Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus:A pilot bioinformatics study

BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Quantitative effect of kerogen type on the hydrocarbon generation potential of Paleogene lacustrine source rocks,Liaohe Western Depression,China

Kerogen types exert a decisive effect on the onset and capacity of hydrocarbon generation of source rocks.Lacustrine source rocks in the Liaohe Western Depression are characterized by thick deposition,high total organic carbon(TOC)content,various kerogen types,and a wide range of thermal maturity.Consequently,their hydrocarbon generation potential and resource estimation can be misinterpreted.In this study,geochemical tests,numerical analysis,hydrocarbon generation kinetics,and basin modeling were integrated to investigate the differential effects of kerogen types on the hydrocarbon generation potential of lacustrine source rocks.Optimized hydrocarbon generation and expulsion(HGE)models of different kerogen types were established quantitatively upon abundant Rock-Eval/TOC/vitrinite reflectance(R_(o))datasets.Three sets of good-excellent source rocks deposited in the fourth(Es4),third(Es3),and first(Es1)members of Paleogene Shahejie Formation,are predominantly types I-II_(1),II_(1)-II_(2),and II-III,respectively.The activation energy of types I-II_(2)kerogen is concentrated(180-230 kcal/mol),whereas that of type III kerogen is widely distributed(150-280 kcal/mol).The original hydrocarbon generation potentials of types I,II_(1),II_(2),and III kerogens are 790,510,270,and 85 mg/g TOC,respectively.The Ro values of the hydrocarbon generation threshold for type I-III source rocks gradually increase from 0.42%to 0.74%,and Ro values of the hydrocarbon expulsion threshold increase from 0.49%to 0.87%.Types I and II_(1)source rocks are characterized by earlier hydrocarbon generation,more rapid hydrocarbon expulsion,and narrower hydrocarbon generation windows than types II_(2)and III source rocks.The kerogen types also affect the HGE history and resource potential.Three types(conventional,tight,and shale oil/gas)and three levels(realistic,expected,and prospective)of hydrocarbon resources of different members in the Liaohe Western Depression are evaluated.Findings suggest that the Es3 member has considerable conventional and unconventional hydrocarbon resources.This study can quantitatively characterize the hydrocarbon generation potential of source rocks with different kerogen types,and facilitate a quick and accurate assessment of hydrocarbon resources,providing strategies for future oil and gas exploration.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.

GENERALIZED FORELLI-RUDIN TYPE OPERATORS BETWEEN SEVERAL FUNCTION SPACES ON THE UNIT BALL OF C^(N)

In this paper,we investigate sufficient and necessary conditions such that generalized Forelli-Rudin type operators T_(λ,τ,k),S_(λ,τ,k),Q_(λ,τ,k)and R_(λ,τ,k)are bounded between Lebesgue type spaces.In order to prove the main results,we first give some bidirectional estimates for several typical integrals.

NORMALIZED SOLUTIONS FOR THE GENERAL KIRCHHOFF TYPE EQUATIONS

In the present paper,we prove the existence,non-existence and multiplicity of positive normalized solutions(λ_(c),u_(c))∈R×H^(1)(R^(N))to the general Kirchhoff problem-M■,satisfying the normalization constraint f_(R)^N u^2dx=c,where M∈C([0,∞))is a given function satisfying some suitable assumptions.Our argument is not by the classical variational method,but by a global branch approach developed by Jeanjean et al.[J Math Pures Appl,2024,183:44–75]and a direct correspondence,so we can handle in a unified way the nonlinearities g(s),which are either mass subcritical,mass critical or mass supercritical.

Platelet indices as predictors of poor glucoregulation in type 2 diabetes mellitus adults at Bishoftu General Hospital,Ethiopia

