The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts...The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.展开更多
Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,w...Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.展开更多
BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,ot...BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.展开更多
BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflamma...BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflammatory bowel disease.Despite current treatments,survival rates for advanced CRC remain low,highlighting the need for better therapeutic strategies.AIM To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14(KIF14)expression within CRC specimens.Additionally,this study aims to investigate the interaction between nitidine chloride(NC)and KIF14,considering their potential as therapeutic targets.METHODS The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining.The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference(SMD)for KIF14 mRNA levels.The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves,along with measures of sensitivity,specificity,and likelihood ratios.Additionally,clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC.Survival analysis established the prognostic value of KIF14 in CRC.The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis,and molecular docking was utilized to explore the targeting affinity between NC and KIF14.RESULTS KIF14 was highly expressed in 208 CRC patients.Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples,with an SMD of 1.92(95%CI:1.49-2.35).The area under the curve was 0.94(95%CI:0.92-0.96),with a sensitivity of 0.85(95%CI:0.78-0.90)and a specificity of 0.90(95%CI:0.85-0.93).The positive and negative likelihood ratios were 8.38(95%CI:5.39-13.02)and 0.17(95%CI:0.11-0.26),respectively.At the single-cell level,significant overexpression of KIF14 was observed in CRC cells(P<0.001),with 35 CRC cell lines dependent on KIF14 for growth.The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets(P<0.05).Binding energy calculations indicated that KIF14 is a potential target for NC(binding energy:10.3 kcal/mol).CONCLUSION KIF14 promotes the growth of CRC cells and acts as an oncogenic factor,potentially serving as a therapeutic target for NC in the treatment of CRC.展开更多
In this editorial,we comment on the article by Qin et al,recently published in the World Journal of Gastrointestinal Oncology.Malignant tumors of the digestive tract represent a significant health threat.Kinesin famil...In this editorial,we comment on the article by Qin et al,recently published in the World Journal of Gastrointestinal Oncology.Malignant tumors of the digestive tract represent a significant health threat.Kinesin family member 14(KIF14),a critical kinesin,is pivotal in the proliferation,migration,and invasion of tumor cells.It has emerged as a focal point in recent studies of malignant tumors in the digestive tract.This article reviews the current research on KIF14 within these tumors and details its significant role in tumor cell behaviors,including proliferation,apo-ptosis,migration,invasion,and angiogenesis,alongside the regulatory mechanisms of the associated intracellular signaling pathways.Additionally,it explores the clinical value of KIF14 as a potential biomarker for early diagnosis,disease monitoring,and prognostic evaluation in malignant tumors of the digestive tract.The article concludes by introducing the potential regulatory role of traditional Chinese medicine,aiming to combine the strengths of both modern and traditional medical approaches to enhance treatment outcomes and prognosis for patients with these tumors.展开更多
BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their...BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.展开更多
Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Her...Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.展开更多
BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age children.AIM To investigate the current statu...BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age children.AIM To investigate the current status of family rearing,parental stress,and behavioral and emotional problems of preschool children and to analyze the mediating effect of the current status of family rearing on parental stress and behavioral/emo-tional problems.METHODS We use convenience sampling to select 258 preschool children in the physical examination center of our hospital from October 2021 to September 2023.The children and their parents were evaluated using a questionnaire survey.Pearson's correlation was used to analyze the correlation between child behavioral and emotional problems and parental stress and family rearing,and the structural equation model was constructed to test the mediating effect.RESULTS The score for behavioral/emotional problems of 258 preschool children