Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective To evaluate the predictive value of different anthropometric indices in as-sessing body fat content in patients with chronic kidney disease(CKD).Methods Bioelectrical im-pedance analysis was used to measure body fat percentage and visceral fat area in 279 non-dialysis CKD patients.Height and body mass were measured to calculate body mass index(BMI).Waist and hip circumferences were measured to calculate waist-to-hip ratio.Skinfold thickness(triceps skinfold thickness and subscapular skinfold thickness)was also measured.Pearson correlation analysis was employed to explore the correlations between anthropometric indices and body fat percentage as well as visceral fat area.Receiver operating characteristic(ROC)curves were plotted,and the DeLong test was conducted to compare the differences in the area under the curve(AUC)of the ROC curves.Results Pearson correlation analysis revealed significant correlations between body fat percentage and BMI(r=0.419,P＜0.001),hip circumference(r=0.450,P＜0.001),triceps skinfold thickness(r=0.229,P＜0.001),and subscapular skinfold thickness(r=0.324,P＜0.001).Significant correlations were also observed between visceral fat area and BMI(r=0.658,P＜0.001),hip circumference(r=0.648,P＜0.001),triceps skinfold thickness(r=0.194,P=0.001),and subscapular skinfold thickness(r=0.333,P＜0.001).ROC curve analysis demonstrated that the triceps skinfold thickness had the largest AUC value(0.732)for diagnosing obesity in CKD patients,with a sensitivity of 62.1％and specificity of 78.8％,indicating a moderate diagnostic performance.BMI and hip circumference had AUC values of 0.806 and 0.804,respectively,for as-sessing visceral obesity in CKD patients,showing good diagnostic performance.In contrast,the waist-to-hip ratio exhibited poor diagnostic value for both overall obesity and visceral obesity.Conclusion Measuring BMI and hip circumference is valuable for diagnosing visceral fat accumula-tion in CKD patients.However,when assessing overall obesity in CKD patients,multiple anthropo-metric indices should be combined for comprehensive evaluation.Additionally,our results indicate that different anthropometric indices have varying diagnostic values for different types of obesity,ne-cessitating appropriate selection based on actual circumstances.

Objective To observe the therapeutic effect of a patented disposable detachable soft injection probe(DDSI probe)for mucosal suturing of the internal orifice in the treatment of high simple anal fistula.Methods From January 2020 to December 2023,12 cases of high simple anal fistula were selected.The DDSI probe was used to accurately locate the internal orifice of the anal fistula.The fistula tract was excised,and the mucosa of the internal orifice was sutured.The time for internal orifice exploration during surgery,Visual Analogue Scale(VAS)scores for pain at 1,3,and 7 d postoperatively,Wexner incontinence scores at 1 month postoperatively,and recurrence rate at 12 months postoperatively were observed.Results The time for internal orifice exploration ranged 2-5 min,with an average of 3.2 min.On postoperative day 1,the VAS scores were 0 in 2 cases,1 in 4 cases,2 in 5 cases,and 3 in 1 case.On postoperative day 3,the VAS scores were 0 in 2 cases,1 in 9 cases,and 2 in 1 case.On postoperative day 7,the VAS scores were 0 in 9 cases and 1 in 3 cases.At 1 month postoperatively,the Wexner incontinence scores were 0 in 10 cases and 1 in 2 cases.Eleven cases were cured,and 1 case recurred(diagnosed at 12 months after surgery).Conclusion The DDSI probe for internal orifice exploration,combined with fistula tract excision and mucosal suturing of the internal orifice,shows satisfactory therapeutic effects in the treatment of high simple anal fistula.

