Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
Multiple morphological abnormalities of sperm flagella(MMAF)is a severe form of asthenoteratozoospermia,characterized by morphological abnormalities and reduced motility of sperm,causing male infertility.Although appr...Multiple morphological abnormalities of sperm flagella(MMAF)is a severe form of asthenoteratozoospermia,characterized by morphological abnormalities and reduced motility of sperm,causing male infertility.Although approximately 60%of MMAF cases can be explained genetically,the etiology of the remaining cases is unclear.Here,we identified two novel compound heterozygous variants in the gene,dynein axonemal heavy chain 10(DNAH10),in three patients from two unrelated Pakistani families using whole-exome sequencing(WES),including one compound heterozygous mutation(DNAH10:c.9409C>A[p.P3137T];c.12946G>C[p.D4316H])in family 1 and another compound heterozygous mutation(DNAH10:c.8849G>A[p.G2950D];c.11509C>T[p.R3687W])in family 2.All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools.Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance.Hematoxylin and eosin(H&E)staining revealed MMAF,including sperm head abnormalities,in the patients.In addition,immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella.These findings broaden the spectrum of DNAH10 variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.展开更多
Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.8...Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.871-4 ACA>A)in the adenylate kinase 7(AK7)gene by whole-exome sequencing in infertile individuals.Spermatozoa from affected individuals exhibited typical MMAF characteristics,including coiled,bent,short,absent,and irregular flagella.Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella.Immunofluorescence staining confirmed the absence of AK7 protein from the patients’spermatozoa,validating the pathogenic nature of the mutation.This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans,expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.展开更多
Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques l...Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.展开更多
Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella(MMAF),which cause severe asthenozoospermia and lead to male infertility,while the causes of approximately 50%of MMAF ...Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella(MMAF),which cause severe asthenozoospermia and lead to male infertility,while the causes of approximately 50%of MMAF cases remain unclear.To reveal the genetic causes of MMAF in an infertile patient,whole-exome sequencing was performed to screen for pathogenic genes,and electron microscope was used to reveal the sperm flagellar ultrastructure.A novel heterozygous missense mutation in the outer dense fiber protein 2(ODF2)gene was detected,which was inherited from the patient’s mother and predicted to be potentially damaging.Transmission electron microscopy revealed that the outer dense fibers were defective in the patient’s sperm tail,which was similar to that of the reported heterozygous Odf2 mutation mouse.Immunostaining of ODF2 showed severe ODF2 expression defects in the patient’s sperm.Therefore,it was concluded that the heterozygous mutation in ODF2 caused MMAF in this case.To evaluate the possibility of assisted reproductive technology(ART)treatment for this patient,intracytoplasmic sperm injection(ICSI)was performed,with the help of a hypo-osmotic swelling test and laser-assisted immotile sperm selection(LAISS)for available sperm screening,and artificial oocyte activation with ionomycin was applied to improve the fertilization rate.Four ICSI cycles were performed,and live birth was achieved in the LAISS-applied cycle,suggesting that LAISS would be valuable in ART treatment for MMAF.展开更多
Multiple morphological abnormalities of the sperm flagella(MMAF)is a specific type of asthenoteratozoospermia,presenting with multiple morphological anomalies in spermatozoa,such as absent,bent,coiled,short,or irregul...Multiple morphological abnormalities of the sperm flagella(MMAF)is a specific type of asthenoteratozoospermia,presenting with multiple morphological anomalies in spermatozoa,such as absent,bent,coiled,short,or irregular caliber flagella.Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins(CFAPs;e.g.,CFAP43,CFAP44,CFAP65,CFAP69,CFAP70,and CFAP251)responsible for the MMAF phenotype in infertile men from different ethnic groups.However,none of them have been identified in infertile Pakistani males with MMAF.In the current study,two Pakistani families with MMAF patients were recruited.Whole-exome sequencing(WES)of patients and their parents was performed.WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families(Family 1:ENST00000357060.3,p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state;Family 2:ENST00000357060.3,p.Thr526Serfs*43 in a homozygous state).Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype.Semiquantitative reverse-transcriptase polymerase chain reaction(qRT-PCR)was carried out to detect the effect of the mutation on mRNA of the affected gene.Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients.To the best of our knowledge,this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype.This study will help researchers and clinicians to understand the genetic etiology of MMAF better.展开更多
