Fosaprepitant for postoperative nausea and vomiting in patients undergoing laparoscopic gastrointestinal surgery: a randomised trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3 receptor antagonist, the incidence is still high in many at-risk patients. Fosaprepitant, a neurokinin-1 receptor antagonist, is an effective antiemetic, but its efficacy and safety in combination antiemetic therapy for preventing PONV remain unclear. METHODS: In this randomised, controlled, double-blind trial, 1154 participants at high risk of PONV and undergoing laparoscopic gastrointestinal surgery were randomly assigned to either a fosaprepitant group (n=577) receiving fosaprepitant 150 mg i.v. dissolved in 0.9% saline 150 ml, or a placebo group (n=577) receiving 0.9% saline 150 ml before anaesthesia induction. Dexamethasone 5 mg i.v. and palonosetron 0.075 i.v. mg were each administered in both groups. The primary outcome was the incidence of PONV (defined as nausea, retching, or vomiting) during the first 24 postoperative hours. RESULTS: The incidence of PONV during the first 24 postoperative hours was lower in the fosaprepitant group (32.4% vs 48.7%; adjusted risk difference -16.9% [95% confidence interval: -22.4 to -11.4%]; adjusted risk ratio 0.65 [95% CI: 0.57 to 0.76]; P<0.001). There were no differences in severe adverse events between groups, but the incidence of intraoperative hypotension was higher (38.0% vs 31.7%, P=0.026) and intraoperative hypertension (40.6% vs 49.2%, P=0.003) was lower in the fosaprepitant group. CONCLUSIONS: Fosaprepitant added to dexamethasone and palonosetron reduced the incidence of PONV in patients at high risk of PONV undergoing laparoscopic gastrointestinal surgery. Notably, it increased the incidence of intraoperative hypotension. CLINICAL TRIAL REGISTRATION: NCT04853147.

A machine learning-based prediction model for delayed clinically important postoperative nausea and vomiting in high-risk patients undergoing laparoscopic gastrointestinal surgery.

BACKGROUND: Delayed clinically important postoperative nausea and vomiting (CIPONV) could lead to significant consequences following surgery. We aimed to develop a prediction model for it using machine learning algorithms utilizing perioperative data from patients undergoing laparoscopic gastrointestinal surgery. METHODS: All 1154 patients in the FDP-PONV trial were enrolled. The optimal features for model development were selected by least absolute shrinkage and selection operator and stepwise regression from 81 perioperative variables. The machine learning algorithm with the best area under the receiver operating characteristic curve (ROCAUC) was determined and assessed. The interpretation of the prediction model was performed by the SHapley Additive Explanations library. RESULTS: Six important predictors were identified. The random forest model showed the best performance in predicting delayed CIPONV, achieving an ROCAUC of 0.737 in the validation cohort. CONCLUSION: This study developed an interpretable model predicting personalized risk for delayed CIPONV, aiding high-risk patient identification and prevention strategies.

MRPL21 promotes HCC proliferation through TP53 mutation-induced apoptotic resistance.

