Anhydroicaritin suppresses tumor progression via the PI3K/AKT signaling pathway in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant tumors. The in vitro experiments on the application of Anhydroicaritin (AHI), the active ingredient of Bushen Huayu Decoction, in HCC treatment remain limited, particularly regarding its molecular mechanism. METHODS: The TCMSP platform was used for drug ingredient screening. The GeneCards database and DisGeNET database are used to collect liver cancer targets. PPI network construction of active component-target intersection target was completed with string database. The GO and KEGG pathway analyses were performed via bioinformatics analysis. The molecular docking was used to confirm AHI's target proteins. The in vitro experiments were performed to validate the effect of AHI on HCC cell and explore the molecular mechanism by western blotting analysis. RESULTS: Through the intersection, 155 intersection targets are finally obtained. The top 15 active ingredients were quercetin, kaempferol, beta-sitosterol, luteolin, beta-carotene, Stigmasterol, naringenin, formononetin, baicalein, Anhydroicaritin, isorhamnetin, licochalcone, 7-O-methylisomucronulatol, aloe-emodin and 8-O-Methylreyusi. The molecular mocking analysis showed that the four active components (quercetin, kaempferol, luteolin and AHI) and targets had a good binding activity (affinity ≤ 5 kcal/mol). In vitro experiments reveled that AHI could suppress tumor proliferation, invasion and metastasis of HCC cells. Further analysis showed that AHI inhibited tumor growth by PI3K/AKT signal pathway in HCC. CONCLUSIONS: The Bushen Huayu Decoction and its active ingredient AHI could fight HCC. The potential mechanism may be associated with inhibiting the activation of PI3K/AKT signal pathway, which may serve as a potential treatment for HCC therapy.

LRPPRC facilitates tumor progression and immune evasion through upregulation of m6A modification of PD-L1 mRNA in hepatocellular carcinoma.

Objective: LRPPRC is a newly discovered N6-methyladenosine (m6A) modification reader, which potentially affects hepatocellular carcinoma (HCC) progression. PD-L1 in tumor cells is essential for tumor immune evasion. This work investigated the LRPPRC-mediated m6A-modification effect on PD-L1 mRNA and immune escape in HCC. Methods: Expression and clinical implication of LRPPRC and PD-L1 were measured in human HCC cohorts. The influence of LRPPRC on malignant behaviors of HCC cells was investigated through in vitro assays and xenograft tumor murine models. The posttranscriptional mechanism of LRPPRC on PD-L1 and anti-tumor immunity was elucidated in HCC cells via RIP, MeRIP-qPCR, RNA stability, immunohistochemical staining, and so forth. Results: LRPPRC exhibited the notable upregulated in human HCC tissues, which was in relation to advanced stage and worse overall survival and disease-free survival. Impaired proliferative capacity and G2/M phage arrest were found in LRPPRC-knockout cells, with increased apoptotic level, and attenuated migratory and invasive abilities. In HCC patients and murine models, LRPPRC presented a positive interaction with PD-L1, with negative associations with CD8+, and CD4+ T-cell infiltrations and chemokines CXCL9, and CXCL10. LRPPRC loss downregulated the expression of PD-L1 and its m6A level in HCC cells. Moreover, LRPPRC suppression mitigated tumor growth in murine models and improved anti-tumor immunity and immune infiltration in tumors. Conclusion: This work unveiled that LRPPRC may posttranscriptionally upregulate PD-L1 partially with an m6A-dependent manner for heightening mRNA stabilization of PD-L1 and provided a new mechanism for m6A regulator-mediated immunosuppression in HCC.

Neutrophil/lymphocyte ratio predicts lymph node metastasis in patients with gastric cancer.

