BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particu...BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particularly in the vertical direction.Endoscopic full-thickness resection(EFTR)has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs,including 132 who underwent endoscopic submucosal dissection(ESD)and 28 who underwent EFTR.Lesions were categorized as<1 cm,1-2 cm,and>2 cm in size.CR rate,en bloc resection rate,operation time,and complications were evaluated.Subgroup analyses and follow-up were also performed.RESULTS EFTR achieved 100%CR rates for lesions<1 cm and 1-2 cm,compared with 67.0%and 50.0%,respectively,in the ESD group.En bloc resection and successful removal of the R-NENs were achieved in all patients.Meanwhile,EFTR showed performance comparable to ESD in terms of operation time,hospitalization cost,and postoperative adverse events,except for a one-day longer hospital stay.We also analyzed the invasion depth of R-NENs based on full-thickness specimens.The data showed that 80%of lesions(<1 cm)and 85.7%of lesions(1-2 cm)had invaded the SM3 level or deeper at the time of resection.For ESD specimens,46.6%(<1 cm)and 89.3%(1-2 cm)of lesions had infiltrated more than 2000μm beneath the muscularis mucosae.CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.展开更多
Neuroendocrine neoplasms(NENs)are relatively rare tumors that arise from peptidergic neurons and neuroendocrine cells.NENs are highly heterogeneous and can occur in any part of the body,with a particular prevalence in...Neuroendocrine neoplasms(NENs)are relatively rare tumors that arise from peptidergic neurons and neuroendocrine cells.NENs are highly heterogeneous and can occur in any part of the body,with a particular prevalence in the digestive system.NENs consist of a range of tumor types and the biological behaviors exhibit significant differences.NENs are classified into well-differentiated neuroendocrine tumors(NETs)and poorly differentiated neuroendocrine carcinomas(NECs).NETs can be further classified and graded into the following three categories:low-grade NETs,grade 1(NET G1);intermediate-grade NET G2;and high-grade NET G3.NECs include large cell-type NEC(LCNEC)and small cell-type NEC(SCNEC),both of which are considered high grade.Currently,the main treatments for advanced NENs are biological treatments,targeted therapy,chemotherapy,and newer treatments that are still under development,such as immunotherapy and peptide receptor radionuclide therapy(PRRT).However,owing to the rarity of NENs,pharmaceutical company investment is limited and few phase Ⅲ studies have targeted advanced NENs.Most current research consists of investigator-initiated phase Ⅰ and Ⅱ clinical trials or largescale retrospective studies.NEN treatment should be chosen carefully because it is cumbersome and complicated,as indicated above.Herein,we comprehensively summarize the clinical application status and research progress for advanced NEN treatment regimens,especially for advanced NETs,which may help to create awareness on NENs among medical professionals across specialties.展开更多
Appendiceal mucinous neoplasms(AMNs)are rare tumors originating from mucin-producing epithelial cells of the appendix.They can exhibit both benign and malignant behavior.They are often incidentally discovered during a...Appendiceal mucinous neoplasms(AMNs)are rare tumors originating from mucin-producing epithelial cells of the appendix.They can exhibit both benign and malignant behavior.They are often incidentally discovered during appendectomy.Clinical presentation ranges from asymptomatic to mimicking acute appendicitis.Histologically,noninvasive AMNs are classified as low-grade AMNs(LAMNs)or high-grade AMNs(HAMNs),whereas invasive tumors are categorized as mucinous adenocarcinomas.Although LAMNs and HAMNs are generally nonmalignant,rupture can lead to pseudomyxoma peritonei(PMP).Surgical resection is the primary diagnostic and therapeutic approach,with intraoperative assessment to prevent rupture.Treatment strategies vary based on findings and include appendectomy,right hemicolectomy,and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Histological diagnosis relies on mucin detection,and immunohistochemical markers such as cytokeratin 20(diffusely positive),cytokeratin 7(often negative),mucin 5AC,and special ATrich sequence-binding protein 2 assist in characterization.Molecular profiling frequently identifies KRAS,GNAS,and TP53 mutations.KRAS mutations are generally associated with a favorable prognosis,whereas GNAS and TP53 mutations correlate with poorer survival outcomes.These findings highlight the potential role of molecular profiling in guiding treatment strategies for AMN and PMP.展开更多
BACKGROUND Pancreatic cystic neoplasms(PCNs)are increasingly detected due to advancements in radiographic techniques,with a prevalence of approximately 15%in the general population.These lesions range from benign to p...BACKGROUND Pancreatic cystic neoplasms(PCNs)are increasingly detected due to advancements in radiographic techniques,with a prevalence of approximately 15%in the general population.These lesions range from benign to premalignant and malignant,posing a diagnostic challenge.Accurate differentiation is critical,as premalignant and malignant PCNs often require surgical intervention,while benign cysts may only need monitoring unless symptomatic.Current diagnostic methods,including cross-sectional imaging,endoscopic ultrasonography,and endoscopic ultrasonography-guided fine-needle aspiration/biopsy,are specialized,not universally available,and have variable accuracy.Clinical and laboratory parameters such as carbohydrate antigen 19-9(CA 19-9),neutrophillymphocyte ratio,platelet-lymphocyte ratio,and red cell distribution width(RDW)have been associated with malignancy risk,though only CA 19-9 is guideline-supported.AIM To assess the malignancy risk of PCNs using preoperative clinical and routine laboratory parameters.METHODS A retrospective cohort study analyzed 70 patients who underwent surgery for PCNs at Ankara Bilkent City Hospital between February 2019 and March 2023.Patients were categorized into group A(benign or low-grade dysplasia,n=40)and group B(malignancy or high-grade dysplasia,n=30)based on postoperative pathology.Preoperative demographic and laboratory parameters,including age,RDW,albumin,and CA 19-9,were compared.Univariate and multivariate logistic regression analyses identified independent predictors of malignancy.Receiver operating characteristic curve analysis evaluated predictive performance,with internal validation using bootstrapping.RESULTS