Objective:To investigate the clinical characteristics and prognosis of patients with locally advanced or metastatic pulmonary neuroendocrine tumors(NETs).Methods:The clinical records of patients with locally advanced or metastatic pulmonary NETs in Peking Uni-versity Cancer Hospital&Institute were selected from January 2014 to June 2024.The clinical characteristics,treatment,and survival pro-gnosis were then analyzed.Results:There were 32 patients,of which 18 were male and 14 female.The median age was 56 years.Nine pa-tients had typical carcinoid and 23 had atypical carcinoid,with six in stage Ⅲ and 26 in stage Ⅳ.The common metastatic sites included the bones(18 cases),lungs(8 cases),pleura(7 cases),and liver(7 cases).The median length of the measurable primary tumor was 5.2 cm,which was mostly located centrally(22 cases).Five among the 16 patients who underwent somatostatin receptor(SSTR)imaging had high SSTR ex-pression.The initial symptoms mainly included respiratory symptoms,and none of them were combined with carcinoid syndrome.For the first-line treatment,19 patients were treated with chemotherapy,seven were treated with targeted therapy,four were treated with soma-tostatin analogs(SSAs),and two were treated with surgery.The best efficacy was evaluated as a partial response in one case(3.1%),stable disease in 23 cases(71.9%),and non-evaluable or unknown in eight cases(25%)in the first-line treatment.The median progression-free sur-vival(mPFS)of patients who received first-line treatment was 5.2 months(95%CI:0.0-13.9).The PFS of targeted therapy was the longest(11.0 months,95%CI:0.0-29.6),but there was no significant difference compared with the PFS of chemotherapy and SSA groups(P>0.05).The longest PFS(24.5 months,95%CI:0.0-58.7)was found in patients treated with chemotherapy combined with radiotherapy,but there was no significant difference compared to the PFS of the combined immunotherapy and combined anti-angiogenesis groups(P>0.05).The survival rates at 1,3,and 5 years were 79.1%,65.5%,and 58.9%,respectively.Cox regression analysis did not identify independent risk factors for prognosis.Conclusions:The initial symptoms of patients with locally advanced or metastatic NETs were mainly respiratory symp-toms but without specific manifestations.Some of them were accompanied by high SSTR expression,and there was generally no carcinoid syndrome.The first-line systemic therapy mainly included chemotherapy and target therapy,with relatively low objective response and high disease control rates.Targeted therapy and combined radiotherapy have longer PFS than that of chemotherapy.The overall survival of pa-tients with pulmonary NETs was good.

Objective:We summarize the clinical characteristics of surgeries in which the thyroid lobe is used as a transfer flap to treat early pharyngeal fistula following total laryngectomy.We also provide useful data for improving the diagnosis and management of this condition.Methods:Retrospective analysis was conducted on data from 8 patients with pharyngocutaneous fistulas after total laryngectomy for laryn-geal and pharyngeal cancer patients admitted to Hunan Provincial People's Hospital(The First Hospital Affiliated to Hunan Normal University)between October 2016 and October 2023.The surgeons performed a double-layer repair technique that included local inversion and a purse-string suture of the fistula using the thyroid lobe as a transfer flap.Clinical data were collected to analyze postoperative outcomes.Results:All eight patients experienced successful pharyngeal fistula repair.Postoperatively,these patients were managed with nasogastric tube feed-ing,liquid diet,and prophylactic antibiotics to prevent infection.After 10 days,their diet was changed to oral liquids,and their nasogastric tubes were removed.All patients were discharged after complete recovery.Conclusions:Use of the thyroid lobe as a transfer flap in a double-layer repair technique involving local inversion of the fistula is an effective method for repairing early pharyngeal fistula after total laryngectomy.This approach offers several advantages,including ease of flap harvesting,shortened operation time,reduced patient discom-fort,high transfer flap survival rate,and rapid postoperative recovery.The clinical efficacy of this technique is well-supported,making it a re-liable option for the management of early pharyngeal leaks.