OBJECTIVE: To identify the independent risk factors of gastric cancer (GC) lymph node metastasis and to determine whether the preoperative neutrophil and lymphocyte ratio (NLR) and the platelet and lymphocyte ratio (PLR) can be used as the indicators of gastric cancer lymph node metastasis. METHODS: The pathological data of 221 patients with gastric cancer were retrospectively analyzed, and the risk factors of lymph node metastasis were evaluated. The relationship between preoperative NLR and PLR and the clinical pathology of patients were analyzed, and the effect of these two indexes on lymph node metastasis was predicted through receiver operating characteristic (ROC) curve. RESULTS: Lymph node metastasis correlated with tumor diameter, depth of invasion, Tumor-Node-Metastasis (TNM) stage, preoperative NLR and preoperative PLR (all P<0.05), but not with gender, age and tumor location (all P>0.05). According to the result of multivariate analysis, the degree of differentiation, depth of invasion, TNM staging and NLR were independent risk factors for GC lymph node metastasis. CONCLUSION: The sensitivity and specificity of PLR, tumor staging and tumor size are lower than NLR. Preoperative NLR can be used as an independent risk factor for the prediction of lymph node metastasis, and one of the effective indicators for predicting the prognosis of patients. Preoperative NLR may be an effective auxiliary tool to assess lymph nodes in GC patients.

Treatment of a large area perioral viral herpes infection following noninvasive ventilation: A case report.

BACKGROUND: Alphaherpesvirus belongs to the Herpesviridae family and has large, monopartite double-stranded linear DNA. It mainly infects the skin, mucosa, and nerves, and can affect various hosts, including humans and other animals. Here, we present a case of a patient seen by the gastroenterology department at our hospital who experienced an oral and perioral herpes infection following treatment with a ventilator. The patient was treated with oral and topical antiviral drugs, furacilin, oral and topical antibiotics, local epinephrine injection, topical thrombin powder, and nutritional and supportive care. A wet wound healing approach was also implemented with good response. CASE SUMMARY: A 73-year-old woman presented to the hospital with a chief complaint of "abdominal pain for 3 d with dizziness for 2 d." She was admitted to the intensive care unit for septic shock and spontaneous peritonitis secondary to cirrhosis and was given antiinflammatory and symptomatic supportive treatment. A ventilator was used to assist breathing for acute respiratory distress syndrome, which developed during her admission. A large area of herpes infection appeared in the perioral region 2 d following noninvasive ventilation. The patient was transferred to the gastroenterology department, at which time she had a body temperature of 37.8 C and a respiratory rate of 18/min. The patient's consciousness was intact, and she no longer had abdominal pain or distension, chest tightness, or asthma. At this point, the infected perioral region changed in appearance and was now accompanied by local bleeding with crusting of blood at the wounds. The surface area of the wounds measured approximately 10 cm × 10 cm. A cluster blisters appeared on the patient's right neck, and ulcers developed in her mouth. On a subjective numerical pain scale, the patient reported a pain level of 2. Overall, her diagnoses other than the oral and perioral herpes infection included: (1) Septic shock; (2) spontaneous peritonitis; (3) abdominal infection; (4) decompensated cirrhosis; and (5) hypoproteinemia. Dermatology was consulted regarding the treatment of the patient's wounds; they suggested treatment with oral antiviral drugs, an intramuscular injection of nutritious nerve drugs, and the application of topical penciclovir and mupirocin around the lips. Stomatology was also consulted and suggested the use of nitrocilin in a local wet application around the lips. CONCLUSION: Through multidisciplinary consultation, the patient's oral and perioral herpes infection was successfully treated with the following combined approach: (1) Application of topical antviral and antibiotic treatments; (2) keeping the wound moist with a wet wound healing strategy; (3) systemic use of oral antiviral drugs; and (4) symptomatic and nutritional supportive care. The patient was discharged from the hospital after successful wound healing.

Suppression of AGTR1 Induces Cellular Senescence in Hepatocellular Carcinoma Through Inactivating ERK Signaling.

