in the CCA cell line,KMBC,by viable cell counting and immunoblotting,respectively.RESULTS:TFF1,TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls,and was unrelated to gene copy number.TFF1 immunoreactivity was strongly increased in both dysplasia and CCA,whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls.By contrast,TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA.Kaplan-Meier analysis found no association of TFF mRNA,protein and copy number with age,gender,histological subtype,and patient survival time.Treatment of KMBC cells with rhTFF2 stimulated proliferation,triggered phosphorylation of EGFR and downstream extracellular signal related kinase(ERK),whereas co-incubation with the EGFR tyrosine kinase inhibitor,PD153035,blocked rhTFF2-dependent proliferation and EGFR/ERK responses.CONCLUSION:TFF mRNA/protein expression is indicative of CCA tumor progression,but not predictive for histological sub-type or survival time.TFF2 is mitogenic in CCA via EGFR/MAPK activation.展开更多
Pregnancy represents a dynamic period with physical and physiological changes in both the mother and her developing fetus. The dramatic 2-3 fold increase in the active hormone 1,25(OH)2D concentrations during the ea...Pregnancy represents a dynamic period with physical and physiological changes in both the mother and her developing fetus. The dramatic 2-3 fold increase in the active hormone 1,25(OH)2D concentrations during the early weeks of pregnancy despite minimal increased calcium demands during that time of gestation and which are sustained throughout pregnancy in both the mother and fetus suggests an immunomodulatory role in preventing fetal rejection by the mother. While there have been numerous observational studies that support the premise of vitamin D's role in maintaining maternal and fetal well-being, until recently, there have been few randomized clinical trials with vitamin D supplementation. One has to exhibit caution, however, even with RCTs, whose results can be problematic when analyzed on an intent-to-treat basis and when there is high non-adherence to protocol (as if often the case), thereby diluting the potential good or harm of a given treatment at higher doses. As such, a biomarker of a drug or in this case "vitamin" or pre-prohormone is better served. For these reasons, the effect of vitamin D therapies using the biomarker circulating 25(OH)D is a far better indicator of true "effect." When pregnancy outcomes are analyzed using the biomarker 25(OH)D instead of treatment dose, there are notable differences in maternal and fetal outcomes across diverse racial/ethnic groups, with improved health in those women who attain a circulating 25(OH)D concentration of at least 100 nmol. L-1 (40 ng. mL-1). Because ,an important issue is the timing or initiation of vitamin D treatment/supplementation, and given the potential effect of vitamin D on placental gene expression and its effects on inflammation within the placenta, it appears crucial to start vitamin D treatment before placentation (and trophoblast invasion); however, this question remains unanswered. Additional work is needed to decipher the vitamin D requirements of pregnant women and the optimal timing of supplementation, taking into account a variety of lifestyles, body types, baseline vitamin D status, and maternal and fetal vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genotypes. Determining the role of vitamin D in nonclassical, immune pathways continues to be a challenge that once answered will substantiate recommendations and public health policies.展开更多
The development of single-cell subclones,which can rapidly switch from dormant to dominant subclones,occur in the natural pathophysiology of multiple myeloma(MM)but is often"pressed"by the standard treatment...The development of single-cell subclones,which can rapidly switch from dormant to dominant subclones,occur in the natural pathophysiology of multiple myeloma(MM)but is often"pressed"by the standard treatment of MM.These emerging subclones present a challenge,providing reservoirs for chemoresistant mutations.Technological advancement is required to track MM subclonal changes,as understanding MM's mechanism of evolution at the cellular level can prompt the development of new targeted ways of treating this disease.Current methods to study the evolution of subclones in MM rely on technologies capable of phenotypically and genotypically characterizing plasma cells,which include immunohistochemistry,flow cytometry,or cytogenetics.Still,all of these technologies may be limited by the sensitivity for picking up rare events.In contrast,more incisive methods such as RNA sequencing,comparative genomic hybridization,or whole-genome sequencing are not yet commonly used in clinical practice.Here we introduce the epidemiological diagnosis and prognosis of MM and review current methods for evaluating MM subclone evolution,such as minimal residual disease/multiparametric flow cytometry/next-generation sequencing,and their respective advantages and disadvantages.In addition,we propose our new single-cell method of evaluation to understand MM's mechanism of evolution at the molecular and cellular level and to prompt the development of new targeted ways of treating this disease,which has a broad prospect.展开更多
