Anti-Tumor Effects and Toxicity Reduction Mechanisms of Prunella vulgaris: A Comprehensive Review.

PURPOSE: To investigate and systematically describe the mechanism of action of Prunella vulgaris (P. vulgaris) against digestive system tumors and related toxicity reduction. METHODS: This study briefly describes the history of medicinal food and the pharmacological effects of P. vulgaris, focusing on the review of the anti-digestive tumor effects of the active ingredients of P. vulgaris and the mechanism of its toxicity reduction. RESULTS: The active ingredients of P. vulgaris may exert anti-tumor effects by inducing the apoptosis of cancer cells, inhibiting angiogenesis, inhibiting the migration and invasion of tumor cells, and inhibiting autophagy. In addition, P. vulgaris active ingredients inhibit the release of inflammatory factors and macrophages and increase the level of indicators of oxidative stress through the modulation of target genes in the pathway to achieve the effect of toxicity reduction. CONCLUSION: The active ingredients in the medicine food homology plant P. vulgaris not only treat digestive system tumors through different mechanisms but also reduce the toxic effects. P. vulgaris is worthy of being explored more deeply.

Use of rocuronium and sugammadex for video-assisted thoracoscopic surgery is associated with reduced duration of chest tube drainage: a propensity score-matched analysis.

BACKGROUND: We investigated the influence of different neuromuscular blocking agents and reversal agents during anaesthesia on early removal of chest tube drainage after video-assisted thoracoscopic surgery (VATS). METHODS: This retrospective single-centre study included patients who underwent VATS after tracheal intubation under general anaesthesia. Patients received either cisatracurium and neostigmine (n=547) or rocuronium and sugammadex (n=151). Quantitative neuromuscular monitoring was used and one chest tube (size 24 Fr) was inserted. To reduce potential bias, 140 patients from each group were matched by propensity score for sex, age, body mass index and indication for VATS. Primary outcome was duration of chest tube drainage after surgery. RESULTS: Use of rocuronium and sugammadex was associated with a shorter duration of chest tube drainage (2 [1-2] vs 2 [1-3] days; P=0.049) and a 63% reduction in delayed chest tube removal (odds ratio 0.37; 95% confidence interval [CI]: 0.20-0.67; P=0.005). This group also had a lower incidence of postoperative atelectasis (P=0.047) and consolidation (P=0.008). Each 1 h increase in the duration of anaesthesia was associated with a 1.57-fold increase in the delayed removal of the chest tube (95% CI: 1.25-1.96; P=0.005). CONCLUSIONS: During general anaesthesia for VATS, compared with cisatracurium and neostigmine, use of rocuronium and sugammadex was associated with a significant decrease in the incidence of postoperative delayed removal of the chest tube, atelectasis, and pulmonary consolidation.

The Role and Mechanism of Perilla frutescens in Cancer Treatment.

Perilla frutescens is an annual herb of the Labiatae family and is widely grown in several countries in Asia. Perilla frutescens is a plant that is used medicinally in its entirety, as seen in its subdivision into perilla seeds, perilla stalks, and perilla leaves, which vary more markedly in their chemical composition. Several studies have shown that Perilla frutescens has a variety of pharmacological effects, including anti-inflammatory, antibacterial, detoxifying, antioxidant, and hepatoprotective. In the absence of a review of Perilla frutescens for the treatment of cancer. This review provides an overview of the chemical composition and molecular mechanisms of Perilla frutescens for cancer treatment. It was found that the main active components of Perilla frutescens producing cancer therapeutic effects were perilla aldehyde (PAH), rosmarinic acid (Ros A), lignan, and isoestrogen (IK). In addition to these, extracts of the leaves and fruits of Perilla frutescens are also included. Among these, perilla seed oil (PSO) has a preventive effect against colorectal cancer due to the presence of omega-3 polyunsaturated fatty acids. This review also provides new ideas and thoughts for scientific innovation and clinical applications related to Perilla frutescens.

Pharmacological Mechanisms and Adjuvant Properties of Licorice Glycyrrhiza in Treating Gastric Cancer.