was(27.54±3.63),the score for parental stress was(87.64±11.34),and the score for parental family rearing was(31.54±5.24).There was a positive correlation between the behavioral and emotional problems of the children and the“hostile/mandatory”parenting style;meanwhile,showed a negative correlation with the“support/participation”parenting style(all P<0.05).The intermediary effect value between the family upbringing of parents in parental stress and children's behavior problems was 29.89%.CONCLUSION Parental family upbringing has a mediating effect between parental stress and behavioral and emotional problems of children.Despite paying attention to the behavioral and emotional problems of preschool-age children,clinical medical staff should provide correct and reasonable parenting advice to their parents to promote the mental health of preschool-age children.展开更多
慢性病患者的长期管理是基层医疗的核心任务之一,患者的规律随访(TR)与疾病预后密切相关。近期Annals of Family Medicine刊发了一篇文章《Teamwork among Primary Care Staff to Achieve Regular Follow-Up of Chronic Patients》,该...慢性病患者的长期管理是基层医疗的核心任务之一,患者的规律随访(TR)与疾病预后密切相关。近期Annals of Family Medicine刊发了一篇文章《Teamwork among Primary Care Staff to Achieve Regular Follow-Up of Chronic Patients》,该文章指出慢性病患者的TR面临多重挑战,既往研究多聚焦于患者个体因素,而忽视了医疗团队动态对随访率的潜在影响。展开更多
The advent of Grover’s algorithm presents a significant threat to classical block cipher security,spurring research into post-quantum secure cipher design.This study engineers quantum circuit implementations for thre...The advent of Grover’s algorithm presents a significant threat to classical block cipher security,spurring research into post-quantum secure cipher design.This study engineers quantum circuit implementations for three versions of the Ballet family block ciphers.The Ballet‑p/k includes a modular-addition operation uncommon in lightweight block ciphers.Quantum ripple-carry adder is implemented for both“32+32”and“64+64”scale to support this operation.Subsequently,qubits,quantum gates count,and quantum circuit depth of three versions of Ballet algorithm are systematically evaluated under quantum computing model,and key recovery attack circuits are constructed based on Grover’s algorithm against each version.The comprehensive analysis shows:Ballet-128/128 fails to NIST Level 1 security,while when the resource accounting is restricted to the Clifford gates and T gates set for the Ballet-128/256 and Ballet-256/256 quantum circuits,the design attains Level 3.展开更多
Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)hav...Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.展开更多
Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
Background and Purpose: In recent years, individual spirituality has been attracting attention, but little research has been conducted as it relates to family spirituality that applies this concept to the family and r...Background and Purpose: In recent years, individual spirituality has been attracting attention, but little research has been conducted as it relates to family spirituality that applies this concept to the family and relates to the meaning of the family’s existence in terms of the entire family. The purpose of this study was to clarify the attributes of family spirituality and the influencing factors of its decline. Methods: Regarding family spirituality, 1) a literature search was conducted using PubMed and reviews of 20 English-language articles;and 2) semi-structured interviews were conducted with 12 Japanese families having elderly members in the household. Data triangulation was performed for both, and a directed content analysis was conducted using Hohashi’s Concentric Sphere Family Environment Theory as the framework. Results: Attributes of family spirituality included 21 categories, such as “I think that my family exists for my children and grandchildren.” Factors influencing the decline in family spirituality included 20 categories in total, including 6 categories of risk/causal/promoting factors such as “lack of caring for family members”;11 categories of preventive/inhibitory/suppression factors such as “healthcare professionals not being close to the family”;and three categories of context-sensitive factors such as “death of a family member.” Conclusions/Implications for Practice: Family intervention requires nurses to understand the attributes of family spirituality and to control the influencing factors of a decline in family spirituality. Through such efforts, families will be able to discover the meaning of the existence of the family and maintain and improve their well-being.展开更多