AIM:To compare the histologic features of the liver in intrahepatic neonatal cholestasis(IHNC)with infectious,genetic-endocrine-metabolic,and idiopathic etiologies. METHODS:Liver biopsies from 86 infants with IHNC wer...AIM:To compare the histologic features of the liver in intrahepatic neonatal cholestasis(IHNC)with infectious,genetic-endocrine-metabolic,and idiopathic etiologies. METHODS:Liver biopsies from 86 infants with IHNC were evaluated.The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life.The following histologic features were evaluated:cholestasis,eosinophilia,giant cells,erythropoiesis,siderosis,portal fibrosis,and the presence of a septum. RESULTS:Based on the diagnosis,patients were classified into three groups:group 1(infectious;n=18),group 2(genetic-endocrine-metabolic;n=18),and group 3(idiopathic;n=50).There were no significant differences with respect to the following variables:cholestasis,eosinophilia,giant cells,siderosis,portalfibrosis,and presence of a septum.A significant difference was observed with respect to erythropoiesis,which was more severe in group 1(Fisher's exact test,P=0.016). CONCLUSION:A significant difference was observed in IHNC of infectious etiology,in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies,whereas there were no significant differences among cholestasis,eosinophilia,giant cells,siderosis,portal fibrosis,and the presence of a septum.展开更多
Objective:To analyze the clinical effect and value of oral administration and external therapy of traditional Chinese medicine for treatment of cervical tuberculous lymphadenopathy.Methods:A total of 56 patients with ...Objective:To analyze the clinical effect and value of oral administration and external therapy of traditional Chinese medicine for treatment of cervical tuberculous lymphadenopathy.Methods:A total of 56 patients with cervical tuberculous lymphadenopathy admitted to our hospital from January 1 to January 2018 were recruited.By using double-blind method,the patients were divided into control group(n=28)and experimental group(n=28).Control group comprised of patients with conventional anti-tuberculosis treatment,while the experimental group comprised of patients treated with oral administration and external therapy of traditional Chinese medicine.Total effective rate,incidence of complication and level of T lymphocyte subsets were compared between the two groups of cervical tuberculous lymphadenopathy patients.Results:Post-treatment data of total effective rate,complication rate,CD3+,CD4+,CD8+,CD4+/CD8+of the experimental group were compared with the control group.P<0.05;statistical analysis showed statistical significance.Post-treatment data of CD3+,CD4+,CD8+,CD4+/CD8+of both control and experimental groups were compared with pre-treatment data.P<0.05;statistical analysis showed statistical significance.Conclusion:Oral administration and external therapy of traditional Chinese medicine possesses significant effect in treatment of cervical tuberculous lymphadenopathy.展开更多
Reactive oxygen species(ROS)have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury(ALI)in adults and bronchopulmonary dysplasia(BPD)in premature infants.Bacter...Reactive oxygen species(ROS)have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury(ALI)in adults and bronchopulmonary dysplasia(BPD)in premature infants.Bacterial infection and oxygen toxicity,which result in pulmonary vascular endot belial injury,contribute to impaired vascular growth and alveolar simplfcation soen in the lungs of premature infants with BPD.Hyperoxia induces ALI,reduces cell proliferation,cauuses DNA damage and promotes cell death by causi ng mitochondrial dys function.The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto fuorescent mitochondrial metabolic coenzymes,NADH and FAD in four different groups of rats.The ratio of these fluorescence signals(NA DH/FAD),referred to as NADH redox ratio(NADH RR)has been used as an indicator of tisue metabolism in injuries.Here,we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide(LPS)exposure in neonatal mat lungs.We examined the tissue redox states of lungs from four groups of rat pups:nomoxic(21%O_(2))pups,hyperoxic(90%O_(2))pups,pups treated with LPS(normoxic+LPS),and pups treated with LPS and hyperoxia(hyperoxic+LPS).Our results show that hyperoxia oxidized the respiratory chain as reflected by a~31%docrease in lung tssue NADH RR as compared to that for normoxic lungs.LPS treatment alone or with hyperoxia had no significant ffect on lung tssue NADH RR as compared to that for normoxic or hyperoxic lungs,respectively.Thus,NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions:hyperoxia and LPS exposure.展开更多
Single nucleotide polymorphisms (SNPs) in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship ...Single nucleotide polymorphisms (SNPs) in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance (AGD), anoscrotal distance (ASD) and penile width (PW). We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families. We used DNA from buccal smears and linear regression models to assess the relationship between anogenital measurements and SNP genotypes with adjustment for covariates. We found that the rs2077647 G allele, located in the coding region of estrogen receptor alpha (ESR1), was associated with a shorter AGD (P=0.02; -7.3 mm, 95% confidence interval (CI): -11.6 to -3.1), and the rs10475 T allele, located in the 3' untranslated region of activating transcription factor 3 (ATF3), was associated with a shorter ASD (-4.3 mm, 95% Ch -7.2 to -1.4), although this result was not significant (P=0.07) after controlling for multiple comparisons. We observed no association between PW and the SNPs tested. Minor alleles for two SNPs in genes that regulate estrogen signaling during male genital development were associated with AGD and ASD, although the significance of the association was marginal. Our findings suggest that AGD and ASD are influenced by heritable factors in genes known to be associated with frank male genital abnormalities such as hvpospadias and crvotorchidism.展开更多
BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease(NAFLD)mirrors the obesity epidemic.NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis,fibrosis and cirrhosis a...BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease(NAFLD)mirrors the obesity epidemic.NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis,fibrosis and cirrhosis and/or hepatocellular carcinoma.Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.AIM To review the early developmental factors associated with NAFLD.METHODS Databases MEDLINE via PubMed,and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30,2021 were assessed.Original research studies that included risk factors associated with early development of NAFLD in human subjects were included.These factors include:Maternal factors,intrauterine and prenatal factors,post-natal factors,genetic and ethnic predisposition,childhood and adolescence environmental factors.Studies were excluded if they were review articles or animal studies,case reports or conference abstracts,or if NAFLD was not clearly defined and assessed radiologically.RESULTS Of 1530 citations identified by electronic search,420 duplicates were removed.Of the 1110 citations screened from title and abstract,80 articles were included in the final analysis.Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3(PNPLA3)and membrane-bound O-acyltransferase domain-containing protein 7(MBOAT7)were associated with increased risk of NAFLD.Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD.Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD.Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.CONCLUSION Maternal metabolic dysfunction during pregnancy,being exclusively breastfed for a longer time postnatally,diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.展开更多
Almost half of infertility cases involve male infertility.Understanding the consequence of a diagnosis of male infertility,as a sole or partial contributor to the couples'infertility,to the mental health of men is...Almost half of infertility cases involve male infertility.Understanding the consequence of a diagnosis of male infertility,as a sole or partial contributor to the couples'infertility,to the mental health of men is required to ensure clinical care meets their psychological needs.The aim of this systematic analysis was to synthesize the evidence regarding whether men diagnosed with male factor infertility experience greater psychological distress than(1)men described as fertile and(2)men in couples with other infertility diagnoses.Online databases were searched using a combination of Medical Subject Headings(MeSH)headings and keywords relating to male infertility and psychological distress.The search yielded 1016 unique publications,of which 23 were included:8 case-control,14 prospective cohort,and 1 data linkage studies.Seven aspects of psychological distress were identified depression,anxiety,self-esteem,quality of life,fertility-related stress,general psychological stress or well-being,and psychiatric conditions.Case-control studies reported that men with male factor infertility have more symptoms of depression,anxiety and general psychological distress,worse quality of some aspects of life,and lower self-esteem than controls.When men with male factor infertility were compared to men in couples with other causes of infertility,there were few differences in the assessed aspects of psychological distress.Despite methodological limitations within the studies,this systematic analysis suggests that the experience of infertility,irrespective of its cause,negatively affects men's mental health and demonstrates the need for assisted reproduction technology(ART)providers to consider men undergoing assisted reproduction as individuals with their own unique support needs.展开更多
Pathogenic variants in methyl-Cp G protein 2(MECP2;OMIM300005)result in an X-linked,severe,and progressive epigenetic disorder,Rett syndrome(RTT,OMIM:312750),that predominantly affects females(Rett,1966).Using Neul’s...Pathogenic variants in methyl-Cp G protein 2(MECP2;OMIM300005)result in an X-linked,severe,and progressive epigenetic disorder,Rett syndrome(RTT,OMIM:312750),that predominantly affects females(Rett,1966).Using Neul’s revised diagnostic criteria,affected individuals can be clinically classified as classic or atypical RTT(Neul et al.,2010).展开更多
文摘Objective:To study the application effect of psychological nursing in pediatric clinical nursing.Method:100 pediatric patients who underwent treatment in our hospital from January 2019 to December 2020 were selected as the research subjects.They were randomly divided into a control group and an observation group,with 50 cases in each group.The control group received routine nursing care,while the observation group received psychological care based on routine nursing care.The nursing compliance,incidence of adverse events,and parental satisfaction of the two groups of pediatric patients were compared and analyzed.Result:Through psychological nursing intervention,it was found that the observation group had better nursing compliance,incidence of adverse events,and parental satisfaction than the control group,P<0.05,the differences are statistically significant.Conclusion:The application of psychological nursing in pediatric clinical nursing can improve the compliance of pediatric care,reduce the incidence of adverse events,enhance parental satisfaction,and have clinical promotion and application value.
