Synthesis of Flavonols and Assessment of Their Biological Activity as Anticancer Agents.

A series of flavanols were synthesized to assess their biological activity against human non-small cell lung cancer cells (A549). Among the sixteen synthesized compounds, it was observed that compounds 6k (3.14 ± 0.29 µM) and 6l (0.46 ± 0.02 µM) exhibited higher potency compared to 5-fluorouracil (5-Fu, 4.98 ± 0.41 µM), a clinical anticancer drug which was used as a positive control. Moreover, compound 6l (4'-bromoflavonol) markedly induced apoptosis of A549 cells through the mitochondrial- and caspase-3-dependent pathways. Consequently, compound 6l might be developed as a candidate for treating or preventing lung cancer.

Reliability and validity tests of the Chinese version of the Geriatric Locomotive Function Scale (GLFS-25) in tumor survivors.

Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P < 0.001). Subsequent confirmatory factor analysis (CFA) extracted four distinct factors: Social Activity Engagement, Daily Living Ability, Pain Experience and Physical Mobility. These factors accounted for 72.668 % of the variance, indicating substantial construct validity for measuring LS among this population. CFA supported the model's fit with the following indices: χ2/df = 1.559, RMSEA = 0.077, GFI = 0.924, CFI = 0.941, NFI = 0.919, and TLI = 0.933. The factor loadings for the four factors ranged from 0.771 to 0.931, indicating the items corresponding to the four factors effectively represented the constructs they were designed to measure. The correlation coefficients among the four factors were between 0.306 and 0.469, all lower than the square roots of the respective AVEs (0.838-0.867). This suggests a moderate correlation among the four factors and a distinct differentiation between them, indicating the Chinese version of the GLFS-25 exhibits strong discriminant validity in Chinese tumor survivors. Reliability testing revealed a high Cronbach's α coefficient for the overall scale at 0.961, with the subscales yielding coefficients of 0.751, 0.836, 0.930, and 0.952. The overall ICC was determined to be 0.935, with subscale ICCs ranging from 0.857 to 0.941, reinforcing the scale's reliability in this context. Conclusions: The Chinese version of the GLFS-25 exhibits strong reliability and validity for the assessment of LS in tumor survivors. It may serve as a diagnostic tool for LS, contributing to the prevention and management of musculoskeletal disorders and enhancing the prognosis for this patient population.

Protocol for a randomised controlled trial: optimisation of perioperative analgesia protocol for uniportal video-assisted thoracoscopic surgery.

INTRODUCTION: Postoperative pain after thoracic surgery impairs patients' quality of life and increases the incidence of respiratory complications. Optimised analgesia strategies include minimally invasive incisions, regional analgesia and early chest tube removal. However, little is known about the optimal analgesic regimen for uniportal video-assisted thoracoscopic surgery (uVATS). METHODS AND ANALYSIS: We will conduct a single-centre, prospective, single-blind, randomised trial. The effects of postoperative analgesia will be tested using thoracic paravertebral block (PVB) in combination with patient-controlled intravenous analgesia (PVB+PCIA), erector spinae plane block (ESPB) in combination with patient-controlled intravenous analgesia (ESPB+PCIA) or PCIA alone; 102 patients undergoing uVATS will be enrolled in this study. Patients will be randomly assigned to the PVB group (30 mL of 0.33% ropivacaine with dexamethasone), ESPB group (40 mL of 0.25% ropivacaine with dexamethasone) or control groups. PCIA with sufentanil will be administered to all patients after surgery. The primary outcome will be total opioid consumption after surgery. Secondary outcomes include postoperative pain score; postoperative chronic pain at rest and during coughing; sensations of touch and pain in the chest wall, non-opioid analgesic consumption; length of stay; ambulation time, the total cost of hospitalisation and long-term postoperative analgesia. Adverse reactions to analgesics and adverse events related to the regional blocks will also be recorded. The statisticians will be blinded to the group allocation. Comparison of the continuous data among the three groups will be performed using a one-way analysis of variance to assess differences among the means. ETHICS AND DISSEMINATION: The results will be published in patient education courses, academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT06016777.

Mechanism study of ubiquitination in T cell development and autoimmune disease.