Licorice is a remarkable traditional Chinese medicine obtained from the dried root and rhizomes of the Glycyrrhiza genus, and t has been utilized in China for many centuries. It consists of more than 300 compounds that are mainly divided into triterpene saponins, flavonoids, polysaccharides, and phenolic components. The active compounds of licorice have been found to possess multiple biological activities, including antitumor, anti-inflammatory, antiviral, antimicrobial, immunoregulatory, cardioprotective, and neuroprotective functions. In addition to providing a brief overview of licorice's adjuvant properties, this review describes and analyzes the pharmacological mechanisms by which licorice components function to treat gastric cancer. Furthermore, licorice compounds are also found to be potent adjuvant chemotherapy agents, as they can improve the quality of life of cancer patients and alleviate chemotherapy-induced adverse effects.

Incidence, characteristics, and outcomes of delirium in patients with noninvasive ventilation: a prospective observational study.

BACKGROUND: Factors that may increase the risk for delirium and the firm knowledge around mechanism for delirium in noninvasive ventilation (NIV) patients is lacking. We investigated the incidence, characteristics, and outcomes of delirium in NIV patients. METHODS: A prospective observational study was performed in an intensive care unit (ICU) of a teaching hospital. Patients in whom NIV was used as a first-line intervention were enrolled. During NIV intervention, delirium was screened using the Confusion Assessment Method for the ICU each day. The association between delirium and poor outcomes (e.g., NIV failure, ICU and hospital mortality) was investigated using forward stepwise multivariate logistic regression analyses. RESULTS: We enrolled 1083 patients. Of these, 196 patients (18.1%) experienced delirium during NIV intervention. Patients with delirium had higher NIV failure rates (37.8% vs. 21.0%, p < 0.01), higher ICU mortality (33.2% vs. 14.3%, p < 0.01), and higher hospital mortality (37.2% vs. 17.0%, p < 0.01) than subjects without delirium. They also had a longer duration of NIV (median 6.3 vs. 3.7 days, p < 0.01), and stayed longer in the ICU (median 9.0 vs. 6.0 days, p < 0.01) and the hospital (median 14.5 vs. 11.0 days, p < 0.01). These results were confirmed in COPD and non-COPD cohorts. According to subtype, compared to hyperactive delirium patients, hypoactive and mixed delirium patients spent more days and many more days on NIV (median 3.4 vs. 6.5 vs. 10.1 days, p < 0.01). Similar outcomes were found for length of stay in the ICU and hospital. However, NIV failure, ICU mortality, and hospital mortality did not differ among the three subtypes. CONCLUSIONS: Delirium is associated with increases in poor outcomes (NIV failure, ICU mortality, and hospital mortality) and the use of medical resources (duration of NIV, and lengths of stay in the ICU and hospital). Regarding subtype, hypoactive and mixed delirium are associated with higher, and much higher, consumption of medical resources, respectively, compared to hyperactive delirium.

GYY4137 attenuates LPS-induced acute lung injury via heme oxygenase-1 modulation.

GYY4137, a slow-releasing hydrogen sulfide (H2S) donor, has been reported to exert anti-inflammatory activity and protect against sepsis. Heme oxygenase-1 (HO-1) is an important anti-inflammatory heat shock protein and plays a similar effect on sepsis. This study investigated the role of GYY4137 in acute lung injury (ALI) via HO-1 regulation. Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide (LPS) and the mechanism of anti-inflammatory effects of GYY4137 was investigated in mice and RAW264.7 cells. GYY4137 reduced the LPS-mediated pulmonary injury and neutrophil infiltration, and inhibited the LPS-induced production of proinflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Moreover, GYY4137 suppressed the LPS-evoked NF-κB activation in RAW264.7 cells. GYY4137, not time-expired GYY4137 significantly induced HO-1 expression compared with the LPS group. The beneficial effects of GYY4137 above were reversed by the HO-1 inhibitor tin protoporphyrin (SnPP). These results suggest an anti-inflammatory effect and a therapeutic role of GYY4137 in LPS-induced ALI via HO-1 regulation.

