A novel mitochondrial function-associated programmed cell death-related prognostic signature for predicting the prognosis of early breast cancer.

Purpose: To screen mitochondrial function-associated PCD-related biomarkers and construct a risk model for predicting the prognosis of early breast cancer. Methods: Data on gene expression levels and clinical information were obtained from the TCGA database, and GSE42568 and GSE58812 datasets were obtained from GEO database. The mitochondrial function-associated programmed cell death (PCD) related genes in early breast cancer were identified, then LASSO logistic regression, SVM-RFE, random forest (RF), and multiple Cox logistic regression analysis were employed to construct a prognostic risk model. Differences in immune infiltration, drug sensitivity, and immunotherapy response were evaluated between groups. Lastly, the qRT-PCR was employed to confirm the key genes. Results: Total 1,478 DEGs were screened between normal and early breast cancer groups, and these DEGs were involved in PI3K-Akt signaling pathway, focal adhesion, and ECM-receptor interaction pathways. Then total 178 mitochondrial function-associated PCD related genes were obtained, followed by a four mitochondrial function-associated PCD related genes prognostic model and nomogram were built. In addition, total 2 immune checkpoint genes were lowly expressed in the high-risk group, including CD47 and LAG3, and the fraction of some immune cells in high- and low-risk groups had significant difference, such as macrophage, eosinophil, mast cell, etc., and the Top3 chemotherapeutics with significant differences were included FH535, MK.2206, and bicalutamide. Finally, the qRT-qPCR results shown that the CREB3L1, CAPG, SPINT1 and GRK3 mRNA expression were in line with the bioinformatics analysis results. Conclusion: Four mitochondrial function-associated PCD-related genes were identified, including CREB3L1, CAPG, SPINT1, and GRK3, and the prognostic risk model and nomogram were established for predicting the survival of early breast cancer patient. The chemotherapeutics, containing FH535, MK.2206, and bicalutamide, might be used for early breast cancer.

A hot and cold tumor­related prognostic signature for stage II colorectal cancer.

Globally, colorectal cancer (CRC) is one of the most lethal and prevalent malignancies. Based on the presence of immune cell infiltration in the tumor microenvironment, CRC can be divided into immunologically 'hot' or 'cold' tumors, which in turn leads to the differential efficacy of immunotherapy. However, the immune characteristics of hot and cold CRC tumors remain largely elusive, prompting further investigation of their properties regarding the tumor microenvironment. In the present study, a predictive model was developed based on the differential expression of proteins between cold and hot CRC tumors. First, the differentially expressed proteins (DEPs) were identified using digital spatial profiling and mass spectrometry-based proteomics analysis, and the pathway features of the DEPs were analyzed using functional enrichment analysis. A novel eight-gene signature prognostic risk model was developed (IDO1, MAT1A, NPEPL1, NT5C, PTGR2, RPL29, TMEM126A and TUBB4B), which was validated using data obtained from The Cancer Genome Atlas. The results revealed that the risk score of the eight-gene signature acted as an independent prognostic indicator in patients with stage II CRC (T3-4N0M0). It was also found that a high-risk score in the eight-gene signature was associated with high immune cell infiltration in patients with CRC. Taken together, these findings revealed some of the differential immune characteristics of hot and cold CRC tumors, and an eight-gene signature prognostic risk model was developed, which may serve as an independent prognostic indicator for patients with stage II CRC (T3-4N0M0).

Mechanism of acupuncture and moxibustion in ameliorating liver injury induced by cisplatin by regulating IRE-1 signaling pathway. / "扶正益肝"é’ˆç¸ç©´æ–¹åŸºäºŽè‚Œé†‡éœ€æ±‚é ¶1ä¿¡å·é€šè·¯æ”¹å–„é¡ºé“‚è‡´å°é¼ è‚æŸä¼¤çš„æœºåˆ¶.