文摘The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.
文摘Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.
基金Supported by The State of So Paulo Research Foundation (Fapesp)and the Coordination for Higher Level Graduates Improvement (Capes)
文摘AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.
基金supported by the grants from South Carolina Spinal Cord Injury Research Fund(No.CIRF2017 I-01)VA award(No.RX2090)
文摘Contusion spinal cord injury(SCI)is a major medical and socio-economic problem globally.The incidence of SCI is highest among young adults due to motor vehicle accidents,military or sports injuries,and violence(Selvarajah et al.,2014).The elderly and children are also at risk due to falls and accidents.SCI causes neurodegeneration,with profound loss of locomotor and sensory functions(Siddiqui et al.,2015).Pain and depression are also prevalent in a majority of SCI patients.Expenses for severe SCI are high:initial hospitalization,rehabilitation,and most likely the continuing need for a caregiver and medical care.SCI survivors with less severe injuries usually face lower but still hefty medical bills.However,people≥50 years old with severe SCI may face medical expenses of over$1.8 million during their lifetimes.These injuries also affect spouses and family members,emotionally and financially,and most injuries jeopardize employment for those affected.
文摘Robust and efficient AUV path planning is a key element for persistence AUV maneuvering in variable underwater environments. To develop such a path planning system, in this study, differential evolution(DE) algorithm is employed. The performance of the DE-based planner in generating time-efficient paths to direct the AUV from its initial conditions to the target of interest is investigated within a complexed 3D underwater environment incorporated with turbulent current vector fields, coastal area,islands, and static/dynamic obstacles. The results of simulations indicate the inherent efficiency of the DE-based path planner as it is capable of extracting feasible areas of a real map to determine the allowed spaces for the vehicle deployment while coping undesired current disturbances, exploiting desirable currents, and avoiding collision boundaries in directing the vehicle to its destination. The results are implementable for a realistic scenario and on-board real AUV as the DE planner satisfies all vehicular and environmental constraints while minimizing the travel time/distance, in a computationally efficient manner.
文摘Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index,and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer patients achieve complete remission after chemotherapy,death still occurs due to relapse of persistent minimal residual disease(MRD) which remaining after initial cytotoxic chemotherapy. Advanced neuroblastoma(NB) is a leading cause of cancer deaths in young children. Retinoids are an important component of advanced NB therapy at the stage of MRD,yet half of all patients treated with 13-cis-retinoic acid still relapse and die. More effective combination therapies,with a lower side-effect profile,are required to improve outcomes for NB. Fenretinide or N-4-hydroxyphenyl retinamide is a synthetic derivative of retinoic acid which works on cancer cells through nuclear receptor-dependent and-independent signalling mechanisms. Moreover,several histone deacetylase inhibitors have entered early phase trials,and,suberoylanilide hydroxamic acid has been approved for use in adult cutaneous T cell lymphoma. A number of studies suggest that retinoid signal activation is necessary for histone deacetylase inhibitor activity. A better understanding of their mechanism of actions will lead to more evidence-based retinoid combination therapies.
