For differentiated thyroid cancer(DTC),which accounts for over 90%of cases and usually has a good prognosis,bone metastasis is not only the main threat to patients'survival and quality of life,but also a difficult problem that needs to be solved urgently in clinical diagnosis and treatment at this stage.Currently,existing clinical guidelines at home and abroad have not yet provided comprehensive management recommendations and precise diagnostic and treatment strategies for bone metastasis in thyroid cancer,making it imperative to promote the implementation of systematic and personalized diagnostic and treatment plans.Therefore,understanding epidemiological characteristics,clarifying the pathogenesis,mastering commonly used diagnostic techniques,exploring the latest treatment progress and evaluating treatment efficacy are crucial for the management of bone metastasis in thyroid cancer.In terms of pathogenesis,bone metastasis in thyroid cancer is mostly osteolytic,regulating the interaction between the bone microenvironment and cancer cells through the release of various cytokines,thus forming a vicious cycle of bone metastasis.Early identification of bone metastasis in DTC is crucial for improving patient prognosis.Its diagnosis can be based on clinical manifestations(such as bone pain,pathological fractures,spinal cord compression and hypercalcemia),laboratory tests(such as red blood cell and platelet counts,serum calcium/phosphorus and bone turnover markers),and imaging examination results[such as X-ray,computed tomography(CT),magnetic resonance imaging(MRI),single photon emission computed tomography(SPECT)/CT,and positron emission tomography(PET)/CT].The treatment of DTC bone metastasis involves multiple modalities,such as surgical treatment,interventional radiological treatment and external beam radiation therapy for local lesions,or the use of radionuclides(131I,89Sr and 153Sm),tyrosine kinase inhibitors(lenvatinib,sorafenib,etc.),or bone-targeting agents(including zoledronic acid,denosumab and 99Tc-methylene diphosphonate)to control the development of systemic bone metastasis.After the treatment of DTC bone metastasis,an efficacy evaluation should be conducted to guide subsequent treatment decisions and predict prognosis.With the increasingly mature multidisciplinary collaborative diagnosis and treatment model today,the diagnosis and treatment of bone metastatic DTC should include surgery,nuclear medicine,radiation and interventional therapy,external beam radiation therapy,medical oncology and clinical laboratory testing to ensure a comprehensive assessment of the patient's condition,make objective decisions on individualized treatment plans,and achieve the goal of preventing disease progression and alleviating symptoms.This article mainly reviewed the epidemiology,pathogenesis,diagnostic methods,treatment strategies and efficacy evaluation of bone metastasis,aiming to clarify the diagnostic and treatment thinking of bone metastasis in thyroid cancer,assist in clinical management,and provide useful references for clinicians to make rapid and accurate diagnosis and precise treatment decisions when facing patients with bone metastatic DTC.

Thyroid cancer is the most common malignant tumor of the endocrine system and head and neck region,mainly including papillary thyroid cancer(PTC),follicular thyroid cancer(FTC),medullary thyroid cancer(MTC)and anaplastic thyroid cancer(ATC).Over the past few decades,the global incidence of thyroid cancer has risen rapidly,nearly doubling in some developed countries.Geographically,thyroid cancer incidence is higher in economically developed regions.Although the fastest increase in incidence has been observed in high-income countries,certain middle-income countries have also reported significant growth.Demographically,the incidence rate is notably higher in women than in men.In China,the incidence of thyroid cancer has increased significantly in recent years,while the mortality rate has remained stable at a low level.Urban areas report higher incidence rates than rural areas,and eastern coastal regions have higher rates compared to central and western regions.The etiology of thyroid cancer is multifaceted,with major risk factors including genetic predisposition,radiation exposure,iodine intake levels,endocrine disruptions,environmental and lifestyle factors.Among these,radiation exposure(particularly ionizing radiation during childhood)is a recognized critical risk factor.In addition,both insufficient and excessive iodine intake can disrupt thyroid function,thereby increasing disease risk.Genetic factors,such as familial clustering and gene(BRAF,RET/PTC,etc.)mutations,have been widely studied,while environmental pollution and modern lifestyles may also contribute to disease onset.Therefore,it is beneficial to conduct early screening for people with a family history of thyroid cancer,reduce unnecessary medical radiation exposure and conduct intervention on lifestyle-related risk factors such as obesity to prevent and control thyroid cancer.Most patients with thyroid cancer have a favorable prognosis.The main factors influencing the prognosis include pathological typing(PTC has a relatively better prognosis,while MTC and ATC have poorer prognoses),clinical staging(patients at TNM stages Ⅰ and Ⅱ have better prognoses,while those at stages Ⅲ and Ⅳ have worse ones),physiological factors(the overall prognosis of females is superior to that of males),genetic factors and environmental factors.Understanding the epidemiological trends and identifying factors influencing the onset and prognosis of thyroid cancer are essential for its prevention,treatment and health management.Future research should focus on identifying high-risk populations and developing targeted interventions to prevent and control thyroid cancer,reduce its disease burden,improve quality of life for patients,and lower healthcare costs.