Objective:To investigate the efficacy of a tripartite collaborative nursing intervention in enhancing resilience among families of pediatric leukemia patients.Methods:Based on Walsh’s family resilience theory and col...Objective:To investigate the efficacy of a tripartite collaborative nursing intervention in enhancing resilience among families of pediatric leukemia patients.Methods:Based on Walsh’s family resilience theory and collaborative nursing principles,and after reviewing a large amount of literature,a tripartite intervention was constructed,which was led by the nursing team,coordinated by medical social workers,and supported by volunteers.Caregivers of pediatric hematology inpatients at a tertiary-level Class A hospital were selected as research subjects.which were divided into a control group(n=30)and an experimental group(n=30)according to a randomized block design.The control group are treated with standard nursing care,which included health education,counseling,and psychological support from nurses.The experimental group,in addition,was provided with a tripartite collaborative nursing intervention for 3 months.Results:The family resilience level,social support,and family function scores of the experimental group were higher than those of the control group,and the differences were statistically significant(P≤0.05).Conclusion:The implementation of tripartite collaborative nursing intervention improves the resilience of families of children suffered from leukemia.展开更多
Hi! I'm Linda.I'm 12 years old.I'm a student.I'm in No.1 middle school(1).Here is a nice photo of my family.These are my parents,Tom and Mary.My mother is a(2)English teacher.My father is a doctor.Thos...Hi! I'm Linda.I'm 12 years old.I'm a student.I'm in No.1 middle school(1).Here is a nice photo of my family.These are my parents,Tom and Mary.My mother is a(2)English teacher.My father is a doctor.Those are my brother and sister.My sister(3)name is Helen.She is 6 years old.My brother is Eric.展开更多
I have a wonderful family.We all like music very much.My mother is a music teacher.She is good at playing the piano and the violin.She also likes singing and she can sing many songs.My father is a doctor.He likes musi...I have a wonderful family.We all like music very much.My mother is a music teacher.She is good at playing the piano and the violin.She also likes singing and she can sing many songs.My father is a doctor.He likes music,too.After he comes back from work,he often listens to music.In fact,playing the flute and the erhu are his favorites.I enjoy playing the guitar though it's difficult to play.I practice playing it every day,so I can play it very well.I once won the second prize at a guitar concert in the city.But my sister thinks playing theguitar is boring.展开更多
一、完形填空阅读短文,掌握其大意,从A、B、C三个选项中选择最佳答案填空。A It's Sunday afternoon.Mike's family are at home.When Mike and his 4 year-old brother Bruce are__1__in their room,Dad is cleaning the livin...一、完形填空阅读短文,掌握其大意,从A、B、C三个选项中选择最佳答案填空。A It's Sunday afternoon.Mike's family are at home.When Mike and his 4 year-old brother Bruce are__1__in their room,Dad is cleaning the living room with the cleaner(吸尘器).展开更多
Academic Medicine:Family,Friends and Fun!I greatly appreciate the honor and opportunity to contribute to the“Legends-in-Urology”series.We are all the product of the collective ideology of medicine and each one of us...Academic Medicine:Family,Friends and Fun!I greatly appreciate the honor and opportunity to contribute to the“Legends-in-Urology”series.We are all the product of the collective ideology of medicine and each one of us contributes to the betterment of mankind.How we provide value to society is on a spectrum and is an amalgam of our personality paired with opportunity.As such,I must credit my“alleged reputation”to factors such as my birth family,mentors and a good helping of happenstance.展开更多
Tom is a 7-year-old American boy.He is a primary school student.He has a big and happy family.He lives with his father,mother,grandfather,and grandmother.He also has an uncle and an aunt.
Exchanging gifts at the holidays is a tradition that dates back to thousands of years ago.Children are typically excused from buying gifts because they cost money kids may not have.But the truth is that some of the be...Exchanging gifts at the holidays is a tradition that dates back to thousands of years ago.Children are typically excused from buying gifts because they cost money kids may not have.But the truth is that some of the best gifts don't cost anything.If you would like to give meaningful gifts to family or friends at the holidays—without having to spend money—here's how you can get started.展开更多
文摘The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.
基金supported by the Key-Area Research and Development Program of Guangdong Province(Grant No.2020B020220003)National Natural Science Foundation of China(32202504)+2 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515030049)Guangdong Rural Revitalization Strategy Special Project(Grant No.2023-NJS-00-003)Special fund for scientific and technological talents introduction of Guangdong Academy of Agricultural Sciences(Grant No.R2021YJ-YB2004)。
文摘Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.
