Erector spinae plane block versus paravertebral block on postoperative quality of recovery in obese patients undergoing laparoscopic sleeve gastrectomy: a randomized controlled trial.

Purpose: To compare the impact of erector spinae plane block (ESPB) and paravertebral block (PVB) on the quality of postoperative recovery (QoR) of patients following laparoscopic sleeve gastrectomy (LSG). Methods: A total of 110 patients who underwent elective LSG under general anesthesia were randomly assigned to receive either ultrasound-guided bilateral ESPB or PVB at T8 levels. Before anesthesia induction, 40 mL of 0.33% ropivacaine was administered. The primary outcome was the QoR-15 score at 24 hours postoperatively. Results: At 24 hours postoperatively, the QoR-15 score was comparable between the ESPB and PVB groups (131 (112-140) vs. 124 (111-142.5), P = 0.525). Consistently, there was no significant difference in QoR-15 scores at 48 hours postoperatively, numerical rating scale (NRS) pain scores at any postoperative time points, time to first ambulation, time to first anal exhaust, postoperative cumulative oxycodone consumption, and incidence of postoperative nausea and vomiting (PONV) between the two groups (all P > 0.05). No nerve block-related complications were observed in either group. Conclusion: In patients undergoing LSG, preoperative bilateral ultrasound-guided ESPB yields comparable postoperative recovery to preoperative bilateral ultrasound-guided PVB.

Effectiveness of a narrative nursing intervention on reproductive concerns in women of childbearing age undergoing cervical cancer surgery: A randomized controlled trial.

OBJECTIVE: This study aims to explore the intervention effects of narrative nursing on the reproductive concerns of cervical cancer patients of childbearing age undergoing surgical treatment. METHODS: Patients undergoing cervical cancer surgery with moderate to severe levels of reproductive concerns, treated between January and December 2023 at a tertiary Grade-A oncology hospital in China, were selected as the research subjects. Patients were randomized into an intervention group and a control group, each consisting of 33 patients. The control group received standard nursing care, while the intervention group received a narrative nursing intervention in addition to standard care. The changes in the levels of reproductive concerns, post-traumatic growth, and quality of life scores before and after the intervention were compared between the two groups. RESULTS: After the intervention, the reproductive concerns scores of the cervical cancer patients in the intervention group (32.53 ± 4.77) were significantly lower than those in the control group (59.29 ± 3.24), with a statistically significant difference (t = 26.143, p < 0.001). The post-traumatic growth scores in the intervention group (86.78 ± 3.52) were significantly higher than those in the control group (68.06 ± 6.24), with a statistically significant difference (t = -14.595, p < 0.001). The quality of life scores in the intervention group (149.00 [IQR = 8.75]) were significantly higher than those in the control group (129.00 [IQR = 13.00]), with a statistically significant difference (z = -5.799, p < 0.001). CONCLUSION: Narrative nursing can effectively alleviate reproductive concerns in cervical cancer patients undergoing surgical treatment, promote positive psychological changes post-trauma, and improve patients' quality of life.

Overexpressing of the GIPC1 protects against pathological cardiac remodelling.

OBJECTIVE: Pathological cardiac remodelling, including cardiac hypertrophy and fibrosis, is a key pathological process in the development of heart failure. However, effective therapeutic approaches are limited. The ß-adrenergic receptors are pivotal signalling molecules in regulating cardiac function. G-alpha interacting protein (GAIP)-interacting protein, C-terminus 1 (GIPC1) is a multifunctional scaffold protein that directly binds to the C-terminus of ß1-adrenergic receptor (ß1-adrenergic receptor). However, little is known about its roles in heart function. Therefore, we investigated the role of GIPC1 in cardiac remodelling and its underlying molecular mechanisms. METHODS: Pathological cardiac remodelling in mice was established via intraperitoneal injection of isoprenaline for 14 d or transverse aortic constriction surgery for 8 weeks. Myh6-driving cardiomyocyte-specific GIPC1 conditional knockout (GIPC1 cKO) mice and adeno-associated virus 9 (AAV9)-mediated GIPC1 overexpression mice were used. The effect of GIPC1 on cardiac remodelling was assessed using echocardiographic, histological, and biochemical analyses. RESULTS: GIPC1 expression was consistently reduced in the cardiac remodelling model. GIPC1 cKO mice exhibited spontaneous abnormalities, including cardiac hypertrophy, fibrosis, and systolic dysfunction. In contrast, AAV9-mediated GIPC1 overexpression in the heart attenuated isoproterenol-induced pathological cardiac remodelling in mice. Mechanistically, GIPC1 interacted with the ß1-adrenergic receptor and stabilised its expression by preventing its ubiquitination and degradation, maintaining the balance of ß1-adrenergic receptor/ß2-adrenergic receptor, and inhibiting hyperactivation of the mitogen-activated protein kinase signalling pathway. CONCLUSIONS: These results suggested that GIPC1 plays a cardioprotective role and is a promising therapeutic target for the treatment of cardiac remodelling and heart failure.

