Prediction of lateral lymph node metastasis in rectal cancer patients based on MRI using clinical, deep transfer learning, radiomic, and fusion models.

Introduction: Lateral lymph node (LLN) metastasis in rectal cancer significantly affects patient treatment and prognosis. This study aimed to comprehensively compare the performance of various predictive models in predicting LLN metastasis. Methods: In this retrospective study, data from 152 rectal cancer patients who underwent lateral lymph node (LLN) dissection were collected. The cohort was divided into a training set (n=86) from Tianjin Union Medical Center (TUMC), and two testing cohorts: testing cohort (TUMC) (n=37) and testing cohort from Gansu Provincial Hospital (GSPH) (n=29). A clinical model was established using clinical data; deep transfer learning models and radiomics models were developed using MRI images of the primary tumor (PT) and largest short-axis LLN (LLLN), visible LLN (VLLN) areas, along with a fusion model that integrates features from both deep transfer learning and radiomics. The diagnostic value of these models for LLN metastasis was analyzed based on postoperative LLN pathology. Results: Models based on LLLN image information generally outperformed those based on PT image information. Rradiomics models based on LLLN demonstrated improved robustness on external testing cohorts compared to those based on VLLN. Specifically, the radiomics model based on LLLN imaging achieved an AUC of 0.741 in the testing cohort (TUMC) and 0.713 in the testing cohort (GSPH) with the extra trees algorithm. Conclusion: Data from LLLN is a more reliable basis for predicting LLN metastasis in rectal cancer patients with suspicious LLN metastasis than data from PT. Among models performing adequately on the internal test set, all showed declines on the external test set, with LLLN_Rad_Models being less affected by scanning parameters and data sources.

A Study of Omentum Reduction on the Improvement of Nausea and vomiting and Gastroesophageal Reflux Symptoms After Laparoscopic Gastric Sleeve Resection.

OBJECTIVE: To investigate the effect of omentum reduction in laparoscopic sleeve gastrectomy (LSG) on the improvement of postoperative nausea and vomiting and gastroesophageal reflux symptoms. METHODS: A retrospective study was performed on the case data of 198 obese patients who underwent LSG in the Department of Obesity and Metabolic Diseases of Xiaolan People's Hospital of Zhongshan from March 2021 to March 2022 and were divided into omentum reduction group and control group, with 99 cases in each group, and the preoperative body mass index (BMI) of the patients was recorded. Age, gender, comorbidities, and comparative analysis of operation time, blood loss, length of hospital stay, postoperative nausea and vomiting score, gastroesophageal reflux GerdQ score, postoperative pain score, weight, and postoperative complications were analyzed. RESULTS: There were no significant differences in preoperative BMI, age, gender and comorbidities between the two groups (P > 0.05), but there were significant differences in intraoperative blood loss and operation time (P < 0.05). There were differences in postoperative nausea and vomiting scores and VAS pain scores between the two groups (P < 0.05). The GerdQ scores of the omental reduction group were 8.11 ± 2.84 points at 1 year, and those in the control group were 7.56 ± 2.67 points, which were 3.97 ± 4.09 points higher than those in the preoperative omentum reduction group and 3.42 ± 3.41 in the control group, with no significant difference (P > 0.05). There was no significant difference in the postoperative excess weight loss rate %EWL and postoperative complications (p > 0.05). CONCLUSION: Omentum reduction can improve short-term nausea and vomiting after LSG, but it cannot significantly improve long-term reflux symptoms.

[Clinical efficacy of double-bundle and double-tunnel enhanced reconstruction in the treatment of anterior cruciate ligament injury].