Noninvasive ventilation for avoidance of reintubation in patients with various cough strength.

BACKGROUND: Reintubation is associated with high mortality. Identification of methods to avoid reintubation is needed. The aim of this study was to assess whether prophylactic noninvasive ventilation (NIV) would benefit patients with various cough strengths. METHODS: We prospectively enrolled 356 patients who successfully passed a spontaneous breathing trial in a respiratory intensive care unit. Before extubation, cough peak flow was measured. After extubation, attending physicians determined whether the patients would receive prophylactic NIV or conventional oxygen treatment (control group). Patients were followed up to 90 days postextubation or death, whichever came first. RESULTS: The median value of cough peak flow was 70 L/minute. Among the patients with cough peak flow ≤70 L/minute, 108 received NIV and 72 received conventional oxygen treatment. In this cohort, NIV reduced reintubation (9 % vs. 35 % at postextubation 72 h, p < 0.01; and 24 % vs. 49 % at postextubation 7 days, p < 0.01) and postextubation 90-day mortality (43 % vs. 61 %, p = 0.02) compared with the control group. Further, use of NIV was an independent protective factor for reintubation (OR = 0.19, p < 0.01 at 72 h postextubation; and OR = 0.33, p < 0.01 at 7 days postextubation) and for death at 90 days postextubation (OR = 0.40, p = 0.02). Among patients with cough peak flow >70 L/minute, 71 received NIV and 105 received conventional oxygen treatment. In this cohort, NIV did not reduce reintubation (6 % vs. 6 % at 72 h postextubation, p > 0.99; and 9 % vs. 9 % at 7 days postextubation, p > 0.99) or postextubation 90-day mortality (21 % vs. 15 %, p = 0.32) compared with the control group. Further, use of NIV was not associated with reintubation or postextubation 90-day mortality. CONCLUSION: In a planned extubated population, prophylactic NIV benefited patients with weak cough but possibly not in patients with strong cough.

Endocan levels in peripheral blood predict outcomes of acute respiratory distress syndrome.

PURPOSE: To investigate the prognostic significance of endocan, compared with procalcitonin (PCT), C-reactive protein (CRP),white blood cells (WBC), neutrophils (N), and clinical severity scores in patients with ARDS. METHODS: A total of 42 patients with ARDS were initially enrolled, and there were 20 nonsurvivors and 22 survivors based on hospital mortality. Plasma levels of biomarkers were measured and the acute physiology and chronic health evaluation II (APACHE II) was calculated on day 1 after the patient met the defining criteria of ARDS. RESULTS: Endocan levels significantly correlated with the APACHE II score in the ARDS group (r = 0.676, P = 0.000, n = 42). Of 42 individuals with ARDS, 20 were dead, and endocan was significantly higher in nonsurvivors than in survivors (median (IQR) 5.01 (2.98-8.44) versus 3.01 (2.36-4.36) ng/mL, P = 0.017). According to the results of the ROC-curve analysis and COX proportional hazards models, endocan can predict mortality of ARDS independently with a hazard ratio of 1.374 (95% CI, 1.150-1.641) and an area of receiver operator characteristic curve (AUROC) of 0.715 (P = 0.017). Moreover, endocan can predict the multiple-organ dysfunction of ARDS. CONCLUSION: Endocan is a promising biomarker to predict the disease severity and mortality in patients with ARDS.

Explore the mechanism of Astragalus membranaceus and Poria cocos drug pair in improving immunity based on network pharmacology.