BACKGROUND AND AIMS: The specific mechanisms underlying the inhibition of hepatocellular carcinoma (HCC) proliferation and metastasis by mitochondrial apoptosis are not yet fully understood. However, it plays a vital role in suppressing HCC's ability to proliferate and spread. The involvement of MRPL21, a member within the family of mitochondrial ribosomal proteins (MRPs), is well-documented in both cellular apoptosis and energy metabolism. This study aims to explore and unravel the underlying mechanisms through which MRPL21 contributes to mitochondrial apoptosis and resistance against apoptosis in HCC. METHODS: To evaluate the level of MRPL21 expression at the gene and protein expression levels, analysis was performed on human liver samples and blood using techniques for quantification. A knockdown plasmid targeting MRPL21 was constructed to investigate its impact on the growth and apoptosis of hepatocellular carcinoma (HCC). To evaluate the impact of MRPL21 knockdown on hepatocellular carcinoma (HCC) cell proliferation and apoptosis, various assays were performed including CCK-8 assays, flow cytometry analysis, detection of reactive oxygen species (ROS), and assessment of mitochondrial membrane potential (MMP). Furthermore, the role of MRPL21 in TP53 mutation was examined using Nutlin-3. RESULTS: In HCC tissues and blood samples, an upregulation of MRPL21 expression was observed when compared to samples obtained from healthy individuals, and it is correlated with a poor prognosis for HCC. Silencing MRPL21 can effectively suppress Hep3B and HCCLM3 cells proliferation by modulating the mitochondrial membrane potential, it triggers the generation of reactive oxygen species (ROS), thereby leading to G0/G1 cell cycle arrest and initiation of early apoptosis. Furthermore, by inhibiting P53 activity, Nutlin-3 treatment can enhance MRPL21-deficiency-mediated apoptosis in Hep3B and HCCLM3 cells. CONCLUSION: Through its influence on TP53 mutation, MRPL21 promotes HCC proliferation and progression while conferring resistance to apoptosis. These findings suggest that MRPL21 holds promise as a valuable biomarker for the treatment of HCC.

IFRD1 promotes tumor cells "low-cost" survival under glutamine starvation via inhibiting histone H1.0 nucleophagy.

Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.

The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity.

In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.

Magnetic Resonance Imaging (MRI) Differential Diagnosis of Meningiomas Using ANOVA.

This work explored the diagnostic value of different subtypes of meningiomas under T2WI low signal based on analysis of variance (ANOVA), and the expression differences of Ki67, VEGF, and P73 in different subtypes were analyzed. 67 patients with meningioma confirmed surgically and pathologically in hospital were selected as the research subjects, whose pathological classification occurs with obvious low signal on T2WI. First, the age distribution of the subjects and the distribution of different subtypes were counted. Then, ANOVA was adopted to analyze the MRI imaging signs of patients with different subtypes of meningioma. Finally, the differences of Ki67, VEGF, and P73 proteins and mRNA expression levels in different subtypes were detected via immunohistochemical assay and qPCR. The results showed that the proportion of patients with transitional meningioma was the most, which was 43.28%, while the proportion of patients with meningeal melanoma was the least, which was 7.46%. In patients with transitional meningioma, the MRI images showed mixed signals in different layers. Fibrous MRI images showed hyalinosis and calcification of collagen fibers in the tumor, with low T2WI signal. Sand-shape MRI images showed double low signals. MRI images of meningeal melanoma showed high signal on T1-weighted Imaging (T1WI) and low signal on T2WI. The protein expression and mRNA levels of Ki67 and P73 in transitional meningioma were evidently higher in contrast to those in fibrous meningioma (P < 0.05). The expression level of VEGF protein and mRNA in meningeal melanoma were notably higher in contrast to those in fibro meningioma (P < 0.05). It was revealed that the MRI images of the four subtypes of meningiomas under ANOVA-based T2WI low signal were quite different, and the expressions of Ki67, P73, and VEGF in different subtypes had significant differences. This work provided a reference basis for the preoperative diagnosis, treatment, and prognosis of meningiomas.

Controlled synthesis of manganese oxohydroxide (MnOOH) and Mn3O4 nanorods using novel reverse micelles.

Novel reverse micelles of high CTAB concentration were successfully developed to synthesize MnOOH (manganese oxyhydroxide) nanorods with uniform diameters of about 10 nm and up to 200 nm in length under mild solution conditions and Mn3O4 nanorods with the same morphology could be obtained by calcining the precursors at 450 degrees C. The morphology and microstructure of the nanorods were investigated by transmission electron microscopy (TEM and HRTEM), XRD and TGA. The results showed that the concentration of CTAB was a key factor for the formation of MnOOH nanorods and only above 0.2 M the nanorods could be obtained. Moreover, the length of nanorods increased with the increase of CTAB concentration, while the diameter of nanorods retained steadily. In this way, the length of nanorods could be easily controlled from tens nanometers to hundreds nanometers by increasing the CTAB concentration from 0.35 M to 1.25 M. In addition, in our experiment the products were almost entirely rod-like shape, which indicated this method should be suitable for mass-producing.

