Mechanisms of Ferroptosis-Related Genes in Gallbladder Cancer Based on Bioinformatics Analysis.

Gallbladder Cancer (GBC) is a lethal malignancy with limited treatment options and poor prognosis. Recent studies have emphasized the role of ferroptosis, a regulated form of cell death, in various cancers, including GBC. We applied bioinformatics methodologies on four GBC datasets to identify differentially expressed genes (DEGs). An intersection of DEGs from the four datasets with ferroptosis and GBC-associated genes was done to identify key ferroptosis-related genes in GBC. GSVA pathway enrichment analysis and immune cell infiltration assessment were conducted to explore their functional roles and interactions. Seven ferroptosis-related genes, EZH2, MUC1, PVT1, GOT1, CDO1, LIFR, and TFAP2A, were identified to be related to GBC. These genes were associated with vital signaling pathways like the G2/M checkpoint and DNA repair and showed significant correlations with immune cell infiltration in GBC. Receiver Operating Characteristic (ROC) curve analysis revealed their high diagnostic potential, with Area Under the Curve (AUC) values ranging from 0.796 to 0.953. Our findings underscore the pivotal role of ferroptosis in GBC and the potential of ferroptosis-related genes as diagnostic biomarkers. This study lays a foundation for further research into ferroptosis-based therapeutic strategies for GBC.

Ginsenoside Rh4 inhibits the malignant progression of multiple myeloma and induces ferroptosis by regulating SIRT2.

Multiple myeloma (MM) has a high mortality rate, and the exploration of therapeutic drugs for MM with low side effects is a hot topic at the moment. Ginsenoside Rh4 has been shown to inhibit tumour growth in many cancers. However, the role of ginsenoside Rh4 in MM and its reaction mechanism have not been reported so far. After the treatment with different concentrations of ginsenoside Rh4, the proliferation of NCI-H929 cells was detected by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining. The cell apoptosis and cycle arrest were detected by flow cytometry and western blot. The thiobarbituric acid-reactive substances (TBARS) production was assessed with TBARS assay, whereas Fe2+ fluorescence assay was used for the measurement of Fe2+ level. The production of reactive oxygen species was evaluated with dichloro-dihydro-fluorescein diacetate staining, and western blot was applied for the estimation of ferroptosis-related proteins. The potential targets of ginsenoside Rh4 were predicted by molecular docking technology and verified by western blot. The transfection efficacy of overexpression-SIRT2 was examined with quantitative reverse transcription polymerase chain reaction and western blot. To figure out the detailed reaction mechanism between ginsenoside Rh4 and SIRT2 in MM, rescue experiments were conducted. We found that ginsenoside Rh4 inhibited cell proliferation, induced cell apoptosis, promoted cycle arrest and facilitated ferroptosis in MM. Moreover, ginsenoside Rh4 inhibited SIRT2 expression in MM cells. The overexpression of SIRT2 reversed the effects of ginsenoside Rh4 on cell proliferation, cell apoptosis, cycle arrest and ferroptosis in MM. Overall, ginsenoside Rh4 inhibited the malignant progression of MM and induced ferroptosis by regulating SIRT2.

[Value of early enteral nutrition in patients with severe heart failure undergoing mechanical ventilation].