T cells play critical role in multiple immune processes including antigen response, tumor immunity, inflammation, self-tolerance maintenance and autoimmune diseases et. Fetal liver or bone marrow-derived thymus-seeding progenitors (TSPs) settle in thymus and undergo T cell-lineage commitment, proliferation, T cell receptor (TCR) rearrangement, and thymic selections driven by microenvironment composed of thymic epithelial cells (TEC), dendritic cells (DC), macrophage and B cells, thus generating T cells with diverse TCR repertoire immunocompetent but not self-reactive. Additionally, some self-reactive thymocytes give rise to Treg with the help of TEC and DC, serving for immune tolerance. The sequential proliferation, cell fate decision, and selection during T cell development and self-tolerance establishment are tightly regulated to ensure the proper immune response without autoimmune reaction. There are remarkable progresses in understanding of the regulatory mechanisms regarding ubiquitination in T cell development and the establishment of self-tolerance in the past few years, which holds great potential for further therapeutic interventions in immune-related diseases.

The Experience of Cervical Cancer Patients Undergoing Hysterectomy: A Qualitative Study.

INTRODUCTION: Due to different social and cultural backgrounds, cervical cancer patients' experience of the treatment process and quality of life after treatment will be different. This study sought to gain in-depth understanding of the experiences of Chinese cervical cancer patients as regards their quality of life and physical symptoms. METHODOLOGY: Semi-structured interviews were used to collect data. We recruited 15 women with cervical cancer in eastern China for in-depth interviews. All data were entered into the NVivo 12 software program for analysis. RESULTS: Four themes emerged from the data: (a) uncertainty; (b) physical suffering; (c) psychological pressure; and (d) challenges of marriage and family. DISCUSSION: Cervical cancer patients showed concerns about the disease itself and the physical discomfort it causes, as well as changes in social relations. Health professionals need to talk about these issues and develop strategies to address them accordingly.

Adjuvant Chemotherapy in Patients with Locally Advanced Upper Tract Urothelial Carcinoma with or without Kidney Transplantation.

Background: The incidence of upper tract urothelial carcinoma (UTUC) is uniquely high in kidney transplant (KT) recipients in Taiwan. The evidence of adjuvant chemotherapy (AC) in UTUC is contradictory. We have sought to determine whether AC is associated with potential benefits related to locally advanced UTUC after KT. Methods: We retrospectively analyzed 134 patients with locally advanced UTUC (at least stage T2) and patients who were administrated AC after unilateral or bilateral nephroureterectomy with bladder cuff excision. Of these 134 patients, 57 patients fulfilled our inclusion criteria. We used 23 KT and 34 non-KT locally advanced UTUC patients for comparison. Results: The mean follow-up time was 52.35 ± 34.56 and 64.71 ± 42.29 months for the KT and non-KT groups, respectively. The five-year disease-free survival (DFS) and overall survival (OS) rates were 45.7% vs. 70.2% and 62.8% vs. 77.6%, for the KT and non-KT groups. The Kaplan-Meier curve and the log rank test revealed significant differences in the DFS and OS rates between the two groups, p = 0.015 and 0.036. The influence of chemotherapy on graft kidney function was mild. Only three in the KT group and two in the non-KT group developed > grade 2 nephrotoxicity. Conclusions: Our study suggested that KT patients with locally advanced UTUC who had been administered AC after surgery presented worse OS and DFS than non-KT patients. KT patients tolerated the AC course well, and their nephrotoxicity levels were mild and acceptable.

circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

Lesion attention guided neural network for contrast-enhanced mammography-based biomarker status prediction in breast cancer.

BACKGROUND AND OBJECTIVE: Accurate identification of molecular biomarker statuses is crucial in cancer diagnosis, treatment, and prognosis. Studies have demonstrated that medical images could be utilized for non-invasive prediction of biomarker statues. The biomarker status-associated features extracted from medical images are essential in developing medical image-based non-invasive prediction models. Contrast-enhanced mammography (CEM) is a promising imaging technique for breast cancer diagnosis. This study aims to develop a neural network-based method to extract biomarker-related image features from CEM images and evaluate the potential of CEM in non-invasive biomarker status prediction. METHODS: An end-to-end learning convolutional neural network with the whole breast images as inputs was proposed to extract CEM features for biomarker status prediction in breast cancer. The network focused on lesion regions and flexibly extracted image features from lesion and peri­tumor regions by employing supervised learning with a smooth L1-based consistency constraint. An image-level weakly supervised segmentation network based on Vision Transformer with cross attention to contrast images of breasts with lesions against the contralateral breast images was developed for automatic lesion segmentation. Finally, prediction models were developed following further selection of significant features and the implementation of random forest-based classification. Results were reported using the area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A dataset from 1203 breast cancer patients was utilized to develop and evaluate the proposed method. Compared to the method without lesion attention and with only lesion regions as inputs, the proposed method performed better at biomarker status prediction. Specifically, it achieved an AUC of 0.71 (95 % confidence interval [CI]: 0.65, 0.77) for Ki-67 and 0.73 (95 % CI: 0.65, 0.80) for human epidermal growth factor receptor 2 (HER2). CONCLUSIONS: A lesion attention-guided neural network was proposed in this work to extract CEM image features for biomarker status prediction in breast cancer. The promising results demonstrated the potential of CEM in non-invasively predicting the biomarker statuses in breast cancer.