Multiple morphological abnormalities of the sperm flagella(MMAF)is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate.Whole-exome sequencing(WES)is used to detec...Multiple morphological abnormalities of the sperm flagella(MMAF)is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate.Whole-exome sequencing(WES)is used to detect pathogenic variants in patients with MMAF.In this study,a novel homozygous frameshift variant(c.6158_6159insT)in dynein axonemal heavy chain 8(DNAH8)from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES.Reverse transcription-polymerase chain reaction(RT-PCR)confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation.Hematoxylin–eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients.Furthermore,an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients'spermatozoa.Collectively,our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.展开更多
Background: Infantile myofibromatosis is an uncommon disorder characterized by multiple fibromatous tumours involving skin, bone, muscle, viscera and subcutaneous tissue. It is a rare benign mesenchymal tumour;most co...Background: Infantile myofibromatosis is an uncommon disorder characterized by multiple fibromatous tumours involving skin, bone, muscle, viscera and subcutaneous tissue. It is a rare benign mesenchymal tumour;most commonly occurs in infancy or early childhood. The clinical presentation can mimic malignant tumours of infancy or childhood. Case Presentation: We describe a rare case of multicentric Infantile myofibromatosis in a 6-month-old infant presenting with multiple scalp swellings and associated skeletal abnormalities (adducted thumbs, clinodactyly and bilateral hallux valgus deformity of great toes). The case required surgical excision of all scalp lesions and orthopedic manipulation of skeletal abnormalities. Conclusion: Infantile myofibromatosis presenting as multiple lesions in the scalp associated with skeletal abnormalities, is very rare. To best of our knowledge, the unique combination of the distinct skeletal abnormalities in infantile myofibromatosis has not been reported so far. This report emphasizes the possibility of skeletal abnormalities in infantile myofibromatosis.展开更多
Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesi...Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesis remains unclear,the progress in multimodal imaging(MMI)has enhanced our understanding of MEWDS.Most cases of MEWDS are idiopathic,lacking a definite cause,and can spontaneously recover;these are what we term classic MEWDS.Consequently,MEWDS is often referred to as the“common cold of the retina”.Simultaneously,patients with other disorders may present with varying degrees of manifestations similar to MEWDS.The resemblance in clinical or imaging findings can lead to misdiagnosis and inappropriate treatment.These MEWDS-like presentations are actually caused by other systemic or ocular disorders with diverse mechanisms.Thus,they differ from classic MEWDS in certain aspects.Using the keywords“MEWDSlike”and“Secondary MEWDS”,we searched for all relevant studies published in the PubMed database from January 2021 to January 2024.Subsequently,we retrospectively summarized the clinical and imaging characteristics of MEWDS,along with the manifestations in other diseases that resembled those of MEWDS,and compared classic MEWDS with these similar presentations.Based on our review,we classified such similar presentations under other conditions into two categories and summarized their features for differential diagnosis.We recommend paying close attention to patients suspected of having MEWDS,as there may be more serious systemic or ocular disorders that require prompt treatment.展开更多