Structural properties and Raman spectroscopy of lipid Langmuir monolayers at the air-water interface.

Spectra of octadecylamine (ODA) Langmuir monolayers and egg phosphatidylcholine (PC)/ODA-mixed monolayers at the air-water interface have been acquired. The organization of the monolayers has been characterized by surface pressure-area isotherms. Application of polarized optical microscopy provides further insight in the domain structures and interactions of the film components. Surface-enhanced Raman scattering (SERS) data indicate that enhancement in Raman spectra can be obtained by strong interaction between headgroups of the surfactants and silver particles in subphase. By mixing ODA with phospholipid molecules and spreading the mixture at the air-water interface, we acquired vibrational information of phospholipid molecules with surfactant-aided SERS effect.

[The structure and properties of self-assembly complex LB films of silver nanoparticles].

The structure and properties of Ag self-assembly films have attracted much attention in the past decade, which are to a large extent influenced by the structure and properties of the nanoparticles. In the present work, the single-layer and multi-layer complex films of silver nanoparticles and their absorbates were fabricated by using self-assembly technique. The interaction of silver nanoparticle and its absorbate was studied using absorption spectroscopy and surface enhanced Raman scattering spectroscopy.The Raman enhanced properties of silver nanoparticles, and the structure and properties of the complex films were also investigated. The experimental results indicate that the interaction of octodecyl amic (OA) and silver nanoparticle takes place via the NH2 substitute and the active site on Ag, and there might exist photocatalysis under the laser excitation. In addition, the product from otcodecyl amic and stearic acid(SA) has a weak interaction with silver nanoparticle, which mainly takes place as spatial encumbrance in the self-assembly complex film.

[Influence of different sol-gel system on the luminescence of nanocrystalline ZnO powder].

ZnO nanopowders were prepared by the sol-gel techniques with two kinds of solvent. Microstructure of powder samples was examined by XRD and TEM. The results indicate that the two ZnO samples have the same crystal and energy band structure. Their photoluminescence (PL) spectra in ultraviolet region are analogous, but their photoluminescence (PL) spectra in visible region are different. The reason is that the two kinds of solvent with different polarity result in the difference in configuration and distribution of the sample surface states in the two systems.

[Influence of different sol-gel systems on the luminescence of nanocrystalline ZnO powders].

ZnO nanopowders were prepared by the sol-gel techniques with two kinds of solvent. Microstructure of the powdersamples was examined by XRD and TEM. The results indicate that two ZnO samples have the same crystal and energy band structure. Their photolurminescence (PL) spectra in the ultraviolet region are analogous, but their photoluminescence (PL) spectra in the visible region are different. The reason is that two kinds of solvent with different polarity result in the difference in configuration and distribution of the sample surface states in the two systems.

[Preparation and luminescence of CeOx/ZnO nanocomposite powders].

CeOx/ZnO nanocomposite powders were prepared by sol-gel process. The powder samples were examined by XRD, TEM, XPS and photoluminescence (PL). PL enhancement of nanocomposite powder at 502 nm compared to pure ZnO was observed when Ce3+ were present in samples. New peak at 603 nm was observed when Ce4+ were present. PL enhancement of nanocomposite powder was correlated with more oxygen vacancies which were caused by Ce3+. The new peak at 603 nm is attributed to new energy transition in the interface of CeO2/ZnO.

[Study on the preparation of nanometer oxide SnO2 gas-sensitive material by sol-gel method].

Based on the sol-gel method, nanosized SnO2 material was prepared, and its structure and properties were studied by XRD, UV and Raman spectra. The XRD result indicated that the SnO2 particles had an ideal nanosize. The diameter of SnO2 particles increased with raising the temperature. The Raman spectrum indicated that the SnO2 nanometer material annealed at low temperature had a large number of O-empties. The UV spectra showed that the sample had stable absorption properties although the particle size changed greatly in the annealed range of 300-500 degrees C. These properties might be utilized in enhancing the performance of SnO2 gas-sensitive devices.