BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-C...BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-CD4 antibody,Teplizumab,has been shown to delay the progression of DM1 and is the only medication approved for this indication.However,more information is needed about the safety profile of this drug.AIM To identify the odds ratios(OR)of systems-based adverse effects for Teplizumab when compared to Placebo.METHODS An extensive systematic review was conducted from the inception of the medication until December 31,2023.All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review.The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO(ID:CRD42024496169).Crude OR were generated using RevMan Software version 5.4.RESULTS After screening and review,5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo.A total of 561 patients were included in the study population.Total adverse effects and system-based adverse effects were studied and reported.We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal(GI)(OR=1.60,95%CI:1.01-2.52,P=0.04),dermatological(OR=6.33,95%CI:4.05-9.88,P<0.00001)and hematological adverse effects(OR=19.03,95%CI:11.09-32.66,P<0.00001).These patients were also significantly likely to have active Epstein-Barr Virus infection(OR=3.16,95%CI:1.51-6.64,P<0.002).While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo,this finding did not reach statistical significance(OR=2.25,95%CI:0.80-6.29,P=0.12).CONCLUSION Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects,primarily related to GI,dermatological,and hematological systems.The total adverse effect data is limited as study populations are small.More studies should be conducted on this medication to better inform the target population of potential adverse effects.展开更多
BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGL...BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.AIM To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.METHODS The systematic review was conducted according to PRISMA recommendations.The protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment.Effect modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering medications.For instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar cardiovascular benefits were not observed in those with myocardial infarction(MI)[9,10].Cardiovascular co-morbidities are not only approximately twice as common but are also associated with dispropor-tionately worse cardiovascular outcomes in patients with T2D,compared to the general population[11].Therefore,it is of clinical importance to investigate whether the combination treatment of GLP-1RA and SGLT-2I could achieve greater cardiovascular benefit,particularly when considering patients with cardiovascular co-morbidities who may not gain sufficient cardiovascular protection from the monotherapies.This systematic review with multiple network meta-regressions was mainly aimed to explore whether combining GLP-1RA and SGLT-2I can provide additional cardiovascular benefit in T2D.Cardiovascular outcomes of these newer antidiabetic medications were also estimated under effect modification of prior cardiovascular diseases.This was to provide clinical insight as to when the combination treatment might be prioritized.展开更多
BACKGROUND Acute leukemia in newborns is also known as neonatal or congenital leukemia(CL)and is a rare disease with an incidence rate of 1-5 per 1000000 live births.After birth,infants with CL exhibit infiltrative cu...BACKGROUND Acute leukemia in newborns is also known as neonatal or congenital leukemia(CL)and is a rare disease with an incidence rate of 1-5 per 1000000 live births.After birth,infants with CL exhibit infiltrative cutaneous nodules,hepatosplenomegaly,thrombocytopenia,and immature leukocytes in the peripheral blood.These symptoms are frequently accompanied by congenital abnormalities including trisomy 21,trisomy 9,trisomy 13,or Turner syndrome.Despite significant advances in disease management,the survival rate is approximately 25%at 2 years.CASE SUMMARY Here,we document a case of trisomy 21-related acute myeloid leukemia(AML)in a female neonate.The baby was sent to the neonatal intensive care unit because of anorexia,poor responsiveness,and respiratory distress.She was diagnosed with AML based on bone marrow aspiration and immunophenotyping.Genetic sequencing identified a mutation in the GATA1 gene.After receiving the diagnosis,the parents decided against medical care for their child,and the baby died at home on day 9 after birth.CONCLUSIONS The newborn infant was diagnosed with trisomy 21-related AML.Genetic sequencing identified a mutation in the GATA1 gene.The parents abandoned medical treatment for their infant after receiving the diagnosis,and the infant died at home on the 9th day after birth.展开更多
BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–b...BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.展开更多
BACKGROUND Lymph node metastasis(LNM)affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma(ESCC).However,reports of the risk factors for LNM have been controversial.AIM ...BACKGROUND Lymph node metastasis(LNM)affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma(ESCC).However,reports of the risk factors for LNM have been controversial.AIM To evaluate risk factors for LNM in T1 ESCC.METHODS We searched Embase,PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC.Included studies were divided into LNM and non-LNM groups.We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features.Odds ratio(OR),mean differences and 95%confidence interval(CI)were assessed using a fixed-effects or randomeffects model.RESULTS Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria.After excluding studies with heterogeneity based on influence analysis,tumor size(OR=1.93,95%CI=1.49-2.50,P<0.001),tumor location(OR=1.46,95%CI=1.17-1.82,P<0.001),macroscopic type(OR=3.17,95%CI=2.33-4.31,P<0.001),T1 substage(OR=6.28,95%CI=4.93-8.00,P<0.001),differentiation(OR=2.11,95%CI=1.64-2.72,P<0.001)and lymphovascular invasion(OR=5.86,95%CI=4.60-7.48,P<0.001)were found to be significantly associated with LNM.Conversely,sex,age and infiltrative growth pattern were not identified as risk factors for LNM.CONCLUSION A tumor size>2 cm,lower location,nonflat macroscopic type,T1b stage,poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.展开更多
Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature t...Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question;2) literature collection based on a parallel search strategy;3) relevant study selection based on search refinement;4) molecular pathway identification;and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis;b) the methylation cycle;and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.展开更多
Hepatocellular carcinoma(HCC)represents the primary carcinoma of the liver and the fourth leading cause of cancer-related deaths.The World Health Organization estimates an increase in cases in the coming years.The ris...Hepatocellular carcinoma(HCC)represents the primary carcinoma of the liver and the fourth leading cause of cancer-related deaths.The World Health Organization estimates an increase in cases in the coming years.The risk factors of HCC are multiple,and the incidence in different countries is closely related to the different risk factors to which the population is exposed.The molecular mechanisms that drive HCC tumorigenesis are extremely complex,but understanding this multistep process is essential for the identification of diagnostic,prognostic,and therapeutic markers.The development of multigenic nextgeneration sequencing panels through the parallel analysis of multiple markers can provide a landscape of the genomic status of the tumor.Considering the literature and our preliminary data based on 36 HCCs,the most frequently altered genes in HCCs are TERT,CTNNB1,and TP53.Over the years,many groups have attempted to classify HCCs on a molecular basis,but a univocal classification has never been achieved.Nevertheless,statistically significant correlations have been found in HCCs between the molecular signature and morphologic features,and this leads us to think that it would be desirable to integrate the approach between anatomic pathology and molecular laboratories.展开更多
In this review a five-membered heterocyclic ring having two adjacent nitrogen atoms known as Pyrazole, we have framed 5-amino-N-substituted pyrazoles in particular focusing on its substantial role as a building block ...In this review a five-membered heterocyclic ring having two adjacent nitrogen atoms known as Pyrazole, we have framed 5-amino-N-substituted pyrazoles in particular focusing on its substantial role as a building block and starting materials for producing enormous heterocyclic skeletons. The existence of this moiety in larger compounds renders them to expose medicinal, pharmacological and biological therapeutic activities. Enormous drugs contain 5-amino-N-substituted pyrazoles such as celecoxib anti-inflammatory, antipsychotic, anti-obesity, analgesic, and antidepressant. We reported various routes of synthesis and the use of these compounds.展开更多
