Diffuse large B-cell lymphoma (DLBCL), a heterogeneous malignancy characterized by distinct genetic and clinical subtypes, remains a therapeutic challenge despite standard R-CHOP chemotherapy. This study systematically investigated the synergistic anti-tumor efficacy and mechanism of the histone deacetylase inhibitor chidamide (CHI) combined with doxorubicin (DOX) in DLBCL models. Through multimodal experimental approaches including CCK8 proliferation assays, senescence-associated β-galactosidase (SA-β-gal) staining analysis, comet assay for DNA damage quantification, and comprehensive western blotting for molecular mechanism elucidation, we identified a potent synergistic interaction between CHI and DOX. By constructing a xenograft tumor model, the synergistic effect of the two drugs and its mechanism in vivo were confirmed. Our research found that CHI showed cell cycle inhibition and apoptosis induction effects on DLBCL cells. When combined with DOX, both synergistically inhibited the proliferation of DLBCL cells and promoted death of DOX-induced senescent cells. Preliminary mechanism studies revealed that CHI can reduce the level of mutant p53, inhibit cell senescence, and induce irreparable DNA damage in DOX-induced senescent tumor cells, ultimately leading them into programmed apoptosis. Thus, the "One-two punch" strategy increased the sensitivity of p53-mutated DLBCL cells to CHI. In summary, our study demonstrates that CHI synergizes with DOX to suppress DLBCL and presents a promising strategy to augment the therapeutic efficacy of DOX.

Cervical cancer, linked to HPV and dysglycemia, lacks clarity on their combined impact. This study explores Ki-67's role in mediating HPV and dysglycemia effects on cervical cancer risk.

This study enrolled patients with abnormal cervical cancer screening results, undergoing colposcopy and conization at Fujian Maternity and Child Health Hospital's Cervical Disease Center from June 2018 to June 2023. Statistical analyses compared baseline characteristics across cervical lesion categories. Multinomial logistic regression examined HPV and dysglycemia associations with LSIL (low-grade squamous intraepithelial lesions), HSIL(high-grade squamous intraepithelial lesions), and cervical cancer, highlighting interaction and mediation analyses involving Ki-67.

A total of 4,115 participants were included: 573 with hyperglycemia, 1,479 with HPV only, and 548 with both HPV and hyperglycemia. Prediabetes and diabetes significantly increased cancer risk (OR: 2.47, 95% CI: 1.75-3.47 and OR: 3.67, 95% CI: 2.41-5.6, respectively). Coexisting hyperglycemia further elevated cervical cancer risk by over three-fold (OR: 3.12, 95% CI: 2.34-4.16) compared to HPV-positive normoglycemics. A significant interaction between hyperglycemia and HPV infection was observed (AP (attributable proportion): 0.69, 95% CI: 0.61-0.77, p<0.001; SI (synergy index): 3.27, 95% CI: 2.5-4.27, p<0.001). Ki-67+ expression accounted for 39.84%, 37.35%, and 55.18% of the total effect of hyperglycemia, HPV, and their combined impact, respectively. Additionally, the combination of dysglycemia and HPV had a significant indirect effect on Ki-67 levels (estimate: 0.08, 95% CI: 0.06- 0.09, p<0.001).

Dysglycemia and HPV infection synergistically elevate cervical cancer risk, possibly influenced by Ki-67. Effective screening and management for both are vital in prevention. Further research is required to validate findings and elucidate molecular mechanisms.

Thyroidectomy may lead to postoperative swallowing difficulties. This study aimed to evaluate the relationship between electromyographic (EMG) changes observed during intraoperative neuromonitoring (IONM) and swallowing problems following lobectomy, total thyroidectomy (TTx), and total thyroidectomy with central lymph node dissection (TTx+CLND), as assessed using high-resolution manometry (HRM).

This prospective study included 36 patients who underwent thyroid lobectomy (n=9), TTx (n=15), or TTx+CLND (n=12) by using IONM. All patients were questioned about dysphagia and underwent HRM preoperatively and at postoperative 6th month. Demographic data, the dominant nodule size, total thyroid volume, IONM findings and HRM results were recorded. The pre-and postoperative changes in HRM results were evaluated according to the clinical characteristics, extent of surgery and IONM data.