The aim of this study was to investigate the key targets and molecular mechanisms of the drug pair Astragalus membranaceus and Poria cocos (HFDP) in the treatment of immunity. We utilized network pharmacology, molecular docking, and immune infiltration techniques in conjunction with data from the GEO database. Previous clinical studies have shown that HFDP has a positive impact on immune function. We first identified the active ingredients and targets of HFDP from the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database, respectively. Next, we retrieved the differentially expressed genes (DEGs) related to immunity from the GEO databases. The intersection targets of the drugs and diseases were then analyzed using the STRING database for protein-protein interaction (PPI) network analysis, and the core targets were determined through topological analysis. Finally, the intersection genes were further analyzed using the DAVID database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, by analyzing the expression and prognostic survival of 12 core targets, 5 core target genes were identified, and molecular docking between the hub genes and immunity was performed. Finally, we used the CIBERSORT algorithm to analyze the immune infiltration of immunity genes In this study, 34 effective ingredients of HFDP, 530 target genes, and 568 differential genes were identified. GO and KEGG analysis showed that the intersection genes of HFDP targets and immunity-related genes were mainly related to complement and coagulation cascades, cytokine receptors, and retinol metabolism pathways. The molecular docking results showed that the 5 core genes had obvious affinity for the active ingredients of HFDP, which could be used as potential targets to improve the immunity of HFDP. Our findings suggest that HFDP is characterized by "multiple components, multiple targets, and multiple pathways" in regulating immunity. It may play an essential role in regulating immunity by regulating the expression and polymorphism of the central target genes ESR1, JUN, CYP3A4, CYP2C9, and SERPINE1.

Molecular mechanism of Saikosaponin-d in the treatment of gastric cancer based on network pharmacology and in vitro experimental verification.

The study aimed to utilize network pharmacology combined with cell experiments to research the mechanism of action of Saikosaponin-d in the treatment of gastric cancer. Drug target genes were obtained from the PubChem database and the Swiss Target Prediction database. Additionally, target genes for gastric cancer were obtained from the GEO database and the Gene Cards database. The core targets were then identified and further analyzed through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GESA enrichment. The clinical relevance of the core targets was assessed using the GEPIA and HPA databases. Molecular docking of drug monomers and core target proteins was performed using Auto Duck Tools and Pymol software. Finally, in vitro cellular experiments including cell viability, apoptosis, cell scratch, transwell invasion, transwell migration, qRT-PCR, and Western blot were conducted to verify these findings of network pharmacology. The network pharmacology analysis predicted that the drug monomers interacted with 54 disease targets. Based on clinical relevance analysis, six core targets were selected: VEGFA, IL2, CASP3, BCL2L1, MMP2, and MMP1. Molecular docking results showed binding activity between the Saikosaponin-d monomer and these core targets. Saikosaponin-d could inhibit gastric cancer cell proliferation, induce apoptosis, and inhibit cell migration and invasion.

Hawthorn with "homology of medicine and food": a review of anticancer effects and mechanisms.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn's anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.

Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification.

BACKGROUND: Pachymic acid (PA) is derived from Poria cocos. PA has a variety of pharmacological and inhibitory effects on various tumors. However, the mechanism of action of PA in gastric cancer (GC) remains unclear. AIM: To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification. METHODS: The GeneCards and OMIM databases were used to derive the GC targets, while the Pharm Mapper database provided the PA targets. Utilizing the STRING database, a protein-protein interaction network was constructed and core targets were screened. The analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were conducted, and molecular docking and clinical correlation analyses were performed on the core targets. Ultimately, the network pharmacology findings were validated through in vitro cell assays, encompassing assessments of cell viability, apoptosis, cell cycle, cloning, and western blot analysis. RESULTS: According to network pharmacology analysis, the core targets were screened, and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC, according to KEGG enrichment analysis. The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation, induce apoptosis, and pause the cell cycle. CONCLUSION: Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets. This has also been supported by in vitro cell studies, which serve as benchmarks for further research.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation.

BACKGROUND: Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear. AIM: To explore the mechanism of YGS anti-gastric cancer and immune regulation. METHODS: Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes. RESULTS: Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets. CONCLUSION: YGS has the effect of anti-gastric cancer and immune regulation.

18ß-glycyrrhetinic acid promotes gastric cancer cell autophagy and inhibits proliferation by regulating miR-328-3p/signal transducer and activator of transcription 3.