BACKGROUND An inconclusive result from BRCA1/2 genetic testing indicates that a genetic variant of uncertain significance is detected.This case constitutes the majority of genetic test results,but studies specifically...BACKGROUND An inconclusive result from BRCA1/2 genetic testing indicates that a genetic variant of uncertain significance is detected.This case constitutes the majority of genetic test results,but studies specifically addressing the psychological adjustment of people with inconclusive results are scarce.AIM To examine psychological outcomes of receiving an uninformative BRCA1/2 test result.METHODS PubMed,PsychInfo,and Cochrane Central Register of Controlled Trials were screened for studies focusing on distress,anxiety,and depression levels in individuals with inconclusive genetic test results.This review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method.RESULTS Studies on psychological outcomes of inconclusive BRCA1/2 focused on general and specific distress,anxiety,and depression.Overall,they produced mixed results.These inconsistent findings are probably due to the uncertainty caused by this type of result,that may also influence the decisions of individuals about surveillance and prophylactic options,reducing their compliance.In addition,this review highlights specific risk and protective factors that affect psychological adjustment in individuals with an inconclusive genetic testing result.CONCLUSION Individuals with inconclusive genetic test results need specific educational programs and support to better understand the meaning of their results in order to be able to make decisions about surveillance and prophylactic options.展开更多
Published by The WJG Press and Elsevier Inc.,PO Box 23451 Beijing 100023,China Fax:+86-(0)10-85381893 E-mail:wjg@wjgnet.com http://www.wjgnet.com The World Journal of Gastroenterology Editorial Board consists of 5...Published by The WJG Press and Elsevier Inc.,PO Box 23451 Beijing 100023,China Fax:+86-(0)10-85381893 E-mail:wjg@wjgnet.com http://www.wjgnet.com The World Journal of Gastroenterology Editorial Board consists of 519 members,representing a team of worldwide experts in gastroenterology and hepatology.They are from 51 countries,including Albania(1),Algeria(1),Argentina(1),Australia(8), Austria(5),Belarus(1),Belgium(6),Brazil(1),Bulgaria(1),Canada(7),China(50),Costa Rica(1),Croatia(1),Denmark(6), Egypt(1),Finland(1),France(18),Germany(35),Greece(2),Hungary(2),Iceland(1),India(5),Iran(1),Ireland(1),Israel(2),Italy(41),Japan(132),Lithuania(1),Macedonia(1),Malaysia(3),Monaco(1),Netherlands(13),Norway(2),Pakistan(1),Philippines(1),Poland(2),Portugal(1),Russia(3),Singapore(2),Slovakia(1),South Africa(2),South Korea(6),Spain(20), Sri Lanka(1),Swaziland(1),Sweden(4),Switzerland(4),Turkey(3),United Kingdom(20),United States(90),Yugoslavia(1). HONORARY EDITORS-IN-CHIEF Ke-Ji Chen,Professor Xiyuan Hospital,Chinese Tranditional Medicine University,Beijing 100091,China. kjchen@public.bta.net.展开更多
BACKGROUND Type 1 diabetes(DT1)in adolescents brings behavioural changes,altered nutritional habits,and eating disorders.AIM To identify and analyze the validated instruments that examine the disordered eating behavio...BACKGROUND Type 1 diabetes(DT1)in adolescents brings behavioural changes,altered nutritional habits,and eating disorders.AIM To identify and analyze the validated instruments that examine the disordered eating behaviour and eating disorders among adolescents with DT1.METHODS An integrative review was accomplished based on the following databases:PubMed,LILACS,CINAHL,Scopus,Web of Science,and Reference Citation Analysis(RCA),including publications in Portuguese,English,or Spanish,without time limit and time published.RESULTS The main instruments to evaluate disordered eating behaviour were The Diabetes Eating Problem Survey-Revised,The Diabetes Eating Problem Survey,and the eating attitudes test-26,and for eating disorders the main instruments used were The Bulimic Investigation Test of Edinburgh,The Binge Eating Scale,The Child Eating Disorder Examination,The five questions of the(Sick,Control,One,Fat and Food),and The Mind Youth Questionnaire.These instruments showed an effect in evaluating risks regarding nutritional habits or feeding grievances,with outcomes related to weight control,inadequate use of insulin,and glycaemia unmanageability.We did not identify publication bias.CONCLUSION Around the world,the most used scale to study the risk of disordered eating behaviour or eating disorder is The Diabetes Eating Problem Survey-Revised.International researchers use this scale to identify high scores in adolescents with DT1 and a relationship with poorer glycemic control and psychological problems related to body image.展开更多