Advancing musculoskeletal tumor diagnosis: Automated segmentation and predictive classification using deep learning and radiomics.

OBJECTIVES: Musculoskeletal (MSK) tumors, given their high mortality rate and heterogeneity, necessitate precise examination and diagnosis to guide clinical treatment effectively. Magnetic resonance imaging (MRI) is pivotal in detecting MSK tumors, as it offers exceptional image contrast between bone and soft tissue. This study aims to enhance the speed of detection and the diagnostic accuracy of MSK tumors through automated segmentation and grading utilizing MRI. MATERIALS AND METHODS: The research included 170 patients (mean age, 58 years ±12 (standard deviation), 84 men) with MSK lesions, who underwent MRI scans from April 2021 to May 2023. We proposed a deep learning (DL) segmentation model MSAPN based on multi-scale attention and pixel-level reconstruction, and compared it with existing algorithms. Using MSAPN-segmented lesions to extract their radiomic features for the benign and malignant classification of tumors. RESULTS: Compared to the most advanced segmentation algorithms, MSAPN demonstrates better performance. The Dice similarity coefficients (DSC) are 0.871 and 0.815 in the testing set and independent validation set, respectively. The radiomics model for classifying benign and malignant lesions achieves an accuracy of 0.890. Moreover, there is no statistically significant difference between the radiomics model based on manual segmentation and MSAPN segmentation. CONCLUSION: This research contributes to the advancement of MSK tumor diagnosis through automated segmentation and predictive classification. The integration of DL algorithms and radiomics shows promising results, and the visualization analysis of feature maps enhances clinical interpretability.

Circulating cytokines levels and osteoarthritis: A Mendelian randomization study.

BACKGROUND: Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA. METHODS: We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results. RESULTS: Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013-1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014-1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003-1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018-1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022-1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000-1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014-1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA. CONCLUSIONS: Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA.

MELK aggravates lung adenocarcinoma by regulating EZH2 ubiquitination and H3K27me3 histone methylation of LATS2.

We tried to elucidate the possible roles of maternal embryonic leucine pull chain kinase (MELK) in lung adenocarcinoma (LUAD) growth and metastasis. Differentially expressed genes in LUAD samples were analysed by the GEPIA database. Clinical tissue samples and cells were collected for MELK, EZH2 and LATS2 expression determination. Co-IP assay was used to verify the interaction between EZH2 and MELK; CHX tracking assay and ubiquitination assay detected the degradation of MELK on EZH2 ubiquitination. ChIP assay detected the enrichment of EZH2 and H3K27me3 on the LATS2 promoter region. LUAD cells were selected for in vitro validation, and the tumorigenic ability of LUAD cells was also observed in a transplantation tumour model of LUAD nude mice. MELK and EZH2 were highly expressed in LUAD samples, while LATS2 was lowly expressed. MELK interacted with EZH2 to inhibit its ubiquitination degradation; EZH2 elevated H3K27me3 modification in the LATS2 promoter to lower LATS2 expression. Silencing MELK or EZH2 or overexpressing LATS2 restrained LUAD cell proliferation and invasion, and facilitated their apoptosis. Silencing MELK or EZH2 or overexpressing LATS2 suppressed tumour formation in nude mice. This study demonstrated that MELK aggravated LUAD by upregulating EZH2 and downregulating LATS2.

Conventional and machine-learning based risk score for patients with early-stage hepatocellular carcinoma.

Background/Aims: The performance of machine-learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. Methods: The study retrospectively enrolled 1411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-to-monocyte ratio, and albumin bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATS-INF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Conclusions: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

Development and validation of a pyroptosis-related prognostic signature associated with osteosarcoma metastasis and immune infiltration.