Sodium Butyrate Ameliorates Deoxynivalenol-Induced Oxidative Stress and Inflammation in the Porcine Liver via NR4A2-Mediated Histone Acetylation.

Mycotoxin-induced liver injury is often accompanied by oxidative stress (OS) and inflammation. This research aimed to explore the potential mechanism of sodium butyrate (NaBu) in modulating hepatic anti-oxidation and anti-inflammation pathways in deoxynivalenol (DON)-exposed piglets. The results show that DON induced liver injury, increased mononuclear cell infiltration, and decreased serum total protein and albumin concentrations. Transcriptomic analysis revealed that reactive oxygen species (ROS) and TNF-α pathways were highly activated upon DON exposure. This is associated with disturbed antioxidant enzymes and increased inflammatory cytokines secretion. Importantly, NaBu effectively reversed the alterations caused by DON. Mechanistically, the ChIP-seq result revealed that NaBu strongly depressed DON-increased enrichment of histone mark H3K27ac at the genes involved in ROS and TNF-α-mediated pathways. Notably, we demonstrated that nuclear receptor NR4A2 was activated by DON and remarkably recovered with the treatment of NaBu. In addition, the enhanced NR4A2 transcriptional binding enrichments at the promoter regions of OS and inflammatory genes were hindered by NaBu in DON-exposed livers. Consistently, elevated H3K9ac and H3K27ac occupancies were also observed at the NR4A2 binding regions. Taken together, our results indicated that a natural antimycotic additive, NaBu, could mitigate hepatic OS and inflammatory responses, possibly via NR4A2-mediated histone acetylation.

LncRNA PVT1 influences breast cancer cells glycolysis through sponging miR-145-5p.

BACKGROUND: Long-non-coding RNA PVT1 (lncRNA PVT1) can be used as an oncogenic regulatory non-coding RNA (ncRNA) for many cancers. However, its function and mechanism in breast cancer (BRCA) are still not clearly elucidated. OBJECTIVE: We attempt to explain the mechanism of PVT1's role in breast cancer from different perspectives. METHODS: We analyzed the expression of PVT1 and its correlation with the breast cancer related clinical data in the The Cancer Genome Atlas (TCGA) database. We used PVT1 overexpression and knockdown lentivirus to infect breast cancer MDA-MB-231 cell line for cell function verification, in vitro using CCK-8 to measure proliferation, flow cytometry to measure apoptosis, transwell test to measure invasion and migration ability, detecting cell extracellular acidification rate (ECAR) to assess glycolysis metabolism and explore the biological functions of PVT1 in breast cancer cells. Transcriptome sequencing was used to analyze the changes of related genes in cells after overexpression of PVT1. In vivo we used a xenograft model to study the effect of PVT1 on breast cancer. RESULTS: PVT1 was up-regulated in breast cancer tissues and was positively correlated with the clinical stage of breast cancer patients. Overexpression of PVT1 in vitro promoted cell proliferation, migration and invasion, and promoted tumor growth in vivo. Knockdown of PVT1 led to the opposite biological consequence. Further bioinformatics analysis showed that PVT1 changes the glycolysis metabolism of tumors through regulation of glycolysis-related genes. In addition, the expression of miR-145-5p is negatively correlated with PVT1. We consider the possibility of PVT1 promoting cell proliferation and metastasis by regulating the aerobic glucose metabolism in breast cancer cells through sponging the miR-145-5p. CONCLUSION: Our results reveal a potential pathway for competing endogenous RNA to regulate breast cancer glucose metabolism. PVT1 regulates glycolysis related genes expression by competitively binding to endogenous miR-145-5p in breast cancer cells to change the metabolic phenotype. This may Provide new ideas for precise molecular therapy targets for breast cancer.