OBJECTIVE: To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL) training injuries. METHODS: Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed. All the cases were underwent ligament reconstruction surgery. Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group, including 13 males and 1 female, aged from 22 to 31 years old with an average of (27.07±7.28) years old, autogenous hamstring tendon was used for ligament reconstruction. There were 15 patients in the enhanced reconstruction group, including 13 males and 2 females, aged from 25 to 34 years old with an average of (29.06±4.23) years old, double tunnel ligament reconstruction, the autogenous hamstring muscle was used as the anteromedial bundle, and the posterolateral bundle was replaced by a high-strength line. The difference between knee tibial anterior distance, Lysholm score, International Knee Literature Committee (IKDC) subjective score, Tegner motor level score and visual analog scale (VAS) at 6th and 12th months after the surgery, limb symmetry index (LSI) were recorded at the last follow-up and surgery-related adverse effects during follow-up. RESULTS: All patients were followed up, ranged from 13 to 15 months with an average of (13.7±0.8) months. There were no serious adverse reactions related to surgery during the period. There was no statistical difference between the preoperative general data and the observation index of the two groups (P>0.05). The difference in tibial anterior distance at 6 and 12 months in the enhanced reconstruction group (1.45±0.62) mm and (1.74±0.78) mm which were lower those that in the conventional reconstruction group (2.42±0.60) mm and (2.51±0.63) mm(P<0.05). There was no significant difference in postoperative Lysholm score, Tegner motor level score, IKDC score, VAS, and limb symmetry index at the last follow-up(P>0.05). CONCLUSION: The enhanced reconstruction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique. The short-term curative effect is satisfactory, and it is suitable for the group with high sports demand.

[Corrigendum] Hispolon inhibits breast cancer cell migration by reversal of epithelial­to­mesenchymal transition via suppressing the ROS/ERK/Slug/E­cadherin pathway.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, with the cell migration assay data shown in Fig. 7 on p. 901, the "TPA" and "TPA + U0126" panels were strikingly similar, such that data which were intended to show the results from differently performed experiments had apparently been derived from the same original source. In addition, it was noted that the "TPA + hispolon" and "TPA + NAC" data panels in Fig. 4B on p. 899 contained overlapping sections. Thirdly, a data panel was shared between Figs. 1 and 4, although this was intentional on the part of the authors as the same experiment was being portrayed in these figures.  The authors were able to re­examine their original data files, and realized that errors were made in asssembling Figs. 4B and 7. The revised versions of Figs. 4 and 7, now containing the correct data for the "TPA + NAC" experiment in Fig. 4B and the Control ("Ctrl") experiment in Fig. 7, are shown on the next two pages. The authors wish to emphasize that the corrections made to these figures do not affect the overall conclusions reported in the paper, and they are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum. All the authors agree to the publication of this corrigendum, and also apologize to the readership for any inconvenience caused. [Oncology Reports 35: 896­904, 2016; DOI: 10.3892/or.2015.4445].

Revealing and reconstructing the 3D Li-ion transportation network for superionic poly(ethylene) oxide conductor.

Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.

Predictive analysis and risk assessment of potentially toxic elements in Beijing gas station soils using machine learning and two-dimensional Monte Carlo simulations.

Gas stations not only serve as sites for oil storage and refueling but also as locations where vehicles frequently brake, significantly enriching the surrounding soil with potentially toxic elements (PTEs). Herein, 117 topsoil samples from gas stations were collected in Beijing to explore the impact of gas stations on PTE accumulation. The analysis revealed that the average Pollution Index (PI) values for Cd, Hg, Pb, Cu, and Zn in the soil samples all exceeded 1. The random forest (RF) model, achieving an AUC score of 0.95, was employed to predict PTE pollution at 372 unsampled gas stations. Additionally, a Positive Matrix Factorization (PMF) model indicated that gas station operations and vehicle emissions were responsible for 70 % of the lead (Pb) enrichment. Probabilistic health risk assessments showed that the carcinogenic risk (CR) and noncarcinogenic risk (NCR) for PTE pollution to adult females were the highest, at 0.451 and 1.61E-05 respectively, but still within acceptable levels. For adult males at contaminated sites, the Pb-associated CR and NCR were approximately twice as high as those at uncontaminated sites, with increases of 107 % and 81 %, respectively. This study provides new insights for managing pollution caused by gas stations.