Objective: Cellular senescence is an effective barrier against tumorigenesis. Hence, it is of significance to characterize key features of cellular senescence and the induction of senescence in hepatocellular carcinoma (HCC) cells via pharmacological interventions. Our study determined the biological roles as well as mechanisms of angiotensin II type I receptor (AGTR1) on cellular senescence in HCC. Methods: Lentivirus vector-mediated overexpression or knockdown of AGTR1 was conducted in HCC cells, respectively. A volume of 8 µM sorafenib was used to induce cellular senescence, and ERK was activated by 30 ng/ml ERK agonist EGF. Proliferation was evaluated via clone formation assay. HCC cell senescence was examined by flow cytometry for cell cycle, senescence-associated ß-galactosidase (SA-ß-gal) staining, and senescence-associated heterochromatin foci (SAHF) analysis. AGTR1, p53, p21, extracellular signal-regulated kinase (ERK), and p-ERK expression were assessed through Western blot or immunofluorescence. Results: AGTR1-knockout HCC cells displayed the attenuated proliferative capacity, G2-M phase arrest, increased expression of p53 and p21, and elevated percentages of SA-ß-gal- and SAHF-positive cells. In sorafenib-exposed HCC cells, overexpressed AGTR1 enhanced the proliferative capacity and alleviated G2-M phase arrest as well as decreased p53 and p21 expression and the proportions of SA-ß-gal- and SAHF-positive cells. Moreover, AGTR1 knockdown attenuated the activity of p-ERK in HCC cells, and ERK agonist ameliorated AGTR1 knockdown-induced cellular senescence. Conclusion: This study demonstrates that suppression of AGTR1 induces cellular senescence in HCC through inactivating ERK signaling. The significant synergistic effect of AGTR1 suppression and sorafenib might represent a potential combination therapy for HCC.

Effect of continuous nursing based on the Omaha System on cancer-related fatigue in patients with lung cancer undergoing chemotherapy: a randomized controlled trial.

BACKGROUND: As one of the important treatments for lung cancer, chemotherapy not only brings hope for the survival of patients, but also influences their body and mind. Most patients have different degrees of fatigue during chemotherapy and after chemotherapy, and the occurrence and aggravation of fatigue do not necessarily occur during hospitalization, there is a lag, mostly occurs in the interval after chemotherapy, therefore, continuous nursing care is very important for patients with lung cancer undergoing chemotherapy. The purpose of this study was to explore the effect of continuous nursing, based on Omaha System theory, on cancer-related fatigue in patients with lung cancer receiving chemotherapy. METHODS: From April 2018 to May 2019, a total of 102 inpatients with lung cancer at a cancer hospital in Hangzhou, China were selected for chemotherapy. A total of 7patients were lost to follow-up during the intervention, leaving 46 and 49 patients randomly assigned to the experimental and control groups, respectively. Participants in the control group received routine nursing after discharge, while those in the experimental group were nursed according to the Omaha System model. RESULTS: After 4 cycles of chemotherapy, scores for total, physical, cognitive, and emotional fatigue were significantly lower in the intervention group than those in the control group (P<0.05). Repeated analysis of variance (ANOVA) showed that there were significant differences in the time-dependent (<0.001) and intervention-dependent (P<0.001) effects on fatigue score, as well as a significant interaction between time and intervention (P<0.001). CONCLUSIONS: Continuous nursing based on Omaha System theory can ameliorate cancer fatigue in patients with lung cancer undergoing chemotherapy.

Pressure Ulcers in the Intensive Care Unit: An Analysis of Skin Barrier Risk Factors.

OBJECTIVE: The aim of this study was to determine whether skin barrier factors were associated with the common complication of pressure ulcers (PrUs) in intensive care unit (ICU) patients. It is unclear whether skin barrier factors influence the development of PrUs. PATIENT POPULATION: The sample was composed of 102 ICU patients (54 men, 48 women). The patients ranged in age from 23 to 88 years, with a mean age of 55.7 (SD, 19.1) years. METHODS: Demographic variables and the score for the Acute Physiology and Chronic Health Evaluation IV were recorded on admission. The Braden Scale assessment and measurements of the skin barrier factors were performed daily. Standard care for the prevention of PrUs was strictly administered, and PrUs that developed were evaluated according to the recommendations of the US National Pressure Ulcer Advisory Panel 2007 (Note: The authors used the 2007 recommendations at the time of their study.). Data were analyzed using descriptive statistics and logistic regression. RESULTS: The mean score for the Braden Scale was 11.2, and the incidence of PrUs was 31.4%. Lower moisture content of the stratum corneum and higher skin surface pH at the lower sacrum and hip were risk factors for PrUs, whereas scapular and heel skin barrier factors were not. CONCLUSION: Nursing strategies aimed at preventing PrUs should place added emphasis on the lower sacral and hip regions.

Combined effects of sivelestat and resveratrol on severe acute pancreatitis-associated lung injury in rats.