BACKGROUND Diabetes is a chronic metabolic syndrome that has become a global public health problem with significant morbidity and mortality.It is a pro-inflammatory and pro-thrombotic condition characterized by increased platelet activation and alterations in platelet indices.However,the use of platelet indices as predictors of poor glucoregulation has not been fully evaluated in this context,and evidence for their role as predictors of poor glycemic status in diabetic patients is limited.AIM To evaluate platelet indices and determine their prognostic significance in relation to inadequate glucoregulation among individuals diagnosed with type 2 diabetes at Bishoftu General Hospital in Ethiopia,from June 15 to August 12,2022.METHODS A comparative cross-sectional study was conducted in 261 participants including 174 individuals with type 2 diabetes mellitus(T2DM)and 87 non-diabetic controls.The systematic random sampling technique was used to select participants.Data were collected using structured questionnaires,physical measurements,checklists,and laboratory tests.Platelet parameters and fasting blood glucose levels were determined from blood samples using Sysmex-XN550 and CobasC311 analyzers,respectively.The hematology analyzer output was checked and participants were also screened for malaria parasites using a prepared blood smear.Collected data were entered into Epi-data version 3.1 and exported to SPSS version 25 for analysis.Theχ^(2) test,Mann-Whitney U test,Kruskal-Wallis test,post hoc test,Spearman correlation,and receiver operating characteristic curve were used for analysis.A P value<0.05 was considered statistically significant.RESULTS The results of our study indicate that diabetic patients have significantly higher levels of platelet distribution width(PDW),mean platelet volume(MPV),platelet large cell ratio(PLCR),and plateletcrit(PCT)compared to healthy individuals(P<0.001).Furthermore,these indices were found to be significantly elevated in individuals with poor glycemic control in T2DM compared to those with good glycemic control and healthy controls.We also observed significant correlations between these indices and various anthropometric and clinical variables.Our findings suggest that PDW,with a cut-off value of 15.75 fL and an area under the curve(AUC)of 0.803,MPV,with a cut-off value of 12.25 fL and an AUC of 0.774,PLCR,with a cut-off value of 36.3%and an AUC of 0.775,and PCT,with a cut-off value of 0.24%and an AUC of 0.761,can serve as predictors of poor glycemic control in patients with diabetes mellitus.CONCLUSION The observed correlation between diabetic patients and a significant increase in platelet indices has highlighted their potential as predictors of poor glycemic control in diabetes.Therefore,regular screening and profiling of platelet indices is recommended as part of the follow-up process for individuals with diabetes mellitus.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

The tangential k-Cauchy-Fueter type operator and Penrose type integral formula on the generalized complex Heisenberg group

The tangential k-Cauchy-Fueter operator and k-CF functions are counterparts of the tangential Cauchy–Riemann operator and CR functions on the Heisenberg group in the theory of several complex variables,respectively.In this paper,we introduce a Lie group that the Heisenberg group can be imbedded into and call it generalized complex Heisenberg.We investigate quaternionic analysis on the generalized complex Heisenberg.We also give the Penrose integral formula for k-CF functions and construct the tangential k-Cauchy-Fueter complex.

Molecular diagnostic approaches in detecting rearranged during transfection oncogene mutations in multiple endocrine neoplasia type 2

Different types of neuroendocrine cancer,including medullary thyroid cancer(MTC)and thyroid C-cell hyperplasia,are part of multiple endocrine neoplasia type 2(MEN2).A proto-oncogene mutation of the rearranged during transfection(RET)gene changes the way that receptor tyrosine kinases work.Multiple endocrine neoplasia,a pathological condition,involves these kinases.When the RET protooncogene changes,it can cause endocrine adenomas and hyperplasia to happen at the same time or one after the other.Pheochromocytoma,medullary thyroid carcinoma,and hyperparathyroidism,alone or in combination,are present in MEN2A patients.Some patients may also have skin lichen amyloidosis or Hirschsprung's disease.Patients with MEN2A often present with MTC.MTC is aggressive and has the worst prognosis,as most patients exhibit lymph node metastasis.MTC is one of the important causes of death in patients with MEN2A.RET mutation analysis aids in identifying MEN2A symptoms and monitoring levels of calcium,thyroid hormones,calcitonin,normetanephrine,fractionated metanephrines,and parathyroid hormone.The earlier diagnosis of MTC significantly improves survival and prompts better management of MEN2A.In this editorial,we will discuss the significance of molecular diagnostic approaches in detecting RET oncogene mutations in MEN2A.

An Algorithm for Short-Circuit Current Interval in Distribution Networks with Inverter Type Distributed Generation Based on Affine Arithmetic

During faults in a distribution network,the output power of a distributed generation(DG)may be uncertain.Moreover,the output currents of distributed power sources are also affected by the output power,resulting in uncertainties in the calculation of the short-circuit current at the time of a fault.Additionally,the impacts of such uncertainties around short-circuit currents will increase with the increase of distributed power sources.Thus,it is very important to develop a method for calculating the short-circuit current while considering the uncertainties in a distribution network.In this study,an affine arithmetic algorithm for calculating short-circuit current intervals in distribution networks with distributed power sources while considering power fluctuations is presented.The proposed algorithm includes two stages.In the first stage,normal operations are considered to establish a conservative interval affine optimization model of injection currents in distributed power sources.Constrained by the fluctuation range of distributed generation power at the moment of fault occurrence,the model can then be used to solve for the fluctuation range of injected current amplitudes in distributed power sources.The second stage is implemented after a malfunction occurs.In this stage,an affine optimization model is first established.This model is developed to characterizes the short-circuit current interval of a transmission line,and is constrained by the fluctuation range of the injected current amplitude of DG during normal operations.Finally,the range of the short-circuit current amplitudes of distribution network lines after a short-circuit fault occurs is predicted.The algorithm proposed in this article obtains an interval range containing accurate results through interval operation.Compared with traditional point value calculation methods,interval calculation methods can provide more reliable analysis and calculation results.The range of short-circuit current amplitude obtained by this algorithm is slightly larger than those obtained using the Monte Carlo algorithm and the Latin hypercube sampling algorithm.Therefore,the proposed algorithm has good suitability and does not require iterative calculations,resulting in a significant improvement in computational speed compared to the Monte Carlo algorithm and the Latin hypercube sampling algorithm.Furthermore,the proposed algorithm can provide more reliable analysis and calculation results,improving the safety and stability of power systems.