DNA methylation profiling deciphers three EMT subtypes with distinct prognoses and therapeutic vulnerabilities in breast cancer.

Background: Epithelial-mesenchymal transition (EMT), deemed a pivotal hallmark of tumours, is intricately regulated by DNA methylation and encompasses multiple states along tumour progression. The potential mechanisms that drive the intrinsic heterogeneity of breast cancer (BC) via EMT transformation have not been identified, presenting a significant obstacle in clinical diagnosis and treatment. Methods: A total of 7,602 patients have been included in this study. We leveraged integrated multiomics data (epigenomic, genomic, and transcriptomic data) to delineate the comprehensive landscape of EMT in BC. Subsequently, a subtyping classifier was developed through a machine learning framework proposed by us. Results: We classified the BC samples into three methylation-driven EMT subtypes with distinct features, namely, C1 (the mammary duct development subtype with TP53 activation), C2 (the immune infiltration subtype with high TP53 mutation), and C3 (the ERBB2 amplification subtype with an unfavorable prognosis). Specifically, patients with the C1 subtype might respond to endocrine therapy or the p53-MDM2 antagonist nutlin-3. Patients with the C2 subtype might benefit from combined therapeutic regimens involving radiotherapy, PARP inhibitors, and immune checkpoint blockade therapy. Patients with the C3 subtype might benefit from anti-HER2 agents such as lapatinib. Notably, to increase the clinical applicability of the EMT subtypes, we devised a 96-gene panel-based classifier via a machine learning framework. Conclusions: Our study identified three methylation-driven EMT subtypes with distinct prognoses and biological traits to capture heterogeneity in BC and provided a rationale for the use of this classification as a powerful tool for developing new strategies for clinical trials.

Crizotinib and its enantiomer suppress ferroptosis by decreasing PE-O-PUFA content.

Ferroptosis is a specific form of cell death characterized by excessive accumulation of cellular lipid peroxides. Ferroptosis is closely associated with various diseases, inhibition of which may help alleviate multi-organ injury caused by ischemia-reperfusion and enhance the anti-tumor effect by promoting the immunity of T cells. However, clinical approved drugs targeting ferroptosis process remain rare. In this study, we unexpectedly found that (R)-crizotinib, the first-generation ALK inhibitor, has potent inhibitory activity against ferroptosis across various cell lines. Moreover, its chiral molecule (S)-crizotinib, which was considered to share no common targets with (R)-crizotinib, also suppresses ferroptosis with an efficacy similar to that of (R)-crizotinib. We further demonstrated that both crizotinib enantiomers inhibit ferroptosis independently of their known targets, but through a common mechanism involving the targeting of AGPAT3-mediated synthesis of ether-linked polyunsaturated fatty acids (PE-O-PUFA), which are known to promote lipid-ROS generation and ferroptosis. In line with their activity in cell lines, (R)-crizotinib and (S)-crizotinib effectively mitigate renal ischemia-reperfusion injury in mice. Furthermore, the two compounds also inhibit lipid-ROS accumulation in CD8+ T cells in draining lymph nodes of B16-F10 subcutaneous xenograft mice, thereby promoting anti-tumor effects. Collectively, our study firstly reports a common activity shared by (R)-crizotinib and (S)-crizotinib in ferroptosis regulation. As a clinically approved drug, (R)-crizotinib has well-established pharmacokinetics and safety, which makes it a promising candidate for repurposing. Given the current lack of FDA-approved ferroptosis inhibitors, our findings suggest therapeutically repurposing (R)-crizotinib as well as its enantiomer (S)-crizotinib for treating ferroptosis-related diseases.

Proteasome Inhibition Induces Apoptosis Through Simultaneous Inactivation of MCL-1/BCL-XL by NOXA Independent of CHOP and JNK Pathways.