The incidence of breast cancer(BC)is on the rise.The effective and precise management of BC continues to be topical.Tumor in-filtrating lymphocytes(TILs),significant biomarkers indicative of the biological behavior of BC,have not been well recognized in clinical prac-tice.There are some impediments,including the lack of a standard protocol for the quantification of TILs,an optimized threshold for TILs,and a repeatable noninvasive method for the assessment of TILs.These issues are the major controversies preventing the use of TILs as bio-markers in the clinical management of BC.Nevertheless,the value of TILs as biomarkers in the assessment of the prognosis and prediction of the response to treatment cannot be neglected,as they show promise in promoting precise and individualized management of BC.We aimed to offer a comprehensive outline of the current controversies and consensus regarding TILs as biomarkers in the management of BC,with the aim of providing a basis for the rational application of TILs as biomarkers.

Objective:To investigate the relationship between SET domain bifurcated 1(SETDB1)expression and trefoil factor 1(TFF1)gene methylation,along with its clinical significance.Methods:Fifty-five lung adenocarcinoma samples and normal tissues of distant cancer were collected from the Affiliated Hospital of Chengde Medical College Hebei Province.TFF1 gene methylation levels were measured by pyrosequencing,relative TFF1 mRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR),and TFF1 and SETDB1 protein expression were quantified via immunohistochemistry.The clinical significance and correlation between TFF1 methyla-tion levels and SETDB1 protein expression were analyzed statistically.In vitro,SETDB1 siRNA or negative control siRNA was transfected into A549 cells.Following transfection,SETDB1 mRNA expression was analyzed using qRT-PCR,and SETDB1 protein expression was evaluated via Western blot.TFF1 methylation was reassessed via pyrosequencing.Results:In lung adenocarcinoma and normal tissues of distant cancer,TFF1 gene methylation rates were(70.16±6.32)%and(12.46±2.22)%,respectively.TFF1 mRNA relative expression levels were 0.56±0.17 for cancer tissues and 1.56±0.22 for the normal tissues of distant cancer.All detected differences were statistically significant(all P<0.05).TFF1 protein expression rates were 29.09%(16/55)for cancer tissues and 65.45%(36/55)for the normal tissues of distant cancer.Additionally,relative positivity rates for SETDB1 protein expression were 74.55%(41/55)and 23.64%(13/55),respectively,and all differences were stat-istically significant(all P<0.05).Western blot analysis showed that SETDB1 protein expression was significantly higher in cancer tissues(72.89±5.27)%,compared to normal tissues of distant cancer(24.27±2.37)%.In contrast,TFF1 protein expressed was markedly lower in can-cer tissues(15.38±2.33)%than in normal tissues of distant cancer(72.72±4.48)%.All differences were statistically significant(all P<0.05).TFF1 methylation and SETDB1 expression were associated with lung adenocarcinoma(r=0.486,P<0.05).Both TFF1 methylation and SETDB1 expression were closely associated with tumor TNM stage,tissue differentiation,and lymph node metastasis(P<0.05).Furthermore,TFF1 methylation increased following SETDB1 downregulation(P<0.05).Conclusions:During lung adenocarcinoma progression,SETDB1 expres-sion correlates with TFF1 methylation,and the highly expressed SETDB1 may play a role in catalyzing TFF1 methylation.

Multiple myeloma(MM)is a malignancy characterized by the abnormal proliferation of clonal plasma cells.It is often associated with coagulation abnormalities,posing risks of thrombosis,thromboembolism,and bleeding,including severe cases,which are related to de-creased quality of life,delayed or discontinued treatment,and reduced survival.Disease,individual-specific factors,and therapeutic agents affect the dynamic balance of coagulation,anticoagulation,and fibrinolytic systems in patients with MM.The diagnosis and treatment of un-derlying coagulation disorders are challenging due to the involvement of multiple mechanisms.In addition,newly introduced therapies such as immunomodulatory drugs,proteasome inhibitors,chimeric antigen receptor-modified T-cell therapy,and monoclonal antibodies also im-pact coagulation in patients with MM.This review discusses the influencing factors,pathophysiological mechanisms,and prevention and treatment strategies for coagulation abnormalities in MM.