Construction and validation of the perioral moisture-related skin damage (PMASD) risk prediction model in patients with colorectal cancer.

This study aims to analyse the risk factors of Peristomal Moisture-Associated Skin Damage (PMASD) in colorectal cancer patients, construct a prediction model, and verify its effect. A total of 375 patients who underwent rectal cancer stoma surgery at the Liaoning Cancer Hospital between January and December 2020 were selected according to the inclusion and exclusion criteria. The clinical data were retrospectively analysed for modelling and internal validation (modelling group). According to the same criteria, the clinical data of 242 patients from January and June 2021 were retrospectively analysed for external validation (validation group). Baseline patient data were recorded. Patients in the modelling group were divided into those with and without PMASD based on the occurrence of PMASD during hospitalisation. Logistic regression analysis was used to examine the factors of PMASD and the PMASD nomogram model of colorectal cancer. Internal model validation was performed with the Bootstrap method, using the ROC and H-L goodness of fit test to evaluate the differentiation and calibration of the model. Last, external validation of the model was performed. In the modelling group, 212 patients with colorectal cancer developed PMASD. According to the results of the logistic regression analysis, high fasting plasma glucose and fasting blood glucose (FPG), a history of radiotherapy, the height of the stoma opening (i.e., flat or lower than the skin surface), and skin folds around the stoma are risk factors for PMASD (OR > 1, P < 0.05). The stool shaping and colostomy are protective factors for PMASD in patients with colorectal cancer (OR < 1, P < 0.05). To establish the prediction of colorectal cancer, patient development of PMASD line, graph model, and internal verification was carried out using the Bootstrap method: H-L test P = 0.846, area under curve, area under the ROC curve (0 > 0.75, 95% CI: 0.778-0, AUC = 0.820). The external validation included the H-L test (P = 0.137, AUC [0.862] > 0.75, 95% CI: 0.815-0.909), with the maximum value of the Youden index as the best cut-off value for the model. The ROC curve had a Youden index of 0.559, a sensitivity of 0.877, and a specificity of 0.657. The prompt model area showed good calibration and discrimination. The PMASD in patients with colorectal cancer is affected by defecation traits, the stoma opening height, stoma type, FPG, skin folds around the stoma, and previous radiotherapy history. The nomogram model can provide an effective means to reasonably predict the risk of PMASD in patients with colorectal cancer.

Expression of FOXA1 Is Associated with the Tumor-Infiltrating M2 Macrophage, Cytotoxic T Lymphocyte, and Effect of Chemotherapy in Bladder Cancer.

PURPOSE: Cisplatin-containing combination chemotherapy has been the standard of care since the late 1980s, but the response rate is <50%. Studies have shown that the efficiency of chemotherapy differs among molecular subtypes of bladder cancer. In this study, we aimed to correlate FOXA1, a marker for differentiation of the basal and luminal subtypes, with tumor immune cell infiltration and the effect of chemotherapy in bladder cancer. MATERIALS AND METHODS: Eighty-three patients with bladder cancer treated with chemotherapy were reviewed. Clinicopathological variables for each case were recorded. FOXA1, M2 tumor-associated macrophage (TAM), dendritic cell (DC), and cytotoxic T lymphocyte (CTL) were examined by immunohistochemistry. The relationship between FOXA1, immune cell infiltration, and clinical response to chemotherapy was assessed. RESULTS: The overall objective response rate was 34%. The objective response rate for tumors with lower FOXA1 expression was 58% and for tumors with higher FOXA1 expression was 12%. Tumors with infiltrated M2 TAM proportion <3% had a higher objective response rate compared with infiltrated M2 TAM proportion >3% tumors (46% vs. 21%, p = 0.02). Tumors with infiltrated CTL proportion >5% had a higher objective response rate compared with infiltrated CTL proportion <5% tumors (50% vs. 17%, p = 0.002). DCs showed no significant differences. We found that the objective response rate for tumors with lower FOXA1 expression, proportion <3% M2 TAM infiltration, and proportion >5% CTL infiltration is 82%. Lower FOXA1 expression was associated with low M2 TAM infiltration and high CTL infiltration. CONCLUSIONS: Thus, we showed that in patients with bladder cancer who received chemotherapy, the higher clinical response rate is associated with low FOXA1 expression, low M2 TAM infiltration, and high CTL infiltration.

Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells.

The serum level of cholesterol and its biosynthetic intermediates are critical indicators to access metabolism-related disorders in humans and animals. However, the molecular actions of these intermediates on gene functions and regulation remained elusive. Here, we show that desmosterol (DES) is the most abundant intermediate involved in cholesterol biosynthesis and is highly enriched in red/brown algae. It exerts a pivotal role in modulating core genes involved in oxidative stress and inflammatory response processes in the ileum epithelial cells (IPI-2I). We observed that the DES extracted from red algae did not affect IPI-2I cell growth or survival. A transcriptomic measurement revealed that the genes enrolled in the oxidative process and cholesterol homeostasis pathway were significantly down-regulated by DES treatment. Consistent with this notion, cellular reactive oxygen species (ROS) levels were markedly decreased in response to DES treatment. In contrast, key inflammatory genes including IL-6, TNF-α, and IFN-γ were remarkably upregulated in the RNA-seq analysis, as further confirmed by qRT-PCR. Given that DES is a specific agonist of nuclear receptor RORγ, we also found that DES caused the elevated expression of RORγ at mRNA and protein levels, suggesting it is a potential mediator under DES administration. Together, these results underscore the vital physiological actions of DES in inflammatory and oxidative processes possibly via RORγ, and may be helpful in anti-oxidation treatment and immunotherapy in the future.

Ranolazine protects against diabetic cardiomyopathy by activating the NOTCH1/NRG1 pathway.

AIMS: Diabetic cardiomyopathy (DCM) is a common diabetes complication that can cause arrhythmia, heart failure, and even sudden death. Ranolazine is an antianginal agent used to treat chronic stable angina and has been demonstrated as an effective treatment for many cardiovascular diseases. However, the mechanism by which ranolazine alleviates DCM is unclear, motivating this study investigating the effects of ranolazine in DCM. MATERIALS AND METHODS: DCM rats were treated with one of three doses of ranolazine (10, 30, and 90 mg/kg/day) for 12 weeks. B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), Notch homolog 1 (NOTCH1), and Neuregulin 1 (NRG1) expression was assayed using western blot and qRT-PCR. Cardiac changes were assayed using echocardiography, CT, HE staining, and Masson's trichrome staining. TUNEL staining and flow cytometry were used to detect cell apoptosis. NOTCH1 inhibitor (DAPT) was used to explore the mechanism of ranolazine. KEY FINDINGS: Compared with the DCM group, the ranolazine groups had no obvious weight loss and significantly decreased blood glucose levels. Ranolazine prevented diabetes-caused cardiac injury. Ranolazine also decreased the number of apoptotic cells and altered the expression of apoptosis-related mRNAs and proteins. Ranolazine-induced NOTCH1 activated NRG1 and inhibited the downstream apoptosis-related pathway, while DAPT partially inhibited ranolazine-induced NOTCH1 and NRG1 expression. SIGNIFICANCE: To our knowledge, this study is the first to demonstrate that ranolazine protects against DCM-induced apoptosis by activating the NOTCH1/NRG1 signaling pathway. Moreover, our study identified new mechanisms involved in DCM.

Transcriptome and chromatin accessibility in porcine intestinal epithelial cells upon Zearalenone exposure.