Breast cancer is one of the most common malignant tumors in women,which posing a serious threat to women's health.With the deepening of the concept of precision treatment,the surgical treatment of breast cancer has made great progress.However,new techniques and ideas have also brought about many controversies.With the popularization of the"de-escalation"concept,performing sentinel lymph node biopsy(SLNB)as an alternative to axillary lymph node dissection(ALND)in specific patients has emerged as a trend.For clinically node-negative early-stage breast cancer with 1-2 positive sentinel lymph nodes(SLN),ALND can be safely omitted with effective axillary radiotherapy.Patients with clinically node-positive early-stage breast cancer can forgo ALND if SLNB proves that they have been downstaged to cN0 by neoadjuvant treatment(NAT).As the two most commonly used axillary surgical staging techniques in SLNB for post-NAT patients,dual-tracer of lymph nodes and targeted axillary dissection(TAD)are considered consistent in oncologic safety.Prophylactic mastectomy is a significant intervention to reduce breast cancer incidence among women at high risk.It has been confirmed that contralateral prophylactic mastectomy(CPM)can reduce the incidence of contralateral breast cancer(CBC)but does not significantly improve the survival outcomes.Enhancing the accessibility of risk assessment methods and establishing precise and effective risk prediction models have emerged as important issues.Above all,the development of breast surgery shows a refinement of risk management and damage control,striving to achieve a safe"de-escalation"in surgical modalities based on individualized treatment.This article summarized and analyzed relevant studies on the aspect of the surgery techniques for breast cancer,aiming to provide new insights into optimizing the clinical diagnosis and treatment of breast cancer.

Background and purpose:Epithelial ovarian cancer(EOC)has a poor prognosis and is prone to developing resistance to platinum-based chemotherapy.Exosomes are currently believed to be involved in platinum resistance in ovarian cancer.This study explored the role and mechanism of exosomes on platinum resistance of ovarian cancer.Methods:Through ultracentrifugation,exosomes were isolated and analyzed using electron microscopy,particle size studies,and Western blot for detailed exosome analysis.We detected the expression levels of exosomal proteins and related signaling pathways.Exosomal protein expression profile was analyzed by proteomics.Key differential proteins were screened by intersecting with existing drug resistance datasets.Furthermore,patients diagnosed with EOC via pathological analysis at the Fudan University Shanghai Cancer Center from August 2023 to August 2024,who underwent surgery and fulfilled the eligibility requirements,were gathered to examine the link between the expression of interferon-stimulated gene 15(ISG15)in serum exosomes and resistance to platinum medication.The expression levels of related proteins in serum exosomes were quantitatively detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic(ROC)curve was plotted to explore the predictive value of serum exosomal protein in ovarian cancer resistance.Results:Exosomes derived from platinum-sensitive and drug-resistant ovarian cancer cells were extracted and proteomic analysis was further performed.We identified 9 differential proteins associated with platinum-resistance and found the key molecule interferon-stimulated gene 15(ISG15).Compared with sensitive cells,the expression of ISG15 in exosomes of drug-resistant ovarian cancer cells was significantly upregulated.Exosome tracer tests showed that exosomes were successfully taken up by ovarian cancer receptor cells.After coculture with drug-resistant exosomes,the expression level of ISG15 in ovarian cancer receptor cells was increased.Knockdown ISG15 in EOC cells decreased the expression of ISG15 in exosomes,and incubation of ISG15-knockdown exosomes decreased the cell viability on the condition of platinum drugs,indicating that ISG15 in exosomes regulated platinum resistance of ovarian cancer cells.Moreover,ISG15 could regulate the expression of multidrug resistance protein 1(MDR1)through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-kappa-light-chain-enchancer of activated B cells(NF-κB)signaling pathway.This study included a total of 87 patients.Clinical serum samples also showed that the expression of ISG15 in exosomes was higher in platinum-resistant ovarian cancer patients than in sensitive ovarian cancer patients.Using serum exosomal ISG15 as an indicator to distinguish between sensitivity and resistance,the area under ROC curve was 0.779(P＜0.05),cutoffvalue was 27.35ng/mL,sensitivity was 70.2%,and specificity was 76.4%.Conclusion:ISG15 in exosomes can regulate the expression of MDR1 in ovarian cancer cells through PI3K/AKT/NF-κB signaling pathway,and promote platinum resistance in ovarian cancer cells.