Objective:To systematically evaluate the clinical efficacy of traditional Chinese medicine(TCM)in auxiliary treatment of grade 1 hypertension.Methods:The China National Knowledge Infrastructure,Wan Fang Data,VIP,PubMe...Objective:To systematically evaluate the clinical efficacy of traditional Chinese medicine(TCM)in auxiliary treatment of grade 1 hypertension.Methods:The China National Knowledge Infrastructure,Wan Fang Data,VIP,PubMed were searched to screen the literature of randomized controlled trials of TCM or non-drug therapies assisting conventional medicine to treat grade 1 hypertension.The search time was from the establishment of the database to October 1,2020.Revman5.3 was used for meta-analysis.Results:8 Chinese literatures were included.The results of the study showed that 24h diastolic blood pressure(DBP),24h systolic blood pressure(SBP),DBP lowering effect and TCM syndrome curative efficacy of the experimental group using TCM was better than that of the control group.However,TCM combined conventional medicine did not show an advantage on SBP lowering effect,antihypertensive efficacy rate and total clinical efficacy rate.Conclusion:TCM has a significant effect on lowering blood pressure for adjuvant treatment of grade 1 hypertension and can significantly improve clinical symptoms.展开更多
Background:Lung cancer is the leading cause of cancer-related death,and non-small-cell lung cancer(NSCLC)is the predominant subtype.Programmed death 1(PD-1)and programmed death-ligand 1(PD-L1)inhibitors are widely use...Background:Lung cancer is the leading cause of cancer-related death,and non-small-cell lung cancer(NSCLC)is the predominant subtype.Programmed death 1(PD-1)and programmed death-ligand 1(PD-L1)inhibitors are widely used to treat stage IV NSCLC.This study systematically reviewed the literature to clarify the impact of PD1/PD-L1 inhibitor treatment on the survival of patients with stage Ⅲ NSCLC.Methods:Randomized phase Ⅲ clinical trials of PD-1/PD-L1 inhibitors administered to patients with stage Ⅲ NSCLC that were written in English and published between November 2012 and November 2022 were eligible for review.The sources of information were the MEDLINE database(last consulted on December 26,2022),ScienceDirect website(last consulted on December 26,2022),and CENTRAL register(last consulted on December 27,2022).The outcomes of interest were overall survival(OS),progression-free survival(PFS),disease-free survival(DFS),and event-free survival(EFS).Risk of bias assessments were performed according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.The findings have been assessed for certainty according to the Grading of Recommendations,Assessment,Development,and Evaluations(GRADE)guidelines.Results:Fourteen eligible studies and 2788 participants were included in the review.The key characteristics used to group the participants were disease histology,percentage of PD-L1 expression in cancer cells,and timeline of therapy.OS and PFS were improved(risk ratio[RR]:0.85;95%confidence interval[CI]:0.75–0.96 and RR:0.75;95%CI:0.70–0.86,respectively)based on the use of PD-L1 inhibitors after chemoradiation and OS was improved using first-line PD-1 inhibitors plus chemotherapy in non-squamous NSCLC(RR:0.40;95%CI:0.17–0.95),with the GRADE results indicating moderate quality of evidence.展开更多
On May 21,2023,the Macao Science Satellite-1B(MSS-1B),a low-inclination,low-latitude,and high-precision scientific exploration satellite for geomagnetic fields and space environments,was successfully launched.The sola...On May 21,2023,the Macao Science Satellite-1B(MSS-1B),a low-inclination,low-latitude,and high-precision scientific exploration satellite for geomagnetic fields and space environments,was successfully launched.The solar X-ray detector(SXD),one of the two major scientific payloads onboard the MSS-1B,has obtained a large amount of solar X-ray radiation data,which reveals the distribution law of the magnetic field in the low Earth orbit,as well as the coupling law of the Earth's magnetic field and the solar radiation and energy particle distributions.First,the overall design of the multi-detection-unit,broad-energy-range,small-volume,and low-power SXD was implemented to achieve the scientific objectives of the mission.Second,the technical indicators of the