Group B patients were older(69.86±9.58 years vs 52.74±16.85 years,P<0.001)and had a higher incidence of diabetes mellitus(57.1%vs 21.4%,P=0.002).RDW(16.2%vs 13.7%,P<0.001),platelet-lymphocyte ratio(178 vs 126,P=0.008),and CA 19-9(21.7 U/mL vs 9.3 U/mL,P=0.009)were significantly higher in group B,while albumin was lower(41 g/L vs 45 g/L,P=0.008).Multivariate analysis identified age[odds ratio=1.067,95%confidence interval(CI):1.014-1.122,P=0.012]and RDW(odds ratio=1.784,95%CI:1.172-2.715,P=0.007)as independent predictors.The area under the curve for age,RDW,and their combination was 0.798(95%CI:0.695-0.900),0.801(95%CI:0.692-0.911),and 0.858(95%CI:0.771-0.944),respectively,with bootstrapped validation confirming stability.Cut-off values of age≥60 years and RDW≥15.5%balanced sensitivity and specificity,increasing malignancy risk 15.3-fold and 22.6-fold,respectively.CONCLUSION Age and RDW are independent predictors of malignancy in PCNs,aiding in patient selection for advanced diagnostics and surgery.Larger,multicenter studies are needed to validate these findings.展开更多
To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cr...To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].展开更多
Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NEN...Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NENs.Historically,GEP-NENs have been regarded as infrequent and slow-growing malignancies;however,recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades.In addition,an increasing number of studies have proven that GEP-NENs result in a limited life expectancy.These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed.Therefore,there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs.In this review,we have summarized the limitations and recent advancements in our comprehension of the epidemiology,clinical presentations,pathology,molecular biology,diagnosis,and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.展开更多
BACKGROUND Pancreatic neuroendocrine neoplasms(pNENs)are rare,heterogeneous tumors accounting for 1%-2%of pancreatic tumors,with significant malignant potential.Intraductal papillary mucinous neoplasm of the bile duct...BACKGROUND Pancreatic neuroendocrine neoplasms(pNENs)are rare,heterogeneous tumors accounting for 1%-2%of pancreatic tumors,with significant malignant potential.Intraductal papillary mucinous neoplasm of the bile duct(IPMN-B)is a rare precancerous lesion in the bile duct system,with potential for malignancy.The combination of pNENs and IPMN-B is exceptionally rare and often leads to misdiagnosis.This study aims to report a rare case of pNENs combined with IPMN-B treated at Yanbian University Hospital to improve understanding and management of this unusual tumor combination.CASE SUMMARY We retrospectively analyzed a case from Yanbian University Hospital.We re-viewed clinical records,imaging findings,endoscopic retrograde cholangiopan-creatography,surgical exploration,and histopathological examination.The pa-tient was diagnosed with pNENs and IPMN-B.Surgical treatment was performed,with follow-up showing effective management and no significant recurrence.CONCLUSION This case represents the first report of pNENs combined with IPMN-B.It high-lights the need for thorough diagnostic evaluation to prevent misdiagnosis and improve treatment strategies.展开更多
BACKGROUND The location of gastric neoplasms can influence the level of technical difficulty and performance of endoscopic submucosal dissection(ESD).There are few studies that analyze the influence of tumor location ...BACKGROUND The location of gastric neoplasms can influence the level of technical difficulty and performance of endoscopic submucosal dissection(ESD).There are few studies that analyze the influence of tumor location in the stomach on ESD outcomes.AIM To compare the clinical efficacy and safety of ESD in the proximal vs distal stomach.METHODS A retrospective analysis was conducted on patients admitted in chronological order who received gastric ESD between 2009 and 2024.Patients were stratified into two groups based on tumor location:Group 1 included patients with tumors in the lower third of the stomach,while Group 2 included those with tumors in the middle or upper third.The following parameters were evaluated for each group:procedure duration,curative resection rate,en bloc resection rate,complete resection rate,incidence of complications,and depth of neoplastic invasion.RESULTS The mean procedure time was 97.07 minutes for lesions located in the distal stomach and 129.08 minutes for those in the proximal stomach(P=0.0011).En bloc resection rates for ESD in the distal and proximal stomach were 97.9%and 85.7%,respectively(P=0.0016),while complete resection rates were 93.9%and 73.4%,respectively(P=0.0002).Curative resection was achieved in 90.9%of distal lesions compared to 65.3%of proximal lesions(P=0.0001).Submucosal invasion was identified in 4.0%of distal lesions and 14.2%of proximal lesions(P=0.013).CONCLUSION ESD performed in the proximal stomach requires a longer procedural time compared to ESD in the distal stomach,independent of lesion size and histopathological characteristics.Additionally,proximal gastric ESD is associated with reduced clinical efficacy and increased incidence of submucosal invasion.展开更多
Mucinous cystic neoplasms of the liver(MCN-L)are rare cystic lesions characterized by mucin-producing epithelium and ovarian-like stroma.Although they constitute fewer than 5%of hepatic cystic lesions,MCN-L poses sign...Mucinous cystic neoplasms of the liver(MCN-L)are rare cystic lesions characterized by mucin-producing epithelium and ovarian-like stroma.Although they constitute fewer than 5%of hepatic cystic lesions,MCN-L poses significant diagnostic challenges due to overlapping features with other cystic lesions and their potential for malignant transformation.Early recognition and definitive surgical intervention are therefore critical to ensure optimal patient outcomes.A literature review was conducted to summarize epidemiology,clinical presentation,diagnostic modalities,and management strategies for MCN-L.Additionally,from 2019 to 2025,9 patients with MCN-L were identified at our center.Clinical data and outcomes were retrospectively analyzed.MCN-L predominantly affects middle-aged women and presents as large,multiloculated cystic lesions without biliary communication.The revised 2010 World Health Organization classification emphasizes the presence of ovarian-like stroma for definitive diagnosis.Contrast-enhanced computed tomography or magnetic resonance imaging are often suggestive but not pathognomonic,reinforcing the need for histopathological confirmation.MCN-L remains a diagnostic and therapeutic challenge due to its resemblance to other cystic liver lesions.Complete surgical resection is the treatment of choice to prevent recurrence and malignant transformation,reinforcing the importance of early intervention.Further research is needed to improve diagnostic accuracy and refine management strategies.展开更多
BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognos...BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognostic nomogram for PDGNEN patients.METHODS We conducted a retrospective study using clinical and pathological data from PDGNEN patients treated at the First Medical Center of the Chinese PLA General Hospital from January 2000 to June 2023.Overall survival(OS)differences were assessed with the Log-rank test and Kaplan-Meier survival curves.Cox regression analysis identified independent risk factors for prognosis.Model performance was evaluated using Harrell’s concordance index,receiver operating characteristic analysis,area under the curve,calibration curves,and decision curve analysis(UDC),including the area under the UDC.RESULTS The study included 336 patients(227 with neuroendocrine carcinoma and 109 with mixed adenoneuroendocrine carcinoma).The average age was 62.7 years.The cohort comprised 80(24.7%)patients in stage I,146(42.9%)in stage II,62(18.1%)in stage III,and 48(14.3%)in stage IV.Significant differences in OS were observed across tumor-node-metastasis stages(P<0.001).Multivariate analysis showed age,Ki-67 index,invasion depth,lymph node metastasis,distant metastasis,and platelet-to-lymphocyte ratio as independent risk factors.We developed a nomogram with a concordance index of 0.779(95%confidence interval:0.743-0.858).Receiver operating characteristic analysis showed area under the curves for 1-year,3-year,and 5-year OS predictions of 0.865,0.850,and 0.890,respectively.The calibration curve demonstrated good agreement with actual outcomes.The area under the UDC for the nomogram vs the 8th American Joint Committee on Cancer tumor-node-metastasis staging system were 0.047 vs 0.027,0.291 vs 0.179,and 0.376 vs 0.216 for 1-year,3-year,and 5-year OS,respectively.CONCLUSION PDGNENs are predominantly found in older men,often in advanced stages at diagnosis,resulting in poor prognosis.The established nomogram demonstrates strong predictive capability and clinical utility.展开更多
Pancreatic cystic neoplasms(PCNs)represent a spectrum of heterogeneous lesions with diverse biological behaviors and malignant potential.This category encompasses relatively common subtypes,such as intraductal papilla...Pancreatic cystic neoplasms(PCNs)represent a spectrum of heterogeneous lesions with diverse biological behaviors and malignant potential.This category encompasses relatively common subtypes,such as intraductal papillary mucinous neoplasms,serous cystic neoplasms,and mucinous cystic neoplasms,alongside relatively rarer entities,including cystic degeneration of solid pancreatic tumors.The widespread use of cross-sectional imaging has led to increased incidental detection of PCNs,subsequently driving a surge in PCN-related medical consultations and interventions;thus,standardized management of PCNs demands heightened attention.Continuous advancements in endoscopic techno-logies,particularly endoscopic ultrasound(EUS)and EUS-guided procedures,now offer diversified diagnostic and therapeutic options,establishing EUS as a pivotal tool for diagnosing,surveillance,and treating PCNs.This review synthesizes current evidence and evolving clinical practices in the endoscopic management of PCNs,emphasizing optimizing preoperative diagnostic accuracy,standardizing endoscopic protocols,implementing subtype-specific risk strati-fication,promoting multidisciplinary team approaches,and addressing challenges in emerging technologies.展开更多
Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the ...Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.展开更多
BACKGROUND Underwater endoscopic mucosal resection(UEMR)has been shown to be a good treatment option for the management of nonpedunculated polyps≥10 mm since its introduction.However,there is a paucity of randomized ...BACKGROUND Underwater endoscopic mucosal resection(UEMR)has been shown to be a good treatment option for the management of nonpedunculated polyps≥10 mm since its introduction.However,there is a paucity of randomized controlled trials(RCTs)in Asia.AIM To compare the efficacy and safety of UEMR with those of conventional EMR(CEMR)in treating nonpedunculated colorectal lesions.METHODS We carried out this RCT at a tertiary hospital from October 2022 to July 2024.Patients with nonpedunculated colorectal neoplasms ranging from 10 mm to 30 mm in size were randomly assigned to either the UEMR or CEMR group.The primary outcome was the curative resection(R0)rate.The secondary outcomes included en bloc resection,procedure time,adverse events,and the number of clips used for defect closure.RESULTS A total of 260 patients with 260 lesions(130 in each UEMR and CEMR group)were recruited.The median age was 58(27-85)years,the male/female ratio was 1.74,and the median lesion size was 20(10-30 mm)mm.Compared with CEMR,UEMR was associated with a significantly greater curative resection(R0)rate(98.4%vs 90.3%;P=0.007),greater en bloc resection rate(100%vs 94.6%;P=0.014),shorter procedure time(65 vs 185 seconds;P<0.001),lower rate of bleeding complications(1.5%vs 10%;P=0.003),and fewer clips used(2 vs 3;P<0.001).No perforations were observed in either group.CONCLUSION Compared with CEMR,UEMR has a higher R0 rate,greater en bloc resection rate,shorter procedure time,fewer bleeding complications,and clips used in the management of nonpedunculated colorectal neoplasms.展开更多