Five (14%) reported de novo postoperative dysphagia. No loss of signal during IONM and postoperative vocal cord palsy were observed. Adverse EMG changes and combined event (CE) occurred in 8 (22%) and 2 (5.5%) patients, respectively. Postoperative upper esophageal sphincter resting pressure (UESRP) significantly decreased from a median of 181 mmHg (range: 12-407 mmHg) to 109 mmHg (range: 8.6-407 mmHg), postoperatively (p=0.03). The percentage of UESRP decrease was 64% (range: -82_20%) and 25% (range: -86 _135%) in patients with and without postoperative de novo dysphagia (p=0.06). In the TTx group, which had significantly larger tumor size and higher thyroid volumes compared to the TTx+CLND group, UESRP decreased by 44%, versus 16% in the TTx+CLND group (p=0.001). Patients who experienced adverse EMG changes exhibited a significantly lower median percentage decrease in UESRP (-3%, range: -54% to 52%) than those without EMG abnormalities (-34%, range: -86% to 135%) (p=0.04). No significant correlation was found between the EMG changes in external branch of superior laryngeal nerve and postoperative UESRP alterations.

This prospective clinical study demonstrated that UESRP decreases after thyroidectomy even in patients without IONM evidence of nerve injuries. Patients with large nodules, high thyroid volume, and new-onset dysphagia tended to show greater reductions in UESRP, whereas those with intraoperative adverse EMG changes exhibited less pronounced decreases. These heterogeneous responses may reflect complex neuromuscular adaptations involving the cricopharyngeus muscle.

This study aimed to identify risk factors for hypocalcemia following differentiated thyroid cancer (DTC) surgery and develop and validate a nomogram model to predict its occurrence.

A retrospective cohort study included 315 DTC patients who underwent surgery between January 2023 and January 2025. Clinical data encompassing demographics, surgical parameters (e.g., central lymph node dissection, capsular invasion, operation time), comorbidities (e.g., diabetes), and preoperative biomarkers (albumin, Lp-PLA2, Nesfatin-1) were analyzed. Variables were screened using univariate analysis, followed by multivariate logistic regression with a backward stepwise selection procedure to identify independent predictors. A nomogram was constructed using RStudio (version 3.4), and its performance was assessed for discrimination and calibration. Internal validation was performed using a bootstrapping technique.

Postoperative hypocalcemia occurred in 32.06% of patients (101/315). Multivariate analysis identified diabetes (OR=2.1, 95%CI: 1.4-3.3), central lymph node dissection (OR=3.4, 95%CI: 2.1-5.6), capsular invasion (OR=2.8, 95%CI: 1.7-4.7), prolonged operation time (OR=1.9, 95%CI: 1.3-3.0), elevated preoperative albumin (OR=1.7, 95%CI: 1.2-2.5), and Lp-PLA2 (OR=2.3, 95%CI: 1.5-3.7) as significant risk factors. Serum Nesfatin-1 emerged as a protective factor (OR=0.6, 95%CI: 0.4-0.9). The nomogram demonstrated excellent discrimination, with an area under the curve (AUC) of 0.850 (95%CI: 0.825-0.930), which remained robust after bootstrap validation (bias-corrected AUC=0.845). The model showed good calibration, confirmed by a calibration plot and the Hosmer-Lemeshow test (P=0.30). Decision curve analysis indicated a strong clinical utility.

This study developed and internally validated a nomogram integrating clinical, surgical, and biochemical predictors to quantify individualized risk of hypocalcemia after DTC surgery. The model shows robust predictive accuracy, offering clinicians a practical tool for preoperative risk stratification and targeted interventions. However, external validation in multicenter cohorts is necessary to enhance generalizability.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms. Complete surgical resection is the mainstay of treatment, yet recurrence remains common even after apparent complete resection. Gastrointestinal stromal tumors carry a notable long-term risk of recurrence even after surgery, underscoring the need for ongoing vigilance. We present a case of very late recurrence of gastric GIST 17 years after complete resection. This case highlights the limitations of current surveillance protocols and raises important questions about tumor biology, genetic risk stratification, and the need for long-term or even lifelong follow-up in selected patients.