Background and purpose:High-throughput detection of plasma cell-free DNA(cfDNA)is widely used for multi-cancer targeted therapy drug screening,and this study investigated the relationship between the type and number of plasma cfDNA class Ⅰ and Ⅱ targeted therapy-related gene variants and cancer survival in patients with non-small cell lung cancer(NSCLC).Methods:The sequencing results and clinical data of NSCLC patients who underwent tumor plasma cfDNA high-throughput sequencing projects in Sun Yat-sen University Cancer Center from 2021 to 2023 were collected.The survival follow-up of enrolled patients was carried out from the day of plasma collection on June 1,2021 to May 27,2024,and GraphPad Prism 8.0 and SPSS Statistics 25.0 were used.Univariate and multivariate statistical analyses were conducted on the types and numbers of class Ⅰ and class Ⅱ targeted therapy-related genes in the survival and clinical data of patients and sequencing results(Ethical approval:B2024-359-01).Results:A total of 313 patients included in this study with NSCLC were categorized into stage Ⅰ 25 patients(7.98%),stageⅡ 20 patients(6.39%),stage Ⅲ 38patients(12.14%),and stage Ⅳ 230 patients(73.48%).Pathological diagnosis results showed that adenocarcinoma accounted for 90.10%,squamous cell carcinoma accounted for 5.11%,large cell carcinoma accounted for 2.87%and other classifications accounted for 1.92%.The number and the percentage of class Ⅰ and class Ⅱ targeted therapy drug-related genes in the plasma cfDNA NSCLC patients were 0(25.24%),1(17.57%),2(19.17%),3(14.38%),4(8.31%),and 5 or more(15.34%).The results of statistical analysis showed that 3 genes with the highest mutation frequencies were EGFR,TP53 and ERBB2,and the mutation frequency of EGFR gene was 36.04%.The mutation frequency of TP53 gene was 30.63%.The mutation frequency of ERBB2 gene was 4.95%.The survival time of patients is related to not only the expression of hotspot targeted genes,but also the number of class Ⅰ and Ⅱ target-related gene variants detected by plasma cfDNA high-throughput sequencing.The survival time of the patients with no targeted therapy-related locus variants after treatment was longer compares with targeted therapy-related locus variants,which can reduce the risk of death by 63.2%.However,patients with a single gene locus variant had longer survival time and lower risk of death than those with multiple driver locus variants,and the measured class Ⅰ and Ⅱ targeted therapy drugs were within 3 genes.Overall,the smaller the number of genes,the longer the survival.Conclusions:The number of class Ⅰ and class Ⅱtargeted therapy-related gene variants in plasma cfDNA high-throughput sequencing also has an effect on the survival of patients after treatment.Plasma cfDNA level detected by high-throughput sequencing could be a prognostic factor for the NSCLC patients.