Background: Multiple sclerosis (MS) is a disease with wide variability in clinical presentation. Bladder dysfunctions are very common in MS patients. Early detection of bladder abnormalities is important to improve th...Background: Multiple sclerosis (MS) is a disease with wide variability in clinical presentation. Bladder dysfunctions are very common in MS patients. Early detection of bladder abnormalities is important to improve the outcome in MS patients. Objectives: The aim of this study is to evaluate the urodynamic detected bladder dysfunctions in relapsing remitting MS patients with mild or without lower urinary tract symptoms. Methods: This is a prospective study for 32 patients with relapsing remitting Multiple Sclerosis from January 2017 to June 2018. We included patients with mild or without lower urinary tract symptoms (LUTS) who had mild to moderate disability. Urodynamic studies were performed for all patients. Results: Urodynamic abnormalities were detected in 22 patients (68.75%). Detrusor overactivity (DO) was present alone in 8 patients (25%);DO combined with detrusor external sphincter dyssynergia in 8 patients (25%);DO with low compliant bladder and impaired contractility in another 4 patients (13%) while DO with low complaint bladder in 2 patients (6%). Bladder dysfunction was correlated to high disability score;longer duration of illness;frequent relapses and the presence of LUTS. Conclusion: Urodynamic abnormalities were found in 68.75% of our patients. This highlights the importance of urodynamic studies in the early evaluation of relapsing remitting Multiple Sclerosis.展开更多
Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have m...Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.展开更多
Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pa...Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.展开更多
BACKGROUND Metachronous multiple esophageal squamous cell carcinomas(ESCCs)may occur in some patients after endoscopic resection.Multiple dysplastic lesions in the esophagus increase risk of multiple squamous cell car...BACKGROUND Metachronous multiple esophageal squamous cell carcinomas(ESCCs)may occur in some patients after endoscopic resection.Multiple dysplastic lesions in the esophagus increase risk of multiple squamous cell carcinomas(SCCs).Endoscopic imaging technology such as narrow band imaging(NBI),can detect early SCC.Lugol chromoendoscopy is also the conventional standard technique for detecting superficial ESCC.However,little is known about the interval from the first SCC to the metachronous SCC.Effective methods to prevent multiple metachronous SCCs are needed in survivors of esophageal SCC.CASE SUMMARY A 56-year-old man showed a slightly elevated reddish area in the middle thoracic esophagus at 30 cm from the incisors on gastroscopy for routine examination.Esophageal mucosa lesion was about 2.5 cm.NBI and magnifying gastroscopy confirmed intra-epithelial papillary loop type B-1 according to the Japan Esophageal Society Classification.Lugol chromoendoscopy was used to evaluate the dysplastic squamous epithelium in the esophagus.Biopsy pathology revealed severe dysplastic squamous epithelium.Computed tomography showed no lymph node metastasis.His complete blood test and tumor markers were within reference values.He had no history of alcohol consumption and smoking.Mucosal lesion was dissected by endoscopic submucosal dissection(ESD).Postoperative pathological results showed moderately differentiated squamous carcinoma.No cancer thrombus was seen in the vasculature,and the surrounding cut edge was not involved.The patient underwent radiotherapy within 2 months after ESD.The multiple Lugol-voiding lesions disappeared,and enhanced chest computed tomography revealed no lymph node metastasis.CONCLUSION This is the first case of multiple dysplastic lesions of esophagus cured by radiotherapy.Radiotherapy after minimally invasive endoscopic treatment might be a safe and effective optional therapeutic strategy to prevent metachronous multiple esophageal SCCs.展开更多
Multiple principal element alloys(MPEAs),also known as high-entropy alloys,have attracted significant attention because of their exceptional mechanical and thermal properties.A critical factor influencing these proper...Multiple principal element alloys(MPEAs),also known as high-entropy alloys,have attracted significant attention because of their exceptional mechanical and thermal properties.A critical factor influencing these properties is suggested to be the presence of chemical short-range order(SRO),characterized by specific atomic arrangements occurring more frequently than in a random distribution.Despite extensive efforts to elucidate SRO,particularly in face-centered cubic(fcc)3d transition metal-based MPEAs,several key aspects remain under debate:the conditions under which SRO forms,the reliability of characterization methods for detecting SRO,and its quantitative impact on mechanical performance.This review summarizes the challenges and unresolved issues in this emerging field,drawing comparisons with well-established research on SRO in binary alloys over the past few decades.Through this cross-system comparison,we aim to provide new insights into SRO from a comprehensive perspective.展开更多