OBJECTIVES: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury in cisplatin (DDP) induced liver injury model mice by observing the changes of inositol-requiring enzyme (IRE) -1 signaling pathway. METHODS: Forty KM mice were randomly divided into control, model, acupuncture and moxibustion groups, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP (10 mg/kg). In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at "Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu" (BL23), and "Zusanli"(ST36), respectively for 6 min, once per day for 7 d. The apoptosis of hepatocytes was detected by TUNEL staining. The expression of phosphorylation(p)-IRE-1α, glucose-regulated protein (Grp) 78 and cysteine aspartic protease (Caspase) -12 in liver tissue were detected by immunohistochemistry and Western blot, respectively. The expression levels of Grp78 and Caspase-12 mRNA in liver tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the apoptosis rate of hepatocytes was increased (P<0.05), the positive expression and protein expression of p-IRE-1α, Grp78, and Caspase-12 were increased (P<0.05), the expression levels of Grp78 and Caspase-12 mRNA were increased (P<0.05) in the model group. Compared with the model group, all these indicators showed opposite trends (P<0.05) in the acupuncture and moxibustion groups. CONCLUSIONS: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating IRE-1 signaling pathway, inhibiting the excessive activation of endoplasmic reticulum stress, and reducing liver cell apoptosis.

Metabolic Heterogeneity of Tumor Cells and its Impact on Colon Cancer Metastasis: Insights from Single-Cell and Bulk Transcriptome Analyses.

Background: Metabolic reprogramming plays a crucial role in the development of colorectal cancer (CRC), influencing tumor heterogeneity, the tumor microenvironment, and metastasis. While the interaction between metabolism and CRC is critical for developing personalized treatments, gaps remain in understanding how tumor cell metabolism affects prognosis. Our study introduces novel insights by integrating single-cell and bulk transcriptome analyses to explore the metabolic landscape within CRC cells and its mechanisms influencing disease progression. This approach allows us to uncover metabolic heterogeneity and identify specific metabolic genes impacting metastasis, which have not been thoroughly examined in previous studies. Methods: We sourced microarray and single-cell RNA sequencing datasets from the Gene Expression Omnibus (GEO) and bulk sequencing data for CRC from The Cancer Genome Atlas (TCGA). We employed Gene Set Variation Analysis (GSVA) to assess metabolic pathway activity, consensus clustering to identify CRC-specific transcriptome subtypes in bulkseq, and rigorous quality controls, including the exclusion of cells with high mitochondrial gene expression in scRNA seq. Advanced analyses such as AUCcell, infercnvCNV, Non-negative Matrix Factorization (NMF), and CytoTRACE were utilized to dissect the cellular landscape and evaluate pathway activities and tumor cell stemness. The hdWGCNA algorithm helped identify prognosis-related hub genes, integrating these findings using a random forest machine learning model. Results: Kaplan-Meier survival curves identified 21 significant metabolic pathways linked to prognosis, with consensus clustering defining three CRC subtypes (C3, C2, C1) based on metabolic activity, which correlated with distinct clinical outcomes. The metabolic activity of the 13 cell subpopulations, particularly the epithelial cell subpopulation with active metabolic levels, was evaluated using AUCcell in scRNA seq. To further analyze tumor cells using infercnv, NMF disaggregated these cells into 10 cellular subpopulations. Among these, the C2 subpopulation exhibited higher stemness and tended to have a poorer prognosis compared to C6 and C0. Conversely, the C8, C3, and C1 subpopulations demonstrated a higher level of the five metabolic pathways, and the C3 and C8 subpopulations tended to have a more favorable prognosis. hdWGCNA identified 20 modules, from which we selected modules primarily expressed in high metabolic tumor subgroups and highly correlated with clinical information, including blue and cyan. By applying variable downscaling of RF to a total of 50 hub genes, seven gene signatures were obtained. Furthermore, molecules that were validated to be protective in GEO were screened alongside related molecules, resulting in the identification of prognostically relevant molecules such as UQCRFS1 and GRSF1. Additionally, the expression of GRSF1 was examined in colon cancer cell lines using qPCR and phenotypically verified by in vitro experiments. Conclusion: Our findings emphasize that high activity in specific metabolic pathways, including pyruvate metabolism and the tricarboxylic acid cycle, correlates with improved colon cancer outcomes, presenting new avenues for metabolic-based therapies. The identification of hub genes like GRSF1 and UQCRFS1 and their link to favorable metabolic profiles offers novel insights into tumor neovascularization and metastasis, with significant clinical implications for targeting metabolic pathways in CRC therapy.