Proteasome inhibitors have been employed in the treatment of relapsed multiple myeloma and mantle cell lymphoma. The observed toxicity caused by proteasome inhibitors is a universal phenotype in numerous cancer cells with different sensitivity. In this study, we investigate the conserved mechanisms underlying the toxicity of the proteasome inhibitor bortezomib using gene editing approaches. Our findings utilizing different caspase knocking out cells reveal that bortezomib induces classic intrinsic apoptosis by activating caspase-9 and caspase-3/7, leading to pore-forming protein GSDME cleavage and subsequent lytic cell death or called secondary necrosis, a phenotype also observed in many apoptosis triggers like TNFα plus CHX, DTT and tunicamycin treatment in HeLa cells. Furthermore, through knocking out of nearly all BH3-only proteins including BIM, BAD, BID, BMF and PUMA, we demonstrate that NOXA is the sole BH3-only protein responsible for bortezomib-induced apoptosis. Of note, NOXA is well known for selectively binding to MCL-1 and A1, but our studies utilizing different BH3 mimetics as well as immunoprecipitation assays indicate that, except for the constitutive interaction of NOXA with MCL-1, the accumulation of NOXA after bortezomib treatment allows it to interact with BCL-XL, then simultaneous relieving suppression on apoptosis by both anti-apoptotic proteins BCL-XL and MCL-1. In addition, though bortezomib-induced significant ER stress and JNK activation were observed in the study, further genetic depletion experiments prove that bortezomib-induced apoptosis occurs independently of ER stress-related apoptosis factor CHOP and JNK. In summary, these results provide a solid conclusion about the critical role of NOXA in inactivation of BCL-XL except MCL-1 in bortezomib-induced apoptosis.

Cadmium Exposure in Male Rats Results in Ovarian Granulosa Cell Apoptosis in Female Offspring and Paternal Genetic Effects.

The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague-Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (p < 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.

PKCα Induced the Generation of Extracellular Vesicles in Activated Platelets to Promote Breast Cancer Metastasis.

Platelet extracellular vesicles (PEVs) play an important role in tumor development. However, the mechanisms underlying their biogenesis have not been fully elucidated. Protein kinase Cα (PKCα) is an important regulator of platelet activation, but the effect of PKCα on EV generation is unclear. We used small-particle flow cytometry and found that the number of PEVs was increased in patients with breast cancer compared to those with benign breast disease. This was accompanied by increased levels of activated PKCα in breast cancer platelets. Treating platelets with the PKCα agonist phorbol 12-myristate 13-acetate (PMA) increased the phosphorylation PKCα and induced PEV production, while the PKCα inhibitor GÖ6976 showed the opposite effects. Notably, incubating platelets from patients with benign tumors with the culture supernatant of MDA-MB-231 cells induced PKCα phosphorylation in the platelets. Mass spectrometry and coimmunoprecipitation assays showed that Dynamin 2 (DNM2), a member of the guanosine-triphosphate-binding protein family, might cooperate with activated PKCα to regulate PEV production by breast cancer platelets. Similar results were observed in a mouse model of lung metastasis. In addition, PEVs were engulfed by breast cancer cells and promoted cancer cell migration and invasion via miR-1297 delivery. These findings suggested that PKCα cooperates with DNM2 to induce PEV generation, and PEV release might triggered by factors in the breast cancer environment.

Laparoscopic partial splenectomy for a giant splenic pseudocyst with elevated CA19-9: a case report.

Introduction and importance: Currently, there is a lack of reliable evidence on the management of splenic cysts, which are rare. Exploring the efficacy of laparoscopic partial splenectomy can aid in the accumulation of treatment-related evidence. Case presentation: Here, we report the case of a 31-year-old female who was diagnosed with a giant splenic cyst with elevated serum CA19-9 and subsequently underwent laparoscopic partial splenectomy. Clinical discussion: The effects of most treatment options for splenic cysts, including percutaneous aspiration and drainage, fenestration, and partial splenectomy, have not been confirmed by high-level evidence. With the development of minimally invasive surgery, laparoscopic partial splenectomy has drawn increasing attention. Additionally, the relationships between tumor markers and splenic cysts need to be further elucidated. Conclusions: Laparoscopic partial splenectomy might be recommended for patients with splenic cysts, especially when the cysts are not completely covered by the splenic parenchyma.

miR-16-5p specifically inhibits IFN-γ-regulated memory T helper cell differentiation in malignant pleural effusion of non-small cell lung cancer.