基金Supported by The Thailand Research Fund through the Royal Golden Jubilee PhD program(grant PHD/0121/2547 code 5LKK/47/B1 to Kosriwong K and Limpaiboon T)Khon Kaen University Research Affairs(grant 48-03-1-01-03)the Centre for Research and Development of Medical Diagnostic Laboratories,Faculty of Associated Medical Sciences(No.06-01), Thailand
文摘AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction(PCR),quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA,precancerous bile duct dysplasia and from disease-free controls.The functional impact of recombinant human(rh) TFF2 peptide treatment on proliferation and epidermal growth factor receptor(EGFR) /mitogenactivated protein kinase(MAPK) signaling was assessed in the CCA cell line,KMBC,by viable cell counting and immunoblotting,respectively.RESULTS:TFF1,TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls,and was unrelated to gene copy number.TFF1 immunoreactivity was strongly increased in both dysplasia and CCA,whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls.By contrast,TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA.Kaplan-Meier analysis found no association of TFF mRNA,protein and copy number with age,gender,histological subtype,and patient survival time.Treatment of KMBC cells with rhTFF2 stimulated proliferation,triggered phosphorylation of EGFR and downstream extracellular signal related kinase(ERK),whereas co-incubation with the EGFR tyrosine kinase inhibitor,PD153035,blocked rhTFF2-dependent proliferation and EGFR/ERK responses.CONCLUSION:TFF mRNA/protein expression is indicative of CCA tumor progression,but not predictive for histological sub-type or survival time.TFF2 is mitogenic in CCA via EGFR/MAPK activation.
基金Funded in part by NIH/NICHD R01 HD043921the Thrasher Research Fund+1 种基金NIH/NCATS UL1 RR029882UL1 TR000062
文摘Pregnancy represents a dynamic period with physical and physiological changes in both the mother and her developing fetus. The dramatic 2-3 fold increase in the active hormone 1,25(OH)2D concentrations during the early weeks of pregnancy despite minimal increased calcium demands during that time of gestation and which are sustained throughout pregnancy in both the mother and fetus suggests an immunomodulatory role in preventing fetal rejection by the mother. While there have been numerous observational studies that support the premise of vitamin D's role in maintaining maternal and fetal well-being, until recently, there have been few randomized clinical trials with vitamin D supplementation. One has to exhibit caution, however, even with RCTs, whose results can be problematic when analyzed on an intent-to-treat basis and when there is high non-adherence to protocol (as if often the case), thereby diluting the potential good or harm of a given treatment at higher doses. As such, a biomarker of a drug or in this case "vitamin" or pre-prohormone is better served. For these reasons, the effect of vitamin D therapies using the biomarker circulating 25(OH)D is a far better indicator of true "effect." When pregnancy outcomes are analyzed using the biomarker 25(OH)D instead of treatment dose, there are notable differences in maternal and fetal outcomes across diverse racial/ethnic groups, with improved health in those women who attain a circulating 25(OH)D concentration of at least 100 nmol. L-1 (40 ng. mL-1). Because ,an important issue is the timing or initiation of vitamin D treatment/supplementation, and given the potential effect of vitamin D on placental gene expression and its effects on inflammation within the placenta, it appears crucial to start vitamin D treatment before placentation (and trophoblast invasion); however, this question remains unanswered. Additional work is needed to decipher the vitamin D requirements of pregnant women and the optimal timing of supplementation, taking into account a variety of lifestyles, body types, baseline vitamin D status, and maternal and fetal vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genotypes. Determining the role of vitamin D in nonclassical, immune pathways continues to be a challenge that once answered will substantiate recommendations and public health policies.
文摘The development of single-cell subclones,which can rapidly switch from dormant to dominant subclones,occur in the natural pathophysiology of multiple myeloma(MM)but is often"pressed"by the standard treatment of MM.These emerging subclones present a challenge,providing reservoirs for chemoresistant mutations.Technological advancement is required to track MM subclonal changes,as understanding MM's mechanism of evolution at the cellular level can prompt the development of new targeted ways of treating this disease.Current methods to study the evolution of subclones in MM rely on technologies capable of phenotypically and genotypically characterizing plasma cells,which include immunohistochemistry,flow cytometry,or cytogenetics.Still,all of these technologies may be limited by the sensitivity for picking up rare events.In contrast,more incisive methods such as RNA sequencing,comparative genomic hybridization,or whole-genome sequencing are not yet commonly used in clinical practice.Here we introduce the epidemiological diagnosis and prognosis of MM and review current methods for evaluating MM subclone evolution,such as minimal residual disease/multiparametric flow cytometry/next-generation sequencing,and their respective advantages and disadvantages.In addition,we propose our new single-cell method of evaluation to understand MM's mechanism of evolution at the molecular and cellular level and to prompt the development of new targeted ways of treating this disease,which has a broad prospect.