Preclinical pharmacokinetic characterization of amdizalisib, a novel PI3Kδ inhibitor for the treatment of hematological malignancies.

Amdizalisib, also named HMPL-689, a novel selective and potent PI3Kδ inhibitor, is currently under Phase II clinical development in China for treating hematological malignancies. The preclinical pharmacokinetics (PK) of amdizalisib were extensively characterized in vitro and in vivo to support the further development of amdizalisib. We characterized the plasma protein binding, blood-to-plasma partition ratio, cell permeability, hepatic microsomal metabolic stability, and drug-drug interaction potential of amdizalisib using in vitro experiments. In vivo PK assessment was undertaken in mice, rats, dogs, and monkeys following a single intravenous or oral administration of amdizalisib. The tissue distribution and excretion of amdizalisib were evaluated in rats. The PK parameters (CL and Vss) of amdizalisib in preclinical species (mice, rats, dogs, and monkeys) were utilized for the human PK projection using the allometric scaling (AS) approach. Amdizalisib was well absorbed and showed low-to-moderate clearance in mice, rats, dogs, and monkeys. It had high cell permeability without P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrate liability. Plasma protein binding of amdizalisib was high (approximately 90%). It was extensively distributed but with a low brain-to-plasma exposure ratio in rats. Amdizalisib was extensively metabolized in vivo, and the recovery rate of the prototype drug was low in the excreta. Amdizalisib and/or its metabolites were primarily excreted via the bile and urine in rats. Amdizalisib showed inhibition potential on P-gp but not on BCRP and was observed to inhibit CYP2C8 and CYP2C9 with IC50 values of 30.4 and 10.7 µM, respectively. It exhibited induction potential on CYP1A2, CYP2B6, CYP3A4, and CYP2C9. The preclinical data from these ADME studies demonstrate a favorable pharmacokinetic profile for amdizalisib, which is expected to support the future clinical development of amdizalisib as a promising anti-cancer agent.

The Effect of Transurethral Holmium Laser Enucleation of the Prostate in the Treatment of High-Risk Elderly Patients with BPH and Its Influence on Quality of Life.

BACKGROUND: Transurethral holmium laser enucleation of the prostate (HoLEP) has a good therapeutic effect on benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the clinical efficacy of HoLEP in the treatment of high-risk elderly patients with BPH and assess its impact on the inflammatory response, vascular endothelial function and quality of life (QoL). METHODS: Patients at high risk of BPH who were hospitalised in Chengde Central Hospital from February 2021 to December 2022 were retrospectively selected as the study objects, and a total of 100 cases were included. The control group underwent transurethral resection of the prostate, and the observation group underwent HoLEP. Perioperative indexes, urodynamic indexes, QoL 6 months after surgery and incidence of postoperative complications were compared between the two groups. Moreover, serum levels of inflammatory factors and vascular endothelial factors were detected in two groups. RESULTS: We found no significant difference in general data between the two groups of patients (p > 0.05). The operation time, perioperative bleeding, bladder flushing time and hospitalisation time of the observation group were significantly shorter than those of the control group (p < 0.05). On the 7th day after surgery, the serum levels of tumour necrosis factor alpha, interleukin-1ß, interleukin-6, vascular endothelial growth factor, basic fibroblast growth factor and endothelin-1 in the observation group were significantly lower than those in the control group (p < 0.05). Six months after surgery, the maximal urinary flow rate and QoL scores of the patients in the observation group were significantly higher than those of the control group (p < 0.05), and the residual urine volume and International Prostate Symptom Score of observation group were significantly lower than those of the control group (p < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group (χ2 = 7.440, p = 0.006). CONCLUSIONS: HoLEP can effectively remove hyperplasia of the prostate and reduce the inflammatory response in the patient's body when treating BPH in high-risk elderly patients. It can also regulate the levels of vascular endothelial factors and effectively improve the patient's QoL.

PRRX1-fused mesenchymal neoplasm: A novel PRRX1::NCOA1 fusion transcript.

PRRX1-fused mesenchymal neoplasm is a recently identified, rare subcutaneous soft tissue neoplasm that is characterized by fusion of PRRX1 (exon 1) with NCOA1 (exon 13) in the majority of reported cases. Although initially considered to be fibroblastic, a possibility of neural or neuroectodermal differentiation has been suggested in a subset of cases. We report a 26-year-old female with a 4.0 cm painless mass located in the subcutis of the left thigh. Microscopically, the tumor was well-circumscribed and multinodular and was composed of relatively monomorphic ovoid to spindle cells arranged in loose fascicles, trabeculae, and cords within alternating myxoid and fibrous matrix, and vascularized stroma. Mitotic figures were scarce and necrosis was not observed. By immunohistochemistry, the neoplastic cells demonstrated focal co-expression of S100 protein and SOX10 and were negative for epithelial membrane antigen, smooth muscle actin, desmin, CD34, STAT6, HMB45, Melan-A, and MUC4. The expression of Rb1 was retained. Targeted RNA-sequencing identified a novel transcript fusion of PRRX1 (exon 1)::NCOA1 (exon 15), which was further confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. The tumor was narrowly excised and no tumor recurrence or metastasis was identified after 13 months of follow-up. In summary, we report a new case of PRRX1-fused mesenchymal neoplasm, expanding the molecular genetic spectrum and providing further support for possible neural or neuroectodermal differentiation of this emerging soft tissue tumor entity.

Application of a virtual ruler (VR) in predicting postoperative rebleeding from esophageal varices in patients with liver cirrhosis.

BACKGROUND: Esophageal variceal diameter (EVD) is one of the most important predictors of variceal bleeding, as well as an important predictor of the effectiveness of endoscopic esophageal varices (EV) treatments. EVD is currently determined using visual inspection by endoscopic operators, meaning that results can vary widely between operators. This approach also means that cases unsuitable for Endoscopic variceal ligation(EVL) can be complicated by postoperative hemorrhage. Thus, the purpose of this study was to explore the value of a virtual ruler (VR) in predicting rebleeding after the endoscopic treatment of EV in patients with cirrhosis. METHODS: We enrolled 588 patients with cirrhosis and EV (with and without gastric varices), who were treated with EVL or Endoscopic injection sclerotherapy (EIS) across three hospitals. We categorized participants into a non-bleeding group and a rebleeding group according to whether they bled again after surgery. We compared basic demographic and clinical data, laboratory tests, EVD, and treatment modalities between the two groups. Potential risk factors for rebleeding after EV operations were analyzed using univariate and multivariable regression analyses. Correlations between esophageal variceal rebleeding and EVD were also analyzed, as was consistency between visual EVD estimates and EVD measured using a VR. RESULTS: Child-Pugh class, Albumin (ALB)levels, Prothrombin Time (PT) levels, EVD (Visual value), EVD(VR value), red sign, and the number of laps used for EVL showed statistically significant differences between the rebleeding and non-bleeding groups. Univariate regression analysis showed that Child-Pugh classification, ALB levels, PT levels, EVD( VR value), and red sign were strongly associated with rebleeding after endoscopic treatment of EV, while multivariable regression analysis showed that Child-Pugh classification, ALB levels, and EVD (VR value) were predictive factors for rebleeding after endoscopic treatment of EV. Differences between visual EVD estimates and VR EVD measurements were large. (Kappa value: 0.391, p < 0.001). However, the two methods showed high agreement for EVD > 1cm (87/95) CONCLUSIONS: EVD (VR value) can more accurately predict rebleeding rates. It can also provide a basis for selecting appropriate endoscopic treatment modalities for EV and effectively circumvent postoperative EV rebleeding.

Design, synthesis, pharmacological evaluation, and computational study of benzo[d] isothiazol-based small molecule inhibitors targeting PD-1/PD-l1 interaction.

Blockade of the programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is an attractive strategy for immunotherapy, but the clinical application of small molecule PD-1/PD-L1 inhibitors remains unclear. In this work, based on BMS-202 and our previous work YLW-106, a series of compounds with benzo[d]isothiazol structure as scaffold were designed and synthesized. Their inhibitory activity against PD-1/PD-L1 interaction was evaluated by a homogeneous time-resolved fluorescence (HTRF) assay. Among them, LLW-018 (27c) exhibited the most potent inhibitory activity with an IC50 value of 2.61 nM. The cellular level assays demonstrated that LLW-018 exhibited low cytotoxicity against Jurkat T and MDA-MB-231. Further cell-based PD-1/PD-L1 blockade bioassays based on PD-1 NFAT-Luc Jurkat cells and PD-L1 TCR Activator CHO cells indicated that LLW-018 could interrupt PD-1/PD-L1 interaction with an IC50 value of 0.88 µM. Multi-computational methods, including molecular docking, molecular dynamics, MM/GBSA, MM/PBSA, Metadynamics, and QM/MM MD were utilized on PD-L1 dimer complexes, which revealed the binding modes and dissociation process of LLW-018 and C2-symmetric small molecule inhibitor LCH1307. These results suggested that LLW-018 exhibited promising potency as a PD-1/PD-L1 inhibitor for further investigation.

[Protective effects and mechanisms of berberine hydrochloride on intestinal mucosal barrier injury in rats with sepsis].

OBJECTIVE: To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism. METHODS: Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue. RESULTS: After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and severe damage to the tight junction complex structure of intestinal epithelial cells, which was significantly improved in the Ber group but less improved in the DAPT group. The levels of serum DAO, iFABP, TNF-α, IL-6 in the LPS group were significantly higher than those in the Sham group, while the above indicators in the Ber group were significantly lower than those in the LPS group [DAO (µg/L): 4.94±0.44 vs. 6.53±0.49, iFABP (ng/L): 709.67±176.97 vs. 1 417.71±431.44, TNF-α (ng/L): 74.70±8.15 vs. 110.36±3.51, IL-6 (ng/L): 77.34±9.80 vs. 101.65±6.92, all P < 0.01], while the above indicators in the DAPT group were significantly higher than those in the Ber group. The results of RT-PCR and Western blotting showed that the mRNA and protein expressions of Occludin, Claudin1, Notch1, and Hes1 in the ileum tissue of LPS group rats were decreased compared to the Sham group, which were significantly increased in the Ber group compared with the LPS group [mRNA expression: Occludin mRNA (2-ΔΔCt): 1.61±0.74 vs. 0.30±0.12, Claudin1 mRNA (2-ΔΔCt): 1.97±0.37 vs. 0.58±0.14, Notch1 mRNA (2-ΔΔCt): 1.29±0.29 vs. 0.36±0.10, Hes1 mRNA (2-ΔΔCt): 1.22±0.39 vs. 0.27±0.04; protein expression: Occludin/GAPDH: 1.17±0.14 vs. 0.74±0.04, Claudin1/GAPDH: 1.14±0.06 vs. 0.58±0.10, Notch1/GAPDH: 0.87±0.11 vs. 0.56±0.09, Hes1/GAPDH: 1.02±0.13 vs. 0.62±0.01; all P < 0.05], while those in the DAPT group were significantly lower than those in the Ber group. CONCLUSIONS: Early use of berberine hydrochloride can significantly improve intestinal mucosal barrier damage in sepsis rats, and its mechanism may be related to inhibiting inflammatory response and regulating the expression of intestinal mechanical barrier tight junction protein through Notch1 signal.

Overview of the interplay between m6A methylation modification and non-coding RNA and their impact on tumor cells.

N6-methyladenosine (m6A) is one of the most common internal modifications in eukaryotic RNA. The presence of m6A on transcripts can affect a series of fundamental cellular processes, including mRNA splicing, nuclear transportation, stability, and translation. The m6A modification is introduced by m6A methyltransferases (writers), removed by demethylases (erasers), and recognized by m6A-binding proteins (readers). Current research has demonstrated that m6A methylation is involved in the regulation of malignant phenotypes in tumors by controlling the expression of cancer-related genes. Non-coding RNAs (ncRNAs) are a diverse group of RNA molecules that do not encode proteins and are widely present in the human genome. This group includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI interaction RNAs (piRNAs). They function as oncogenes or tumor suppressors through various mechanisms, regulating the initiation and progression of cancer. Previous studies on m6A primarily focused on coding RNAs, but recent discoveries have revealed the significant regulatory role of m6A in ncRNAs. Simultaneously, ncRNAs also exert their influence by modulating the stability, splicing, translation, and other biological processes of m6A-related enzymes. The interplay between m6A and ncRNAs collectively contributes to the occurrence and progression of malignant tumors in humans. This review provides an overview of the interactions between m6A regulatory factors and ncRNAs and their impact on tumors.

Harnessing virus flexibility to selectively capture and profile rare circulating target cells for precise cancer subtyping.

The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young's modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL-1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.

Comparison of Outcomes Between Partial and Radical Laparoscopic Nephrectomy for Localized Renal Tumors Larger Than Four Centimeters: A Systematic Review and Meta-Analysis.

Background: Earlier studies have juxtaposed different laparoscopic methods for treating renal tumors; however, extensive evidence with a particular focus on large kidney tumors remains lacking. The objective of this meta-analysis was to assess the perioperative outcomes, kidney performance, and cancer-related results of laparoscopic partial nephrectomy (LPN) versus laparoscopic radical nephrectomy (LRN) for treating extensive, localized, non-metastatic kidney tumors (cT1b-cT2N0M0). Methods: We systematically searched multiple databases from database inception until December 2023 for relevant studies. Selected data were analyzed with the Cochrane Collaboration's Review Manager 5.4 software using a random-effects model. Outcomes were expressed as odds ratios and weighted mean differences with 95% confidence intervals, considering a P value of < 0.05 as significant. Results: Data from nine studies encompassing 1,303 patients (529 LPN, 774 LRN) revealed that LPN was associated with lengthier surgeries and increased blood loss compared to LRN. While LPN exhibited higher postoperative complication rates, the disparity did not reach statistical significance. LPN led to improved postoperative renal function, manifesting as a reduced estimated glomerular filtration rate (eGFR) decline and fewer incidents of new chronic kidney disease cases. Both groups demonstrated comparable tumor recurrence and overall mortality rates, but LPN exhibited significantly lower cancer-specific mortality rates. Conclusions: LPN, despite longer operative times and greater intraoperative blood loss, was found to be superior to LRN in preserving postoperative renal function. Oncologically, LPN and LRN have comparable overall mortality rates, but LPN showed a significant advantage in terms of lower cancer-specific mortality rates.

Association between surgical delays for femoral neck fractures and early postoperative complications in young and middle-aged adults: A study based on the national inpatient sample database.

BACKGROUND: Femoral neck fractures (FNF) in young and middle-aged adults are primarily caused by high-energy injuries in traffic accidents. Surgical delays often occur due to transportation issues, preoperative evaluations, and economic burdens. METHODS: A retrospective analysis was conducted on young and middle-aged FNF patients undergoing reduction and internal fixation surgeries from 2010 to 2019 with the use of the National Inpatient Sample database. Logistic regression analysis was used to assess the relationship between surgical delays and complications, and the independent risk factors contributing to delays. Categorical variables were investigated via a chi-square test, while continuous variables including Elixhauser Comorbidity Index (ECI) scores, length of hospital stay (LOS), and total medical costs were analyzed via t-test or rank-sum test. RESULTS: 9,204 patients undergoing reduction and internal fixation surgeries were included. In the delayed group, patients had higher ECI scores, longer hospital stays, higher expenses, and increased inpatient mortality (1.61% vs. 0.28 %, P < 0.0001). Longer surgical delays were associated with higher risks of complications, including femoral head osteonecrosis, internal fixation loosening and breakage, and respiratory complications. Fluid and electrolyte disorders, metastatic cancer, pulmonary circulation disorders, and renal failure were identified as independent risk factors for surgical delays. Except for anemia (OR=2.37, P < 0.0001), no significant differences in early postoperative complications were found between open-reduction and closed-reduction internal fixation (ORIF/CRIF) surgeries. CONCLUSION: Early surgical intervention, within a 2-days period after injury, seems to be crucial for young adults with FNF. If CRIF is challenging in some cases, ORIF can be another choice.

Experimental Study on the Effects of Carbonated Steel Slag Fine Aggregate on the Expansion Rate, Mechanical Properties and Carbonation Depth of Mortar.

Steel slag is the main by-product of the steel industry and can be used to produce steel slag fine aggregate (SSFA). SSFA can be used as a fine aggregate in mortar or concrete. However, SSFA contains f-CaO, which is the main reason for the expansion damage of mortar and concrete. In this study, the carbonation treatment of SSFA was adopted to reduce the f-CaO content; the influence of the carbonation time on the content of f-CaO in the SSFA was studied; and the effects of the carbonated SSFA replacement ratio on the expansion rate, mechanical properties and carbonation depth of mortar were investigated through tests. The results showed that as the carbonation time increased, the content of f-CaO in the SSFA gradually decreased. Compared to the mortar specimens with carbonated SSFA, the specimens with uncarbonated SSFA showed faster and more severe damage and a higher expansion rate. When the replacement ratio of carbonated SSFA was less than 45%, the carbonated SSFA had an inhibitory effect on the expansion development of the specimens. The compressive strengths of the specimens with a carbonated SSFA replacement ratio of 60% and 45% were 1.29% and 6.81% higher than those of the specimens with an uncarbonated SSFA replacement ratio of 60% and 45%, respectively. Carbonation treatment could improve the replacement ratio of SSFA while ensuring the compressive strength of specimens. Compared with mortar specimens with uncarbonated SSFA, the anti-carbonation performance of mortar specimens with carbonated SSFA was reduced.

Natural Rubber/Styrene-Butadiene Rubber Blend Composites Potentially Applied in Damping Bearings.

Natural rubber (NR) composites have been widely applied in damping products to reduce harmful vibrations, while rubber with only a single composition barely meets performance requirements. In this study, rubber blend composites including various ratios of NR and styrene butadiene rubber (SBR) were prepared via the conventional mechanical blending method. The effects of the rubber components on the compression set, compression fatigue temperature rising and the thermal oxidative aging properties of the NR/SBR blend composites were investigated. Meanwhile, the dynamic mechanical thermal analyzer and rubber processing analyzer were used to characterize the dynamic viscoelasticity of the NR/SBR blend composites. It was shown that, with the increase in the SBR ratio, the vulcanization rate of the composites increased significantly, while the compression fatigue temperature rising of the composites decreased gradually from 47 °C (0% SBR ratio) to 31 °C (50% SBR ratio). The compression set of the composites remained at ~33% when the SBR ratio was no more than 20%, and increased gradually when the SBR ratio was more than 20%.

Expanding the Spectrum of NUTM1 -Rearranged Sarcoma : A Clinicopathologic and Molecular Genetic Study of 8 Cases.

Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1 -rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51 y; median: 56 y). Tumors occurred in the colon (2), abdomen (2), jejunum (1), esophagus (1), lung (1) and infraorbital region (1). At diagnosis, 6 patients presented with metastatic disease. Tumor size ranged from 1 to 10.5 cm (mean: 6 cm; median: 5.5 cm). Histologically, 4 tumors were composed of primitive small round cells to epithelioid cells intermixed with variable spindle cells, while 3 tumors consisted exclusively of small round cells to epithelioid cells and 1 tumor consisted predominantly of high-grade spindle cells. The neoplastic cells were arranged in solid sheets, nests, or intersecting fascicles. Mitotic activity ranged from 1 to 15/10 HPF (median: 5/10 HPF). Other features included rhabdoid phenotype (4/8), pronounced nuclear convolutions (2/8), prominent stromal hyalinization (2/8), focally myxoid stroma (1/8), foci of osteoclasts (1/8), and necrosis (1/8). By immunohistochemistry, all tumors showed diffuse and strong nuclear staining of NUT protein, with variable expression of pancytokeratin (AE1/AE3) (2/8), CK18 (1/8), CD99 (3/8), NKX2.2 (2/8), cyclin D1 (2/8), desmin (2/8), BCOR (2/8), S100 (1/8), TLE1 (1/8), and synaptophysin (1/8). Seven of 8 tumors demonstrated NUTM1 rearrangement by fluorescence in situ hybridization analysis. RNA-sequencing analysis identified MXD4::NUTM1 (3/7), MXI1::NUTM1 (3/7), and MGA::NUTM1 (1/7) fusions, respectively. DNA-based methylation profiling performed in 2 cases revealed distinct methylation cluster differing from those of NUT carcinoma and undifferentiated small round cell and spindle cell sarcomas. At follow-up (range: 4 to 24 mo), 1 patient experienced recurrence at 8.5 months, 4 patients were alive with metastatic disease (5, 10, 11, and 24 mo after diagnosis), 3 patients remained well with no signs of recurrence or metastasis (4, 6, and 12 mo after diagnosis). Our study further demonstrated that NUTM1 -rearranged sarcoma had a broad range of clinicopathologic spectrum. NUT immunohistochemistry should be included in the diagnostic approach of monotonous undifferentiated small round, epithelioid to high-grade spindle cell malignancies that difficult to classify by conventional means. DNA-based methylation profiling might provide a promising tool in the epigenetic classification of undifferentiated sarcomas.

Systematic review and meta-analysis of current evidences in endograft therapy vs. medical treatment for Spontaneous Isolated Superior Mesenteric Artery Dissection.

OBJECTIVE: Endovascular stent therapy (EST) for spontaneous isolated superior mesenteric artery dissection (SISMAD) is gaining popularity, yet the treatment strategy - BMT or EST - remains debatable. METHODS: A meta-analysis examined all randomized trials and observational studies exploring the relative merits and potential risks of EST vs. BMT in treating SISMAD patients. Key outcomes included early and long-term adverse effects, with odds ratios (ORs) and 95% confidence intervals (CI) calculated. A random- or fixed-effects model was selected according to a 50% heterogeneity threshold. RESULTS: 9 observational studies involving a total of 672 SISMAD patients (303 EST), met our selection criteria. We discovered no noteworthy distinctions between the EST group and the BMT group in terms of early symptoms' alleviation, reinterventions, or all-cause mortality. However, patients receiving EST management will be hospitalized longer than those receiving BMT (EST: 13.2 ± 5.1 months vs. BMT: 7.0 ± 2.2 months, P < 0.01). In the long run, EST was found to significantly contribute to a higher rate of complete remodeling (OR: 4.53, CI: 3.01 ~ 6.81, P < 0.01; heterogeneity, I2 = 50%) and a lower incidence of aneurysm formation (OR: 0.19, CI: 0.06 ~ 0.6, P < 0.01; heterogeneity, I2 = 0%) than BMT. However, there are no significant differences between ESTand BMTin terms of all-cause mortality, recurrent syndrome, reintervention, and SMA stenosis or occlusion. CONCLUSION: EST can effectively prevent the formation of aneurysmal dissection and improve SISMAD remodeling. Both EST and BMT are similar in reducing long-term mortality, recurrent symptoms, severe SMA stenosis or occlusion, and the need for reintervention in patients with SISMAD.

Engineering an enzyme-like catalytic sensor for on-site dual-mode evaluation of total antioxidant capacity.

A novel Fe-MoOx nanozyme, engineered with enhanced peroxidase (POD)-like activity through strategic doping and the creation of oxygen vacancies, is introduced to catalyze the oxidation of TMB with high efficiency. Furthermore, Fe-MoOx is responsive to single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms related to antioxidants and can serve as a desirable nanozyme for total antioxidant capacity (TAC) determination. The TAC colorimetric platform can reach a low LOD of 0.512 µM in solution and 24.316 µM in the smartphone-mediated RGB hydrogel (AA as the standard). As proof of concept, the practical application in real samples was explored. The work paves a promising avenue to design diverse nanozymes for visual on-site inspection of food quality.