Background: The mechanism for memory T helper (Th) cell differentiation in malignant pleural effusion (MPE) of non-small cell lung cancer (NSCLC) is poorly understood. MicroRNAs (miRNAs), as small non-coding RNA that regulate gene expression, play a crucial role in the regulation of memory Th cell differentiation. However, whether miRNAs can inhibit the differentiation of memory Th cells in MPE of NSCLC has not been reported. This study aimed to explore miR-16-5p specifically inhibits interferon-gamma (IFN-γ)-regulated memory Th cell differentiation in MPE of NSCLC. Methods: A total of 30 patients with NSCLC and 30 age- and sex-matched patients, who were clinically diagnosed as benign pleural effusion (BPE) of lung disease and had not received any intervention, were collected. The expression of nucleic acids, miRNAs, and cytokines was detected by polymerase chain reaction (PCR), miRNA microarray, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and western blotting. Results: The expression of CD4+CD69+ T cells in NSCLC with MPE was lower than that in lung disease BPE. CD4+CD69+ T cells highly express CD45RO+ and mainly secrete anti-tumor cytokines IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α). The expression of miR-16-5p in CD4+CD69+ CD45RO+ T cells in MPE was higher than that in BPE. Moreover, miR-16-5p can bind to both IFN-γ promoter and its 5'untranslated region (5'-UTR), suggesting that IFN-γ may be the target gene directly affected by miR-16-5p. IFN-γ also affects the differentiation of memory CD4+ T cells by regulating T-bet. Conclusions: We believe that miR-16-5p may regulate the decrease of differentiation of naïve CD4+ T cells into memory CD4+CD69+ T cells through its target gene IFN-γ in MPE, thus reducing the number of cytokines that produce anti-tumor effects. It may be the main reason for the low response rate of lung cancer with MPE immunotherapy.

Hypofractionated radiotherapy plus PD-1 antibody and SOX chemotherapy as second-line therapy in metastatic pancreatic cancer: a single-arm, phase II clinical trial.

PURPOSE: To assess the efficacy and safety of concurrent hypofractionated radiotherapy plus anti-PD-1 antibody and SOX chemotherapy in the treatment of metastatic pancreatic cancer (mPC) after failure of first-line chemotherapy. METHODS: Patients with pathologically confirmed mPC who failed standard first-line chemotherapy were enrolled. The patients were treated with a regimen of hypofractionated radiotherapy, SOX chemotherapy, and immune checkpoint inhibitors at our institution. We collected the patients' clinical information and outcome measurements. The median progression-free survival (mPFS) was the primary endpoint of the study, followed by disease control rate (DCR), objective response rate (ORR), median overall survival (mOS) and safety. Exploratory analyses included biomarkers related to the benefits. RESULTS: Between February 24, 2021, and August 30, 2023, twenty-five patients were enrolled in the study, and twenty-three patients who received at least one dose of the study agent had objective efficacy evaluation. The mPFS was 5.48 months, the mOS was 6.57 months, and the DCR and ORR were 69.5% and 30.4%, respectively. Among the seven patients who achieved a PR, the median duration of the response was 7.41 months. On-treatment decreased serum CA19-9 levels were associated with better overall survival. Besides, pretreatment inflammatory markers were associated with tumor response and survival. CONCLUSIONS: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with these combination therapies in patients with refractory mPC. On-treatment decreased serum CA19-9 levels and pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) might be biomarkers related to clinical benefits. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=130211 , identifier: ChiCTR2100049799, date of registration: 2021-08-09.