文摘AIM:To compare the histologic features of the liver in intrahepatic neonatal cholestasis(IHNC)with infectious,genetic-endocrine-metabolic,and idiopathic etiologies. METHODS:Liver biopsies from 86 infants with IHNC were evaluated.The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life.The following histologic features were evaluated:cholestasis,eosinophilia,giant cells,erythropoiesis,siderosis,portal fibrosis,and the presence of a septum. RESULTS:Based on the diagnosis,patients were classified into three groups:group 1(infectious;n=18),group 2(genetic-endocrine-metabolic;n=18),and group 3(idiopathic;n=50).There were no significant differences with respect to the following variables:cholestasis,eosinophilia,giant cells,siderosis,portalfibrosis,and presence of a septum.A significant difference was observed with respect to erythropoiesis,which was more severe in group 1(Fisher's exact test,P=0.016). CONCLUSION:A significant difference was observed in IHNC of infectious etiology,in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies,whereas there were no significant differences among cholestasis,eosinophilia,giant cells,siderosis,portal fibrosis,and the presence of a septum.
文摘Objective:To analyze the clinical effect and value of oral administration and external therapy of traditional Chinese medicine for treatment of cervical tuberculous lymphadenopathy.Methods:A total of 56 patients with cervical tuberculous lymphadenopathy admitted to our hospital from January 1 to January 2018 were recruited.By using double-blind method,the patients were divided into control group(n=28)and experimental group(n=28).Control group comprised of patients with conventional anti-tuberculosis treatment,while the experimental group comprised of patients treated with oral administration and external therapy of traditional Chinese medicine.Total effective rate,incidence of complication and level of T lymphocyte subsets were compared between the two groups of cervical tuberculous lymphadenopathy patients.Results:Post-treatment data of total effective rate,complication rate,CD3+,CD4+,CD8+,CD4+/CD8+of the experimental group were compared with the control group.P<0.05;statistical analysis showed statistical significance.Post-treatment data of CD3+,CD4+,CD8+,CD4+/CD8+of both control and experimental groups were compared with pre-treatment data.P<0.05;statistical analysis showed statistical significance.Conclusion:Oral administration and external therapy of traditional Chinese medicine possesses significant effect in treatment of cervical tuberculous lymphadenopathy.
基金We acknowledge the support of University of Wisconsin Milwaukee RGI 7 Grant,Clinical and Translational Science Institute(CTSI)KL2 Grant NIH 8Kl2TR000056 and NIH 8UL1TR000055Wisconsin Applied Research grant(Wi-ARG),grant UL1RR031973 from Clinical and Translational Science Institute and Advancing Healthier Wisconsin Foundation of Medical College of WI,Milwaukee,WI(GGK),NIH Grants 2R01 HL057268 and 1RO3 HD065841(GGK)the Department of Veterans'Affairs.
文摘Reactive oxygen species(ROS)have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury(ALI)in adults and bronchopulmonary dysplasia(BPD)in premature infants.Bacterial infection and oxygen toxicity,which result in pulmonary vascular endot belial injury,contribute to impaired vascular growth and alveolar simplfcation soen in the lungs of premature infants with BPD.Hyperoxia induces ALI,reduces cell proliferation,cauuses DNA damage and promotes cell death by causi ng mitochondrial dys function.The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto fuorescent mitochondrial metabolic coenzymes,NADH and FAD in four different groups of rats.The ratio of these fluorescence signals(NA DH/FAD),referred to as NADH redox ratio(NADH RR)has been used as an indicator of tisue metabolism in injuries.Here,we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide(LPS)exposure in neonatal mat lungs.We examined the tissue redox states of lungs from four groups of rat pups:nomoxic(21%O_(2))pups,hyperoxic(90%O_(2))pups,pups treated with LPS(normoxic+LPS),and pups treated with LPS and hyperoxia(hyperoxic+LPS).Our results show that hyperoxia oxidized the respiratory chain as reflected by a~31%docrease in lung tssue NADH RR as compared to that for normoxic lungs.LPS treatment alone or with hyperoxia had no significant ffect on lung tssue NADH RR as compared to that for normoxic or hyperoxic lungs,respectively.Thus,NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions:hyperoxia and LPS exposure.
