Objective To investigate the association of the total burden of cerebral small vessel disease （CSVD） with the level of tumor necrosis factor-α（TNF-α） and prognosis in patients with ischemic stroke （AIS）. Methods A total of 120 patients with AIS who were admitted to our hospital from January 2022 to December 2023 were enrolled as subjects， and all patients underwent cranial MRI scanning. Baseline data and TNF-α level were compared between the patients with different total burden scores of CSVD， and the correlation between TNF-α level and CSVD total burden score was analyzed. TNF-α level and CSVD total burden score were compared between the AIS patients with different prognoses to investigate the influence of TNF-α and CSVD total burden score on the short-term prognosis of AIS， as well as their value in predicting the short-term prognosis of AIS. Results There were significant differences in age， the proportion of patients with hyperlipidemia， the proportion of patients with smoking， and the levels of TNF-α and Hcy between the patients with different CSVD total burden scores （P<0.05）. The level of TNF-α was positively correlated with the number of lacunar cerebral infarcts， Fazekas score of white matter lesions， and EPV score （r=0.654， 0.775， 0.820， P<0.05）， but it had no linear correlation with the number of cerebral microbleeds （r=-0.035，P>0.05）. The logistic regression analysis showed that before correction， age， hyperlipidemia， smoking， TNF-α，and Hcy were significantly correlated with lacunar infarction， white matter lesions， EPV severity， cerebral microbleeds，and CSVD total burden score （P<0.05）， and after correction， TNF-α was still significantly correlated with lacunar infarction， white matter lesions，cerebral microbleeds， EPV severity， and CSVD total burden scores （P<0.05）. There were significant differences in CSVD total burden score and TNF-α between the patients with a good prognosis and those with a poor prognosis（P<0.05）.TNF-α combined with CSVD total burden score had the largest area under the receiver operating characteristic curve（AUC） of 0.912 in predicting the short-term prognosis of AIS，which was significantly higher than the AUC of TNF-α or CSVD total burden score used alone（P<0.05）. Conclusion The increase in TNF-α level has a certain relationship with CSVD total burden score and short-term prognosis in AIS patients， and the combination of TNF-α level and CSVD total burden score has a relatively high clinical application value in predicting the short-term prognosis of AIS patients.
Prognosis

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

Objective To investigate the association of blood pressure variability （BPV） with early neurological deterioration （END） and prognosis in patients with acute mild non-disabling ischemic stroke. Methods The patients with acute mild non-disabling ischemic stroke who were admitted to Stroke Center of Affiliated Hospital of Inner Mongolia University for Nationalities from January 2022 to August 2024 were enrolled， and according to the presence or absence of END， they were divided into non-END group and END group. General information， clinical data， and outcome measures were collected from all patients， and a binary logistic regression analysis was performed to determine independent risk factors for END. According to the modified Rankin Scale （mRS） score， the patients were divided into good prognosis group （mRS score ≤2 points） and poor prognosis group （mRS score >2 points）， and a univariate logistic regression analysis was performed to investigate the influence of END on the 90-day neurological function prognosis of patients. Results A total of 61 patients were enrolled， with 14 patients in the END group and 47 patients in the non-END group. There was a significant difference in the coefficient of systolic pressure variation between the END group and the non-END group （P<0.05）. The binary logistic regression analysis showed that systolic BPV（BPV>75%） was an independent risk factor for END （OR=14.000， 95%CI 1.471‒133.233，P=0.011）.Compared with the non-END group， the END group had a significantly higher proportion of patients with a poor 90-day prognosis.Of all patients， there were 11 patients with poor prognosis and 50 patients with good prognosis on day 90. The univariate logistic regression analysis showed that END （OR=19.556，95%CI 4.038‒94.696，P<0.001） was an independent risk factor for poor prognosis. Conclusion In patients with acute mild non-disabling ischemic stroke， the increase in coefficient of systolic pressure variation is an independent risk factor for END and affects the prognosis of neurological function on day 90.
Prognosis

BACKGROUND

Early-stage endometrial cancer often presents with favorable survival rates, but high-risk factors, including TP53 mutations and high-grade serous pathology, can lead to recurrence and poor prognosis. The standard primary treatment for endometrial cancer is surgical staging, and lymph node metastases significantly impact adjuvant therapy decisions. The subgroup of p53-abnormal (p53abn) indicates the worst prognosis and potential benefits from adjuvant chemotherapy. Molecular classification, while recommended, faces practical challenges due to resource constraints.

OBJECTIVES

The study aimed to assess the incidence of p53 abnormal expression in clinical stage 1 endometrial cancer cases that underwent surgery at a government tertiary hospital, and assess its relationship with clinicopathologic factors and pelvic and paraaortic lymph node metastasis (LNM).