Background and purpose:Polo-like kinase 4(PLK4)is a cell cycle regulatory protein,which is closely related to the occurrence and development of a variety of malignant tumors.The aim of this study was to investigate the role of PLK4 in the proliferation,invasion and apoptosis of oral squamous cell carcinoma(OSCC).Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)and the University of Alabama at Birmingham Cancer Data Analysis Portal(UALCAN)were used to analyze the expression of PLK4 in head and neck squamous cell carcinoma and surrounding normal tissues.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot were employed to evaluate the mRNA and protein expression of PLK4 in OSCC cells.We further analyzed PLK4,phosphoinositide 3-kinase(PI3K),phosphorylated phosphoinositide 3-kinase(p-PI3K),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),survivin,and cyclin D1 protein expression.The effects of PLK4 on cell proliferation,apoptosis and invasion were analyzed by cell counting kit-8(CCK-8)assay,flow cytometry and transwell assay.In addition,12 4-week-old SPF BALB/c female nude mice were divided into sh-NC group(n=6)and sh-PLK4 group(n=6)by random number table method.The sh-NC/sh-PLK4 cells were injected into the right anterior armpit of nude mice for subcutaneous tumor formation.The body weight,tumor volume and tumor weight of the two groups of nude mice were observed,and the stripped tumor tissues were analyzed by H-E staining.The animal experiments were approved by the Animal Experiment Center of Shandong Second Medical University(No:2024SDL840).Results:The results of GEPIA2 and UALCAN online databases showed that PLK4 was highly expressed in OSCC compared with normal tissues.In addition,PLK4 was highly expressed in OSCC cell lines(HN6,Cal-27,SCC-4,SCC-9,SCC-25)compared with oral mucosal epithelial cells(P＜0.05).Western blot results showed that the expression levels of PI3K/AKT signaling pathway proteins p-PI3K,p-AKT,cyclin D1 and survivin were decreased after PLK4 knockdown and increased after PLK4 overexpression in OSCC cells(P＜0.05).The cell proliferation activity and the number of transmembrane cells were positively correlated with the decrease and increase of PLK4 expression(P＜0.05),while the cell apoptotic rate was negatively correlated(P＜0.05),indicating that cell proliferation and apoptosis were both affected.In addition,compared with the sh-NC group,the tumor volume and weight of the nude mice in the sh-PLK4 group were decreased(P＜0.05),while there was no significant difference in the body weight of the nude mice between the two groups(P＞0.05).Moreover,the nuclear atypia of tumor tissues in sh-PLK4 group was lower than that in sh-NC group(P＜0.05).Conclusion:PLK4 can regulate the invasion,proliferation and apoptosis of OSCC cells,potentially through the activation of PI3K/AKT signaling pathway.

Background and purpose:There are few studies on the quality of life after transanal total mesorectal excision(TaTME)for rectal cancer,and there is a lack of evidence-based research.This study aimed to evaluate the impact of TaTME in comparison to laparoscopic total mesorectal excision(LaTME)on postoperative quality of life in patients.Methods:A retrospective analysis was conducted on clinical and pathological data from rectal cancer patients who underwent LaTME and TaTME between September 2019 and September 2022 at Renhe Hospital,Baoshan District,Shanghai,and Fudan University Shanghai Cancer Center.All the patients completed a set of validated questionnaires one year postoperatively,including the EORCT QLQ-C30,Low Anterior Resection Syndrome(LARS)score,International Prostate Symptom Score(IPSS),Generalized Anxiety Disorder-7(GAD-7),and Patient Health Questionnaire-9(PHQ-9).Comparative analysis of these survey results was performed.The study was approved by the Ethics Committee of Renhe Hospital,Baoshan District,Shanghai.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:A total of 39 patients in the TaTME group and 38 patients in the LaTME group were included.There were no statistically significant differences between two groups regarding demographic variables such as gender and age,as well as clinical factors including tumor distance from the anal verge,tumor stage,and preoperative neoadjuvant treatment protocols.Analysis of EORCT QLQ-C30 results indicated equivalent overall quality of life between the two groups;however,the TaTME group reported significantly more severe insomnia(P=0.020).No significant differences were observed in LARS severity or total scores between the groups,though the TaTME group demonstrated superior functional outcomes in terms of incontinence for liquid stools and clustering of stools(P=0.007,P=0.004).Additionally,both groups exhibited comparable results in IPSS,and levels of depression and anxiety.Conclusion:The findings suggest that TaTME and LaTME yield similar outcomes in terms of anal and urinary function,overall quality of life,and psychological health,indicating that it is a viable and safe alternative to LaTME in terms of postoperative quality of life.