instrument were decomposed into various components,and the key technologies,such as collimator,processing circuit,thermal,and payload dataset designs,were reviewed.Third,the backgrounds,including electronic noise,cosmic diffuse X-ray background,and high-energy background in the Earth's radiation belts in and out of the field of view,were analyzed for the instrument.Then,the ground calibrations of the energy response,detection efficiency,and temperature-dependent peak drift of the SXD flight model were conducted.Finally,the in-orbit temperature,energy spectrum data,background,and solar flare process observation of the instrument in the in-orbit test stage are presented,verifying the instrument design,analysis,and ground calibration,providing a foundation for obtaining accurate solar X-ray radiation data,and achieving the scientific objectives of the satellite.展开更多
文摘BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-CD4 antibody,Teplizumab,has been shown to delay the progression of DM1 and is the only medication approved for this indication.However,more information is needed about the safety profile of this drug.AIM To identify the odds ratios(OR)of systems-based adverse effects for Teplizumab when compared to Placebo.METHODS An extensive systematic review was conducted from the inception of the medication until December 31,2023.All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review.The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO(ID:CRD42024496169).Crude OR were generated using RevMan Software version 5.4.RESULTS After screening and review,5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo.A total of 561 patients were included in the study population.Total adverse effects and system-based adverse effects were studied and reported.We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal(GI)(OR=1.60,95%CI:1.01-2.52,P=0.04),dermatological(OR=6.33,95%CI:4.05-9.88,P<0.00001)and hematological adverse effects(OR=19.03,95%CI:11.09-32.66,P<0.00001).These patients were also significantly likely to have active Epstein-Barr Virus infection(OR=3.16,95%CI:1.51-6.64,P<0.002).While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo,this finding did not reach statistical significance(OR=2.25,95%CI:0.80-6.29,P=0.12).CONCLUSION Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects,primarily related to GI,dermatological,and hematological systems.The total adverse effect data is limited as study populations are small.More studies should be conducted on this medication to better inform the target population of potential adverse effects.
基金Supported by China Scholarship Council,No.202006920018Key Talent Program for Medical Applications of Nuclear Technology,No.XKTJ-HRC2021007+2 种基金the Second Affiliated Hospital of Soochow University,No.SDFEYBS1815 and No.SDFEYBS2008National Natural Science Foundation of China,No.82170831The Jiangsu Innovation&Career Fund for PhD 2019.
文摘BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.AIM To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.METHODS The systematic review was conducted according to PRISMA recommendations.The protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment.Effect modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering medications.For instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar cardiovascular benefits were not observed in those with myocardial infarction(MI)[9,10].Cardiovascular co-morbidities are not only approximately twice as common but are also associated with dispropor-tionately worse cardiovascular outcomes in patients with T2D,compared to the general population[11].Therefore,it is of clinical importance to investigate whether the combination treatment of GLP-1RA and SGLT-2I could achieve greater cardiovascular benefit,particularly when considering patients with cardiovascular co-morbidities who may not gain sufficient cardiovascular protection from the monotherapies.This systematic review with multiple network meta-regressions was mainly aimed to explore whether combining GLP-1RA and SGLT-2I can provide additional cardiovascular benefit in T2D.Cardiovascular outcomes of these newer antidiabetic medications were also estimated under effect modification of prior cardiovascular diseases.This was to provide clinical insight as to when the combination treatment might be prioritized.
基金Supported by Project of Regional Science Foundation of National Natural Science Foundation,No.82060033Project of Scientific and Technological Innovation Talent Team in Guizhou Province,No.CXTD[2021]002.