OBJECTIVE: To observe the effect of early enteral nutrition (EEN) on nutritional indicators and clinical outcomes in patients with severe heart failure undergoing mechanical ventilation. METHODS: Thirty-four patients with severe heart failure (grade III-IV of cardiac function) and pulmonary infections undergoing mechanical ventilation admitted to intensive care unit (ICU) of Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from May 2017 to April 2018 were enrolled. They were randomly divided into EEN group and delayed enteral nutrition (DEN) group. Both groups were given routine treatment, including mechanical ventilation, improvement of cardiac function, anti-infection, protection of vital organ function, regulation of blood sugar and adjustment of electrolyte and acid-base balance. The patients in EEN group received enteral nutrition (EN) within 48 hours after ICU admission, and in DEN group, EN was started after the patients had spent the early stage of stress and had stable vital signs (48 hours after ICU admission). The changes in serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), nutritional indicators and liver function indicators at ICU admission and 7 days after treatment were compared between the two groups. The time needed for patients to reach EN target, duration of mechanical ventilation, length of ICU stay, and the 28-day mortality were recorded, and complications were observed. RESULTS: There was no significant difference in serum BNP, CRP, nutritional indicators or liver function indicators at ICU admission between the two groups. After treatment for 7 days, BNP and CRP in both groups were decreased significantly as compared with those at ICU admission [BNP (ng/L): 592.1±370.9 vs. 2 517.7±1 163.4 in EEN group, 621.9±418.8 vs. 2 251.5±1 006.8 in DEN group; CRP (mg/L): 46.0±19.6 vs. 59.8±22.5 in EEN group, 40.5±18.8 vs. 61.2±24.6 in DEN group, all P < 0.05], pre-albumin (PA) and transferrin (TF) were significantly increased [PA (g/L): 0.18±0.05 vs. 0.15±0.06 in EEN group, 0.17±0.04 vs. 0.12±0.06 in DEN group; TF (g/L): 1.6±0.4 vs. 1.5±0.4 in EEN group, 1.7±0.5 vs. 1.4±0.5 in DEN group, all P < 0.05]. However, there was no significant difference in the above indicators after treatment between the two groups (all P > 0.05). There was no significant change in liver function after treatment in both groups. The EN treatment was successfully completed in both groups. Some patients developed abdominal distension and diarrhea in varying degrees, which were alleviated by slowing down the infusion rate, supplemented by gastrointestinal motility drugs and intestinal flora adjustment drugs. The time needed to reach EN target in EEN group was significantly earlier than that in DEN group (hours: 42.4±10.2 vs. 53.8±17.1, P < 0.05), the duration of mechanical ventilation (days: 14.2±8.7 vs. 13.4±7.9), the length of ICU stay (days: 17.8±6.7 vs. 18.3±5.6) and 28-day mortality [5.9% (1/17) vs. 11.8% (2/17)] showed no significant difference as compared with those in DEN group (all P > 0.05), and it did not increase the incidence of aspiration pneumonia [23.5% (4/17) vs. 17.7% (3/17), P > 0.05]. CONCLUSIONS: EEN could help to achieve nutritional goals as soon as possible, improve the nutritional status of the body, and provide conditions and basis for further treatment of severe heart failure patients.

Pain Management during Rehabilitation after Distal Radius Fracture Stabilized with Volar Locking Plate: A Prospective Cohort Study.

INTRODUCTION: Internal fixation with volar locking plate (VLP) was widely adopted as a first-line choice in treatment of distal radius fracture (DRF). METHODS: Total 315 patients with distal radius fracture receiving VLP fixation were included for analysis in this study. The rehabilitation protocol was started immediately after surgery for all patients. During the initial two weeks after surgery, 149 patients received 200 mg celecoxib twice per day, 89 received buprenorphine transdermal patch at 5 µg/h, and 77 received 13 mg codeine plus 200 mg ibuprofen twice per day for pain management. Visual analog scale (VAS) scores of pain at rest, daily activity, and rehabilitative exercise were measured, respectively, every week according to the experiences of the past week in the initial six weeks after surgery. Functional outcomes including range of motion (ROM) for extension, flexion, pronation, supination, ulnar and radial abduction, the disabilities of arm, shoulder, and hand (DASH) score and the validated patient rated wrist evaluation (PRWE), and grip strength were collected at one, three, and six months after surgery. RESULTS: We showed that patients receiving transdermal buprenorphine and codeine/ibuprofen had decreased VAS scores during rehabilitative exercise, better compliance to the rehabilitation program, and thus faster functional recovery. CONCLUSIONS: We recommend transdermal buprenorphine or codeine/ibuprofen for pain management during rehabilitation after distal radius fracture stabilized with VLP.