Objective To explore the effects of aberrant O-glycosylation modifications induced by the knockout of Cosmc or T-synthase genes on the expression profiles of miRNAs in exosomes derived from colorectal cancer cells and to reveal the molecular mechanisms of O-glycosylation in the development of colorectal cancer and identify potential biomarkers for early diagnosis and treatment.Methods This research specifically targets the Cosmc or T-synthase genes in the human colorectal cancer cell line HCT116 to create stable cell lines exhibiting abnormal O-glycosylation with CRISPR/Cas-9 gene editing technology.Exosomes originating from these colorectal cancer cells were isolated and authenticated.A microarray chip equipped with primer sequences for 16 miRNAs closely associated with colorectal cancer was employed to assess the differential expression of miRNAs within these exosomes with fluorescent quantitative polymerase chain reaction(PCR).And then,a cohort of miRNAs that exhibited significant and consistent changes in expression levels across the exosomes from both cell lines was selected.These miRNAs were further validated independently with traditional fluorescent quantitative PCR.Subsequently,data from The Cancer Genome Atlas Program(TCGA)database containing patient information on colorectal cancer was harnessed.Employing R programming language,Gene Set Enrichment Analysis(GSEA)was conducted on the upregulated miRNA to investigate the downstream pathways significantly impacted and the malignant biological behaviors they may influence.Results The absence of either Cosmc or T-synthase genes results in the dysregulation of O-glycosylation in colorectal cancer cells,leading to the exposure of Tn antigens.This,in turn,affects the expression levels of specific miRNAs in exosomes derived from these cells.Specifically,the expression of hsa-miR-125b-1-3p was downregulated,while that of hsa-miR-218-5p was upregulated.Notably,hsa-miR-218-5p were found to be closely associated with the epithelial-mesenchymal transition(EMT)process in tumor cells,which is a key mechanism in cancer progression.Conclusion It elucidates that the aberrant O-glycosylation mediated by the knockout of Cosmc or T-synthase genes significantly influences the expression of certain miRNAs in exosomes from colorectal cancer cells,potentially affect the EMT process in colorectal cancer and thereby promoting distant metastasis.Given the inherent stability and detectability advantages of colorectal cancer-derived exosomes,the altered expression levels of miRNAs within these exosomes may serve as indicators of the stated of abnormal O-glycosylation in colorectal cancer.These findings suggest that exosomal miRNAs have potential as biomarkers for monitoring disease progression and therapeutic efficacy.Consequently,this could pave the way for more personalized diagnostic and treatment strategies tailored to individual colorectal cancer patients,enhancing the precision and effectiveness of clinical management.

Objective To investigate the prognostic value of serum interferon-γ(IFN-γ),mannose-binding lectin(MBL)and soluble Fas(sFas)expression levels in patients with multiple myeloma(MM).Methods A total of 150 MM patients diagnosed in our hospital were included in this study and used as the research subjects.According to ISS staging,patients were separated into the stage Ⅰ group(46 cases),the stage Ⅱ group(54 cases)and the stage Ⅲ group(50 cases).According to the survival status of MM patients,they were assigned into the survival group(n=98)and the death group(n=52).Enzyme linked immunosorbent assay(ELISA)was applied to detect expression levels of serum IFN-γ,MBL and sFas.The influencing factors of prognostic mortality in MM patients were analyzed by Cox proportional hazard regression model.The receiver operating curve(ROC)was plotted to analyze the diagnostic value of serum IFN-γ,MBL and sFas expression levels in the prognostic mortality of MM patients.Results With the improvement of ISS stage,the serum Ca level of patients increased significantly(P＜0.05).With the improvement of ISS staging,the expression level of serum IFN-γ was greatly decreased,while the levels of serum MBL and sFas were significantly increased(P＜0.05).The serum IFN-γ level was significantly lower in the death group than that of the survival group,while the serum MBL and sFas levels were significantly higher(P＜0.05).The proportion of ISS Ⅲ stage and the level of serum Ca were significantly higher in the death group than those in the survival group(P＜0.05).Elevated serum levels of MBL,sFas and Ca and ISS stage Ⅲ were risk factors for death within three years in patients with MM,and elevated serum IFN-γ level was protective factor for death within three years in patients with MM(P＜0.05).The AUC of prognostic mortality in patients with combined serum IFN-γ,MBL and sFas in the diagnosis of MM was 0.977,which was better than that of patients diagnosed alone(Z=3.481,3.952 and 3.832,P＜0.05).Conclusion The decreased serum IFN-γ expression and the increased MBL and sFas levels are related to the three-year prognosis of MM patients,and the combination of the three has predictive value for death of MM patients,and which can be used as a biomarker for the prognosis evaluation of MM patients.