基金Supported by the National Oncology Care Support Program,No.25000.056766/2015-64.
文摘BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.
基金Natural Science Foundation of Shandong Province,No.ZR2020QH185Scientific Research Nurturing Fund of The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,No.QYPY2020NSFC0803+2 种基金Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220415Guangxi Medical University Teacher Teaching Ability Development Project,No.2022JFA02Guangxi Medical University Undergraduate Education and Teaching Reform Project,No.2023Y05.
文摘BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflammatory bowel disease.Despite current treatments,survival rates for advanced CRC remain low,highlighting the need for better therapeutic strategies.AIM To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14(KIF14)expression within CRC specimens.Additionally,this study aims to investigate the interaction between nitidine chloride(NC)and KIF14,considering their potential as therapeutic targets.METHODS The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining.The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference(SMD)for KIF14 mRNA levels.The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves,along with measures of sensitivity,specificity,and likelihood ratios.Additionally,clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC.Survival analysis established the prognostic value of KIF14 in CRC.The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis,and molecular docking was utilized to explore the targeting affinity between NC and KIF14.RESULTS KIF14 was highly expressed in 208 CRC patients.Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples,with an SMD of 1.92(95%CI:1.49-2.35).The area under the curve was 0.94(95%CI:0.92-0.96),with a sensitivity of 0.85(95%CI:0.78-0.90)and a specificity of 0.90(95%CI:0.85-0.93).The positive and negative likelihood ratios were 8.38(95%CI:5.39-13.02)and 0.17(95%CI:0.11-0.26),respectively.At the single-cell level,significant overexpression of KIF14 was observed in CRC cells(P<0.001),with 35 CRC cell lines dependent on KIF14 for growth.The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets(P<0.05).Binding energy calculations indicated that KIF14 is a potential target for NC(binding energy:10.3 kcal/mol).CONCLUSION KIF14 promotes the growth of CRC cells and acts as an oncogenic factor,potentially serving as a therapeutic target for NC in the treatment of CRC.
基金Supported by the 2023 Government-funded Project of the Outstanding Talents Training Program in Clinical Medicine,No.ZF2023165Key Research and Development Projects of Hebei Province,No.18277731D+1 种基金Natural Science Foundation of Hebei Province,No.H202423105Hebei Provincial Administration of Traditional Chinese Medicine,Scientific Research Project,No.2020014.
文摘In this editorial,we comment on the article by Qin et al,recently published in the World Journal of Gastrointestinal Oncology.Malignant tumors of the digestive tract represent a significant health threat.Kinesin family member 14(KIF14),a critical kinesin,is pivotal in the proliferation,migration,and invasion of tumor cells.It has emerged as a focal point in recent studies of malignant tumors in the digestive tract.This article reviews the current research on KIF14 within these tumors and details its significant role in tumor cell behaviors,including proliferation,apo-ptosis,migration,invasion,and angiogenesis,alongside the regulatory mechanisms of the associated intracellular signaling pathways.Additionally,it explores the clinical value of KIF14 as a potential biomarker for early diagnosis,disease monitoring,and prognostic evaluation in malignant tumors of the digestive tract.The article concludes by introducing the potential regulatory role of traditional Chinese medicine,aiming to combine the strengths of both modern and traditional medical approaches to enhance treatment outcomes and prognosis for patients with these tumors.
基金Supported by the Chongqing Medical University Program for Youth Innovation in Future Medicine,No.W0019Chongqing Municipal Education Commission’s 14th Five-Year Key Discipline Support Project,No.20240101 and No.20240102。
文摘BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.