文摘BACKGROUND Acute leukemia in newborns is also known as neonatal or congenital leukemia(CL)and is a rare disease with an incidence rate of 1-5 per 1000000 live births.After birth,infants with CL exhibit infiltrative cutaneous nodules,hepatosplenomegaly,thrombocytopenia,and immature leukocytes in the peripheral blood.These symptoms are frequently accompanied by congenital abnormalities including trisomy 21,trisomy 9,trisomy 13,or Turner syndrome.Despite significant advances in disease management,the survival rate is approximately 25%at 2 years.CASE SUMMARY Here,we document a case of trisomy 21-related acute myeloid leukemia(AML)in a female neonate.The baby was sent to the neonatal intensive care unit because of anorexia,poor responsiveness,and respiratory distress.She was diagnosed with AML based on bone marrow aspiration and immunophenotyping.Genetic sequencing identified a mutation in the GATA1 gene.After receiving the diagnosis,the parents decided against medical care for their child,and the baby died at home on day 9 after birth.CONCLUSIONS The newborn infant was diagnosed with trisomy 21-related AML.Genetic sequencing identified a mutation in the GATA1 gene.The parents abandoned medical treatment for their infant after receiving the diagnosis,and the infant died at home on the 9th day after birth.
基金the Nazarbayev University Faculty Development Competitive Research Grant 2020-2022,No.240919FD3912.
文摘BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.
文摘BACKGROUND Lymph node metastasis(LNM)affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma(ESCC).However,reports of the risk factors for LNM have been controversial.AIM To evaluate risk factors for LNM in T1 ESCC.METHODS We searched Embase,PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC.Included studies were divided into LNM and non-LNM groups.We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features.Odds ratio(OR),mean differences and 95%confidence interval(CI)were assessed using a fixed-effects or randomeffects model.RESULTS Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria.After excluding studies with heterogeneity based on influence analysis,tumor size(OR=1.93,95%CI=1.49-2.50,P<0.001),tumor location(OR=1.46,95%CI=1.17-1.82,P<0.001),macroscopic type(OR=3.17,95%CI=2.33-4.31,P<0.001),T1 substage(OR=6.28,95%CI=4.93-8.00,P<0.001),differentiation(OR=2.11,95%CI=1.64-2.72,P<0.001)and lymphovascular invasion(OR=5.86,95%CI=4.60-7.48,P<0.001)were found to be significantly associated with LNM.Conversely,sex,age and infiltrative growth pattern were not identified as risk factors for LNM.CONCLUSION A tumor size>2 cm,lower location,nonflat macroscopic type,T1b stage,poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.
文摘Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question;2) literature collection based on a parallel search strategy;3) relevant study selection based on search refinement;4) molecular pathway identification;and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis;b) the methylation cycle;and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.
文摘Hepatocellular carcinoma(HCC)represents the primary carcinoma of the liver and the fourth leading cause of cancer-related deaths.The World Health Organization estimates an increase in cases in the coming years.The risk factors of HCC are multiple,and the incidence in different countries is closely related to the different risk factors to which the population is exposed.The molecular mechanisms that drive HCC tumorigenesis are extremely complex,but understanding this multistep process is essential for the identification of diagnostic,prognostic,and therapeutic markers.The development of multigenic nextgeneration sequencing panels through the parallel analysis of multiple markers can provide a landscape of the genomic status of the tumor.Considering the literature and our preliminary data based on 36 HCCs,the most frequently altered genes in HCCs are TERT,CTNNB1,and TP53.Over the years,many groups have attempted to classify HCCs on a molecular basis,but a univocal classification has never been achieved.Nevertheless,statistically significant correlations have been found in HCCs between the molecular signature and morphologic features,and this leads us to think that it would be desirable to integrate the approach between anatomic pathology and molecular laboratories.
文摘In this review a five-membered heterocyclic ring having two adjacent nitrogen atoms known as Pyrazole, we have framed 5-amino-N-substituted pyrazoles in particular focusing on its substantial role as a building block and starting materials for producing enormous heterocyclic skeletons. The existence of this moiety in larger compounds renders them to expose medicinal, pharmacological and biological therapeutic activities. Enormous drugs contain 5-amino-N-substituted pyrazoles such as celecoxib anti-inflammatory, antipsychotic, anti-obesity, analgesic, and antidepressant. We reported various routes of synthesis and the use of these compounds.