Pyroptosis is a programmed cell death, which has garnered increasing attention because it relates to the immune and therapy response. However, few studies focus on the application of pyroptosis-related genes (PRGs) in predicting osteosarcoma (OS) patients' prognoses. In this study, the gene expression and clinical information of OS patients were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Based on these PRGs and unsupervised clustering analysis, all OS samples can be classified into 2 clusters. The 8 key differential expressions for PRGs (LAG3, ITGAM, CCL2, TLR4, IL2RA, PTPRC, FCGR2B, and CD5) were established through the univariate Cox regression and utilized to calculate the risk score of all samples. According to the 8-gene signature, OS samples can be divided into high and low-risk groups and correlation analysis can be performed using immune cell infiltration and immune checkpoints. Finally, we developed a nomogram to improve the PRG-predictive model in clinical application. We verified the predictive performance using receiver operating characteristic (ROC) and calibration curves. There were significant differences in survival, immune cell infiltration and immune checkpoints between the low and high-risk groups. A nomogram was developed with clinical indicators and the risk scores were effective in predicting the prognosis of patients with OS. In this study, a prognostic model was constructed based on 8 PRGs were proved to be independent prognostic factors of OS and associated with tumor immune microenvironment. These 8 prognostic genes were involved in OS development and may serve as new targets for developing therapeutic drugs.

Analysis on status quo and related factors of delays in diagnosis and treatment of breast cancer in Ningxia Hui Autonomous Region.

This study aimed to explore factors contributing to the delays in the diagnosis and treatment of breast cancer (BC) in Ningxia Hui Autonomous Region. We conducted a cohort analysis of 1012 patients with BC diagnosed at the General Hospital of Ningxia Medical University between January 2018 and December 2019. Sociodemographic data were collected through questionnaires, and clinical data were gathered and analyzed from relevant databases. Furthermore, observations were made regarding delays in the diagnosis and treatment of BC, followed by an analysis of the correlations between patient delay and both sociological factors within the population and clinical factors specific to patients with BC. Subsequently, the factors associated with patient delay and system delay were examined using Cox regression analysis, along with the inclusion of neoadjuvant therapy. In the prevention and treatment of BC in Ningxia, the patient delay rate was 33.20%, the diagnosis delay rate was 17.89%, the treatment delay rate was 0.0099% and the system delay rate was 41.60%. There was a higher proportion of patient delay and system delay in aged patients (age ≥ 61 years) with rural registered permanent residence (RPR), multiple clinical symptoms (such as nipple spillage, axillary abnormalities, etc), a T4 tumor size classification, and the initial use of neoadjuvant therapy. Besides, significant positive correlations were observed between patient delay and system delay time with BC stage. Patients aged 51 to 60 and those with molecular types (Limanal1B: ki-67 > 14%, Limanal1B: HER-2 positive) were prone to patient delay, whereas molecular characteristics influenced system delay, unrelated to sociodemographic factors. The study identifies significant age, residency, and tumor molecular subtype correlations with diagnostic and treatment delays in Ningxia's patients with BC, predominantly affecting women aged 41 to 60, especially urban dwellers. These findings underscore the need for targeted interventions to reduce delays and improve BC care in this region.

Chemotherapy versus chemotherapy plus immune checkpoint inhibitors for the first-line treatment of unresectable thymic carcinoma: A multicenter retrospective study.

Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC. In this study, data of patients with unresectable TC diagnosed from January 2017 were retrospectively collected from multiple centers. Treatment response, progression-free survival (PFS), overall survival (OS), survival-independent prognostic factor, and adverse events (AEs) were further analyzed. As a result, a total of 93 patients with unresectable TC were enrolled, of which 54 received first-line chemotherapy, and 39 received chemotherapy plus immune checkpoint inhibitors (ICIs). The objective response rate was 50% (27/54) in the chemotherapy group and 76.9% (30/39) in the chemotherapy plus ICIs group. The chemotherapy plus ICIs group achieved significant median PFS benefit (8.8 vs. 34.9 months, p < .001) and median OS benefit (41.8 months vs. not reached, p = .025). Multivariate analysis showed that ICIs and local therapy were independent prognostic factors for PFS. In addition, 17 patients developed immune-related AEs (IRAEs), of which 15 (38.5%) had Grade 1 or 2 IRAEs and 2 (5.1%) had Grade 3 IRAEs in the chemotherapy plus ICIs group. In conclusion, the efficacy of chemotherapy plus ICIs is superior to chemotherapy, and the adverse effects are manageable in patients with unresectable TC.

Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAL in glioma.