Zearalenone (ZEA) is one of the main mycotoxins widely spread in contaminated cereal crops, which poses a great threat to food safety as well as human and animal health. Biological control strategies are emerging as important solutions to eliminate mycotoxin contaminations. However, molecular mechanisms underlying ZEA cytotoxic effects are only partly understood. Noncoding RNAs and chromatin accessibilities are important regulators of gene expression and implicate in a variety of biological processes. Here, we established a study model of porcine intestinal epithelial cells upon ZEA exposure and presented a RNA-seq dataset for mRNA, microRNA, and lncRNA profiling in 18 experimental samples. In addition, chromatin accessibilities of four samples were also explored by ATAC-seq. This dataset will shed new light on gene expression profiling and transcriptional regulation of animal cells in the response to ZEA exposure, which further contributes to detecting biomarkers and drug targets for predicting and controlling ZEA contamination.

Both FOXO3a and FOXO1 are involved in the HGF-protective pathway against apoptosis in endothelial cells.

Hepatocyte growth factor (HGF) was identified as an endogenous tissue protective agent against apoptosis in many cell types. The mechanism by which HGF protects primary endothelial cells (ECs) has not yet been completely elucidated. FOXO1 and FOXO3a, two members of the FOXO family, are the most abundant FOXO isoforms in mature endothelial cells. In this study, we aimed to explore whether FOXO1 and FOXO3a play similar roles in HGF-mediated protection against apoptosis in mature endothelial cells. Our result showed that HGF prevented ECs from oxidative-stress induced apoptosis in part by inducing the phosphorylation of FOXO proteins. FOXO1 and FOXO3a are equally important in this process by regulating the expression of Bim, PUMA, FasL, and TRAIL.

[Distribution and enrichment characteristics of organochlorine pesticides in water and halobios from Qingbang Island in Zhoushan, China].

A total of 14 biological samples and 3 water samples were collected from the Qingbang Island. The concentrations of OCPs in the samples were determined by GC-ECD to investigate the distribution, composition, source and potential health risks of these compounds in the study area. The results showed that OCPs were detected in all samples. The detection ratios of OCPs were 100%. Concentrations of HCHs and DDTs ranged from 0.09 ng x g(-1) to 11.51 ng x g(-1) and 0. 02 ng x g(-1) to 56.15 ng x g(-1), respectively. Compared with other regions, the pollution of OCPs in Qingbang Island stayed at a low level. Distribution characteristics of OCPs in halobios from Qingbang Island indicated that changes in the upwelling and fronts were the main factors that affected the distribution of OCPs. Source analysis showed that HCHs and DDTs in halobios were mainly originated from the external. In addition, OCPs residues were far below the National Food Safety Standard. The estimated daily intake of OCPs from the halobios tested was also below the acceptable daily intake(ADI) recommended by FAO/WHO, indicating little health risk in halobios consumption for local residents.

Piperine: bioactivities and structural modifications.

Piperine is a simple alkaloid isolated from the seeds of Piper nigrum. Piperine and its derivatives exhibited a wide range of biological properties such as antitumor activity, antioxidant activity, antiinflammatory activity, antimycobacterial activity, insecticidal activity, etc. Although five excellent reviews have recently been described by Srinivasan in 2007, Mao in 2011, Butt in 2013, and Meghwal in 2013, respectively, their topics were mainly focused on the biological effects. Therefore, in the present review, the progress in the structural modifications on the aliphatic chain and the amide moiety of piperine was reported. Meanwhile, the biological activities and structure-activity relationship of piperine and its derivatives were also described.