BACKGROUND Gamma-glutamyl transferase(GGT)is a known surrogate marker of hepatic dysfunction and oxidative stress.It has recently been reported to be associated with metabolic diseases,cardiovascular diseases,and mali...BACKGROUND Gamma-glutamyl transferase(GGT)is a known surrogate marker of hepatic dysfunction and oxidative stress.It has recently been reported to be associated with metabolic diseases,cardiovascular diseases,and malignancies including pancreatic cancer.However,data on its association with pancreatic cystic neo-plasm(PCN),is unknown.AIM To investigate the association of GGT with the incidence of PCN.METHODS In this nationwide retrospective cohort study,participants who received general health checkup by National Health Insurance Service in 2009 were included.Newly diagnosed PCNs from one year after the checkup to 2020 were identified.Participants were divided into quartiles based on GGT levels.Multivariable cox proportional hazard models estimated the risk of PCNs according to GGT quartiles(Q1-Q4).Subgroup analyses by age,sex,and comorbidities,and sensitivity analyses varying lag periods and GGT categorizations were performed.RESULTS There were 28940 cases of PCNs among 2655665 eligible participants.The incidence rate was 1.09 cases per 1000 person-years,with a median follow-up of 10.32(interquartile range:10.09-10.58)years.In multivariate regression analysis,adjusted hazard ratios for GGT quartiles using Q1 group as a reference were:1.04[95%confidence interval(CI):1.005-1.075]for Q2,1.065(95%CI:1.03-1.102)for Q3,and 1.109(95%CI:1.07-1.15)for Q4.Subgroup analysis showed consistent results across age,sex,and comorbidities.In sensitivity analyses,the association remained robust even at 3-year and 5-year lag periods.A clear dose-response relationship was also observed when using GGT deciles(All P for trend<0.001).CONCLUSION Higher GGT level is associated with increased risk of PCNs.Therefore,serum GGT levels might have a role as a biomarker for the development of PCNs.展开更多
In this article,we discussed the article by Zeng et al,published in a recent issue of the World Journal of Gastroenterology.The publication represents a significant advancement in the prognostic evaluation of rectal n...In this article,we discussed the article by Zeng et al,published in a recent issue of the World Journal of Gastroenterology.The publication represents a significant advancement in the prognostic evaluation of rectal neuroendocrine neoplasms.The GATIS score is a single nomogram model that incorporates five key progno-stic factors:Tumor grade;T stage;tumor size;age;and the prognostic nutritional index.This innovation optimizes the prognostic process,delivering more accurate predictions of overall survival and progression-free survival compared to tradi-tional TNM staging and World Health Organization classification systems.The findings of the study were based on a retrospective analysis spanning 12 years and involving 1408 patients from 17 reference centers in China.In this editorial,we specifically examined the strengths and limitations of the study,the clinical implications of the GATIS score,and the questions arising from its conclusions.展开更多
Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leadin...Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leading to aberrant proliferation and survival of hematopoietic cells.Alongside the challenges of drug resistance and side effects,identifying novel compounds that selectively target JAK2^(V617F)could provide more effective and safer therapeutic options for patients with MPNs.Materials and Methods:We employed computational approaches like high-throughput virtual screening,molecular dynamics simulations(MDS),and binding free energy calculations to identify inhibitors targeting wild and mutant JAK2 kinases.JAK2^(V617F)positive HEL,wild type JAK2 positive TF-1,and non-cancerous Vero cells were used for in vitro validations.Results:SBLJ23 emerged as a top candidate inhibitor with specificity for JAK2^(V617F).Protein-ligand interaction studies and MDS revealed stable interactions and binding of SBLJ23 over the simulation period,with Root Mean Square Deviation(RMSD)indicating consistent binding after 1t15ns.SBLJ23 displayed a half maximal inhibitory concentration(IC_(50))value of 522.4 nM against the JAK2 enzyme.The compound exhibited inhibition of cell proliferation in HEL and TF-1 cells,with half maximal cell growth inhibitory concentration(GI 50)values of 2.51 and 15.87μM,respectively.Moreover,SBLJ23 induced G 2/M cell cycle arrest in HEL cells to facilitate apoptosis in these cell lines.The compound significantly reduced the percentage of phospho JAK2 and phospho STAT3 in HEL cells.Conclusion:High binding affinity,stable interaction profile,favorable binding free energy,and in vitro validations claim SBLJ23 as a potential lead compound against JAK2^(V617F)and suggest further development and optimization towards clinical application in managing myeloproliferative neoplasms.展开更多
Objective:This study aims to develop a deep multiscale image learning system(DMILS)to differentiate malignant from benign thyroid follicular neoplasms on multiscale whole-slide images(WSIs)of intraoperative frozen pat...Objective:This study aims to develop a deep multiscale image learning system(DMILS)to differentiate malignant from benign thyroid follicular neoplasms on multiscale whole-slide images(WSIs)of intraoperative frozen pathological images.Methods:A total of 1,213 patients were divided into training and validation sets,an internal test set,a pooled external test set,and a pooled prospective test set at three centers.DMILS was constructed using a deep learningbased weakly supervised method based on multiscale WSIs at 10×,20×,and 40×magnifications.The performance of the DMILS was compared with that of a single magnification and validated in two pathologist-unidentified subsets.Results:The DMILS yielded good performance,with areas under the receiver operating characteristic curves(AUCs)of 0.848,0.857,0.810,and 0.787 in the training and validation sets,internal test set,pooled external test set,and pooled prospective test set,respectively.The AUC of the DMILS was higher than that of a single magnification,with 0.788 of 10×,0.824 of 20×,and 0.775 of 40×in the internal test set.Moreover,DMILS yielded satisfactory performance on the two pathologist-unidentified subsets.Furthermore,the most indicative region predicted by DMILS is the follicular epithelium.Conclusions:DMILS has good performance in differentiating thyroid follicular neoplasms on multiscale WSIs of intraoperative frozen pathological images.展开更多
目的探讨肺癌术后患者运动训练行为感知的潜在类别及其相关影响因素。方法采用便利抽样法选取2024年3—12月广西某三级甲等医院胸心管外科的肺癌术后患者为研究对象。采用一般资料调查表、肺癌患者运动训练行为感知量表、中文版恐动症Ta...目的探讨肺癌术后患者运动训练行为感知的潜在类别及其相关影响因素。方法采用便利抽样法选取2024年3—12月广西某三级甲等医院胸心管外科的肺癌术后患者为研究对象。采用一般资料调查表、肺癌患者运动训练行为感知量表、中文版恐动症Tampa评分表(Tampa scale for kinesiophobia,TSK)、领悟社会支持量表(perceived social support scale,PSSS)进行调查。使用潜在剖面分析探究肺癌术后患者运动训练行为感知的潜在类别,采用无序多分类logistic回归分析其相关影响因素。结果共纳入242例肺癌术后患者,其运动训练行为感知分为3个类别:高感知-身体康复益处型(85例,占35.1%),中感知-信息障碍型(60例,占25.2%),低感知-心理与疾病症状障碍型(97例,占39.7%)。多元logistic回归分析结果显示,年龄、文化程度、疼痛程度、TSK得分以及PSSS得分情况是运动训练行为感知的影响因素。结论肺癌术后患者的运动训练行为感知存在显著的分类特征,建议临床护理人员根据患者的运动训练行为感知潜在类别给予个性化干预措施,以提高患者的运动训练行为感知及运动持久性。展开更多
基金Supported by National Natural Science Foundation of China,No.82004298Jiangsu Graduate Research and Practice Innovation Program,China,No.KYCX23_2090.