BACKGROUND: Gastric cancer (GC) is one of the most common cancer types worldwide, and its prevention and treatment methods have garnered much attention. As the active ingredient of licorice, 18ß-glycyrrhetinic acid (18ß-GRA) has a variety of pharmacological effects. The aim of this study was to explore the effective target of 18ß-GRA in the treatment of GC, in order to provide effective ideas for the clinical prevention and treatment of GC. AIM: To investigate the mechanism of 18ß-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells. METHODS: Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs (miRNAs) in GC cells after 18ß-GRA intervention. Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability, cell colony formation ability was detected by the clone formation assay, and flow cytometry was used to detect the cell cycle and apoptosis. A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells. Tumor tissue morphology was observed by hematoxylin and eosin staining, and microtubule-associated protein light chain 3 (LC3) expression was detected by immunohistochemistry. TransmiR, STRING, and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3 (STAT3)-related information. Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction (qPCR) and the expression levels of STAT3, phosphorylated STAT3 (p-STAT3), and LC3 were detected by western blot analysis. The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system. AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label. LC3 was labeled and autophagy flow was observed under a confocal laser microscope. RESULTS: The expression of miR-328-3p was significantly upregulated after 18ß-GRA intervention in AGS cells (P = 4.51E-06). Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability, arrested the cell cycle in the G0/G1 phase, promoted cell apoptosis, and inhibited the growth of subcutaneous tumors in BALB/c nude mice (P < 0.01). No obvious necrosis was observed in the tumor tissue in the negative control group (no drug intervention or lentivirus transfection) and vector group (the blank vector for lentivirus transfection), and more cells were loose and necrotic in the miR-328-3p group. Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3, and STAT3 was closely related to autophagy markers such as p62. After overexpressing miR-328-3p, the expression level of STAT3 mRNA was significantly decreased (P < 0.01) and p-STAT3 was downregulated (P < 0.05). The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT3 3' untranslated regions of the wild-type reporter vector group was significantly decreased (P < 0.001). Overexpressed miR-328-3p combined with bafilomycin A1 (Baf A1) was used to detect the expression of LC3 II. Compared with the vector group, the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated (P < 0.05), and compared with the Baf A1 group, the expression level of LC3 II in the overexpressed miR-328-3p + Baf A1 group was upregulated (P < 0.01). The expression of LC3 II was detected after intervention of 18ß-GRA in GC cells, and the results were consistent with the results of miR-328-3p overexpression (P < 0.05). Additional studies showed that 18ß-GRA promoted autophagy flow by promoting autophagosome synthesis (P < 0.001). qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention (P < 0.05). Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention (P < 0.05). CONCLUSION: 18ß-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway.

Exploring the molecular mechanism of glycyrrhetinic acid in the treatment of gastric cancer based on network pharmacology and experimental validation.

There is a wide range of pharmacological effects for glycyrrhetinic acid (GRA). Previous studies have shown that GRA could inhibit the proliferation of tumor cells, showing a promising value in the treatment of gastric cancer (GC). Nonetheless, the precise mechanism of the effect of GRA on GC remains unclear. We explored cellular and molecular mechanisms of GRA based on network pharmacology and in vitro experimental validation. In this study, we predicted 156 potential therapeutic targets for GC with GRA from public databases. We then screened the hub targets using protein-protein interaction network (PPI) and conducted clinical correlation analysis. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that GRA made anti-GC effects through multiple targets and pathways, particularly the MAPK signaling pathway. Next, molecular docking results revealed a potential interaction between GRA and MAPK3. In addition, qRT-PCR experiments revealed that 18ß-GRA was able to suppress mRNA expression of KRAS, ERK1 and ERK2 in AGS cells. Western blotting results also revealed that 18ß-GRA was able to suppress the expression of KRAS and p-ERK1/2 proteins in AGS cells. Additionally, immunofluorescence assays revealed that 18ß-GRA inhibited p-ERK1/2 nuclear translocation in AGS cells. These results systematically reveal that 18ß-GRA may have anti-tumor effects on GC by modulating the MAPK signaling pathway.