Safety and Postoperative Outcomes of Regional versus Global Ischemia for Partial Nephrectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: To analyze current evidence comparing the safety and outcomes of regional and global ischemia for partial nephrectomy (PN). MATERIALS AND METHODS: A systematic search of the PubMed and Web of Science databases was conducted in May 2014 to identify studies comparing the safety and outcomes of regional and global ischemia for PN. A systematic review and meta-analysis was also performed. RESULTS: Six retrospective observational studies were selected for the analysis, including 363 patients who underwent PN (162 regional ischemia and 201 global ischemia cases). Operation times were not statistically different [weighted mean difference (WMD) = 20.35 min, 95% CI: -0.28-40.97, p = 0.05], but estimated blood loss was significantly higher in the regional ischemia group (WMD = 52.04 ml, 95% CI: 14.30-89.78, p = 0.007) than in the global ischemia group. Complication rates [odds ratio (OR) = 1.16; 95% CI: 0.63-2.15, p = 0.63] and blood transfusion rates (OR = 1.85; 95% CI: 0.86-4.01, p = 0.12) of the two groups were not significantly different. The regional ischemia group showed better postoperative renal function (WMD = 4.23 ml/min, 95% CI: 2.61-5.85, p < 0.00001) than the global ischemia group, and all cases in the regional ischemia group showed negative margins. CONCLUSIONS: Regional ischemia is as safe to perform as global ischemia, and the former leads to better postoperative renal functions than the latter. These findings support the application of regional ischemia for PN.

Anti human immunodeficiency virus type 1 (HIV-1) agents 4. Discovery of 5,5'-(p-phenylenebisazo)-8-hydroxyquinoline sulfonates as new HIV-1 inhibitors in vitro.

To search for compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, ten 5,5'-(p-phenylenebisazo)-8-hydroxyquinoline sulfonates (4a-j) were synthesized and preliminarily evaluated as HIV-1 inhibitors in vitro for the first time. Some compounds demonstrated anti-HIV-1 activity, especially 5,5'-(p-phenylenebisazo)-8-hydroxyquinoline p-ethylbenzenesulfonate (4g) and 5,5'-(p-phenylenebisazo)-8-hydroxyquinoline p-chlorobenzenesulfonate (4i) showed the more potent anti-HIV-1 activity with 50% effective concentration (EC(50)) values of 2.59 and 4.01 microg/ml, and therapeutic index (TI) values of 31.77 and 24.51, respectively.

[Anti-apoptotic effects of mesenchymal stem cells on cardiac myocytes: in vitro study with rats].

OBJECTIVE: To investigate the anti-apoptotic effects of mesenchymal stem cells (MSCs) on hypoxia-injured cardiac myocytes. METHODS: MSCs were isolated from the bone marrow of 6 - 8 week-old Sprague-Dawley rats. Cardiac myocytes from neonatal rat were cultured under hypoxia, then the hypoxia-injured cardiac myocytes were divided into 3 groups: cultured alone (control group), co-cultured with the MSCs, or co-cultured in MSC-conditioned media in conditions of anoxia (95% N(2) + 5% CO(2), continuous hypoxia group) or normoxia [hypoxia/reoxygen (H/R) group] for 72 hours. The cell apoptosis was measured by Hoechst staining, and Western blotting was used to test the protein expression of Bcl-2 and Bax in the cardiac myocytes. RESULTS: The apoptotic rate of the cardiac myocytes cultured under hypoxia was 51.6% +/- 2.4%, significantly higher than those of the cardiac myocytes co-cultured with MSCs and MSC-conditioned media respectively (15.1% +/- 5.4% and 24.0% +/- 4.2% respectively, both P < 0.001). The apoptotic rate of the H/R group was 20.9% +/- 2.7%, significant higher than that of the MSC group (11.5% +/- 3.7%, P < 0.05), however, not significantly different from that of the MSC-conditioned media group (20.1% +/- 4.2%, P > 0.05). The protein expression of Bcl-2 was not significantly different among different groups. The Bax protein expression of the MSC group and MSC-conditioned media group were 2.28 +/- 0.46 and 3.01 +/- 0.26 respectively, both significantly lower than that of the control group (7.62 +/- 1.28, both P < 0.05). The decreased expression of Bax in the cardiac myocytes was greatly related to the decreasing of apoptosis. CONCLUSION: Co-cultured MSCs show significant anti-apoptotic effects on cardiac myocytes both in continuous hypoxia and in H/R conditions with the possible mechanism of direct cell to cell interaction and paracrine of cytokines which effect the expression of Bax in the myocytes.