Survival prognostic analysis of laparoscopic D2 radical resection for locally advanced gastric cancer: A multicenter cohort study.

BACKGROUND: With the development of minimally invasive surgical techniques, the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer (GC) has gradually increased. However, the effect of this procedure on survival and prognosis remains controversial. This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence, guide clinical decision-making, optimize treatment strategies, and improve the survival rate and quality of life of patients. AIM: To investigate the survival prognosis and influencing factors of laparoscopic D2 radical resection for locally advanced GC patients. METHODS: A retrospective cohort study was performed. Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected. There were 442 males and 210 females. The mean age was 57 ± 12 years. All patients underwent a laparoscopic D2 radical operation for distal GC. The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence, metastasis, and survival. The follow-up period ended in December 2023. Normally distributed data are expressed as the mean ± SD, and normally distributed data are expressed as M (Q1, Q3) or M (range). Statistical data are expressed as absolute numbers or percentages; the χ 2 test was used for comparisons between groups, and the Mann-Whitney U nonparametric test was used for comparisons of rank data. The life table method was used to calculate the survival rate, the Kaplan-Meier method was used to construct survival curves, the log rank test was used for survival analysis, and the Cox risk regression model was used for univariate and multifactor analysis. RESULTS: The median overall survival (OS) time for the 652 patients was 81 months, with a 10-year OS rate of 46.1%. Patients with TNM stages II and III had 10-year OS rates of 59.6% and 37.5%, respectively, which were significantly different (P < 0.05). Univariate analysis indicated that factors such as age, maximum tumor diameter, tumor differentiation grade (low to undifferentiated), pathological TNM stage, pathological T stage, pathological N stage (N2, N3), and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer [hazard ratio (HR): 1.45, 1.64, 1.45, 1.64, 1.37, 2.05, 1.30, 1.68, 3.08, and 0.56 with confidence intervals (CIs) of 1.15-1.84, 1.32-2.03, 1.05-1.77, 1.62-2.59, 1.05-1.61, 1.17-2.42, 2.15-4.41, and 0.44-0.70, respectively; P < 0.05]. Multifactor analysis revealed that a tumor diameter greater than 4 cm, low tumor differentiation, and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients (HR: 1.48, 1.44, 1.81 with a 95%CI: 1.19-1.84). Additionally, postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate (HR: 0.57, 95%CI: 0.45-0.73; P < 0.05). CONCLUSION: A maximum tumor diameter exceeding 4 cm, low tumor differentiation, and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC. Conversely, postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.

PD-1/PD-L1 axis is involved in the interaction between microglial polarization and glioma.

The tumor microenvironment plays a vital role in glioblastoma growth and invasion. PD-1 and PD-L1 modulate the immunity in the brain tumor microenvironment. However, the underlying mechanisms remain unclear. In the present study, in vivo and in vitro experiments were conducted to reveal the effects of PD-1/PD-L1 on the crosstalk between microglia and glioma. Results showed that glioma cells secreted PD-L1 to the peritumoral areas, particularly microglia containing highly expressed PD-1. In the early stages of glioma, microglia mainly polarized into the pro-inflammatory subtype (M1). Subsequently, the secreted PD-L1 accumulated and bound to PD-1 on microglia, facilitating their polarization toward the microglial anti-inflammatory (M2) subtype primarily via the STAT3 signaling pathway. The role of PD-1/PD-L1 in M2 polarization of microglia was partially due to PD-1/PD-L1 depletion or application of BMS-1166, a novel inhibitor of PD-1/PD-L1. Consistently, co-culturing with microglia promoted glioma cell growth and invasion, and blocking PD-1/PD-L1 significantly suppressed these processes. Our findings reveal that the PD-1/PD-L1 axis engages in the microglial M2 polarization in the glioma microenvironment and promotes tumor growth and invasion.

Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study.

Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.

Radiomics approach to distinguish between benign and malignant soft tissue tumors on magnetic resonance imaging.

Objective: To build a radiomics signature based on MRI images and evaluate its capability for preoperatively identifying the benign and malignant Soft tissue neoplasms (STTs). Materials and methods: 193 patients (99 malignant STTs and 94 benign STTs) were at random segmented into a training cohort (69 malignant STTs and 65 benign STTs) and a validation cohort (30 malignant STTs and 29 benign STTs) with a portion of 7:3. Radiomics features were extracted from T2 with fat saturation and T1 with fat saturation and gadolinium contrast images. Radiomics signature was developed by the least absolute shrinkage and selection operator (LASSO) logistic regression model. The receiver that operated characteristics curve (ROC) analysis was used to assess radiomics signature's prediction performance. Inner validation was performed on an autonomous cohort that contained 40 patients. Results: A radiomics was developed by a total of 16 radiomics features (5 original shape features and 11 were wavelet features) achieved favorable predictive efficacy. Malignant STTs showed higher radiomics score than benign STTs in both training cohort and validation cohort. A good prediction performance was shown by the radiomics signature in both training cohorts and validation cohorts. The training cohorts and validation cohorts had an area under curves (AUCs) of 0.885 and 0.841, respectively. Conclusions: A radiomics signature based on MRI images can be a trustworthy imaging biomarker for identification of the benign and malignant STTs, which could help guide treatment strategies.