Multiple quantum well(MQW) Ⅲ-nitride diodes that can simultaneously emit and detect light feature an overlapping region between their electroluminescence and responsivity spectra, which allows them to be simultaneous...Multiple quantum well(MQW) Ⅲ-nitride diodes that can simultaneously emit and detect light feature an overlapping region between their electroluminescence and responsivity spectra, which allows them to be simultaneously used as both a transmitter and a receiver in a wireless light communication system. Here, we demonstrate a mobile light communication system using a time-division multiplexing(TDM) scheme to achieve bidirectional data transmission via the same optical channel.Two identical blue MQW diodes are defined by software as a transmitter or a receiver. To address the light alignment issue, an image identification module integrated with a gimbal stabilizer is used to automatically detect the locations of moving targets;thus, underwater audio communication is realized via a mobile blue-light TDM communication mode. This approach not only uses a single link but also integrates mobile nodes in a practical network.展开更多
The envisioned 6G wireless networks demand advanced Multiple Access (MA) schemes capable of supporting ultra-low latency, massive connectivity, high spectral efficiency, and energy efficiency (EE), especially as the c...The envisioned 6G wireless networks demand advanced Multiple Access (MA) schemes capable of supporting ultra-low latency, massive connectivity, high spectral efficiency, and energy efficiency (EE), especially as the current 5G networks have not achieved the promised 5G goals, including the projected 2000 times EE improvement over the legacy 4G Long Term Evolution (LTE) networks. This paper provides a comprehensive survey of Artificial Intelligence (AI)-enabled MA techniques, emphasizing their roles in Spectrum Sensing (SS), Dynamic Resource Allocation (DRA), user scheduling, interference mitigation, and protocol adaptation. In particular, we systematically analyze the progression of traditional and modern MA schemes, from Orthogonal Multiple Access (OMA)-based approaches like Time Division Multiple Access (TDMA) and Frequency Division Multiple Access (FDMA) to advanced Non-Orthogonal Multiple Access (NOMA) methods, including power domain-NOMA, Sparse Code Multiple Access (SCMA), and Rate Splitting Multiple Access (RSMA). The study further categorizes AI techniques—such as Machine Learning (ML), Deep Learning (DL), Reinforcement Learning (RL), Federated Learning (FL), and Explainable AI (XAI)—and maps them to practical challenges in Dynamic Spectrum Management (DSM), protocol optimization, and real-time distributed decision-making. Optimization strategies, including metaheuristics and multi-agent learning frameworks, are reviewed to illustrate the potential of AI in enhancing energy efficiency, system responsiveness, and cross-layer RA. Additionally, the review addresses security, privacy, and trust concerns, highlighting solutions like privacy-preserving ML, FL, and XAI in 6G and beyond. By identifying research gaps, challenges, and future directions, this work offers a structured resource for researchers and practitioners aiming to integrate AI into 6G MA systems for intelligent, scalable, and secure wireless communications.展开更多
Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the...Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML), which is a disease with Philadelphia (Ph) chromosome as the major abnormality. In the present study, we report a 76-year-old patient suspected of having AML with eosinophilic differentiation (AML-M4), which in clinical tests resembles CML blast crisis with multiple chromosomal abnormalities. Isochromosome 21 [i(21)(q10)] was the most recurrent feature noted in metaphases with 46 chromosomes. Ring chromosome, tetraploid endoreduplication, recurrent aneuploid clones with loss of X chromosome, monosomy 17, monosomy 7, and structural variation translocation (9;14) were also observed in this patient. Fluorescent in situ hybridization (FISH) confirmed the absence of Ph chromosome. This report shows how cytogenetic analyses revealed atypical structural aberrations in the M4 subtype of AML.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple pri...BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.展开更多
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
基金supported by the National Natural Science Foundation of China(No.32100689)the National Key Research and Development Program of China(No.2021YFC2700202,No.2022YFA0806303,and No.2022YFC2702601)+1 种基金the Global Select Project(No.DJK-LX-2022010)of the Institute of Health and MedicineHefei Comprehensive National Science Center,and the Joint Fund for New Medicine of USTC(No.YD9100002034).