Differential Expression of Genes Related to Fruit Development and Capsaicinoids Synthesis in Habanero Pepper Plants Grown in Contrasting Soil Types

Habanero pepper(Capsicum chinense Jacq.)is a crop of economic relevance in the Peninsula of Yucatan.Its fruits have a high level of capsaicinoids compared to peppers grown in other regions of the world,which gives them industrial importance.Soil is an important factor that affects pepper development,nutritional quality,and capsaicinoid content.However,the effect of soil type on fruit development and capsaicinoid metabolism has been little understood.This work aimed to compare the effect of soils with contrasting characteristics,black soil(BS)and red soil(RS),on the expression of genes related to the development of fruits,and capsaicinoid synthesis using a transcriptomic analysis of the habanero pepper fruits.Plants growing in RS had bigger fruits and higher expression of genes related to floral development,fruit abscission,and softening which suggests that RS stimulates fruit development from early stages until maturation stages.Fruits from plants growing in BS had enrichment in metabolic pathways related to growth,sugars,and photosynthesis.Besides,these fruits had higher capsaicinoid accumulation at 25 days post-anthesis,and higher expression of genes related to the branched-chain amino acids metabolism(ketol-acid reductisomerase KARI),pentose phosphate pathway and production of NADPH(glucose-6-phosphate-1-dehydrogenase G6PDH),and proteasome and vesicular traffic in cells(26S proteasome regulatory subunit T4 RPT4),which suggest that BS is better in the early stimulation of pathways related to the nutritional quality and capsaicinoid metabolism in the fruits.

Effect of Types and Orders of Electromagnetic Field Finite Element Meshes on Power Communication Harmonic Parameters Calculation Results of Tubular Hydrogenerators

In generator design field,waveform total harmonic distortion(THD)and telephone harmonic factor(THF)are parameters commonly used to measure the impact of generator no-load voltage harmonics on the power communication quality.Tubular hydrogenerators are considered the optimal generator for exploiting low-head,high-flow hydro resources,and they have seen increasingly widespread application in China's power systems recent years.However,owing to the compact and constrained internal space of such generators,their internal magnetic-field harmonics are pronounced.Therefore,accurate calculation of their THD and THF is crucial during the analysis and design stages to ensure the quality of power communication.Especially in the electromagnetic field finite element modeling analysis of such generators,the type and order of the finite element meshes may have a significant impact on the THD and THF calculation results,which warrants in-depth research.To address this,this study takes a real 34 MW large tubular hydrogenerator as an example,and establishes its electromagnetic field finite element model under no-load conditions.Two types of meshes,five mesh densities,and two mesh orders are analyzed to reveal the effect of electromagnetic field finite element mesh types and orders on the calculation results of THD and THF for such generators.

The Prevalence Type of the Meniscus Tear in Patients with Anterior Cruciate Ligament (ACL) Injury, in Abu Arish General Hospital, Jazan, KSA

Background: The anterior cruciate ligament (ACL) is the main structure that prevents the forward movement of the tibia about the femur Meniscus tear which is a common finding in patients with anterior cruciate ligament (ACL) injury. Aim: To investigate the prevalence of types of meniscus tears in patients with Anterior Cruciate Ligament (ACL) Injury. Methods: A retrospective study was conducted among inpatients. Clinical evaluation included side-to-side difference in anterior tibial translation (ATT) as measured by a KT-1000 arthrometer (MEDmetric Corp) and a grade of pivot-shift test at final follow-up in all patients. Subsequent meniscal tear was defined by symptoms of joint line pain and/or locking or joint effusion requiring surgical treatment. Results: Most of patients were males (92.6%). The patients were categorized into 5 groups according to age with a mean of age 32.8 ± 10.6. The most common causes of ACL injury were falling down (43.2%), trauma (38.1%) or knee torsion (18.8%). Medial meniscal tear was found in 92 knees (55.7%), while lateral meniscal tear was found in 19 knees (10.8%) and the most common type was the longitudinal tear that was found in 31 knees (17.6%). Similarly, 66.7% of the meniscal flap tears and half of the meniscal bucket-handle tears were significantly associated with loose body (P Conclusion: The present study demonstrated that meniscus tears are more common in individuals with chronic ACL rupture. The main factors contributing to ACL injury were classified as falls, trauma, and knee torsion. Gender was identified as a critical determinant in the etiology of ACL injury. The occurrence of a ramp lesion was associated longitudinal meniscal tears, whereas chodoral injury was associated with the majority of meniscal flap tears and meniscal bucket-handle tears.