Despite extensive research and clinical efforts made in the management of acute pancre-atitis during the past few decades, to date no effective cure is available and the mortality from severe acute pancre-atitis remains high. Given that lung is the primary cause of early death in acute pancreatitis patients, novel therapeutic approaches aiming to prevent lung injury have become a subject of intensive investigation. In a previous study, we demonstrated that sivelestat, a specific inhibitor of neutrophil elastase, is effective in protecting against lung failure in rats with taurocholate-induced acute pancreatitis. As part of the analyses extended from that study, the present study aimed to evaluate the role of sivelestat and/or resveratrol in the protection against acute pancreatitis-associated lung injury. The extended analyses demonstrated the following: (1) sodium taurocholate induced apparent lung injury and dysfunction manifested by histological anomalies, including vacuolization and apoptosis of the cells in the lung, as well as biochemical aberrations in the blood (an increase in amylase concentration and a decrease in partial arterial oxygen pressure) and increases in activities of reactive oxygen species, interleukin 6, myeloperoxidase, neutrophil elastase, lung edema, bronchotracho alveolar lavage protein concentration, and bronchotracho alveolar lavage cell infiltration in the lung; and (2) in lung tissues, either sivelestat or resveratrol treatment effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. In addition, combined treatment with both sivelestat and resveratrol demonstrated additive protective effects on pancreatitis-associated lung injury compared with single treatment.

Renoprotective activity of sivelestat in severe acute pancreatitis in rats.

Acute pancreatitis, affecting 382,014 individuals annually in China, is life-threatening in its severe form. Since acute pancreatitis-associated morbidity or mortality is attributable mainly to functional failure of the vital organs, significant research efforts have focused on the identification of novel agents with potential organ-protective properties in the hope of developing approaches to improve the outcome of acute pancreatitis. In a previous study, we demonstrated that sivelestat, a specific inhibitor of neutrophil elastase (NE), is effective in protecting against lung failure in rats with taurocholate-induced acute pancreatitis. As part of the analyses extended from that study, the present study aimed to evaluate the role of sivelestat in the protection against acute pancreatitis-associated renal injury. Renal histopathology and major renal function parameters were analyzed in renal tissue and blood specimens collected from rats with acute pancreatitis induced by the surgical administration of sodium taurocholate in the presence or absence of sivelestat treatment and in sham-operated control rats at various time-points. The extended analyses demonstrated that: i) sodium taurocholate induced apparent renal injury and dysfunction manifested by histological anomalies, including vacuolization and apoptosis of the cells of the tubular epithelial lining in the kidney, as well as biochemical aberrations in the blood (increases in levels of blood urea nitrogen, creatinine and tumor necrosis factor-α) and renal tissue (robust increases in NE activity and induced neutrophil chemoattractant-1 levels); and ii) sivelestat treatment effectively attenuated all taurocholate-induced histological anomalies and biochemical aberrations. These observations strongly suggest that the NE inhibitor, sivelestat, is effective in protecting against acute pancreatitis-associated renal injury.

Potential of sivelestat in protection against severe acute pancreatitis-associated lung injury in rats.

The incidence of acute pancreatitis has been rising worldwide in the past few decades. Despite extensive research efforts, the population-based mortality from acute pancreatitis remains high. Since dysfunction of multiple vital organs, most importantly the lungs, is the major cause of early death in acute pancreatitis patients, developing effective strategies to manage lung injury has become one of the focuses of recent research efforts aiming at improving the outcome of patients with acute pancreatitis. In this study, we attempted to create a rat model of acute pancreatitis through intraductal infusion of taurocholate and to evaluate the potential of sivelestat, a synthetic neutrophil elastase inhibitor, in protection against acute pancreatitis-associated lung injury using this rat model. The results demonstrated that: (1) 5% sodium taurocholate successfully induced histopathologic and biochemical abnormalities in the circulation, lung and pancreas characteristic of human acute pancreatitis, including an increase in amylase concentration and a decrease in partial arterial oxygen pressure (PaO2) in the blood, increases in activities of myeloperoxidase (MPO) (a lung injury marker) and neutrophil elastase (a quantitative indicator of neutrophil infiltration), and levels of malondialdehyde (an indicator of lipid peroxidation) and tumor necrosis factor-alpha (a major inflammatory mediator) in the lung; (2) intravenous administration of sivelestat effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. Our findings have validated the taurocholate model of acute pancreatitis and demonstrated great therapeutic potential for sivelestat in managing acute pancreatitis-associated lung injury.