Efficacy of MAGE-A4 long peptide as a universal immunoprevention cancer vaccine.

BACKGROUND: The clinical application of peptide vaccines in tumor immunotherapy holds significant promise. Peptide-based tumor vaccines are currently subject to certain limitations in clinical trials, including the challenge of inducing a sustained response from CD4+ T helper cells and cytotoxic T lymphocytes (CTL), as well as human leukocyte antigen (HLA) restrictions. METHODS: Through the utilization of biological information methodology, a screening process was conducted to identify three potential long peptides that are specifically targeted by the MAGE-A4 antigen. The candidate long peptides were subjected to in vitro testing using human peripheral blood lymphocytes as samples to evaluate their immunogenicity and immune function. The antitumor properties and preliminary mechanism of the long peptide vaccine were investigated through the use of a mouse model designed for the prevention of triple negative breast cancer (TNBC). RESULTS: Three predicted multi-epitope long peptides targeting MAGE-A4 have shown to have a strong immunogenicity, with a total positive rate of 72% across different HLA subtypes in Chinese populations. they can also increase the levels of the costimulatory factor CD137 and tumor necrosis factor-alpha (TNF-α), activate T cells, and boost the cytotoxic activity. Results from an animal study have revealed that the long-peptide vaccine, both on its own and in combination with R848, has displayed impressive anti-tumor and target-specific capabilities. Moreover, it has the ability to increase the expression of effector memory T cells and central memory T cells. CONCLUSIONS: This study was the first to screen three multi-epitope long peptides targeting MAGE-A4 and assess their immunogenicity, immune function, and potential as adjuvant peptides. The results showed that the MAGE-A4 long peptide vaccine can be used as a novel immunoprophylaxis method to prevent TNBC. Moreover, the proposed development model is capable of screening multiple target antigens, which lead to its clinical application.

Somatic and germline aberrations in homologous recombination repair genes among Chinese high-risk breast cancer patients by multi-gene next-generation sequencing.

INTRODUCTION: Recently, genes involved in homologous recombination repair (HRR) pathway have been extensively studied. However, the landscapes of HRR gene mutations remain poorly defined in Chinese high-risk breast cancer (BC) patients. Our study aims to identify the status of germline and somatic HRR gene mutations and their association with clinicopathological features in these patients. MATERIALS AND METHODS: A total of 100 high-risk BC patients from our institution who underwent paired peripheral blood germline and BC tissues somatic 26 genes next-generation sequencing (NGS) from January 2018 to July 2023 were enrolled for retrospective analysis. RESULTS: Out of 100 high-risk BC patients, 55 (55%) had at least one germline or somatic mutation in HRR genes. Among them, 22% carried germline pathogenic variants (19 BRCA1/2 and 3 non-BRCA genes), 9% harbored somatic pathogenic mutations (3 BRCA1/2 and 6 non-BRCA genes). Among high-risk factors, family history and early onset BC showed a correlation with HRR gene mutations (p < 0.05). BRCA1 germline and HRR gene somatic mutations showed a correlation with TNBC, but BRCA2 germline mutations were associated with Luminal B/HER2-negative BC (p < 0.05). Patients with HRR gene somatic pathogenic variant more likely had a lympho-vascular invasion and distant metastasis (p < 0.05). CONCLUSION: The prevalence of HRR gene germline and somatic mutations were higher in Chinese BC patients with high risk factors. We strongly recommend that these high-risk BC patients receive comprehensive gene mutation testing, especially HRR genes, which are not only related to genetic consultation for BC patients and provide a theoretical basis for necessary prevention and individualized treatment.

Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity.

Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated metabolic gene across human cancers. Mutant IDH1 (mIDH1) generates the oncometabolite (R)-2-hydroxyglutarate, disrupting enzymes involved in epigenetics and other processes. A hallmark of IDH1-mutant solid tumors is T cell exclusion, whereas mIDH1 inhibition in preclinical models restores antitumor immunity. Here, we define a cell-autonomous mechanism of mIDH1-driven immune evasion. IDH1-mutant solid tumors show selective hypermethylation and silencing of the cytoplasmic double-stranded DNA (dsDNA) sensor CGAS, compromising innate immune signaling. mIDH1 inhibition restores DNA demethylation, derepressing CGAS and transposable element (TE) subclasses. dsDNA produced by TE-reverse transcriptase (TE-RT) activates cGAS, triggering viral mimicry and stimulating antitumor immunity. In summary, we demonstrate that mIDH1 epigenetically suppresses innate immunity and link endogenous RT activity to the mechanism of action of a US Food and Drug Administration-approved oncology drug.

Laparoscopic Ureteric Reconstruction After Partial Ureterectomy for Locally Advanced and Recurrent Pelvic Malignancies (with Video).

BACKGROUND: The urinary tract is one of the most frequently involved organs in advanced non-urologic pelvic malignances. Extensive resection of ureteric organs is mandatory during a curative surgery. Urinary reconstruction after partial ureterectomy, the most challenging situation, is associated with a higher incidence of complication than cystectomy, especially when performed with laparoscopy. Furthermore, to date, no generally accepted strategy for urinary reconstruction after extensive tumor resection with partial ureterectomy has been established. METHODS: The study identified and scrutinized intraoperative videos and clinical records of patients with locally advanced or recurrent pelvic malignancies who underwent segmental ureterectomy during en bloc resection of advanced tumors between February 2020 and February 2024. RESULTS: The study enrolled nine patients, including four cases managed by ureteroureteral anastomosis, two cases managed by ureteroneocystomy, two cases managed by Boari flap reconstruction, and one case managed by ileal interposition. In all nine cases, R0 margins were obtained, and no case needed conversion to laparotomy. No clinical evidence of postoperative urinary leakage was identified. The median follow-up period was 14 months (range, 5-19 months). In three of the nine cases, recurrence was identified, at the 3rd, 18th, and 19th month follow-up evaluations, respectively. One patient died of systemic metastasis. CONCLUSIONS: Laparoscopic ureteric reconstruction is feasible for patients who undergo segmental ureterectomy during extensive surgery for locally advanced or recurrent pelvic malignancies. A low anastomotic leakage rate and favorable postoperative renal function could be achieved in this study when anastomosis was performed laparoscopically.

The application of dynamic contrast-enhanced ultrasonography in immediate distinguishing residual tumour from benign periablational enhancement after hepatocellular carcinoma radiofrequency ablation.

AIM: This study set out to access the performance of quantitative analysis of contrast-enhanced ultrasound (CEUS) in distinguishing between benign periablational enhancement (BPE) and residual tumor (RT) following radiofrequency ablation (RFA). MATERIALS AND METHODS: 165 tumors from 124 patients with hepatocellular carcinoma between 2021 and 2023 underwent RFA, contrast-enhanced computed tomography (CECT), and CEUS in less than 24 hours. Analysis was done on the quantitative parameters from RT and BPE found by CEUS. RESULTS: Complete ablation was obtained in 89.1% of lesions. When compared to BPE, RT had significantly greater peak intensity (PI), time to peak (TTP), area under the curve (AUC), ratio of PI and base intensity (PI/BI), and enhanced intensity (EI) values (all p<0.05). PI, TTP, AUC, PI/BI, and EI had large areas under the receiver operating (ROC) curves. A binary logistic regression analysis, respectively, demonstrated that PI and PI/BI were independent favorable prognostic variables. CONCLUSIONS: Multiple parameters of quantitative analysis of CEUS can aid in distinguishing immediately between RT and BPE lesions. PI and PI/BI may be a more promising parameter. Immediate CEUS evaluation following RFA may allow immediate retreatment of RT during the same operation time, which reduces patients' hospital stays and financial costs.