文摘BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particularly in the vertical direction.Endoscopic full-thickness resection(EFTR)has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs,including 132 who underwent endoscopic submucosal dissection(ESD)and 28 who underwent EFTR.Lesions were categorized as<1 cm,1-2 cm,and>2 cm in size.CR rate,en bloc resection rate,operation time,and complications were evaluated.Subgroup analyses and follow-up were also performed.RESULTS EFTR achieved 100%CR rates for lesions<1 cm and 1-2 cm,compared with 67.0%and 50.0%,respectively,in the ESD group.En bloc resection and successful removal of the R-NENs were achieved in all patients.Meanwhile,EFTR showed performance comparable to ESD in terms of operation time,hospitalization cost,and postoperative adverse events,except for a one-day longer hospital stay.We also analyzed the invasion depth of R-NENs based on full-thickness specimens.The data showed that 80%of lesions(<1 cm)and 85.7%of lesions(1-2 cm)had invaded the SM3 level or deeper at the time of resection.For ESD specimens,46.6%(<1 cm)and 89.3%(1-2 cm)of lesions had infiltrated more than 2000μm beneath the muscularis mucosae.CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.
文摘Neuroendocrine neoplasms(NENs)are relatively rare tumors that arise from peptidergic neurons and neuroendocrine cells.NENs are highly heterogeneous and can occur in any part of the body,with a particular prevalence in the digestive system.NENs consist of a range of tumor types and the biological behaviors exhibit significant differences.NENs are classified into well-differentiated neuroendocrine tumors(NETs)and poorly differentiated neuroendocrine carcinomas(NECs).NETs can be further classified and graded into the following three categories:low-grade NETs,grade 1(NET G1);intermediate-grade NET G2;and high-grade NET G3.NECs include large cell-type NEC(LCNEC)and small cell-type NEC(SCNEC),both of which are considered high grade.Currently,the main treatments for advanced NENs are biological treatments,targeted therapy,chemotherapy,and newer treatments that are still under development,such as immunotherapy and peptide receptor radionuclide therapy(PRRT).However,owing to the rarity of NENs,pharmaceutical company investment is limited and few phase Ⅲ studies have targeted advanced NENs.Most current research consists of investigator-initiated phase Ⅰ and Ⅱ clinical trials or largescale retrospective studies.NEN treatment should be chosen carefully because it is cumbersome and complicated,as indicated above.Herein,we comprehensively summarize the clinical application status and research progress for advanced NEN treatment regimens,especially for advanced NETs,which may help to create awareness on NENs among medical professionals across specialties.
文摘Appendiceal mucinous neoplasms(AMNs)are rare tumors originating from mucin-producing epithelial cells of the appendix.They can exhibit both benign and malignant behavior.They are often incidentally discovered during appendectomy.Clinical presentation ranges from asymptomatic to mimicking acute appendicitis.Histologically,noninvasive AMNs are classified as low-grade AMNs(LAMNs)or high-grade AMNs(HAMNs),whereas invasive tumors are categorized as mucinous adenocarcinomas.Although LAMNs and HAMNs are generally nonmalignant,rupture can lead to pseudomyxoma peritonei(PMP).Surgical resection is the primary diagnostic and therapeutic approach,with intraoperative assessment to prevent rupture.Treatment strategies vary based on findings and include appendectomy,right hemicolectomy,and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Histological diagnosis relies on mucin detection,and immunohistochemical markers such as cytokeratin 20(diffusely positive),cytokeratin 7(often negative),mucin 5AC,and special ATrich sequence-binding protein 2 assist in characterization.Molecular profiling frequently identifies KRAS,GNAS,and TP53 mutations.KRAS mutations are generally associated with a favorable prognosis,whereas GNAS and TP53 mutations correlate with poorer survival outcomes.These findings highlight the potential role of molecular profiling in guiding treatment strategies for AMN and PMP.