Occupational exposure accounts for the second preventable risk factor for bladder cancer (BC), after smoking.

This study aimed to extract evidence-based data from the systematic reviews that included studies primarily from the past 30 years, based on a clearly defined method of exposure assessment.

A literature search in PubMed, Web of Science, ScienceDirect, and Embase was conducted using variations of the keywords "BC," "occupational exposure," and/or "occupation." The inclusion criteria for the umbrella review were the following: systematic reviews and meta-analyses focused on occupational exposure, with a clear definition of the exposure assessment, a risk estimate for BC, and a majority of data from 1993 to 2023. We did not include other forms of reviews or systematic reviews focused on the general population and environmental exposure. Data were synthesized based either on occupations or on occupational hazards. After the overlap checking, the remaining reviews were assessed for quality using AMSTAR 2 criteria and afterwards classified for high, moderate, or low evidence using the GRADE scale.

We found relevant associations with a high level of evidence for firefighters, hairdressers, painters, workers in the petroleum industry, and dry cleaners exposed to tetrachloroethylene. Concerning hazards, exposure to ortho-toluidine was also confirmed to be a risk by recent studies. Welders, veterans, and those exposed to hexavalent chromium at higher risk need more well-designed studies to be confirmed.

Despite longstanding recognition of certain risks, occupational exposure remains insufficiently investigated. Recent data support the inclusion of occupations and hazards in the individual risk assessment for BC.

Carney complex is a rare autosomal dominant genetic syndrome that may involve multiple endocrine glands. As the disease progresses, different symptoms gradually emerge. Follow-up is crucial for early diagnosis and treatment of each neoplasm. Case report: A 3.8-year-old Han Chinese male patient presented with acne for one year. He was diagnosed with Carney complex for Cushing's syndrome caused by an adrenal adenoma, precocious puberty mainly caused by a large cell calcifying Sertoli cell tumour of the testis. Left adrenalectomy and a treatment for precocious puberty, including aromatase inhibitor therapy, were prescribed. The patient experienced complete relief from Cushing's syndrome and showed an improvement in predicted adult height. Attention-deficit hyperactivity disorder impaired the patient's attention. Both the patient and his parents were receiving behavior management training. Carney complex patients need close follow-up. Adrenal adenoma is also a possible pathological type of adrenal lesion in this complex. Multidrug combination therapy could have a good effect on precocious puberty. Attention-deficit hyperactivity disorder was present as a comorbid condition, the underlying mechanism of which in patients with Carney complex requires further investigation. Collaboration among multidisciplinary teams is crucial for prognosis.

Fluorescence Lifetime Imaging Microscopy (FLIM) is an imaging technique that allows for the visualization of the cellular microenvironment by measuring the decay time of endogenous fluorescent molecules. Its advent has allowed the acquisition of information on previously undetectable aspects of the tissue environment, which also includes some mechanisms involving immune checkpoints. Understanding the level of interaction with their ligands is of paramount importance when stratifying patients for immunotherapy, as traditional methods such as immunohistochemistry (IHC) were found to be ineffective in predicting responders.

This review analyzes the current literature on FLIM as a means of predicting targets' responsiveness to ICIs by examining the most relevant databases. Following PRISMA guidelines, we identified the relevant literature. The predefined objective of this review was to evaluate the potential of FLIM as a predictive biomarker of responsiveness to immune checkpoint inhibitors (ICIs). Eligibility criteria included original studies (clinical or preclinical) reporting on the use of FLIM to assess tumor or immune microenvironment in the context of ICI therapy. Reviews, case reports, editorials, and abstracts without full text were excluded.

Research suggests that interaction, not expression, is positively correlated with the effectiveness of ICI treatment. FLIM, in combination with FRET, allows for the quantification of the interactions within the tumor microenvironment.