文摘BACKGROUND An inconclusive result from BRCA1/2 genetic testing indicates that a genetic variant of uncertain significance is detected.This case constitutes the majority of genetic test results,but studies specifically addressing the psychological adjustment of people with inconclusive results are scarce.AIM To examine psychological outcomes of receiving an uninformative BRCA1/2 test result.METHODS PubMed,PsychInfo,and Cochrane Central Register of Controlled Trials were screened for studies focusing on distress,anxiety,and depression levels in individuals with inconclusive genetic test results.This review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method.RESULTS Studies on psychological outcomes of inconclusive BRCA1/2 focused on general and specific distress,anxiety,and depression.Overall,they produced mixed results.These inconsistent findings are probably due to the uncertainty caused by this type of result,that may also influence the decisions of individuals about surveillance and prophylactic options,reducing their compliance.In addition,this review highlights specific risk and protective factors that affect psychological adjustment in individuals with an inconclusive genetic testing result.CONCLUSION Individuals with inconclusive genetic test results need specific educational programs and support to better understand the meaning of their results in order to be able to make decisions about surveillance and prophylactic options.
文摘Published by The WJG Press and Elsevier Inc.,PO Box 23451 Beijing 100023,China Fax:+86-(0)10-85381893 E-mail:wjg@wjgnet.com http://www.wjgnet.com The World Journal of Gastroenterology Editorial Board consists of 519 members,representing a team of worldwide experts in gastroenterology and hepatology.They are from 51 countries,including Albania(1),Algeria(1),Argentina(1),Australia(8), Austria(5),Belarus(1),Belgium(6),Brazil(1),Bulgaria(1),Canada(7),China(50),Costa Rica(1),Croatia(1),Denmark(6), Egypt(1),Finland(1),France(18),Germany(35),Greece(2),Hungary(2),Iceland(1),India(5),Iran(1),Ireland(1),Israel(2),Italy(41),Japan(132),Lithuania(1),Macedonia(1),Malaysia(3),Monaco(1),Netherlands(13),Norway(2),Pakistan(1),Philippines(1),Poland(2),Portugal(1),Russia(3),Singapore(2),Slovakia(1),South Africa(2),South Korea(6),Spain(20), Sri Lanka(1),Swaziland(1),Sweden(4),Switzerland(4),Turkey(3),United Kingdom(20),United States(90),Yugoslavia(1). HONORARY EDITORS-IN-CHIEF Ke-Ji Chen,Professor Xiyuan Hospital,Chinese Tranditional Medicine University,Beijing 100091,China. kjchen@public.bta.net.
文摘BACKGROUND Type 1 diabetes(DT1)in adolescents brings behavioural changes,altered nutritional habits,and eating disorders.AIM To identify and analyze the validated instruments that examine the disordered eating behaviour and eating disorders among adolescents with DT1.METHODS An integrative review was accomplished based on the following databases:PubMed,LILACS,CINAHL,Scopus,Web of Science,and Reference Citation Analysis(RCA),including publications in Portuguese,English,or Spanish,without time limit and time published.RESULTS The main instruments to evaluate disordered eating behaviour were The Diabetes Eating Problem Survey-Revised,The Diabetes Eating Problem Survey,and the eating attitudes test-26,and for eating disorders the main instruments used were The Bulimic Investigation Test of Edinburgh,The Binge Eating Scale,The Child Eating Disorder Examination,The five questions of the(Sick,Control,One,Fat and Food),and The Mind Youth Questionnaire.These instruments showed an effect in evaluating risks regarding nutritional habits or feeding grievances,with outcomes related to weight control,inadequate use of insulin,and glycaemia unmanageability.We did not identify publication bias.CONCLUSION Around the world,the most used scale to study the risk of disordered eating behaviour or eating disorder is The Diabetes Eating Problem Survey-Revised.International researchers use this scale to identify high scores in adolescents with DT1 and a relationship with poorer glycemic control and psychological problems related to body image.