文摘Single nucleotide polymorphisms (SNPs) in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance (AGD), anoscrotal distance (ASD) and penile width (PW). We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families. We used DNA from buccal smears and linear regression models to assess the relationship between anogenital measurements and SNP genotypes with adjustment for covariates. We found that the rs2077647 G allele, located in the coding region of estrogen receptor alpha (ESR1), was associated with a shorter AGD (P=0.02; -7.3 mm, 95% confidence interval (CI): -11.6 to -3.1), and the rs10475 T allele, located in the 3' untranslated region of activating transcription factor 3 (ATF3), was associated with a shorter ASD (-4.3 mm, 95% Ch -7.2 to -1.4), although this result was not significant (P=0.07) after controlling for multiple comparisons. We observed no association between PW and the SNPs tested. Minor alleles for two SNPs in genes that regulate estrogen signaling during male genital development were associated with AGD and ASD, although the significance of the association was marginal. Our findings suggest that AGD and ASD are influenced by heritable factors in genes known to be associated with frank male genital abnormalities such as hvpospadias and crvotorchidism.
文摘BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease(NAFLD)mirrors the obesity epidemic.NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis,fibrosis and cirrhosis and/or hepatocellular carcinoma.Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.AIM To review the early developmental factors associated with NAFLD.METHODS Databases MEDLINE via PubMed,and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30,2021 were assessed.Original research studies that included risk factors associated with early development of NAFLD in human subjects were included.These factors include:Maternal factors,intrauterine and prenatal factors,post-natal factors,genetic and ethnic predisposition,childhood and adolescence environmental factors.Studies were excluded if they were review articles or animal studies,case reports or conference abstracts,or if NAFLD was not clearly defined and assessed radiologically.RESULTS Of 1530 citations identified by electronic search,420 duplicates were removed.Of the 1110 citations screened from title and abstract,80 articles were included in the final analysis.Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3(PNPLA3)and membrane-bound O-acyltransferase domain-containing protein 7(MBOAT7)were associated with increased risk of NAFLD.Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD.Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD.Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.CONCLUSION Maternal metabolic dysfunction during pregnancy,being exclusively breastfed for a longer time postnatally,diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.
文摘Almost half of infertility cases involve male infertility.Understanding the consequence of a diagnosis of male infertility,as a sole or partial contributor to the couples'infertility,to the mental health of men is required to ensure clinical care meets their psychological needs.The aim of this systematic analysis was to synthesize the evidence regarding whether men diagnosed with male factor infertility experience greater psychological distress than(1)men described as fertile and(2)men in couples with other infertility diagnoses.Online databases were searched using a combination of Medical Subject Headings(MeSH)headings and keywords relating to male infertility and psychological distress.The search yielded 1016 unique publications,of which 23 were included:8 case-control,14 prospective cohort,and 1 data linkage studies.Seven aspects of psychological distress were identified depression,anxiety,self-esteem,quality of life,fertility-related stress,general psychological stress or well-being,and psychiatric conditions.Case-control studies reported that men with male factor infertility have more symptoms of depression,anxiety and general psychological distress,worse quality of some aspects of life,and lower self-esteem than controls.When men with male factor infertility were compared to men in couples with other causes of infertility,there were few differences in the assessed aspects of psychological distress.Despite methodological limitations within the studies,this systematic analysis suggests that the experience of infertility,irrespective of its cause,negatively affects men's mental health and demonstrates the need for assisted reproduction technology(ART)providers to consider men undergoing assisted reproduction as individuals with their own unique support needs.
基金supported by the Victorian Government’s Operational Infrastructure Support ProgramResearch Training Program scholarship(to S.K.)+2 种基金supported by Italian Ministry of Health Young Investigator(GR-2011-02347754 to E.L.)Fondazione Istituto di Ricerca PediatricaeCittàdella Speranza(18-04 to E.L.)supported by the Australian NHMRC Centre of Research Excellence in Speech and Language Neurobiology(CRE-SLANG)(1116976)
文摘Pathogenic variants in methyl-Cp G protein 2(MECP2;OMIM300005)result in an X-linked,severe,and progressive epigenetic disorder,Rett syndrome(RTT,OMIM:312750),that predominantly affects females(Rett,1966).Using Neul’s revised diagnostic criteria,affected individuals can be clinically classified as classic or atypical RTT(Neul et al.,2010).