文摘BACKGROUND Pancreatic cystic neoplasms(PCNs)are increasingly detected due to advancements in radiographic techniques,with a prevalence of approximately 15%in the general population.These lesions range from benign to premalignant and malignant,posing a diagnostic challenge.Accurate differentiation is critical,as premalignant and malignant PCNs often require surgical intervention,while benign cysts may only need monitoring unless symptomatic.Current diagnostic methods,including cross-sectional imaging,endoscopic ultrasonography,and endoscopic ultrasonography-guided fine-needle aspiration/biopsy,are specialized,not universally available,and have variable accuracy.Clinical and laboratory parameters such as carbohydrate antigen 19-9(CA 19-9),neutrophillymphocyte ratio,platelet-lymphocyte ratio,and red cell distribution width(RDW)have been associated with malignancy risk,though only CA 19-9 is guideline-supported.AIM To assess the malignancy risk of PCNs using preoperative clinical and routine laboratory parameters.METHODS A retrospective cohort study analyzed 70 patients who underwent surgery for PCNs at Ankara Bilkent City Hospital between February 2019 and March 2023.Patients were categorized into group A(benign or low-grade dysplasia,n=40)and group B(malignancy or high-grade dysplasia,n=30)based on postoperative pathology.Preoperative demographic and laboratory parameters,including age,RDW,albumin,and CA 19-9,were compared.Univariate and multivariate logistic regression analyses identified independent predictors of malignancy.Receiver operating characteristic curve analysis evaluated predictive performance,with internal validation using bootstrapping.RESULTS Group B patients were older(69.86±9.58 years vs 52.74±16.85 years,P<0.001)and had a higher incidence of diabetes mellitus(57.1%vs 21.4%,P=0.002).RDW(16.2%vs 13.7%,P<0.001),platelet-lymphocyte ratio(178 vs 126,P=0.008),and CA 19-9(21.7 U/mL vs 9.3 U/mL,P=0.009)were significantly higher in group B,while albumin was lower(41 g/L vs 45 g/L,P=0.008).Multivariate analysis identified age[odds ratio=1.067,95%confidence interval(CI):1.014-1.122,P=0.012]and RDW(odds ratio=1.784,95%CI:1.172-2.715,P=0.007)as independent predictors.The area under the curve for age,RDW,and their combination was 0.798(95%CI:0.695-0.900),0.801(95%CI:0.692-0.911),and 0.858(95%CI:0.771-0.944),respectively,with bootstrapped validation confirming stability.Cut-off values of age≥60 years and RDW≥15.5%balanced sensitivity and specificity,increasing malignancy risk 15.3-fold and 22.6-fold,respectively.CONCLUSION Age and RDW are independent predictors of malignancy in PCNs,aiding in patient selection for advanced diagnostics and surgery.Larger,multicenter studies are needed to validate these findings.
文摘To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].
基金supported by the National Natural Science Foundation of China(82104596)the Shenzhen Key Medical Discipline Construction Fund&Sanming Project of Medicine in Shenzhen(SZSM202111002)+1 种基金the Medicine-Engineering Interdisciplinary Research Foundation of Shenzhen University(2023YG019)the Shenzhen Science and Technology Program(GJHZ20220913143005010)。
文摘Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NENs.Historically,GEP-NENs have been regarded as infrequent and slow-growing malignancies;however,recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades.In addition,an increasing number of studies have proven that GEP-NENs result in a limited life expectancy.These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed.Therefore,there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs.In this review,we have summarized the limitations and recent advancements in our comprehension of the epidemiology,clinical presentations,pathology,molecular biology,diagnosis,and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.
文摘BACKGROUND Pancreatic neuroendocrine neoplasms(pNENs)are rare,heterogeneous tumors accounting for 1%-2%of pancreatic tumors,with significant malignant potential.Intraductal papillary mucinous neoplasm of the bile duct(IPMN-B)is a rare precancerous lesion in the bile duct system,with potential for malignancy.The combination of pNENs and IPMN-B is exceptionally rare and often leads to misdiagnosis.This study aims to report a rare case of pNENs combined with IPMN-B treated at Yanbian University Hospital to improve understanding and management of this unusual tumor combination.CASE SUMMARY We retrospectively analyzed a case from Yanbian University Hospital.We re-viewed clinical records,imaging findings,endoscopic retrograde cholangiopan-creatography,surgical exploration,and histopathological examination.The pa-tient was diagnosed with pNENs and IPMN-B.Surgical treatment was performed,with follow-up showing effective management and no significant recurrence.CONCLUSION This case represents the first report of pNENs combined with IPMN-B.It high-lights the need for thorough diagnostic evaluation to prevent misdiagnosis and improve treatment strategies.
文摘BACKGROUND The location of gastric neoplasms can influence the level of technical difficulty and performance of endoscopic submucosal dissection(ESD).There are few studies that analyze the influence of tumor location in the stomach on ESD outcomes.AIM To compare the clinical efficacy and safety of ESD in the proximal vs distal stomach.METHODS A retrospective analysis was conducted on patients admitted in chronological order who received gastric ESD between 2009 and 2024.Patients were stratified into two groups based on tumor location:Group 1 included patients with tumors in the lower third of the stomach,while Group 2 included those with tumors in the middle or upper third.The following parameters were evaluated for each group:procedure duration,curative resection rate,en bloc resection rate,complete resection rate,incidence of complications,and depth of neoplastic invasion.RESULTS The mean procedure time was 97.07 minutes for lesions located in the distal stomach and 129.08 minutes for those in the proximal stomach(P=0.0011).En bloc resection rates for ESD in the distal and proximal stomach were 97.9%and 85.7%,respectively(P=0.0016),while complete resection rates were 93.9%and 73.4%,respectively(P=0.0002).Curative resection was achieved in 90.9%of distal lesions compared to 65.3%of proximal lesions(P=0.0001).Submucosal invasion was identified in 4.0%of distal lesions and 14.2%of proximal lesions(P=0.013).CONCLUSION ESD performed in the proximal stomach requires a longer procedural time compared to ESD in the distal stomach,independent of lesion size and histopathological characteristics.Additionally,proximal gastric ESD is associated with reduced clinical efficacy and increased incidence of submucosal invasion.
文摘Mucinous cystic neoplasms of the liver(MCN-L)are rare cystic lesions characterized by mucin-producing epithelium and ovarian-like stroma.Although they constitute fewer than 5%of hepatic cystic lesions,MCN-L poses significant diagnostic challenges due to overlapping features with other cystic lesions and their potential for malignant transformation.Early recognition and definitive surgical intervention are therefore critical to ensure optimal patient outcomes.A literature review was conducted to summarize epidemiology,clinical presentation,diagnostic modalities,and management strategies for MCN-L.Additionally,from 2019 to 2025,9 patients with MCN-L were identified at our center.Clinical data and outcomes were retrospectively analyzed.MCN-L predominantly affects middle-aged women and presents as large,multiloculated cystic lesions without biliary communication.The revised 2010 World Health Organization classification emphasizes the presence of ovarian-like stroma for definitive diagnosis.Contrast-enhanced computed tomography or magnetic resonance imaging are often suggestive but not pathognomonic,reinforcing the need for histopathological confirmation.MCN-L remains a diagnostic and therapeutic challenge due to its resemblance to other cystic liver lesions.Complete surgical resection is the treatment of choice to prevent recurrence and malignant transformation,reinforcing the importance of early intervention.Further research is needed to improve diagnostic accuracy and refine management strategies.