基金supported by the National Key Research and Development Program of China,No.2022YFC2402701(to WC)Key International(Regional)Joint Research Program of the National Natural Science Foundation of China,No.81820108009(to SY)+5 种基金the National Natural Science Foundation of China,Nos.81970890(to WC)and 82371148(to WG)Fujian Provincial Healthcare Young and Middle-aged Backbone Talent Training Project,No.2023GGA035(to XC)Spring City Planthe High-level Talent Promotion and Training Project of Kunming,No.2022SCP001(to SY)the Natural Science Foundation of Hainan Province of China,No.824MS052(to XS)the Sixth Medical Center of Chinese PLA General Hospital Innovation Cultivation,No.CXPY202116(to LX)。
文摘Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.
基金Supported by the Shijiazhuang Science and Technology Research and Development Program,No.221460383.
文摘BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age children.AIM To investigate the current status of family rearing,parental stress,and behavioral and emotional problems of preschool children and to analyze the mediating effect of the current status of family rearing on parental stress and behavioral/emo-tional problems.METHODS We use convenience sampling to select 258 preschool children in the physical examination center of our hospital from October 2021 to September 2023.The children and their parents were evaluated using a questionnaire survey.Pearson's correlation was used to analyze the correlation between child behavioral and emotional problems and parental stress and family rearing,and the structural equation model was constructed to test the mediating effect.RESULTS The score for behavioral/emotional problems of 258 preschool children was(27.54±3.63),the score for parental stress was(87.64±11.34),and the score for parental family rearing was(31.54±5.24).There was a positive correlation between the behavioral and emotional problems of the children and the“hostile/mandatory”parenting style;meanwhile,showed a negative correlation with the“support/participation”parenting style(all P<0.05).The intermediary effect value between the family upbringing of parents in parental stress and children's behavior problems was 29.89%.CONCLUSION Parental family upbringing has a mediating effect between parental stress and behavioral and emotional problems of children.Despite paying attention to the behavioral and emotional problems of preschool-age children,clinical medical staff should provide correct and reasonable parenting advice to their parents to promote the mental health of preschool-age children.
文摘慢性病患者的长期管理是基层医疗的核心任务之一,患者的规律随访(TR)与疾病预后密切相关。近期Annals of Family Medicine刊发了一篇文章《Teamwork among Primary Care Staff to Achieve Regular Follow-Up of Chronic Patients》,该文章指出慢性病患者的TR面临多重挑战,既往研究多聚焦于患者个体因素,而忽视了医疗团队动态对随访率的潜在影响。
基金State Key Lab of Processors,Institute of Computing Technology,Chinese Academy of Sciences(CLQ202516)the Fundamental Research Funds for the Central Universities of China(3282025047,3282024051,3282024009)。
文摘The advent of Grover’s algorithm presents a significant threat to classical block cipher security,spurring research into post-quantum secure cipher design.This study engineers quantum circuit implementations for three versions of the Ballet family block ciphers.The Ballet‑p/k includes a modular-addition operation uncommon in lightweight block ciphers.Quantum ripple-carry adder is implemented for both“32+32”and“64+64”scale to support this operation.Subsequently,qubits,quantum gates count,and quantum circuit depth of three versions of Ballet algorithm are systematically evaluated under quantum computing model,and key recovery attack circuits are constructed based on Grover’s algorithm against each version.The comprehensive analysis shows:Ballet-128/128 fails to NIST Level 1 security,while when the resource accounting is restricted to the Clifford gates and T gates set for the Ballet-128/256 and Ballet-256/256 quantum circuits,the design attains Level 3.
文摘Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
文摘Background and Purpose: In recent years, individual spirituality has been attracting attention, but little research has been conducted as it relates to family spirituality that applies this concept to the family and relates to the meaning of the family’s existence in terms of the entire family. The purpose of this study was to clarify the attributes of family spirituality and the influencing factors of its decline. Methods: Regarding family spirituality, 1) a literature search was conducted using PubMed and reviews of 20 English-language articles;and 2) semi-structured interviews were conducted with 12 Japanese families having elderly members in the household. Data triangulation was performed for both, and a directed content analysis was conducted using Hohashi’s Concentric Sphere Family Environment Theory as the framework. Results: Attributes of family spirituality included 21 categories, such as “I think that my family exists for my children and grandchildren.” Factors influencing the decline in family spirituality included 20 categories in total, including 6 categories of risk/causal/promoting factors such as “lack of caring for family members”;11 categories of preventive/inhibitory/suppression factors such as “healthcare professionals not being close to the family”;and three categories of context-sensitive factors such as “death of a family member.” Conclusions/Implications for Practice: Family intervention requires nurses to understand the attributes of family spirituality and to control the influencing factors of a decline in family spirituality. Through such efforts, families will be able to discover the meaning of the existence of the family and maintain and improve their well-being.
基金Hubei Provincial Department of Education Humanities and Social Sciences Youth Project(Project No.:19Q137)Hubei Provincial Department of Education Humanities and Social Sciences Youth Project(Project No.:23Q183)。
文摘Objective:To investigate the efficacy of a tripartite collaborative nursing intervention in enhancing resilience among families of pediatric leukemia patients.Methods:Based on Walsh’s family resilience theory and collaborative nursing principles,and after reviewing a large amount of literature,a tripartite intervention was constructed,which was led by the nursing team,coordinated by medical social workers,and supported by volunteers.Caregivers of pediatric hematology inpatients at a tertiary-level Class A hospital were selected as research subjects.which were divided into a control group(n=30)and an experimental group(n=30)according to a randomized block design.The control group are treated with standard nursing care,which included health education,counseling,and psychological support from nurses.The experimental group,in addition,was provided with a tripartite collaborative nursing intervention for 3 months.Results:The family resilience level,social support,and family function scores of the experimental group were higher than those of the control group,and the differences were statistically significant(P≤0.05).Conclusion:The implementation of tripartite collaborative nursing intervention improves the resilience of families of children suffered from leukemia.
文摘Hi! I'm Linda.I'm 12 years old.I'm a student.I'm in No.1 middle school(1).Here is a nice photo of my family.These are my parents,Tom and Mary.My mother is a(2)English teacher.My father is a doctor.Those are my brother and sister.My sister(3)name is Helen.She is 6 years old.My brother is Eric.
文摘I have a wonderful family.We all like music very much.My mother is a music teacher.She is good at playing the piano and the violin.She also likes singing and she can sing many songs.My father is a doctor.He likes music,too.After he comes back from work,he often listens to music.In fact,playing the flute and the erhu are his favorites.I enjoy playing the guitar though it's difficult to play.I practice playing it every day,so I can play it very well.I once won the second prize at a guitar concert in the city.But my sister thinks playing theguitar is boring.
文摘一、完形填空阅读短文,掌握其大意,从A、B、C三个选项中选择最佳答案填空。A It's Sunday afternoon.Mike's family are at home.When Mike and his 4 year-old brother Bruce are__1__in their room,Dad is cleaning the living room with the cleaner(吸尘器).
文摘Academic Medicine:Family,Friends and Fun!I greatly appreciate the honor and opportunity to contribute to the“Legends-in-Urology”series.We are all the product of the collective ideology of medicine and each one of us contributes to the betterment of mankind.How we provide value to society is on a spectrum and is an amalgam of our personality paired with opportunity.As such,I must credit my“alleged reputation”to factors such as my birth family,mentors and a good helping of happenstance.
文摘Tom is a 7-year-old American boy.He is a primary school student.He has a big and happy family.He lives with his father,mother,grandfather,and grandmother.He also has an uncle and an aunt.
文摘Exchanging gifts at the holidays is a tradition that dates back to thousands of years ago.Children are typically excused from buying gifts because they cost money kids may not have.But the truth is that some of the best gifts don't cost anything.If you would like to give meaningful gifts to family or friends at the holidays—without having to spend money—here's how you can get started.