Background and purpose:For few of early-stage breast cancers who are undiagnosed by core needle biopsy,the delayed diagnosis rate of intraoperative rapid frozen section pathological examination is unclear.The purpose of this retrospective cohort study was to investigate the clinical application value of frozen sections in this situation.Methods:This study reviewed data of 876 breast cancer patients that were undiagnosed by core needle biopsy in Fudan University Shanghai Cancer Center from May 1,2006 to December 31,2019.Clinical characteristics and image data and pathological data of patients were collected.The correlation between clinical features and delayed diagnosis rate(DDR)of frozen section was explored using logistic regression analysis,then a nomogram was constructed to predict the probability of delayed diagnosis.This study was approved by Ethics Committee of Fudan University Shanghai Cancer Center(No.:050432-4-2108*).Results:A total of 876 patients met the inclusion standards.The intraoperative diagnosis rate of frozen section for breast cancers that were undiagnosed by core needle biopsy was 67.7%,and the DDR was 32.3%.In multivariate analysis,papillary lesion[odds ratio(OR)=4.251,95%CI:2.804-6.492;P＜0.001)and sclerosing adenosis(OR=3.727;95%CI:1.897-7.376;P＜0.001)accompanied by atypical epithelial hyperplasia on core needle biopsy(CNB)were positive correlation factors of delayed diagnosis,while clustered microcalcifications on mammography(OR=0.345;95%CI:0.216-0.543;P＜0.001)and ultrasonic category 4C-5 according to Breast Imaging Reporting and Data System(BI-RADS)(OR=0.250;95%CI:0.081-0.777;P=0.016)were positive correlation factors of intraoperative diagnosis.The nomogram constructed by these factors could better predict the delayed diagnosis rate of frozen section and screen out low delayed diagnosis population.Conclusion:Frozen section has a certain delayed diagnosis rate for breast cancer that is not clearly diagnosed by core needle biopsy.The method of model prediction can effectively eliminate the delayed diagnosis cases and avoid some unnecessary frozen sections.

Isolated axillary recurrence(AR)after breast cancer surgery is one of the critical factors influencing patients'prognosis.With advancements in diagnostic and therapeutic techniques,the clinical understanding of AR has progressively deepened.However,due to the low incidence of AR,systematic studies on its clinical features remain limited.High-quality clinical trials,such as ACOSOG Z0011 and AMAROS,have demonstrated that in patients with varying statuses of sentinel lymph node,axillary lymph node dissection(ALND)and sentinel lymph node dissection(SLND)provide comparable control of AR.In recent years,the trend towards de-escalation axillary surgery has advanced the development of less invasive techniques such as targeted axillary lymph node dissection.The SOUND trial further confirmed the safety and feasibility of omitting axillary surgery in patients with tumors≤2 cm.In addition,a series of clinical studies have identified a variety of potential high-risk factors,including patient age,number of positive lymph nodes,high Ki-67 proliferation,extranodal extension,and axillary soft tissue infiltration.However,there is no broad consensus regarding the association of these factors with AR.This review comprehensively summarized the clinical characteristics,risk factors and personalized management strategies of AR,with an emphasis on the impact of different axillary surgical approaches,radiotherapy and systemic therapy on the AR risk.In addition,more high-quality clinical studies are urgently needed to further clarify prognostic factors and optimize individualized treatment strategies,so as to provide more precise management for patients.