文摘BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognostic nomogram for PDGNEN patients.METHODS We conducted a retrospective study using clinical and pathological data from PDGNEN patients treated at the First Medical Center of the Chinese PLA General Hospital from January 2000 to June 2023.Overall survival(OS)differences were assessed with the Log-rank test and Kaplan-Meier survival curves.Cox regression analysis identified independent risk factors for prognosis.Model performance was evaluated using Harrell’s concordance index,receiver operating characteristic analysis,area under the curve,calibration curves,and decision curve analysis(UDC),including the area under the UDC.RESULTS The study included 336 patients(227 with neuroendocrine carcinoma and 109 with mixed adenoneuroendocrine carcinoma).The average age was 62.7 years.The cohort comprised 80(24.7%)patients in stage I,146(42.9%)in stage II,62(18.1%)in stage III,and 48(14.3%)in stage IV.Significant differences in OS were observed across tumor-node-metastasis stages(P<0.001).Multivariate analysis showed age,Ki-67 index,invasion depth,lymph node metastasis,distant metastasis,and platelet-to-lymphocyte ratio as independent risk factors.We developed a nomogram with a concordance index of 0.779(95%confidence interval:0.743-0.858).Receiver operating characteristic analysis showed area under the curves for 1-year,3-year,and 5-year OS predictions of 0.865,0.850,and 0.890,respectively.The calibration curve demonstrated good agreement with actual outcomes.The area under the UDC for the nomogram vs the 8th American Joint Committee on Cancer tumor-node-metastasis staging system were 0.047 vs 0.027,0.291 vs 0.179,and 0.376 vs 0.216 for 1-year,3-year,and 5-year OS,respectively.CONCLUSION PDGNENs are predominantly found in older men,often in advanced stages at diagnosis,resulting in poor prognosis.The established nomogram demonstrates strong predictive capability and clinical utility.
基金Supported by the Education and Teaching Reform Project of the First Clinical College of Chongqing Medical University,No.CMER202305Natural Science Foundation of Tibet Autonomous Region,No.XZ2024ZR-ZY100(Z)Program for Youth Innovation in Future Medicine,Chongqing Medical University,No.W0138.
文摘Pancreatic cystic neoplasms(PCNs)represent a spectrum of heterogeneous lesions with diverse biological behaviors and malignant potential.This category encompasses relatively common subtypes,such as intraductal papillary mucinous neoplasms,serous cystic neoplasms,and mucinous cystic neoplasms,alongside relatively rarer entities,including cystic degeneration of solid pancreatic tumors.The widespread use of cross-sectional imaging has led to increased incidental detection of PCNs,subsequently driving a surge in PCN-related medical consultations and interventions;thus,standardized management of PCNs demands heightened attention.Continuous advancements in endoscopic techno-logies,particularly endoscopic ultrasound(EUS)and EUS-guided procedures,now offer diversified diagnostic and therapeutic options,establishing EUS as a pivotal tool for diagnosing,surveillance,and treating PCNs.This review synthesizes current evidence and evolving clinical practices in the endoscopic management of PCNs,emphasizing optimizing preoperative diagnostic accuracy,standardizing endoscopic protocols,implementing subtype-specific risk strati-fication,promoting multidisciplinary team approaches,and addressing challenges in emerging technologies.
文摘Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.
文摘BACKGROUND Underwater endoscopic mucosal resection(UEMR)has been shown to be a good treatment option for the management of nonpedunculated polyps≥10 mm since its introduction.However,there is a paucity of randomized controlled trials(RCTs)in Asia.AIM To compare the efficacy and safety of UEMR with those of conventional EMR(CEMR)in treating nonpedunculated colorectal lesions.METHODS We carried out this RCT at a tertiary hospital from October 2022 to July 2024.Patients with nonpedunculated colorectal neoplasms ranging from 10 mm to 30 mm in size were randomly assigned to either the UEMR or CEMR group.The primary outcome was the curative resection(R0)rate.The secondary outcomes included en bloc resection,procedure time,adverse events,and the number of clips used for defect closure.RESULTS A total of 260 patients with 260 lesions(130 in each UEMR and CEMR group)were recruited.The median age was 58(27-85)years,the male/female ratio was 1.74,and the median lesion size was 20(10-30 mm)mm.Compared with CEMR,UEMR was associated with a significantly greater curative resection(R0)rate(98.4%vs 90.3%;P=0.007),greater en bloc resection rate(100%vs 94.6%;P=0.014),shorter procedure time(65 vs 185 seconds;P<0.001),lower rate of bleeding complications(1.5%vs 10%;P=0.003),and fewer clips used(2 vs 3;P<0.001).No perforations were observed in either group.CONCLUSION Compared with CEMR,UEMR has a higher R0 rate,greater en bloc resection rate,shorter procedure time,fewer bleeding complications,and clips used in the management of nonpedunculated colorectal neoplasms.