METHODS

A cross-sectional retrospective analysis was conducted on clinical early-stage endometrial cancer cases that underwent surgical primary treatment between January 2018 and December 2022. Patient records were reviewed to gather demographics, surgical information, and pathological evaluations. Preoperative clinical staging was determined through imaging, and surgical staging involved comprehensive lymphadenectomy. Immunohistochemistry studies for p53 were carried out on formalin-fixed paraffin-embedded tissue samples.

RESULTS

A total of 233 endometrial cancer cases were included. The mean age at diagnosis was 53.7 years. Common comorbidities included hypertension (47.2%) and dyslipidemia (20.6%). Most cases were endometrioid histology (82.8%) and low-grade tumors (85.8%). Tumor grade (p=0.010), myometrial invasion (p<0.001) and lymphovascular space invasion (p<0.001) significantly correlated with lymph node metastasis. However, tumor size and p53abn were not significantly associated with lymph node metastasis. p53abn overexpression was significantly associated with non-endometrioid histology at 33% and Grade 3 tumors at 23%. Preoperative grading demonstrated moderate reliability (0.51) with postoperative grading, with an agreement of 65.4%.

CONCLUSION

Tumor grade, myometrial invasion, and LVSI were all significantly associated with lymph node involvement. While p53 immunohistochemical stains show promise in predicting metastasis and has been associated with tumor aggressiveness, this should still be correlated with clinicopathological parameters to carry out a more accurate risk stratification of early-stage patients.

Therapeutics ; Survival Rate ; Risk Factors ; Recurrence ; Prognosis ; Pathology ; Endometrial Neoplasms ; Immunohistochemistry ; Tumor Suppressor Protein P53 ; Lymph Node Excision ; Risk Assessment

Introduction: Primary aldosteronism (PA) is a common yet underdiagnosed cause of secondary hypertension, associated with increased cardiovascular and renal morbidity. Early detection and subtype-directed management significantly improve outcomes. However, adherence to recommended diagnostic pathways in real-world practice remains variable. Case: We conducted a retrospective audit of patients diagnosed with PA in a Malaysian tertiary centre from January 2018 to December 2025. Data collected included demographics, clinical presentation, biochemical parameters, diagnostic workup (aldosterone-renin ratio [ARR], confirmatory testing, adrenal imaging, and adrenal venous sampling [AVS]), treatment modality, and outcomes. Audit standards were based on established international guidelines. A total of 14 patients were included, with equal gender distribution. The cohort comprised 57% Malay and 43% Chinese. Most patients presented with hypertension (mean ~170/100 mmHg), and hypokalemia was present in approximately 70% of the patients. ARR and adrenal imaging were performed in all patients (100%), while confirmatory testing was conducted in 85% of the patients. However, AVS utilization remained limited (50%). Contributing factors included failed cannulation, technical challenges in overweight patients, preference for medical therapy, refusal of surgery, and limited access to AVS services. The majority had unilateral adrenal adenoma (~75%). Treatment was divided between surgical (55%) and medical (45%) approaches. Post-treatment, hypokalemia resolved in 90% of patients, with a significant reduction in antihypertensive burden and complete hypertension resolution in approximately 35% of the patients. Quality of life improved in most patients. Conclusion This audit demonstrates good adherence to initial screening and imaging in PA but highlights suboptimal utilization of AVS. Barriers to AVS utilization are multifactorial, encompassing technical, patient-related, and system level limitations. Addressing these barriers is essential to optimize subtype-directed management and improve longterm cardiovascular outcomes in patients with PA. Despite this, clinical outcomes were favorable. Strengthening adherence to diagnostic pathways, particularly subtype confirmation, may further improve patient outcomes.
Hyperaldosteronism ; Treatment Outcome ; Retrospective Studies

Introduction: Diabetes mellitus (DM) is a significant comorbidity associated with adverse tuberculosis (TB) treatment outcomes and remains an ongoing clinical challenge. Chronic hyperglycemia impairs host immune responses, particularly macrophage function, leading to delayed bacillary clearance. This contributes to poorer outcomes, including delayed sputum conversion, prolonged treatment duration, relapse, and increased mortality. Poor glycemic control is a key modifiable factor influencing these outcomes. This study aimed to evaluate the impact of glycemic control at diagnosis on TB treatment outcomes in a Malaysian cohort. Methodology: A retrospective cross-sectional audit was conducted using the TB clinic registry at Hospital Sungai Buloh from 2022 to 2025. Adult patients (≥18 years) with confirmed TB (any form) and DM (Type 1 or Type 2) with complete records were included. Of 241 patients screened, 131 were included after exclusions due to incomplete records (29.9%), transfer (29.9%), loss to follow-up (19.9%), and drug-resistant TB (2.9%). Data collected included demographics, hemoglobin A1c (HbA1c) at diagnosis, sputum conversion duration, treatment duration, type of DM therapy, and clinical outcomes. Results: The cohort had a mean age of 53 years, with 97% having Type 2 DM. Mean HbA1c at diagnosis was 10.5%. Poorer glycemic control was associated with delayed sputum conversion. Patients who achieved sputum conversion by 8 weeks had an average HbA1c of 9.6%, compared to 11.8% in those with delayed conversion. Longer treatment duration was associated with higher HbA1c (mean 10.5, 8.6, and 11.8% for 6-, 12-, and 18-month regimens, respectively). Relapse analysis demonstrated a trend towards higher HbA1c with increasing relapse episodes (11.2, 13.75, and 14.5% for one, two, and three relapses, respectively). Overall mortality was 17% (22/131), with markedly higher mean HbA1c in deceased patients compared to survivors (16.0% vs 10.5%). Conclusion Poor glycemic control at TB diagnosis is associated with delayed sputum conversion, prolonged treatment duration, and increased mortality. These findings are consistent with regional evidence, including a South Asian systematic review (Gautam et al., 2021), demonstrating higher mortality and treatment failure in patients with TB and DM. Early and aggressive optimization of glycemic control, alongside standard anti-TB therapy, is essential to improve outcomes.
Humans ; Glycemic Control ; Retrospective Studies ; Diabetes Mellitus ; Treatment Outcome ; Tuberculosis

OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

OBJECTIVES: To analyze the association of CHMP2B expression level of with clinicopathological characteristics and prognosis of clear cell renal cell carcinoma (CRCC) and the possible role of CHMP2B in tumorigenesis and progression of CRCC. METHODS: RNAseq data of CRCC were downloaded from the TCGA database for analysis of CHMP2B expression levels in tumor and adjacent tissues and their correlation with clinicopathological characteristics of the patients. Survival outcomes of the patients with high and low CHMP2B expressions were analyzed using the Kaplan-Meier model, and the COX risk regression model was used for identifying the prognostic factors of the patients. The correlation between CHMP2B expression and immune infiltration, its co-expressed genes, and the effect of CHMP2B gene mutations on immunotherapy responses, and its immunohistochemical expression in CRCC and normal tissues were analyzed. Clinical samples of CRCC were collected to examine CHMP2B expressions using RT-PCR, and cell experiment was carried out to test the effect of CHMP2B overexpression on biological behaviors of CRCC cells. RESULTS: CHMP2B was significantly under-expressed in renal cancer tissues, and its overexpression obviously inhibited the proliferation of CRCC cells in vitro. CHMP2B expression level was significantly correlated with age, gender, lymph node metastasis, and tumor stage, and the patients with low CHMP2B expression had poor survival outcomes. Enrichment and co-expression gene analyses suggested that CHMP2B was mainly involved in viral outgrowth, necrotic apoptosis, endocytosis, and immune-regulatory processes in kidney cancer. CONCLUSIONS CHMP2B is lowly expressed in renal cancer tissues to affect tumor progression and tumor immune processes, and may serve as a prognostic biomarker and therapeutic target for CRCC.
Humans ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/metabolism* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Male ; Female ; Gene Expression Regulation, Neoplastic

OBJECTIVES: To investigate the association of NUF2 expression with tumor prognosis and its regulatory role in tumor microenvironment. METHODS: We analyzed NUF2 expression, its prognostic value, and is immune-related functions across different cancer types using datasets from the Human Protein Atlas (HPA), TCGA, GTEx, CCLE, and TIMER. RT-qPCR, Western blotting, and immunohistochemistry were used to detect NUF2 expression in liver cancer cell lines and tissue and blood samples from patients with liver cancer. GO, KEGG, and GSEA analyses were conducted to explore the molecular mechanisms of NUF2 and its related genes, and a competitive endogenous RNA (ceRNA) network for NUF2 in liver cancer was constructed. RESULTS: NUF2 expression was upregulated in the tumor tissues of 27 cancers and was associated with clinical stages in several cancers. High NUF2 expressions were correlated with poor overall survival, disease-specific survival, progression-free survival, and disease-free survival of cancer patients. NUF2 expression levels were positively correlated with tumor mutational burden, microsatellite instability, infiltrating immune cells, immune cell marker genes and immune checkpoint genes in different cancers. RT-qPCR, Western blotting, and immunohistochemistry confirmed that NUF2 expression was upregulated in liver cancer cell lines and tumor tissues and blood samples of liver cancer patients, and was decreased significantly after operation. GO, KEGG and GSEA analyses indicated that NUF2 was involved in chromosome segregation and cell cycle and was associated with glycine, serine and threonine metabolism. CONCLUSIONS NUF2 expression is upregulated in 27 cancers and is associated with clinical stage and poor prognosis in some malignancies. NUF2 expression is closely correlated with immune cell infiltration in different cancers, suggesting its potential value for predicting immunotherapy response in these cancers.
Humans ; Prognosis ; Immunotherapy ; Tumor Microenvironment ; Liver Neoplasms/metabolism* ; Cell Line, Tumor ; Neoplasms/genetics* ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics*