Search

In pancreatic cancer, KRAS G12D can trigger pancreatic cancer initiation and development. Rapid tumor growth is often accompanied by excess intracellular reactive oxygen species (ROS) production, which is unfavorable to tumor. However, the regulation of intracellular ROS levels in KRAS mutant pancreatic cancer remains unclear. In this study, we establish BxPC3 stable cell strains expressing KRAS wild type (WT) and G12D mutation and find unchanged ROS levels despite higher glycolysis and proliferation viability in KRAS mutant cells than KRAS WT cells. The key hydrogen sulfide (H 2S)-generating enzyme cystathionine-γ-lyase (CSE) is upregulated in KRAS mutant BxPC3 cells, and its knockdown significantly increases intracellular ROS levels and decreases cell glycolysis and proliferation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated by KRAS mutation to promote CSE transcription. An Nrf2 binding site (‒47/‒39 bp) in the CSE promoter is verified. CSE overexpression and the addition of NaHS after Nrf2 knockdown or inhibition by brusatol decreases ROS levels and rescues cell proliferation. Our study reveals the regulatory mechanism of intracellular ROS levels in KRAS mutant pancreatic cancer cells, which provides a potential target for pancreatic cancer therapy.

Object To analyze the difference of economics cost between biliary surgeons and general surgeons in performing cholecystectomy for gallbladder benign diseases and the influence of specialization of surgery on patients. Methods The general information, hospitalization expenses and postoperative hospital stay of the patients with gallbladder benign diseases undergoing cholecystectomy from 2009 to 2018 in Zhongshan Hospital were analyzed retrospectively. Results There were 11 635 cases included in this study through the searching notes and manual review dividing 4 350 cases in biliary surgeon group and 7 285 cases in general surgeon group. There was no significant difference in ratio of laparosco-pic surgery between two groups(P=0.198). Total cost in biliary surgeon group was significantly higher than that in general surgeon group during 2009—2018, (15 721.60±9 888.82) yuan vs.(12 529.88±9 382.23) yuan. The increase in operative cost, (5 110.43±1 416.40) yuan vs. (4 601.24±1 601.65) yuan, material cost, (4 458.73±2 967.35 ) yuan vs. (4 080.49±2 377.83) yuan, drug cost, (1 808.32±2 771.20 ) yuan vs. (1 562.51±3 648.92) yuan, self-paying drug cost, (806.63±1 285.11) yuan vs. (637.14±1 071.00) yuan, and nursing cost, (165.24±296.55 ) yuan vs. (129.24±398.01) yuan, P

In ternary nitrides, the Ga0.9Fe3.1N sample has ultimately been prepared through solid‐gas preparation for the gallium‐richest phase GaFe3N. The substitution of gallium atoms for iron atoms weakens the saturation magnetization of ferromagnetic γʹ‐Fe4N and induces the transmission from ferromagnetism to antiferromagnetism. A new magnetic behavior, defined as the spin glassy magnetic state, has been observed in the temperature‐dependent magnetic performance measurement process for Ga0.9Fe3.1N. The magnetic competition between ferromagnetic and antiferromagnetic Fe–Fe bonds will lead to the spin frustration of the magnetic system. And even the positional disorders caused by substitution, will all be responsible for the spin glassy behavior in Ga0.9Fe3.1N. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been shown to play important roles in tumour development and tumour immunology. However, genome‐wide characterisation of circRNAs and their roles in the immunology and immunotherapy of gallbladder carcinoma (GBC) has been lacking. We present a comprehensive characterisation of the circRNA landscape in GBC, revealing GBC‐specific circRNAs. Our analysis found that circRNAs are significantly enriched in cell proliferation and are involved in cancer‐related hallmarks. In particular, circAATF was upregulated in GBC, which was positively correlated with AATF mRNA expression, and promoted GBC cell growth. Through integrating computational and experimental approaches, we revealed that circAATF is positively associated with the CD4+ T cell abundance and PD‐L1 level, and enhances the clinical benefits of anti‐PD‐L1 immunotherapy for GBC. We further demonstrate that circAATF elevates the PD‐L1 level by activating phosphorylated AKT and acting as a sponge for miR‐142‐5p. CircAATF is positively associated with CD4+ T cells and PD‐L1 levels and shows potential to aid anti‐PD‐L1 immunotherapy for GBC. Our study provides insights into roles of circAATF in the tumour development and immunology of GBC and accelerates the development of therapeutic strategies for GBC immunotherapy. Highlights: We present a comprehensive characterisation of circRNA landscape in gallbladder carcinoma (GBC).CircAATF is positively associated with CD4+ T cell abundance and PD‐L1 expression and is shown to promote PD‐L1 treatment in mouse model.CircAATF can elevate PD‐L1 level through phosphorylated AKT and linear AATF, which upregulates PD‐L1 by acting as a sponge of miR‐142‐5p. [ABSTRACT FROM AUTHOR]

Objective To evaluate the value of contrast-enhanced ultrasound (CEUS) in the preoperative diagnosis of gallbladder cancer (GBC) and xanthogranulomatous cholecystitis (XGC). Methods Eighty-one patients with GBC and with XGC in Department of General Surgery Zhongshan Hospital during 2016 and 2018 were analyzed retrospectively for comparing the accuracy of imaging examination to diagnose GBC and XGC between transabdominal ultrasound(TAUS) and CEUS. Results Thirty-nine patients with GBC and 42 patients with XGC diagnosed by pathological examination postope-ratively were recruited in this study. Radical surgery was done in 31 cases with GBC and palliative resection of gallbladder for the rest. The patients underwent both TAUS and CEUS preoperatively. The accuracy of CEUS in the assessment of patients with gallbladder disease (62/81, 76.5%) was higher than that of TAUS (43/81, 53.1%) (P=0.002) significantly. The accuracy of CEUS in the diagnosis of GBC (32/39, 82.1%) was significantly higher than TAUS (21/39, 53.8%), P=0.007. CEUS had sensitivity of 82.1% and positive predictive value of 72.7% and negative predictive value of 81.1%, which were significantly higher than those of TAUS, respectively. All the patients with XGC had cholecystectomy. Conclusions CEUS is a more effective approach for GBC with a promising diagnostic value than TAUS.

Choledochal cysts (CCs) are an important risk factor for cholangiocarcinoma, though their etiology remains debated. Given the vital role of bile fluid in digestive processes within the biliary system, examining such mechanisms from the perspective of bile fluid dynamics may offer additional insights for clinical use. This study utilized magnetic resonance imaging (MRI)-based patient-specific scans for detailed reconstruction and further employed the computational fluid dynamic method to assess the physiological functions of each system, including refilling and emptying processes. The impact of bile rheological property was also examined. Key biomechanical parameters—pressure and wall shear stress (WSS)—were displayed on a two-dimensional plane via surface mapping for enhanced visualization and comparative analysis. Outcomes demonstrated a significant reduction in bile flow velocity in CCs patients due to common bile duct's anatomical features and bile's shear-thinning, non-Newtonian nature, with a notable increase in pressure drop observed. In healthy biliary systems, WSS variations were minimal; however, in CCs patients, extreme WSS differences were found, with the highest WSS in the segmental bile duct and the lowest in the dilatation area, presenting a magnitude difference of approximately 1000. CCs one showed WSS levels 100–250 times higher than healthy ones in the common bile duct. Bile rheological properties substantially affect pressure and WSS patterns, particularly WSS, where pathological bile caused a tenfold increase in WSS compared to healthy bile. The findings aimed to enhance the understanding of biliary fluid mechanics in CCs and offer insights into selected fluidic variables for future microfluidic chip experiments. [ABSTRACT FROM AUTHOR]

The rapid development of miniaturized, high-frequency, and highly integrated microelectronic devices has brought about critical issues in electromagnetic compatibility and thermal management. In recent years, there has been significant interest in lightweight polymer-based composites that offer both electromagnetic interference (EMI) shielding and thermal conductivity. One promising approach involves constructing three-dimensional (3D) interconnection networks using functional fillers in the polymer matrix. These networks have been proven effective in enhancing the thermal and electrical conductivity of the composites. This mini-review focuses on the preparation and properties of 3D network-reinforced polymer composites, specifically those incorporating metal, carbon, ceramic, and hybrid networks. By comparing the effects of different filler types and distribution on the composite materials, the advantages of 3D interconnected conductive networks in polymer composites are highlighted. Additionally, this review addresses the challenges faced in the field of multifunctional thermal management and electromagnetic protection materials and provides insights into future development trends and application prospects of 3D structured composites. [ABSTRACT FROM AUTHOR]