文摘Multiple morphological abnormalities of sperm flagella(MMAF)is a severe form of asthenoteratozoospermia,characterized by morphological abnormalities and reduced motility of sperm,causing male infertility.Although approximately 60%of MMAF cases can be explained genetically,the etiology of the remaining cases is unclear.Here,we identified two novel compound heterozygous variants in the gene,dynein axonemal heavy chain 10(DNAH10),in three patients from two unrelated Pakistani families using whole-exome sequencing(WES),including one compound heterozygous mutation(DNAH10:c.9409C>A[p.P3137T];c.12946G>C[p.D4316H])in family 1 and another compound heterozygous mutation(DNAH10:c.8849G>A[p.G2950D];c.11509C>T[p.R3687W])in family 2.All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools.Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance.Hematoxylin and eosin(H&E)staining revealed MMAF,including sperm head abnormalities,in the patients.In addition,immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella.These findings broaden the spectrum of DNAH10 variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.
基金supported by the National Key Research and Development Program of China(No.2021YFC2700202,No.2022YFA0806303,and No.2022YFC2702601)the Global Select Project of the Institute of Health and Medicine,Hefei Comprehensive National Science Center(DJK-LX-2022010)the Joint Fund for New Medicine of USTC(YD9100002034).
文摘Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.871-4 ACA>A)in the adenylate kinase 7(AK7)gene by whole-exome sequencing in infertile individuals.Spermatozoa from affected individuals exhibited typical MMAF characteristics,including coiled,bent,short,absent,and irregular flagella.Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella.Immunofluorescence staining confirmed the absence of AK7 protein from the patients’spermatozoa,validating the pathogenic nature of the mutation.This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans,expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
文摘Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.
基金supported by grant from the National Key Research and Development Program of China(No.2017YFC1002003).
文摘Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella(MMAF),which cause severe asthenozoospermia and lead to male infertility,while the causes of approximately 50%of MMAF cases remain unclear.To reveal the genetic causes of MMAF in an infertile patient,whole-exome sequencing was performed to screen for pathogenic genes,and electron microscope was used to reveal the sperm flagellar ultrastructure.A novel heterozygous missense mutation in the outer dense fiber protein 2(ODF2)gene was detected,which was inherited from the patient’s mother and predicted to be potentially damaging.Transmission electron microscopy revealed that the outer dense fibers were defective in the patient’s sperm tail,which was similar to that of the reported heterozygous Odf2 mutation mouse.Immunostaining of ODF2 showed severe ODF2 expression defects in the patient’s sperm.Therefore,it was concluded that the heterozygous mutation in ODF2 caused MMAF in this case.To evaluate the possibility of assisted reproductive technology(ART)treatment for this patient,intracytoplasmic sperm injection(ICSI)was performed,with the help of a hypo-osmotic swelling test and laser-assisted immotile sperm selection(LAISS)for available sperm screening,and artificial oocyte activation with ionomycin was applied to improve the fertilization rate.Four ICSI cycles were performed,and live birth was achieved in the LAISS-applied cycle,suggesting that LAISS would be valuable in ART treatment for MMAF.
基金This work was supported by the National Natural Science Foundation of China(No.32070850)the National Natural Science Foundation of China(No.31630050,31890780,and 32061143006)+2 种基金the National Key Research and Developmental Program of China(2018YFC1003900,2019YFA0802600,and 2016YFC1000600)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB19000000)the Fundamental Research Funds for the Central Universities(No.YD2070002006).