Deacetylase Sirtuin 1 mitigates type I IFN- and type II IFN-induced signaling and antiviral immunity.

Type I and type II IFNs are important immune modulators in both innate and adaptive immunity. They transmit signaling by activating JAK-STAT pathways. Sirtuin 1 (SIRT1), a class III NAD+-dependent deacetylase, has multiple functions in a variety of physiological processes. Here, we characterized the novel functions of SIRT1 in the regulation of type I and type II IFN-induced signaling. Overexpression of SIRT1 inhibited type I and type II IFN-induced interferon-stimulated response element activation. In contrast, knockout of SIRT1 promoted type I and type II IFN-induced expression of ISGs and inhibited viral replication. Treatment with SIRT1 inhibitor EX527 had similar positive effects. SIRT1 physically associated with STAT1 or STAT3, and this interaction was enhanced by IFN stimulation or viral infection. By deacetylating STAT1 at K673 and STAT3 at K679/K685/K707/K709, SIRT1 downregulated the phosphorylation of STAT1 (Y701) and STAT3 (Y705). Sirt1+/- primary peritoneal macrophages and Sirt1+/- mice exhibited enhanced IFN-induced signaling and antiviral activity. Thus, SIRT1 is a novel negative regulator of type I and type II IFN-induced signaling through its deacetylase activity.IMPORTANCESIRT1 has been reported in the precise regulation of antiviral (RNA and DNA) immunity. However, its functions in type I and type II IFN-induced signaling are still unclear. In this study, we deciphered the important functions of SIRT1 in both type I and type II IFN-induced JAK-STAT signaling and explored the potential acting mechanisms. It is helpful for understanding the regulatory roles of SIRT1 at different levels of IFN signaling. It also consolidates the notion that SIRT1 is an important target for intervention in viral infection, inflammatory diseases, or even interferon-related therapies.

Ultrasonic features of automated breast volume scanner (ABVS) and handheld ultrasound (HHUS) combined with molecular biomarkers in predicting axillary lymph node metastasis of clinical T1-T2 breast cancer.

Background: In the post-American College of Surgeons Oncology Group Z0011 trial era, clinicians are attempting to preoperatively evaluate axillary lymph node (ALN) status using ultrasound. However, the value of preoperative ultrasound examination remains uncertain. The study aimed to investigate the ultrasonic features of automated breast volume scanner (ABVS) and handheld ultrasound (HHUS), in combination with molecular biomarkers, to predict the risk of ALN metastasis (ALNM) in clinical T1-T2 breast cancer. Methods: A retrospective case-control analysis was conducted on 168 patients with clinical T1-T2 breast cancer at Peking University First Hospital between January 2013 and August 2021. Preoperative ABVS and HHUS examinations were performed. According to the pathology results of the ALN, patients were divided into metastatic and nonmetastatic groups. Logistic regression analyses were used to analyze the ultrasonic characteristics of ABVS and HHUS on clinical T1-T2 breast cancer, and molecular biomarkers were incorporated to predict the risk of ALNM. Results: Of the 168 patients, 88 (52.4%) had ipsilateral ALNM while 80 (47.6%) had no ipsilateral ALNM. The univariate analysis showed that shorter tumor-skin distance (P=0.011), the Adler blood flow grade of II-III (P=0.014), and larger tumor size on ABVS (P<0.001) were associated with ALNM. The multivariate logistic analysis showed that these three risk factors, including the tumor-skin distance [odds ratio (OR) =0.279; P=0.024], the Adler blood flow grade (OR =2.164; P=0.046), and the tumor size on ABVS (OR =1.033; P=0.002), were independent predictive parameters. Conclusions: The tumor-skin distance, tumor size on ABVS, and Adler blood flow grade have diagnostic value for ALNM in clinical T1-T2 breast cancer.

Circular olefin copolymers made de novo from ethylene and α-olefins.

