Humans ; Female ; Receptors, Estrogen/metabolism* ; Breast Neoplasms/metabolism* ; Receptors, Progesterone/metabolism* ; Immunohistochemistry ; Estrogen Receptor alpha

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.
Male ; Female ; Humans ; Child ; Stroke Volume ; Retrospective Studies ; Ventricular Function, Left ; Phenotype ; Cardiomyopathy, Dilated/diagnosis* ; Mutation ; ATPases Associated with Diverse Cellular Activities/genetics* ; Membrane Proteins/genetics* ; Mitochondrial Proteins/genetics*

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20⁺B cells, CD4⁺T cells, and FOXP3⁺Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20⁺B cells, CD4⁺T cells and FOXP3⁺Treg cells in LELC may suggest a better prognosis.
Humans ; Lymphocytes, Tumor-Infiltrating ; Herpesvirus 4, Human ; Clinical Relevance ; Prognosis ; Carcinoma, Squamous Cell/pathology* ; Forkhead Transcription Factors

Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.
Male ; Female ; Humans ; Adult ; Middle Aged ; Thymoma/genetics* ; In Situ Hybridization, Fluorescence ; Transcription Factors/genetics* ; Mutation ; Thymus Neoplasms/genetics*

Humans ; Mesothelioma, Malignant/diagnosis* ; Diagnosis, Differential ; Adenocarcinoma/pathology* ; Mesothelioma/pathology* ; Lung Neoplasms/pathology* ; Biomarkers, Tumor ; Pleural Neoplasms/diagnosis* ; Extracellular Matrix Proteins

Humans ; Receptor, trkA/genetics* ; Neoplasms/genetics* ; Biomarkers, Tumor ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics*

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
Male ; Female ; Humans ; Prognosis ; Neoplasm Staging ; Retrospective Studies ; Nomograms ; Lymph Nodes/pathology* ; Risk Factors ; Colonic Neoplasms/surgery*

Objective: Intraoperative localization of the ureter can contribute to accurate dissection and minimize ureteral injury in colorectal surgery. We aim to summarize a single center's experience of fluorescence ureteral visualization using methylene blue (MB) and explore its visualization efficiency. Methods: This is a descriptive case-series-study. Clinical data of patients who had undergone laparoscopic colorectal surgery and fluorescence visualization of the ureter in the Gastrointestinal Surgery Department of Guangdong Provincial People's Hospital from March 2022 to May 2022 were retrospectively collected. Patients with incomplete surgery videos, renal insufficiency, or allergic reactions were excluded. MB was infused with 0.9% NaCl at 1.0 mg/kg in 100 mL of normal saline for 5 to 15 minutes during laparoscopic exploration. Imaging was performed using a device developed in-house by OptoMedic (Guangdong, China) that operates at 660nm to achieve excitation of MB. Clinical information, MB dosage, rate of successful fluorescence, time to fluorescence, operation time, blood loss, intraoperative blood oxygen levels, pathological staging, changes in renal function, and post-operative complications were retrospectively analyzed. Results: The study cohort comprised 27 patients (24 men and 3 women) with an average age of (60.25±16.95) years and an average body mass index of (21.72±3.42) kg/m². The dosage of MB was 0.3-1.0 mg/kg and the infusion time was 5-15 minutes. Fluorescence signals were detected in all patients. The median time to signal detection was 20 (range, 10 to 40) minutes after MB infusion. The range of intraoperative blood oxygen fluctuation averaged 2.5% (range, 0 to 7.0%). The median change in creatine concentration was -1.3 (range, -17.2 to 29.2) µmol/L. No patients had complications associated with use of MB. Fluorescence visualization of the ureter was very valuable clinically in two patients (thick mesentery, stage T4). Conclusion: MB is a safe and effective means of visualizing the ureter by fluorescence during laparoscopic colorectal surgery, especially when the procedure is difficult. MB in a dosage of less than 1 mg/kg can slowly infused for more than 5 minutes during laparoscopic exploration. During the infusion, attention must be paid to blood oxygen fluctuations.
Male ; Humans ; Female ; Adult ; Middle Aged ; Aged ; Ureter/surgery* ; Methylene Blue ; Retrospective Studies ; Infusions, Intravenous ; Colorectal Surgery ; Laparoscopy/methods* ; Digestive System Surgical Procedures

Acute Lung Injury ; Animals ; Autophagy ; Explosions ; Lung ; Rats ; Rats, Sprague-Dawley

Objective: To analyze the effect of intervention programs and influencing factors regarding the community "5+1" staged diabetes target management on patients with type 2 diabetes mellitus (T2DM) and to provide evidence for improving the quality of life (QOL). Methods: A total of 12 community health service centers from Shanxi province, Jiangsu province, and Ningxia Hui autonomous region were selected as intervention group and control group, by stratified cluster sampling method. "5+1" model was used in intervention groups and basic public health services model was applied in control groups for this two-year follow-up. Data was collected through a questionnaire on demographic and disease-related information, while the QOL was measured with SF-36. Multiple linear regression and conducted by SAS 9.4. Results: A total of 2 467 subjects were included at baseline and 1 924 had completed a two-year-long management service. After intervention programs being implemented, the net effect of PCS score between the intervention and the control groups was 13.6, with the net effect of MCS score as 29.8. Results from the multiple linear regression showed that the main factors affecting PCS scores included age, type of medical insurance, baseline PCS score and regions of residency. Main factors related to MCS score included age, type of medical insurance, baseline MCS score, hypertension, and region of residency. Conclusion: Community "5+1" staged diabetes target management model presented favorable effect of improving the QOL on T2DM patients.
Community Health Services/organization & administration* ; Diabetes Mellitus, Type 2/therapy* ; Humans ; Hypertension ; Program Evaluation ; Quality of Life ; Self Care ; Self-Management ; Surveys and Questionnaires