文摘BACKGROUND Gamma-glutamyl transferase(GGT)is a known surrogate marker of hepatic dysfunction and oxidative stress.It has recently been reported to be associated with metabolic diseases,cardiovascular diseases,and malignancies including pancreatic cancer.However,data on its association with pancreatic cystic neo-plasm(PCN),is unknown.AIM To investigate the association of GGT with the incidence of PCN.METHODS In this nationwide retrospective cohort study,participants who received general health checkup by National Health Insurance Service in 2009 were included.Newly diagnosed PCNs from one year after the checkup to 2020 were identified.Participants were divided into quartiles based on GGT levels.Multivariable cox proportional hazard models estimated the risk of PCNs according to GGT quartiles(Q1-Q4).Subgroup analyses by age,sex,and comorbidities,and sensitivity analyses varying lag periods and GGT categorizations were performed.RESULTS There were 28940 cases of PCNs among 2655665 eligible participants.The incidence rate was 1.09 cases per 1000 person-years,with a median follow-up of 10.32(interquartile range:10.09-10.58)years.In multivariate regression analysis,adjusted hazard ratios for GGT quartiles using Q1 group as a reference were:1.04[95%confidence interval(CI):1.005-1.075]for Q2,1.065(95%CI:1.03-1.102)for Q3,and 1.109(95%CI:1.07-1.15)for Q4.Subgroup analysis showed consistent results across age,sex,and comorbidities.In sensitivity analyses,the association remained robust even at 3-year and 5-year lag periods.A clear dose-response relationship was also observed when using GGT deciles(All P for trend<0.001).CONCLUSION Higher GGT level is associated with increased risk of PCNs.Therefore,serum GGT levels might have a role as a biomarker for the development of PCNs.
文摘In this article,we discussed the article by Zeng et al,published in a recent issue of the World Journal of Gastroenterology.The publication represents a significant advancement in the prognostic evaluation of rectal neuroendocrine neoplasms.The GATIS score is a single nomogram model that incorporates five key progno-stic factors:Tumor grade;T stage;tumor size;age;and the prognostic nutritional index.This innovation optimizes the prognostic process,delivering more accurate predictions of overall survival and progression-free survival compared to tradi-tional TNM staging and World Health Organization classification systems.The findings of the study were based on a retrospective analysis spanning 12 years and involving 1408 patients from 17 reference centers in China.In this editorial,we specifically examined the strengths and limitations of the study,the clinical implications of the GATIS score,and the questions arising from its conclusions.
文摘Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leading to aberrant proliferation and survival of hematopoietic cells.Alongside the challenges of drug resistance and side effects,identifying novel compounds that selectively target JAK2^(V617F)could provide more effective and safer therapeutic options for patients with MPNs.Materials and Methods:We employed computational approaches like high-throughput virtual screening,molecular dynamics simulations(MDS),and binding free energy calculations to identify inhibitors targeting wild and mutant JAK2 kinases.JAK2^(V617F)positive HEL,wild type JAK2 positive TF-1,and non-cancerous Vero cells were used for in vitro validations.Results:SBLJ23 emerged as a top candidate inhibitor with specificity for JAK2^(V617F).Protein-ligand interaction studies and MDS revealed stable interactions and binding of SBLJ23 over the simulation period,with Root Mean Square Deviation(RMSD)indicating consistent binding after 1t15ns.SBLJ23 displayed a half maximal inhibitory concentration(IC_(50))value of 522.4 nM against the JAK2 enzyme.The compound exhibited inhibition of cell proliferation in HEL and TF-1 cells,with half maximal cell growth inhibitory concentration(GI 50)values of 2.51 and 15.87μM,respectively.Moreover,SBLJ23 induced G 2/M cell cycle arrest in HEL cells to facilitate apoptosis in these cell lines.The compound significantly reduced the percentage of phospho JAK2 and phospho STAT3 in HEL cells.Conclusion:High binding affinity,stable interaction profile,favorable binding free energy,and in vitro validations claim SBLJ23 as a potential lead compound against JAK2^(V617F)and suggest further development and optimization towards clinical application in managing myeloproliferative neoplasms.
基金supported by the Taishan Scholar Project(No.ts20190991,tsqn202211378)the Key R&D Project of Shandong Province(No.2022CXPT023)the General Program of National Natural Science Foundation of China(No.82371933)。
文摘Objective:This study aims to develop a deep multiscale image learning system(DMILS)to differentiate malignant from benign thyroid follicular neoplasms on multiscale whole-slide images(WSIs)of intraoperative frozen pathological images.Methods:A total of 1,213 patients were divided into training and validation sets,an internal test set,a pooled external test set,and a pooled prospective test set at three centers.DMILS was constructed using a deep learningbased weakly supervised method based on multiscale WSIs at 10×,20×,and 40×magnifications.The performance of the DMILS was compared with that of a single magnification and validated in two pathologist-unidentified subsets.Results:The DMILS yielded good performance,with areas under the receiver operating characteristic curves(AUCs)of 0.848,0.857,0.810,and 0.787 in the training and validation sets,internal test set,pooled external test set,and pooled prospective test set,respectively.The AUC of the DMILS was higher than that of a single magnification,with 0.788 of 10×,0.824 of 20×,and 0.775 of 40×in the internal test set.Moreover,DMILS yielded satisfactory performance on the two pathologist-unidentified subsets.Furthermore,the most indicative region predicted by DMILS is the follicular epithelium.Conclusions:DMILS has good performance in differentiating thyroid follicular neoplasms on multiscale WSIs of intraoperative frozen pathological images.
文摘目的探讨肺癌术后患者运动训练行为感知的潜在类别及其相关影响因素。方法采用便利抽样法选取2024年3—12月广西某三级甲等医院胸心管外科的肺癌术后患者为研究对象。采用一般资料调查表、肺癌患者运动训练行为感知量表、中文版恐动症Tampa评分表(Tampa scale for kinesiophobia,TSK)、领悟社会支持量表(perceived social support scale,PSSS)进行调查。使用潜在剖面分析探究肺癌术后患者运动训练行为感知的潜在类别,采用无序多分类logistic回归分析其相关影响因素。结果共纳入242例肺癌术后患者,其运动训练行为感知分为3个类别:高感知-身体康复益处型(85例,占35.1%),中感知-信息障碍型(60例,占25.2%),低感知-心理与疾病症状障碍型(97例,占39.7%)。多元logistic回归分析结果显示,年龄、文化程度、疼痛程度、TSK得分以及PSSS得分情况是运动训练行为感知的影响因素。结论肺癌术后患者的运动训练行为感知存在显著的分类特征,建议临床护理人员根据患者的运动训练行为感知潜在类别给予个性化干预措施,以提高患者的运动训练行为感知及运动持久性。