Ethylene/α-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle. However, synthesis of circular ethylene/α-olefin copolymers, including high-volume, linear low-density PE as well as high-value olefin elastomers and block copolymers, presents a particular challenge due to difficulties in introducing branches while simultaneously installing chemical recyclability and directly using industrial ethylene and α-olefin feedstocks. Here we show that coupling of industrial coordination copolymerization of ethylene and α-olefins with a designed functionalized chain-transfer agent, followed by modular assembly of the resulting AB telechelic polyolefin building blocks by polycondensation, affords a series of ester-linked PE-based copolymers. These new materials not only retain thermomechanical properties of PE-based materials but also exhibit full chemical circularity via simple transesterification and markedly enhanced adhesion to polar surfaces.

Combined ATAC-seq, RNA-seq, and GWAS analysis reveals glycogen metabolism regulatory network in Jinjiang oyster ( Crassostrea ariakensis).

Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters. The Jinjiang oyster ( Crassostrea ariakensis) is an economically and ecologically important species in China. In the present study, RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) were performed to investigate gene expression and chromatin accessibility variations in oysters with different glycogen contents. Analysis identified 9 483 differentially expressed genes (DEGs) and 7 215 genes with significantly differential chromatin accessibility (DCAGs) were obtained, with an overlap of 2 600 genes between them. Notably, a significant proportion of these genes were enriched in pathways related to glycogen metabolism, including "Glycogen metabolic process" and "Starch and sucrose metabolism". In addition, genome-wide association study (GWAS) identified 526 single nucleotide polymorphism (SNP) loci associated with glycogen content. These loci corresponded to 241 genes, 63 of which were categorized as both DEGs and DCAGs. This study enriches basic research data and provides insights into the molecular mechanisms underlying the regulation of glycogen metabolism in C. ariakensis.

Appendiceal goblet cell carcinoma: comparison of classification and staging systems with evaluation of the prognostic role of immunohistochemistry stains

Background: Goblet cell carcinoma (GCC) of the appendix is a unique lesion that exhibits features of both adenocarcinoma and neuroendocrine tumors. Due to the rarity of this cancer, multiple grading (e.g., Tang, Yozu, and Lee) and staging systems (e.g., tumor, lymph nodes, and metastasis [TNM]) have been developed for classification. This study aimed to compare commonly used classification systems and evaluate the prognostic effectiveness immunohistochemical staining may or may not have for appendiceal GCC. Methods: An electronic medical records review of patients who were diagnosed with GCC of the appendix in our hospital system from 2010 to 2020. The data were collected regarding the age at diagnosis, gender, initial diagnosis at presentation, operation(s) performed, final pathology results, current survival status, and year of recurrent disease or death year. Results: Ten patients were evaluated. Seventy percent of the patients were above the age of 50 years at diagnosis. Postdischarge survival ranged from 1 month to 109 months postdiagnosis. Two patients expired from GCC at 13- and 54-months following diagnosis. When comparing the classification systems, Lee categorized more patients as high risk than Tang and Yozu. Immunohistochemical staining was analyzed using four staining methods: Ki67, E-cadherin, Beta-catenin, and p53. Tumor, lymph nodes, and metastasis staging has supportive evidence for worsening prognosis and overall survival secondary to the depth of invasion of the tumor. Conclusion: Tumor, lymph nodes, and metastasis staging may be superior to the other classification systems in predicting overall mortality. Our study demonstrated that immunohistochemistry staining does not appear to have a significant impact in determining the prognosis for GCC of the appendix. (AU)

Catch the Calcium: T-Cell Histiocyte-Rich B-Cell Lymphoma Presenting as Hypercalcemia.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is an extremely rare and aggressive subtype of diffuse large B-cell lymphoma (DLBCL) that typically presents in middle-aged patients and carries a poor prognosis. Hypercalcemia presenting as the initial manifestation of the disease is rare, with only one other case reported in the literature. We report a case of a 90-year-old male who presented with progressive lethargy and unintentional weight loss. Initial workup showed elevated serum calcium of 14.6 mg/dL, corrected for albumin, and creatinine of 1.51 mg/dL. He had a suppressed iPTH of 6.3 pg/mL and normal PTHrP (13 pg/mL). Computed tomography (CT) scan of the abdomen and pelvis was performed to rule out underlying malignancy, which showed splenomegaly and enlarged retrocrural and porta hepatis lymph nodes. Bone marrow biopsy was performed to evaluate for hematological malignancy, which revealed findings diagnostic of THRLBCL. While rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the mainstay therapies for DLBCL and has been shown to have comparable outcomes in THRLBCL, there are documented concerns with its toxicity profile limiting the ability of older patients (60 years and older) to complete therapy. Our patient was treated with R-mini-CHOP, which is much better tolerated in this patient demographic. R-mini-CHOP features decreased doses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with the conventional dose of rituximab. This case discusses a rare subtype of non-Hodgkin lymphoma presenting with a unique manifestation of hypercalcemia. We highlight the importance of thorough investigation for causes of hypercalcemia as well as the efficacy and tolerability of R-mini-CHOP in this elderly patient demographic.

