Intracranial aneurysms (IAs) often go undetected until rupture, leading to significant morbidity and mortality. Identifying biomarkers for early detection of IAs is crucial. The current study attempted to identify core genes linked with IAs and determine their relevance through Mendelian randomization. Limma helped identify differentially expressed genes between IAs and control superficial temporal artery samples. WGCNA was utilized to find IA-related modules and associated genes, which were further evaluated using KEGG and GO analyses to ascertain their potential roles. Five highly associated genes were screened with the CytoHubba plugin of Cytoscape software. ROC curves assessed the diagnostic efficacy of these genes. A two-sample Mendelian randomization evaluated the causal relationship between the core gene PTRPC and IAs, along with its correlation with immune infiltration. WGCNA and differential expression analysis depicted 584 related genes involved in cellular metabolism and chemokine activity. PTPRC was among the top highly associated genes identified through Cytoscape. It showed significant diagnostic value for IAs. Moreover, mendelian randomization depicted that PTPRC in CD4+ T cells is related to IA risk, with an OR of 0.63538 (95 % CI = 0.41636–0.96959, p = 0.03545). No reverse causal relationship was observed between PTPRC and IAs, with an OR of 0.99947 (95 % CI = 0.99719–1.00176, p = 0.65022). Additionally, immune cell infiltration results indicated a positive correlation between PTPRC in IAs with neutrophils and unactivated dendritic cells and a negative association with regulatory T cells (Tregs). PTPRC was identified as a core gene linked with IAs, providing evidence for IA diagnosis and studying molecular mechanisms.

This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Abstract Background Adding platinum to anthracycline- and taxane-based neoadjuvant chemotherapy has improved pathological complete response (pCR) and event-free survival(EFS) in patients with triple-negative breast cancer (TNBC). However, the efficacy for TNBC of combining taxane and platinum without anthracycline remains controversial. Methods The HELEN-001 trial was a randomized, phase 2 controlled, and open-label investigation carried out in China at 6 hospitals. Participants who were aged 18–70 years old, were histologically confirmed for TNBC clinical stage II–III, suitable for potentially curative surgery, and had an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 were selected for this trial. Participants were randomized into two equal groups; those who received docetaxel plus cisplatin (75 mg/m2, respectively) and those who received docetaxel plus doxorubicin and cyclophosphamide (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2). These regimens were given every 3 weeks for 6 cycles. Randomization was stratified by tumor size and nodal status. The primary endpoint was the number of individuals achieving a pCR (ypT0/isN0). The trial was registered with chictr.org (number ChiCTR-1800019501). Findings: Between November, 2018, and June, 2022, 212 patients were selected (n = 106/treatment arm). The number of individuals who achieved pCR after docetaxel plus cisplatin treatment was 51.9%, and that of those who attained pCR after docetaxel plus doxorubicin and cyclophosphamide was 35.8% (P = 0.019). After median follow-up of 29 months[interquartile range (IQR), 21 to 41], 14 of 106 patients (13.2%) in the docetaxel plus cisplatin group and 18 of 106 patients (17.0%) in the docetaxel plus doxorubicin and cyclophosphamide group had event-free survival (EFS) events [95% confidence interval (CI) = 0.377 to 1.526, hazard ratio (HR) = 0.759, P = 0.492]. The incidence of grade 3 or 4 events was similar in both groups [57 (54%) vs. 51 (48%)]. No treatment-associated deaths were identified in both groups. Interpretation: In stage II to III TNBC, the docetaxel plus cisplatin regimen achieved higher pCR rates than docetaxel plus doxorubicin and cyclophosphamide, with a comparable toxicity profile. Consistent with literature, the taxane plus cisplatin regimen demonstrated a favorable risk-to-benefit profile and could serve as an optimal neoadjuvant chemotherapy option for patients with high-risk TNBC.

Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis in vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.

Abstract Objectives To identify the predictors of incomplete percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and evaluate the impact of incomplete RFA (iRFA) on the overall survival (OS) of patients and new intrahepatic metastases (NIHM). Methods We prospectively analyzed the data of patients with CLM who received percutaneous RFA. Dynamic contrast-enhanced computed tomography was used to assess ablation. All CLMs were divided into development and internal validation cohorts. We analyzed the predictive factors of iRFA in the development cohort and assessed the status of NIHM and OS of all patients through the Kaplan–Meier method. Results One hundred and sixty-four patients (mean age, 60.6 ± 11.3 years; 104 men) with 338 tumors were included in this study. Perivascular tumor location, tumor size ≥ 20 mm, and minimal ablative margin were independent predictors of iRFA. The area under the receiver operating characteristic curve was 0.884 and 0.857 for the development and internal validation cohorts, respectively. NIHM were more likely to occur in the iRFA group than in the complete RFA (cRFA) group (χ2 = 26.811, P < 0.001). The estimated median OS was 45 months, and the cumulative OS for 1, 3, and 5 years was 92.2%, 59.7%, and 41.2%, respectively. The OS of the iRFA group was 39 months shorter than that of the cRFA group (χ2 = 12.269, P < 0.001). Conclusions Non-perivascular tumor location, tumor size < 2 cm, and a sufficient minimum ablation margin are essential for cRFA. Incomplete RFAs are related to the occurrence of NIHM and a much shorter OS.