文摘Multiple morphological abnormalities of the sperm flagella(MMAF)is a specific type of asthenoteratozoospermia,presenting with multiple morphological anomalies in spermatozoa,such as absent,bent,coiled,short,or irregular caliber flagella.Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins(CFAPs;e.g.,CFAP43,CFAP44,CFAP65,CFAP69,CFAP70,and CFAP251)responsible for the MMAF phenotype in infertile men from different ethnic groups.However,none of them have been identified in infertile Pakistani males with MMAF.In the current study,two Pakistani families with MMAF patients were recruited.Whole-exome sequencing(WES)of patients and their parents was performed.WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families(Family 1:ENST00000357060.3,p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state;Family 2:ENST00000357060.3,p.Thr526Serfs*43 in a homozygous state).Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype.Semiquantitative reverse-transcriptase polymerase chain reaction(qRT-PCR)was carried out to detect the effect of the mutation on mRNA of the affected gene.Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients.To the best of our knowledge,this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype.This study will help researchers and clinicians to understand the genetic etiology of MMAF better.
基金This work was supported by the National Natural Science Foundation of China(No.31871514,No.81971333,and No.82071709)the National Key Research and Development Program of China(2019YFA0802600 and 2021YFC2700202)。
文摘Multiple morphological abnormalities of the sperm flagella(MMAF)is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate.Whole-exome sequencing(WES)is used to detect pathogenic variants in patients with MMAF.In this study,a novel homozygous frameshift variant(c.6158_6159insT)in dynein axonemal heavy chain 8(DNAH8)from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES.Reverse transcription-polymerase chain reaction(RT-PCR)confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation.Hematoxylin–eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients.Furthermore,an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients'spermatozoa.Collectively,our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.
文摘Background: Infantile myofibromatosis is an uncommon disorder characterized by multiple fibromatous tumours involving skin, bone, muscle, viscera and subcutaneous tissue. It is a rare benign mesenchymal tumour;most commonly occurs in infancy or early childhood. The clinical presentation can mimic malignant tumours of infancy or childhood. Case Presentation: We describe a rare case of multicentric Infantile myofibromatosis in a 6-month-old infant presenting with multiple scalp swellings and associated skeletal abnormalities (adducted thumbs, clinodactyly and bilateral hallux valgus deformity of great toes). The case required surgical excision of all scalp lesions and orthopedic manipulation of skeletal abnormalities. Conclusion: Infantile myofibromatosis presenting as multiple lesions in the scalp associated with skeletal abnormalities, is very rare. To best of our knowledge, the unique combination of the distinct skeletal abnormalities in infantile myofibromatosis has not been reported so far. This report emphasizes the possibility of skeletal abnormalities in infantile myofibromatosis.
文摘Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesis remains unclear,the progress in multimodal imaging(MMI)has enhanced our understanding of MEWDS.Most cases of MEWDS are idiopathic,lacking a definite cause,and can spontaneously recover;these are what we term classic MEWDS.Consequently,MEWDS is often referred to as the“common cold of the retina”.Simultaneously,patients with other disorders may present with varying degrees of manifestations similar to MEWDS.The resemblance in clinical or imaging findings can lead to misdiagnosis and inappropriate treatment.These MEWDS-like presentations are actually caused by other systemic or ocular disorders with diverse mechanisms.Thus,they differ from classic MEWDS in certain aspects.Using the keywords“MEWDSlike”and“Secondary MEWDS”,we searched for all relevant studies published in the PubMed database from January 2021 to January 2024.Subsequently,we retrospectively summarized the clinical and imaging characteristics of MEWDS,along with the manifestations in other diseases that resembled those of MEWDS,and compared classic MEWDS with these similar presentations.Based on our review,we classified such similar presentations under other conditions into two categories and summarized their features for differential diagnosis.We recommend paying close attention to patients suspected of having MEWDS,as there may be more serious systemic or ocular disorders that require prompt treatment.