Early-stage serous fallopian tube carcinoma.

Primary fallopian tube carcinoma (PFTC) is a rare disease. Its location, close association with epithelial ovarian carcinoma, and lack of specific signs and symptoms make diagnosis challenging especially in its early stages. We report a postmenopausal patient who presented with a 2-month history of abdominopelvic pain with watery vaginal discharge. Imaging findings showed a 7 cm complex left adnexal mass. The patient underwent a robotic-assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy and surgical staging. Findings were significant for stage IA serous fallopian tube carcinoma. PFTC is sometimes missed preoperatively and intraoperatively. Available literature review has focused on the clinical and imaging characteristics of PFTC to aid in timely disease diagnosis. Minimally invasive surgery is a viable option in the diagnosis and management of early-stage ovarian cancer due to improved visualisation of pelvic structures, decreased length of hospital stay, decreased estimated blood loss and lower postoperative complication rates compared with laparotomy.

Strategy of functional nucleic acids-mediated isothermal amplification for detection of foodborne microbial contaminants: A review.

Foodborne microbial contamination (FMC) is the leading cause of food poisoning and foodborne illness. The foodborne microbial detection methods based on isothermal amplification have high sensitivity and short detection time, and functional nucleic acids (FNAs) could extend the detectable object of isothermal amplification to mycotoxins. Therefore, the strategy of FNAs-mediated isothermal amplification has been emergingly applied in biosensors for foodborne microbial contaminants detection, making biosensors more sensitive with lower cost and less dependent on nanomaterials for signal output. Here, the mechanism of six isothermal amplification technologies and their application in detecting FMC is firstly introduced. Then the strategy of FNAs-mediated isothermal amplification is systematically discussed from perspectives of FNAs' versatility including recognition elements (Aptamer, DNAzyme), programming tools (DNA tweezer, DNA walker and CRISPR-Cas) and signal units (G-quadruplex, FNAs-based nanomaterials). Finally, challenges and prospects are presented in terms of addressing the issue of nonspecific amplification reaction, developing better FNAs-based sensing elements and eliminating food matrix effects.

Lipidomic analysis identifies long-chain acylcarnitine as a target for ischemic stroke.

INTRODUCTION: Lipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance. METHODS: Untargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes. RESULTS: Long-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage. CONCLUSION: LCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS.

Fulminant Presentation of Budd-Chiari Syndrome Secondary to COVID-19 Infection.

Budd-Chiari syndrome (BCS) is a rare condition characterized by the obstruction of hepatic venous outflow. It is estimated to affect 1 in 100,000 people worldwide. In cases of new BCS, inherited and acquired hypercoagulability states must be evaluated. Coronavirus disease 2019 (COVID-19) can induce a hypercoagulable state because of its extensive inflammatory response, and while it has been reported to cause portal vein thrombosis, it rarely causes BCS. This article presents a case of a 22-year-old man who developed fulminant symptoms and was subsequently diagnosed with BCS and portal vein thrombosis secondary to COVID-19 infection, after ruling out other inherited and acquired causes of BCS. In addition, a literature review is provided to understand the presentation and management of such patients. Although most patients improve with medical management, this article emphasizes the consideration of liver transplant for patients who do not improve.

Multicenter evaluation of a simple and sensitive nucleic acid self-testing for SARS-CoV-2.

A rapid and accurate COVID-19 diagnosis is a prerequisite for blocking the source of infection as soon as possible and taking the appropriate medical action. Herein, we developed GeneClick, a device for nucleic acid self-testing of SARS-CoV-2, consisting of three modules: a sampling kit, a microfluidic chip-based disposable cartridge, and an amplification reader. In addition, we evaluated the clinical performance of GeneClick using 2162 nasal swabs collected at three medical institutions, using three commercial RT-qPCR kits and an antigen self-test as references. Compared to RT-qPCR, the sensitivity and specificity of the GeneClick assay were 97.93% and 99.72%, respectively, with a kappa value of 0.979 (P â€‹< â€‹0.01). Of the 2162 samples, 2076 were also tested for SARS-CoV-2 antigens. Among the 314 positive samples identified by GeneClick assay, 63 samples were undetected by antigen tests. Overall, the GeneClick nucleic acid self-test demonstrated higher accuracy than the antigen-based detection. Based on the additional features, including simple operation, affordable price, portable device, and reliability of smartphone APP-driven sampling and result reporting, GeneClick offers a powerful tool for field-based SARS-CoV-2 detection in primary healthcare institutions or at-home use.