文摘Objective:To systematically evaluate the clinical efficacy of traditional Chinese medicine(TCM)in auxiliary treatment of grade 1 hypertension.Methods:The China National Knowledge Infrastructure,Wan Fang Data,VIP,PubMed were searched to screen the literature of randomized controlled trials of TCM or non-drug therapies assisting conventional medicine to treat grade 1 hypertension.The search time was from the establishment of the database to October 1,2020.Revman5.3 was used for meta-analysis.Results:8 Chinese literatures were included.The results of the study showed that 24h diastolic blood pressure(DBP),24h systolic blood pressure(SBP),DBP lowering effect and TCM syndrome curative efficacy of the experimental group using TCM was better than that of the control group.However,TCM combined conventional medicine did not show an advantage on SBP lowering effect,antihypertensive efficacy rate and total clinical efficacy rate.Conclusion:TCM has a significant effect on lowering blood pressure for adjuvant treatment of grade 1 hypertension and can significantly improve clinical symptoms.
文摘Background:Lung cancer is the leading cause of cancer-related death,and non-small-cell lung cancer(NSCLC)is the predominant subtype.Programmed death 1(PD-1)and programmed death-ligand 1(PD-L1)inhibitors are widely used to treat stage IV NSCLC.This study systematically reviewed the literature to clarify the impact of PD1/PD-L1 inhibitor treatment on the survival of patients with stage Ⅲ NSCLC.Methods:Randomized phase Ⅲ clinical trials of PD-1/PD-L1 inhibitors administered to patients with stage Ⅲ NSCLC that were written in English and published between November 2012 and November 2022 were eligible for review.The sources of information were the MEDLINE database(last consulted on December 26,2022),ScienceDirect website(last consulted on December 26,2022),and CENTRAL register(last consulted on December 27,2022).The outcomes of interest were overall survival(OS),progression-free survival(PFS),disease-free survival(DFS),and event-free survival(EFS).Risk of bias assessments were performed according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.The findings have been assessed for certainty according to the Grading of Recommendations,Assessment,Development,and Evaluations(GRADE)guidelines.Results:Fourteen eligible studies and 2788 participants were included in the review.The key characteristics used to group the participants were disease histology,percentage of PD-L1 expression in cancer cells,and timeline of therapy.OS and PFS were improved(risk ratio[RR]:0.85;95%confidence interval[CI]:0.75–0.96 and RR:0.75;95%CI:0.70–0.86,respectively)based on the use of PD-L1 inhibitors after chemoradiation and OS was improved using first-line PD-1 inhibitors plus chemotherapy in non-squamous NSCLC(RR:0.40;95%CI:0.17–0.95),with the GRADE results indicating moderate quality of evidence.
基金supported by the National Natural Science Foundation of China(Grant No.42327802)the National Key R&D Program of China(Grant No.2022YFF0708100)。
文摘On May 21,2023,the Macao Science Satellite-1B(MSS-1B),a low-inclination,low-latitude,and high-precision scientific exploration satellite for geomagnetic fields and space environments,was successfully launched.The solar X-ray detector(SXD),one of the two major scientific payloads onboard the MSS-1B,has obtained a large amount of solar X-ray radiation data,which reveals the distribution law of the magnetic field in the low Earth orbit,as well as the coupling law of the Earth's magnetic field and the solar radiation and energy particle distributions.First,the overall design of the multi-detection-unit,broad-energy-range,small-volume,and low-power SXD was implemented to achieve the scientific objectives of the mission.Second,the technical indicators of the instrument were decomposed into various components,and the key technologies,such as collimator,processing circuit,thermal,and payload dataset designs,were reviewed.Third,the backgrounds,including electronic noise,cosmic diffuse X-ray background,and high-energy background in the Earth's radiation belts in and out of the field of view,were analyzed for the instrument.Then,the ground calibrations of the energy response,detection efficiency,and temperature-dependent peak drift of the SXD flight model were conducted.Finally,the in-orbit temperature,energy spectrum data,background,and solar flare process observation of the instrument in the in-orbit test stage are presented,verifying the instrument design,analysis,and ground calibration,providing a foundation for obtaining accurate solar X-ray radiation data,and achieving the scientific objectives of the satellite.