文摘Background: Multiple sclerosis (MS) is a disease with wide variability in clinical presentation. Bladder dysfunctions are very common in MS patients. Early detection of bladder abnormalities is important to improve the outcome in MS patients. Objectives: The aim of this study is to evaluate the urodynamic detected bladder dysfunctions in relapsing remitting MS patients with mild or without lower urinary tract symptoms. Methods: This is a prospective study for 32 patients with relapsing remitting Multiple Sclerosis from January 2017 to June 2018. We included patients with mild or without lower urinary tract symptoms (LUTS) who had mild to moderate disability. Urodynamic studies were performed for all patients. Results: Urodynamic abnormalities were detected in 22 patients (68.75%). Detrusor overactivity (DO) was present alone in 8 patients (25%);DO combined with detrusor external sphincter dyssynergia in 8 patients (25%);DO with low compliant bladder and impaired contractility in another 4 patients (13%) while DO with low complaint bladder in 2 patients (6%). Bladder dysfunction was correlated to high disability score;longer duration of illness;frequent relapses and the presence of LUTS. Conclusion: Urodynamic abnormalities were found in 68.75% of our patients. This highlights the importance of urodynamic studies in the early evaluation of relapsing remitting Multiple Sclerosis.
基金supported by grant from the National Natural Science Foundation of China(Grant No.82300231).
文摘Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金Private DonationLa Trobe Research Focus AreasMultiple Sclerosis Australia,Grant/Award Number:20-032。
文摘Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.
基金Supported by Jinhua City Science and Technology Plan Projects,No.2022-4-145.
文摘BACKGROUND Metachronous multiple esophageal squamous cell carcinomas(ESCCs)may occur in some patients after endoscopic resection.Multiple dysplastic lesions in the esophagus increase risk of multiple squamous cell carcinomas(SCCs).Endoscopic imaging technology such as narrow band imaging(NBI),can detect early SCC.Lugol chromoendoscopy is also the conventional standard technique for detecting superficial ESCC.However,little is known about the interval from the first SCC to the metachronous SCC.Effective methods to prevent multiple metachronous SCCs are needed in survivors of esophageal SCC.CASE SUMMARY A 56-year-old man showed a slightly elevated reddish area in the middle thoracic esophagus at 30 cm from the incisors on gastroscopy for routine examination.Esophageal mucosa lesion was about 2.5 cm.NBI and magnifying gastroscopy confirmed intra-epithelial papillary loop type B-1 according to the Japan Esophageal Society Classification.Lugol chromoendoscopy was used to evaluate the dysplastic squamous epithelium in the esophagus.Biopsy pathology revealed severe dysplastic squamous epithelium.Computed tomography showed no lymph node metastasis.His complete blood test and tumor markers were within reference values.He had no history of alcohol consumption and smoking.Mucosal lesion was dissected by endoscopic submucosal dissection(ESD).Postoperative pathological results showed moderately differentiated squamous carcinoma.No cancer thrombus was seen in the vasculature,and the surrounding cut edge was not involved.The patient underwent radiotherapy within 2 months after ESD.The multiple Lugol-voiding lesions disappeared,and enhanced chest computed tomography revealed no lymph node metastasis.CONCLUSION This is the first case of multiple dysplastic lesions of esophagus cured by radiotherapy.Radiotherapy after minimally invasive endoscopic treatment might be a safe and effective optional therapeutic strategy to prevent metachronous multiple esophageal SCCs.
基金supported by the Shanghai Key Laboratory of Material Frontiers Research in Extreme Environments,China(Grant No.22dz2260800)the Shanghai Science and Technology Committee,China(Grant No.22JC1410300).
文摘Multiple principal element alloys(MPEAs),also known as high-entropy alloys,have attracted significant attention because of their exceptional mechanical and thermal properties.A critical factor influencing these properties is suggested to be the presence of chemical short-range order(SRO),characterized by specific atomic arrangements occurring more frequently than in a random distribution.Despite extensive efforts to elucidate SRO,particularly in face-centered cubic(fcc)3d transition metal-based MPEAs,several key aspects remain under debate:the conditions under which SRO forms,the reliability of characterization methods for detecting SRO,and its quantitative impact on mechanical performance.This review summarizes the challenges and unresolved issues in this emerging field,drawing comparisons with well-established research on SRO in binary alloys over the past few decades.Through this cross-system comparison,we aim to provide new insights into SRO from a comprehensive perspective.