Peritoneal mesothelioma(PeM),which originates in cells in the visceral and mural layers of the peritoneum,is a rare and highly aggressive malignant tumor that accounts for approximately 15%of all mesotheliomas.The disease is characterized by insidious onset and poor prognosis,and its mechanisms of tumorigenesis and progression have not been fully elucidated.Asbestos exposure is a major risk factor for mesothelioma.Effective treatment options alternative to cytoreductive surgery(CRS),hyperthermic intraperitoneal chemotherapy(HIPEC),and platinum/pemetrexed(conventional treatments)are currently lacking.Immunotherapy,which mobilizes the immune system,has shown initial efficacy in patients with advanced mesotheliomas.However,additional real-world clinical trials and studies on immuno-therapeutic targets remain needed.This article reviews progress in PeM-related immunotherapy clinical studies and potential targets in PeM treatment.

Objective:To actively screen the dynamic colonization of Enterobacteriaceae in the gastrointestinal tract of tumor patients and explore the homology between carbapenem-resistant Enterobacteriaceae(CRE)colonized in the gastrointestinal tracts of these patients and the bacteria causing bloodstream infections,to provide meaningful reference data for diagnosis and treatment by clinicians.Methods:A total of 32 strains of gram-negative bacilli were isolated from 353 intestinal specimens of tumor patients at The First Affiliated Hospital of Henan University of Science and Technology from December 2021 to November 2022.The bacterial identification instruments VITEK 2 Com-pact,a carbapenemase detection kit using colloidal gold immunochromatography,and polymerase chain reaction(PCR)were used to de-tectdrug resistance genes and phenotypes.Pulsed-field gel electrophoresis(PFGE)was used to analyze and compare the homology between CRE strains in the intestinal tract of patients and pathogenic microorganisms causing bloodstream infections.Results:Among the 32 strains of Gram-negative bacilli screened from the gastrointestinal tract of cancer patients,6 strains(1.6%,6/353)were carbapenem-resistant Kleb-siella pneumoniae(CRKp).All six CRKp strains harbored blaKPC gene.The proportion of CRE is 3.3%(12/353).Bloodstream infection oc-curred in 2 patients with intestinal colonization of Klebsiella pneumoniae,which was caused by the same CRKp strain as intestinal coloniza-tion.Conclusions:The proportion of CRE intestinal colonization in tumor patients was not high;however,under certain circumstances,CRE colonized in the intestines of tumor patients can cause ectopic infections else where in the body,including the bloodstream,which should be closely monitored.The findings indicate the importance of increased attention to critically ill patients who have undergone multiple hospital-izations with long hospitalization times,as well as early screening for intestine-colonizing microorganisms and rational regulation of the anti-biotic usage.

Objective:To explore the relationship between basic transcription factor 3(BTF3)and glioblastoma multiforme(GBM)cell migra-tion,invasion,and proliferation.Methods:The expression levels of BTF3 in GBM tissues were analyzed using The Cancer Genome Atlas(TCGA),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and The University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)online databases.The effects of inhibiting BTF3 on the malignant biological properties of GBM cells were assessed using the cell scratch,plate colony formation,Cell Counting Kit(CCK)-8,and Transwell assays,and the effect of BTF3 knockdown on Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway-related protein expression levels in GBM cells was determined using Western blot.In addition,GBM cells stably transfected with KD-BTF3 were subcutaneously injected into nude mice,and tumor sizes were analyzed.Western blot was performed to verify the expression of JAK2/STAT3 signaling pathway-related proteins in the tumor tissues.Results:1)BTF3 was highly expressed in GBM cells.2)After BTF3 knockdown,the malignant biological properties of GBM cells were signific-antly decreased.3)After BTF3 knockdown,phosphorylated(p)-JAK2 and p-STAT3 expressions were downregulated,JAK2 and STAT3 expres-sions were unchanged,and p21 expression was increased.4)BTF3 knockdown inhibited GBM tumorigenesis.Therefore,the expression of JAK2/STAT3 signaling pathway-related proteins was consistent with the in vitro results.Conclusions:BTF3 is highly expressed in GBM and regulates the proliferation,migration,and invasion of GBM cells through the JAK2/STAT3 signaling pathway.