The scope of the review is to assist researchers in further exploring this technology for possible applications and for future drug interaction studies.

While CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy demonstrates remarkable efficacy in relapsed/refractory (R/R) ALL, its application in earlier treatment lines requires further investigation. This study aimed to evaluate the efficacy, safety, and cellular kinetics of CD19 CAR-T therapy in pediatric B-cell ALL (B-ALL) patients with minimal residual disease (MRD) positivity or chemotherapy intolerance.

Between 2017 and 2021, 50 eligible pediatric B-ALL patients (with positive MRD or chemotherapy intolerance) received CD19 CAR-T therapy. Efficacy endpoints included complete remission (CR), MRD-negative CR (MRD-CR), overall survival (OS), and leukemia-free survival (LFS). CAR-T cellular kinetics parameters (C_max, AUC_0-28d, persistence) were quantified via qPCR and correlated with clinical outcomes. Safety assessment covered cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections.

At day 28 post-infusion, the CR and MRD-CR rates were 98% and 96%, respectively. With a median follow-up of 68.7 months, the 5-year OS and LFS rates were 74.9% and 67.8%. Multivariate analysis identified prolonged B-cell aplasia (BCA) duration (HR = 0.969, p = 0.021) and female sex (HR = 0.235, p = 0.032) as independent protective factors for LFS. Cellular kinetics analysis showed effective in vivo expansion in 98% of patients, with a median C_max of 30,860 copies/μg DNA and a median time-to-peak of 10.5 days. The MRD-CR group at day 28 exhibited significantly higher C_max and AUC_0-28d (p = 0.017; p = 0.029) and superior CAR-T persistence (p = 0.030) compared to the non-MRD-CR group. Pre-infusion tumor burden levels did not significantly impact CAR-T expansion or duration. BCA duration positively correlated with CAR-T persistence (r=0.570, p < 0.001), but CAR-T expansion parameters (Cmax and AUC0-28d) did not significantly influence BCA. Regarding safety, grade ≥3 CRS occurred in 16% of patients, and ICANS in 10%. Pre-infusion MRD ≥ 10^-3 was an independent predictor of severe CRS.

CD19 CAR-T therapy demonstrates highly effective MRD clearance and provides long-term survival benefits with a manageable safety profile in pediatric B-ALL patients with MRD positivity or chemotherapy intolerance. Effective CAR-T expansion occurs even at low tumor burdens. These findings support the potential for advancing CAR-T therapy into earlier treatment lines, although its value requires further validation in prospective studies.

Statins are commonly used for cardiovascular diseases and recent studies have supported their anti-cancer role in numerous human malignancies. This study aims to investigate their prognostic impact in lung cancer patients receiving immune checkpoint inhibitors (ICIs).

A retrospective analysis was performed based on the clinical data from 235 lung cancer patients who received ICI therapy between 2019 and 2024 in three hospitals. The correlation of statin use with overall survival (OS) or progression-free survival (PFS) was analyzed. Then, a comprehensive bioinformatics analysis was used to identify prognostic target genes of statins and investigate their correlation with immune infiltration, followed by validation in an independent cohort and cellular experiments.

In the whole cohort, 80 patients (34.0%) received statins. The statin users had a significantly better OS and PFS than the non-statin users. Statin use was an independent favorable prognostic factor for ICI-treated lung cancer patients. Transcription factor RAR-related orphan receptor alpha (RORA) was identified as a favorable prognostic target gene of statins. RORA was found to be downregulated in lung cancer tissues and correlated with infiltration of some immune cells. In the validation cohort, RORA expression was positively correlated with CD8⁺ T cell infiltration in lung cancer tissues, and improved prognosis in lung cancer patients receiving ICIs. Atorvastatin treatment increased RORA expression and RORA knockdown partly antagonized the inhibitory role of Atorvastatin on the malignant characteristics of lung cancer cells in vitro.

Statin use was significantly correlated with improved prognosis in lung cancer patients receiving ICIs. Statins may enhance ICI efficacy partly through RORA. Due to study limitations, the actual role of statins and their target genes in anti-cancer immunity needs further investigations.