基金jointly supported by the National Natural Science Foundation of China (U21A20495)Natural Science Foundation of Jiangsu Province (BG2024023)+1 种基金National Key Research and Development Program of China (2022YFE0112000)111 Project (D17018)。
文摘Multiple quantum well(MQW) Ⅲ-nitride diodes that can simultaneously emit and detect light feature an overlapping region between their electroluminescence and responsivity spectra, which allows them to be simultaneously used as both a transmitter and a receiver in a wireless light communication system. Here, we demonstrate a mobile light communication system using a time-division multiplexing(TDM) scheme to achieve bidirectional data transmission via the same optical channel.Two identical blue MQW diodes are defined by software as a transmitter or a receiver. To address the light alignment issue, an image identification module integrated with a gimbal stabilizer is used to automatically detect the locations of moving targets;thus, underwater audio communication is realized via a mobile blue-light TDM communication mode. This approach not only uses a single link but also integrates mobile nodes in a practical network.
文摘The envisioned 6G wireless networks demand advanced Multiple Access (MA) schemes capable of supporting ultra-low latency, massive connectivity, high spectral efficiency, and energy efficiency (EE), especially as the current 5G networks have not achieved the promised 5G goals, including the projected 2000 times EE improvement over the legacy 4G Long Term Evolution (LTE) networks. This paper provides a comprehensive survey of Artificial Intelligence (AI)-enabled MA techniques, emphasizing their roles in Spectrum Sensing (SS), Dynamic Resource Allocation (DRA), user scheduling, interference mitigation, and protocol adaptation. In particular, we systematically analyze the progression of traditional and modern MA schemes, from Orthogonal Multiple Access (OMA)-based approaches like Time Division Multiple Access (TDMA) and Frequency Division Multiple Access (FDMA) to advanced Non-Orthogonal Multiple Access (NOMA) methods, including power domain-NOMA, Sparse Code Multiple Access (SCMA), and Rate Splitting Multiple Access (RSMA). The study further categorizes AI techniques—such as Machine Learning (ML), Deep Learning (DL), Reinforcement Learning (RL), Federated Learning (FL), and Explainable AI (XAI)—and maps them to practical challenges in Dynamic Spectrum Management (DSM), protocol optimization, and real-time distributed decision-making. Optimization strategies, including metaheuristics and multi-agent learning frameworks, are reviewed to illustrate the potential of AI in enhancing energy efficiency, system responsiveness, and cross-layer RA. Additionally, the review addresses security, privacy, and trust concerns, highlighting solutions like privacy-preserving ML, FL, and XAI in 6G and beyond. By identifying research gaps, challenges, and future directions, this work offers a structured resource for researchers and practitioners aiming to integrate AI into 6G MA systems for intelligent, scalable, and secure wireless communications.
基金supported by a grant from Kerala State Council for Science, Technology and Environment(KSCSTE), Govt. of Kerala, India
文摘Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML), which is a disease with Philadelphia (Ph) chromosome as the major abnormality. In the present study, we report a 76-year-old patient suspected of having AML with eosinophilic differentiation (AML-M4), which in clinical tests resembles CML blast crisis with multiple chromosomal abnormalities. Isochromosome 21 [i(21)(q10)] was the most recurrent feature noted in metaphases with 46 chromosomes. Ring chromosome, tetraploid endoreduplication, recurrent aneuploid clones with loss of X chromosome, monosomy 17, monosomy 7, and structural variation translocation (9;14) were also observed in this patient. Fluorescent in situ hybridization (FISH) confirmed the absence of Ph chromosome. This report shows how cytogenetic analyses revealed atypical structural aberrations in the M4 subtype of AML.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金Supported by Gansu Provincial Natural Science Foundation,No.21JR1RA010In-Hospital Research Fund of Gansu Provincial Hospital,No.23GSSYD-5.
文摘BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.