Clinical data indicates that glioma patients have poor treatment outcomes and clinical prognosis. The role of olfactory signaling pathway-related genes (OSPRGs) in glioma has not been fully elucidated. In this study, we aimed to investigate the role and relationship between OSPRGs and glioma. Univariate and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts, and the target gene (G Protein Subunit Alpha L, GNAL) was screened. The association of GNAL expression with clinicopathological characteristics, gene mutation landscape, tumor immune microenvironment (TIME), deoxyribonucleic acid (DNA) methylation, and naris-occlusion controlled genes (NOCGs) was performed. Immunohistochemistry was used to evaluate GNAL level in glioma. Further analysis was conducted to evaluate the drug sensitivity, immunotherapy response, and functional enrichment of GNAL. GNAL was an independent prognostic factor, and patients with low GNAL expression have a poor prognosis. Expression of GNAL was closely associated with clinicopathological characteristics, DNA methylation, and several immune-related pathways. Immune infiltration analysis indicated that GNAL levels were negatively correlated with immune scores. GNAL low-expression group showed efficacy with anti-PD-1 therapy. Ten compounds with significantly different half-maximal inhibitory concentration (IC50) values between the GNAL high and low-expression groups were identified. Furthermore, its expression was associated with several immune cells, immune-related genes, and NOCGs. The expression of GNAL is closely associated with clinicopathological characteristics, TIME, and the response to therapeutic interventions, highlighting its potential as a prognostic biomarker for glioma.

Endogenous H2S-activated Ag nanoparticles embedded in programmed DNA-cubes for specific visualization of colorectal cancer cells.

To avoid the unexpected aggregation and reduce the cytotoxicity of nanomaterials as optical probes in cell imaging applications, we propose a programmed DNA-cube as a carrier for silver nanoparticles (Ag NPs) to construct a specific hydrogen sulfide (H2S) responsive platform (Ag NP@DNA-cube) for diagnosing colorectal cancer (CRC) in this study. The DNA-cube maintains good dispersion of Ag NPs while providing excellent biocompatibility. Based on the characteristic overexpression of endogenous H2S in CRC cells, the Ag NPs are etched by H2S within target cells into silver sulfide quantum dots, thereby selectively illuminating the target cells. The Ag NP@DNA-cube exhibits a specific fluorescence response to CRC cells and achieves satisfactory imaging.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma.

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1ß (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1ß, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

Neoadjuvant chemoimmunotherapy for locally advanced esophageal squamous cell carcinoma: Data from literature review and a real-world analysis.

BACKGROUND: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real-world study and a meta-analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. METHODS: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1-, 2-, and 3-year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1-year recurrence rate, R0 resection rate and adverse events. Moreover, a meta-analysis of 27 published literatures was also conducted for comparison. RESULTS: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1-, 2-, and 3-year OS rates were 91.41% (95% CI: 85.15%-95.63%), 75.00% (95% CI: 66.58%-82.23%) and 64.84% (95% CI: 55.91%-73.07%).ORR and DCR were 31.2% (95% CI: 23.31-39.99) and 64.1% (95% CI: 55.15%-72.38%), and the 1-year recurrence rate was 26.7% (95% CI: 22.5%-38.1%). Treatment-related events occurred in 96.1% but were acceptable. In a meta-analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1-year recurrence rate of 12%. CONCLUSION: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed.

An ultrasound-based histogram analysis model for prediction of tumour stroma ratio in pleomorphic adenoma of the salivary gland.

OBJECTIVES: Preoperative identification of different stromal subtypes of pleomorphic adenoma (PA) of the salivary gland is crucial for making treatment decisions. We aimed to develop and validate a model based on histogram analysis (HA) of ultrasound (US) images for predicting tumour stroma ratio (TSR) in salivary gland PA. METHODS: A total of 219 PA patients were divided into low-TSR (stroma-low) and high-TSR (stroma-high) groups and enrolled in a training cohort (n = 151) and a validation cohort (n = 68). The least absolute shrinkage and selection operator regression algorithm was used to screen the most optimal clinical, US, and HA features. The selected features were entered into multivariable logistic regression analyses for further selection of independent predictors. Different models, including the nomogram model, the clinic-US (Clin + US) model, and the HA model, were built based on independent predictors using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts. RESULTS: Lesion size, shape, cystic areas, vascularity, HA_mean, and HA_skewness were identified as independent predictors for constructing the nomogram model. The nomogram model incorporating the clinical, US, and HA features achieved areas under the curve of 0.839 and 0.852 in the training and validation cohorts, respectively, demonstrating good predictive performance and calibration. Decision curve analysis and clinical impact curves further confirmed its clinical usefulness. CONCLUSIONS: The nomogram model we developed offers a practical tool for preoperative TSR prediction in PA, potentially enhancing clinical decision-making.