Type 2 diabetes in children and adolescents:Exploring the disease heterogeneity and research gaps to optimum management

Over the past 20 years,the incidence and prevalence of type 2 diabetes mellitus(T2DM)in children and adolescents have increased,particularly in racial and ethnic minorities.Despite the rise in T2DM in children and adolescents,the pathophysiology and progression of disease in this population are not clearly understood.Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM.Furthermore,the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients,mostly due to the challenges of implementing clinical trials.A better understanding of the mechanisms underlying the development and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies.This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.

Rapid Prototype Development Approach for Genetic Programming

Genetic Programming (GP) is an important approach to deal with complex problem analysis and modeling, and has been applied in a wide range of areas. The development of GP involves various aspects, including design of genetic operators, evolutionary controls and implementations of heuristic strategy, evaluations and other mechanisms. When designing genetic operators, it is necessary to consider the possible limitations of encoding methods of individuals. And when selecting evolutionary control strategies, it is also necessary to balance search efficiency and diversity based on representation characteristics as well as the problem itself. More importantly, all of these matters, among others, have to be implemented through tedious coding work. Therefore, GP development is both complex and time-consuming. To overcome some of these difficulties that hinder the enhancement of GP development efficiency, we explore the feasibility of mutual assistance among GP variants, and then propose a rapid GP prototyping development method based on πGrammatical Evolution (πGE). It is demonstrated through regression analysis experiments that not only is this method beneficial for the GP developers to get rid of some tedious implementations, but also enables them to concentrate on the essence of the referred problem, such as individual representation, decoding means and evaluation. Additionally, it provides new insights into the roles of individual delineations in phenotypes and semantic research of individuals.

Analysis of The Effect of General Medicine-Based Education in Type 2 Diabetes Mellitus Patients in Neijiang City, China

Objective:To investigate and analyze the current situation of cognition,attitude,behavior,and influencing factors of Type 2 Diabetes Mellitus(T2DM)patients in Neijiang City,and to explore the effectiveness of the application of the education program based on the popularization of science in general medicine.Methods:Seventy cases of T2DM patients in Neijiang City were selected and randomly divided into 35 cases each in the observation group and the control group.The observation group received general medicine science education intervention and the control group received traditional health education.Indicators such as cognitive level,attitude,and behavioral change between the two groups were compared to assess the effect of general medical science education.Results:Before the intervention,there was no difference between the two groups in terms of knowledge,beliefs,and behaviors in general medicine,glycemic control,body mass index(BMI),and satisfaction with health education(P>0.05).After 3 months of the intervention,there was a highly significant difference in the aforementioned levels between the two groups(P<0.05).Conclusion:The approach of general medicine popularization had a significant effect on the treatment and management of T2DM patients in Neijiang City.It improved the patient’s cognitive level and self-management ability of the disease,increased their treatment adherence,and improved the therapeutic effect.

Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer

BACKGROUND Type II diabetes mellitus(T2DM)has been associated with increased risk of colon cancer(CC)and worse prognosis in patients with metastases.The effects of T2DM on postoperative chemoresistance rate(CRR)and long-term disease-free survival(DFS)and overall survival(OS)in patients with stage III CC who receive curative resection remain controversial.AIM To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage III CC.METHODS This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage III CC from 2018 to 2021.Based on preoperative T2DM history,the patients were categorized into non-DM(n=160)and DM groups(n=118).The latter was further divided into well-controlled(n=73)and poorly controlled(n=45)groups depending on the status of glycemic control.DFS,OS,and CRR were compared between the groups and Cox regression analysis was used to identify risk factors.RESULTS Patients in the DM and non-DM groups demonstrated similar DFS,OS,and CRR(DFS:72.03%vs 78.75%,P=0.178;OS:81.36%vs 83.12%,P=0.638;CRR:14.41%vs 7.5%,P=0.063).Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM(DFS:62.22%vs 78.07%,P=0.021;OS:71.11%vs 87.67%,P=0.011;CRR:24.40%vs 8.22%,P=0.015).High preoperative fasting plasma glucose[DFS:Hazard ratio(HR)=2.684,P<0.001;OS:HR=2.105,P=0.019;CRR:HR=2.214,P=0.005]and glycosylated hemoglobin levels(DFS:HR=2.344,P=0.006;OS:HR=2.119,P=0.021;CRR:HR=2.449,P=0.009)indicated significantly poor prognosis and high CRR,while T2DM history did not(DFS:HR=1.178,P=0.327;OS:HR=0.933,P=0.739;CRR:HR=0.997,P=0.581).CONCLUSION Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels,but not T2DM history,were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage III CC.