Research progress of ginger in the treatment of gastrointestinal tumors.

Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors.

MiR-204-3p overexpression inhibits gastric carcinoma cell proliferation by inhibiting the MAPK pathway and RIP1/MLK1 necroptosis pathway to promote apoptosis.

BACKGROUND: Gastric carcinoma (GC) is the third most frequent cause of cancer-related death, highlighting the pressing need for novel clinical treatment options. In this regard, microRNAs (miRNAs) have emerged as a promising therapeutic strategy. Studies have shown that miRNAs can regulate related signaling pathways, acting as tumor suppressors or tumor promoters. AIM: To explore the effect of miR-204-3p on GC cells. METHODS: We measured the expression levels of miR-204-3p in GC cells using quantitative real-time polymerase chain reaction, followed by the delivery of miR-204-3p overexpression and miR-204-3p knockdown vectors into GC cells. CCK-8 was used to detect the effect of miR-204-3p on the proliferation of GC cells, and the colony formation ability of GC cells was detected by the clonal formation assay. The effects of miR-204-3p on GC cell cycle and apoptosis were detected by flow cytometry. The BABL/c nude mouse subcutaneous tumor model using MKN-45 cells was constructed to verify the effect of miR-204-3p on the tumorigenicity of GC cells. Furthermore, the study investigated the effects of miR-204-3p on various proteins related to the MAPK signaling pathway, necroptosis signaling pathway and apoptosis signaling pathway on GC cells using Western blot techniques. RESULTS: Firstly, we found that the expression of miR-204-3p in GC was low. When treated with the lentivirus overexpression vector, miR-204-3p expression significantly increased, but the lentivirus knockout vector had no significant effect on miR-204-3p. In vitro experiments confirmed that miR-204-3p overexpression inhibited GC cell viability, promoted cell apoptosis, blocked the cell cycle, and inhibited colony formation ability. In vivo animal experiments confirmed that miR-204-3p overexpression inhibited subcutaneous tumorigenesis ability in BABL/c nude mice. Simultaneously, our results verified that miR-204-3p overexpression can inhibit GC cell proliferation by inhibiting protein expression levels of KRAS and p-ERK1/2 in the MAPK pathway, as well as inhibiting protein expression levels of p-RIP1 and p-MLK1 in the necroptosis pathway to promote the BCL-2/BAX/Caspase-3 apoptosis pathway. CONCLUSION: MiR-204-3p overexpression inhibited GC cell proliferation by inhibiting the MAPK pathway and necroptosis pathway to promote apoptosis of GC cells. Thus, miR-204-3p may represent a new potential therapeutic target for GC.

Dual-mode weaning strategy for difficult-weaning tracheotomy patients: a feasibility study.

BACKGROUND: Tracheotomy patients who are difficult to wean from ventilation consume a substantial portion of intensive care unit (ICU) resources. These patients also typically undergo a long period of mechanical ventilation (MV) and have a high mortality rate. The efficacy of a dual-mode weaning strategy (alternation of invasive and noninvasive MV) in tracheotomy patients who are difficult to wean is unknown. METHODS: We performed this prospective, randomized, controlled trial in a 17-bed respiratory ICU from July 2009 to October 2011. After tracheotomy, patients who failed for 3 consecutive days in a spontaneous breathing trial were enrolled (n = 32) and randomly allocated to either the dual-mode (n = 15) or conventional (n = 17) weaning group. RESULTS: Compared with the conventional group, patients in the dual-mode group had a shorter duration of MV during the entire study (median 38 days, interquartile range [IQR]: 28-53 vs 59, IQR: 39-88, P = 0.03) and after randomization (median 10 days, IQR: 4-21 vs 37, IQR: 16-51, P < 0.01). They also had a shorter ICU stay (median 44 days, IQR: 32-54 vs 72, IQR: 52-102, P = 0.01), a lower mortality rate during weaning (1 of 15 vs 7 of 17, P = 0.04), and a lower rate of pulmonary infection after randomization (3 of 15 vs 12 of 17, P < 0.01). CONCLUSIONS: Dual-mode weaning is a promising strategy for treating tracheotomy patients who are difficult to wean. In a small cohort of patients with tracheotomies, we demonstrated that dual-mode weaning reduced the total duration of MV and ICU stay; we recommend additional studies to assess its effect on pulmonary infections and mortality.