Objective:To observe the longitudinal changes of symptoms in the irradiation area of patients with postoperative radiotherapy for breast cancer,and investigate the correlative symptom indexes for predicting acute radiation dermatitis during radiotherapy.Methods:This study was designed as a prospective longitudinal study.A total of 103 patients with breast cancer who received three-dimensional con-formal radiotherapy in The Fourth Hospital of Hebei Medical University from May 2022 to December 2022 were enrolled using convenience and purposive sampling methods.The patients received a total of 50 Gy/25 radiotherapy sessions.We conducted weekly observations of five symptoms-itching,pain,swelling,burning,and tightness-in the irradiated area,for a total of six weeks.The incidence of symptoms associ-ated with radiation dermatitis across different severity levels was compared.We calculated the optimal number of symptoms for the occur-rence of grade 2 or higher radiation dermatitis,evaluated the predictive effect using the subject's work characteristic curve(ROC),and com-pared the risk of radiation dermatitis with the number of symptoms by applying a binary Logistic regression.Results:A total of 103 patients were included in the study.The total severity scores of symptoms were 0(0,0),0(0,0),0(0,1),1(0,2),2(1,3),3(2,4),respectively,show-ing a gradually increasing trend.From the 20 Gy/10-fraction radiotherapy point onward to the completion of radiotherapy,symptom scores exhibited statistically significant deviations from baseline values(P<0.001).From the beginning of 30 Gy/15 sessions to the end of radiother-apy,symptom scores were higher in patients with grade 2 and above dermatitis compared to those with dermatitis of less than grade 2(Z=2.12,2.81,4.08,P=0.034,0.005,0.001);at the end of 50Gy/25 sessions,the incidence rates of pruritus,pain,swelling,tightness,and burning were 68.9%(71 cases),68.9%(71 cases),46.6%(48 cases),36.9%(38 cases),and 15.5%(16 cases),respectively.At the 30 Gy/15 and 40 Gy/20 radiotherapy sessions,the optimal number of predicted symptoms were two and three,respectively.The corresponding areas under the ROC curve were 0.632 and 0.666.Sensitivity values were 48.6%and 43.2%,while specificity values reached 77.3%and 81.8%,re-spectively(95%CI:0.517-0.746,0.558-0.775,P=0.027,0.005).The subjects were assigned into low-risk and high-risk groups using the op-timal cut-off values,and binary Logistic regression showed that the risks of grade 2 and higher radiation dermatitis in the high-risk group were 3.39 and 3.58 times higher than that in the low-risk group(OR=3.388,95%CI:1.400-8.197,P=0.007;OR=3.584,95%CI:1.430-8.985,P=0.006).Conclusions:The symptoms of radiation dermatitis have appeared early and worsened with the severity of dermatitis.We should closely observe these symptoms throughout treatment.The risk of grade 2 and above radiation dermatitis increased when the number of symptoms was≥2 at 30 Gy/15 times and≥3 at 40 Gy/20 times.

Objective:To investigate the value of a computed tomography(CT)radiomics-based model for predicting the efficacy of neoad-juvant immunotherapy combined with chemotherapy for locally advanced gastric cancer(LAGC).Methods:Data on 114 patients with LAGC who underwent radical surgery after neoadjuvant immunotherapy combined with chemotherapy at The Second Affiliated Hospital of Xingtai Medical College between June 2019 and June 2021 were retrospectively collected.These patients'data were divided into a training set(n=67)and a validation set(n=47)based on the time of admission.High-throughput features were extracted from baseline portal phase CT images of all patients,and the selected features were used to construct the radiomics prediction model.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)and calibration curves.The prognostic ability of the model was assessed using Kaplan-Meier curves.Results:Based on the maximum relevancy min-redundancy(mRMR)algorithm and least absolute shrinkage and selection operator(LASSO)regression model,5 out of 584 assessed features were incorporated into the radiomics(Rad)score.The respect-ive areas under the curve for predicting pathological complete response(pCR)in the training and validation sets were 0.865 and 0.830,re-spectively,and good fits were obtained(Hosmer-Lemeshow test:P>0.05).The optimal cut-off value for the Rad score was determined based on the Youden index.Patients with high Rad scores had significantly higher 3-year recurrence-free survival rates(82.7%vs.60.4%in the training set and 78.9%vs.53.8%in the validation set)and 3-year overall survival rates(78.9%vs.60.2%in the training set and 79.3%vs.50.0%in the validation set)than those with low Rad scores(P<0.05).Conclusions:The CT radiomics prediction model effectively predicted the pathological response and prognosis of patients with LAGC after neoadjuvant immunotherapy combined with chemotherapy and is ex-pected to serve as a practical clinical tool.