Urological cancers such as bladder or prostate cancer represent one of the most malignant tumors that accounts for an extremely high mortality. However, conventionally standard diagnostics for urological cancers are hardly available in low-resource settings. We developed herein a hand-held fluorescent imaging platform by integrating a multiplexed isothermal exponential amplification reaction (EXPAR) with a microgel-enriched methodology for sensitive profiling of quaternary microRNAs (miRNAs) in urine and quick diagnosis of urological cancers at the early stage. The target miRNA mixtures in the urine underwent four parallel EXPARs without cross-reactivity, followed by surface concentration and hybridization by the encoded polyacrylamide microgels. This mix-and-read strategy allowed for one-pot analysis of several key miRNAs simultaneously and provided 5-fold enhancement in fluorescent detection sensitivities compared to the individual EXPAR-based assays. Four urinary miRNAs (let-7a, miRNA-155, -223, and -143) could be quantitatively determined in a wide linear range from 50 fM to 30 nM, with the limits of detection at femtomolar levels. Using a smartphone-based imaging microreader, healthy and cancerous cohorts with prostate, bladder, and renal cell cancers could be discriminated in 30 min with the accuracy >83% using linear discriminant analysis. The developed detection platform has proven to be a portable, noninvasive, and useful complement to the toolbox for miRNA-based liquid biopsies, which holds immense potential and advantage for regular and large-scale applications in early cancer diagnosis.

Objective To evaluate the efficacy of early clinical interventions for children with global developmental delay. Methods A total of 127 initial subjects with GDD met the complete inclusion criteria. Seven cases were excluded due to withdrawal or refusal for follow-up. Eventually, the remaining 120 children were divided into two groups based on different treatment regimens: an experimental group and a control group. Ninety children received individualized treatment in the experimental group, while 30 children, due to various reasons, did not receive inpatient treatment and only underwent home-based intervention therapy in the control group. The developmental progress under different intervention methods was compared, and their clinical effectiveness was analyzed. Results Both groups of patients showed no significant differences in general characteristics such as gender and age (p > 0.05), demonstrating comparability. The initial comparison of developmental quotient scores in all patients before treatment revealed no significant differences. Post-treatment, there was improvement observed in both groups. However, children in the experimental group exhibited significantly higher scores in gross motor skills, fine motor skills, adaptability, language, and personal-social skills compared to those in the control group (p < 0.05). Additionally, the clinical effective rate in the experimental group was notably higher than that in the control group (p < 0.05). Conclusion The combined use of acupuncture with home-based intervention therapy demonstrates favorable therapeutic outcomes in young children with comprehensive developmental delays. This approach has the potential to enhance gross motor skills, fine motor skills, cognition, language, and overall intellectual development in affected children.

Background aimsDendritic cell (DC)-based immunotherapy is a promising approach to treat cancer. However, key aspects governing the reproducible manufacturing of high-quality DC remain incompletely defined. Here, we show that the time window between leukapheresis and DC manufacturing is critical. MethodsTranscriptomic profiling by RNA-seq was used to unbiasedly characterize cellular states during each step of DC manufacturing process, and functional assays were used to determine the anti-tumor activities of DC. ResultsDuring preclinical development of a DC-based cytotherapy platform, CUD-002 (NCT05270720), we found that DC quality varied among different batches, even though commonly used DC maturation markers CD80, CD83 and CD86 were indistinguishable. Multivariate analysis indicated that DC quality was negatively associated with the shipping time from the leukapheresis site to the manufacturing center. To investigate the potential effect of shipping time, we stored leukapheresis materials from three donors for 0, 1, 2 or 3 days before DC manufacturing. For each step, we carried out RNA-seq analysis to unbiasedly characterize cellular states. Integrated bioinformatic analyses indicated that longer storage time reduced the expression of several transcription factors to attenuate interferon pathways. ConclusionsConsistently, we found that 3-day storage of leukapheresis materials significantly lowered the efficiency to generate DC but also impaired DC responses to inflammatory signals, resulting in inferior antigen-presentation and cytotoxic T-cell activities. Thus, we recommend using leukapheresis materials within 48 h to manufacture therapeutic DCs.