Impact of HACOR Score on Noninvasive Ventilation Failure in Non-COPD Patients with Acute-on-Chronic Respiratory Failure.

Background: A rating scale that takes into account heart rate, acidosis, consciousness, oxygenation, and respiratory rate (the HACOR score) has been used to predict noninvasive ventilation (NIV) failure in patients with chronic obstructive pulmonary disease (COPD). However, the HACOR score has not been used to predict NIV failure in non-COPD patients with acute-on-chronic respiratory failure. Methods: This study was performed in the respiratory intensive care unit of a teaching hospital. Data had been collected prospectively between June 2011 and January 2019. We enrolled non-COPD patients who received NIV due to acute-on-chronic respiratory failure, pH < 7.35, and PaCO2 >45 mmHg. NIV failure was defined as requiring intubation or dying during NIV. The HACOR score was determined at initiation and after 1-2, 12, and 24 h of NIV. Scores can range from 0 to 27, with higher scores indicating a higher risk of NIV failure. Results: A total of 148 patients were enrolled in the study, 52 with sleep apnea-hypopnea syndrome, 34 with chronic thoracic sequelae, 31 with bronchiectasis, 14 with chest wall deformity, 5 with obesity-hypoventilation syndrome, and 12 with other conditions. Of the patients, 19 (13%) experienced NIV failure. From initiation to 24 h of NIV, the HACOR scores of patients who experienced NIV failure were much higher than those of patients who received successful NIV. The area under the receiver operating characteristic curve was 0.69, 0.91, 0.91, and 0.94 when the HACOR score was tested at initiation and after 1-2, 12, and 24 h of NIV, respectively. To obtain the best sensitivity and specificity, the cutoff value at initiation was 7 with a sensitivity of 68% and a specificity of 61%. After 1-2 h of NIV, it was 5 with a sensitivity of 90% and a specificity of 85%. After 12 h of NIV, it was 4 with a sensitivity of 82% and a specificity of 91%. After 24 h of NIV, it was 2 with a sensitivity of 100% and a specificity of 76%. Conclusions: The HACOR score has high sensitivity and specificity for predicting NIV failure among non-COPD patients who receive NIV due to acute-on-chronic respiratory failure with respiratory acidosis.

Predictors of the Failure of Noninvasive Ventilation in Patients With Acute Respiratory Failure Caused by Severe Acute Pancreatitis: A Prospective Observational Study.

OBJECTIVE: The aim of the study was to identify risk factors associated with the failure of noninvasive ventilation (NIV) in patients with severe acute pancreatitis (SAP). METHODS: Patients who received NIV as a first-line therapy because of acute respiratory failure caused by SAP were enrolled. RESULTS: A total of 133 patients were enrolled. Of the patients, 32 (24%) experienced NIV failure. Male sex (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.48-12.22), older age (OR, 1.04; 95% CI, 1.01-1.08), a higher Acute Physiology and Chronic Health Evaluation II score (OR, 1.18; 95% CI, 1.03-1.36), and a procalcitonin level greater than 3.8 ng/mL (OR, 6.28; 95% CI, 2.04-19.31) were independently associated with NIV failure. The receiver operating characteristic curves for predicting NIV failure were 0.67, 0.72, and 0.76 tested by age, procalcitonin, and Acute Physiology and Chronic Health Evaluation II score, respectively. From initiation to 24 hours, the patients in the NIV failure group had a higher proportion of Glasgow Coma Scale scores of 14 or less, a higher proportion of pH ≤7.35, and higher respiratory rates than ones in the successful NIV group. CONCLUSIONS: One of 4 SAP patients experience NIV failure. Age, sex, disease severity, level of inflammation, and vital signs can be used to predict NIV failure.