Background and purpose:Tumor necrosis factor alpha-induced protein 8(TNFAIP8),also called TIPE,plays critical regulatory roles in various malignancies,yet its molecular mechanisms in metabolic reprogramming of triple-negative breast cancer(TNBC)remain elusive.This study aimed to elucidate how TIPE regulates the expression of the glycolytic key enzyme lactate dehydrogenase A to influence TNBC cell proliferation and glycolytic reprogramming,thereby providing potential molecular targets for TNBC therapy.Methods:Stable TIPE-knockdown MDA-MB-231 cell lines were established using a lentiviral shRNA system and selected with puromycin.Transcriptome sequencing was used to analyze TIPE's impact on TNBC glycolytic pathways.Extracellular acidification rate(ECAR)was measured using the Seahorse XF Analyzer,complemented by lactate production assays to evaluate glycolytic capacity.Co-IP/MS was carried out to identify TIPE-interacting proteins,with subsequent validation of TIPE-LDHA interaction through co-transfection of TIPE-Myc and LDHA-Flag plasmids in HEK-293T cells.Protein stability was assessed via cycloheximide(CHX)chase and ubiquitination assays.The cell counting kit-8(CCK-8)assay and animal experiments(Approval Number for Animal Ethics:202212007)were conducted to investigate how TIPE affects the proliferation and glucometabolic reprogramming of TNBC by mediating LDHA.Results:TIPE promoted glycolytic metabolic reprogramming in TNBC.Knockdown of TIPE significantly inhibited TNBC glycolytic activity and glycolytic capacity(P＜0.001).TIPE interacted with the key glycolytic enzyme LDHA and suppressed its degradation rate through a ubiquitination-dependent mechanism.Cellular experiments demonstrated that TIPE mediated LDHA to enhance TNBC cell proliferation(P＜0.001)and glycolytic activity(P＜0.001).Animal studies confirmed that TIPE knockdown significantly suppressed tumor volume(P＜0.05)and weight(P＜0.01),with a positive correlation between TIPE and LDHA expression levels in tumor tissues.Conclusion:TIPE enhances TNBC cell proliferation and glycolytic capacity by inhibiting LDHA ubiquitination-mediated degradation.

Histone lactylation is a novel type of post-translational modification,where a lactate molecule covalently binds to the lysine residues of histones.This modification plays a key role in cellular metabolic reprogramming,particularly in digestive system tumorigenesis and progression.In recent years,the role of histone lactylation in various malignancies has been increasingly recognized,highlighting its broad impact on tumor biology and clinical potential.This article focused on the research progress of histone lactylation in digestive system cancers,specifically analyzing its mechanisms in major gastrointestinal cancers such as gastric cancer,liver cancer,and colon cancer.Studies have shown that lactylation modifies histone lysine residues directly,regulating tumor cell gene expression and chromatin conformation,thereby promoting tumor proliferation,invasion,and metastasis.Lactylation affects histone-DNA interactions,altering chromatin openness and enhancing the transcriptional activity of oncogenes.In addition,targeted therapies that modulate lactation levels or inhibit lactation-related enzymes,such as lactate dehydrogenase inhibitors,lactate production inhibitors,and specific histone lactonases,are effective in inhibiting tumorigenesis and progression and have demonstrated potential therapeutic efficacy in preclinical models.This article systematically summarized the mechanisms of histone lactylation in various types of gastrointestinal cancers,offering new research directions and theoretical support for targeted therapeutic strategies based on lactylation modification.

Background and purpose:With the increasing use of medical imaging examinations,Computed tomography(CT)scans have become one of the primary sources of effective dose.This study analyzed the correlation between radiation dose,image quality and body composition in thyroid CT to provide a data foundation for better control of radiation dose and image quality in the future.Methods:A retrospective analysis was conducted on patients who underwent thyroid CT scans at Fudan University Shanghai Cancer Center from January 2015 to December 2019.CT values and standard deviations(SD)of the homogeneous parenchyma of the thyroid were collected,and CT values and SD values of adjacent subcutaneous fat tissue were measured with the same region of interest(ROI)size.All data were measured three times to obtain the average value,and the volume CT dose index(CTDIvol)and dose-length product(DLP)were recorded.Effective dose values and signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)for various parts were calculated.All patients underwent bone density examinations,and patient height,weight,body mass index(BMI),body surface area(BSA),and the percentage of muscle and fat in the spine and thighs were recorded.Results:A total of 104 patients were enrolled in this study.The SNR of thyroid CT images and the percentage of spinal muscle(r=0.284,P=0.004),CNR of thyroid CT images and the percentage of spinal fat(r=0.197,P=0.045),and the effective dose of thyroid CT images and age,weight,BMI,thigh fat percentage,and body surface area(r=0.221,0.247,0.260,0.262,and 0.222;P=0.024,0.011,0.008,0.007 and 0.024)were positively correlated.While,SNR and age,weight,BMI,and the percentage of spinal fat(r=-0.292,-0.198,-0.207,and-0.284;P=0.003,0.044,0.035,0.004),CNR and the percentage of spinal muscle(r=-0.197,P=0.045),and the effective dose and the percentage of thigh muscle(r=-0.262,P=0.007)were negatively correlated.Conclusion:The radiation dose in thyroid CT is correlated with female body composition.The image quality is related to female body composition,providing a data foundation for better control of radiation dose and image quality in the future.