Magnetic resonance imaging radiomics-based prediction of clinically significant prostate cancer in equivocal PI-RADS 3 lesions in the transitional zone.

Purpose: This bi-institutional study aimed to establish a robust model for predicting clinically significant prostate cancer (csPCa) (pathological grade group ≥ 2) in PI-RADS 3 lesions in the transition zone by comparing the performance of combination models. Materials and methods: This study included 243 consecutive men who underwent 3-Tesla magnetic resonance imaging (MRI) and ultrasound-guided transrectal biopsy from January 2020 and April 2022 which is divided into a training cohort of 170 patients and a separate testing cohort of 73 patients. T2WI and DWI images were manually segmented for PI-RADS 3 lesions for the mean ADC and radiomic analysis. Predictive clinical factors were identified using both univariate and multivariate logistic models. The least absolute shrinkage and selection operator (LASSO) regression models were deployed for feature selection and for constructing radiomic signatures. We developed nine models utilizing clinical factors, radiological features, and radiomics, leveraging logistic and XGboost methods. The performances of these models was subsequently compared using Receiver Operating Characteristic (ROC) analysis and the Delong test. Results: Out of the 243 participants with a median age of 70 years, 30 were diagnosed with csPCa, leaving 213 without a csPCa diagnosis. Prostate-specific antigen density (PSAD) stood out as the only significant clinical factor (odds ratio [OR], 1.068; 95% confidence interval [CI], 1.029-1.115), discovered through the univariate and multivariate logistic models. Seven radiomic features correlated with csPCa prediction. Notably, the XGboost model outperformed eight other models (AUC of the training cohort: 0.949, and validation cohort: 0.913). However, it did not surpass the PSAD+MADC model (P > 0.05) in the training and testing cohorts (AUC, 0.949 vs. 0.888 and 0.913 vs. 0.854, respectively). Conclusion: The machine learning XGboost model presented the best performance in predicting csPCa in PI-RADS 3 lesions within the transitional zone. However, the addition of radiomic classifiers did not display any significant enhancement over the compound model of clinical and radiological findings. The most exemplary and generalized option for quantitative prostate evaluation was Mean ADC+PSAD.

Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

ent-Atisane Diterpenoids from Euphorbia helioscopia and Their Anti-inflammatory Activities.

Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.

Berberine enhances autophagic flux by activating the Nrf2 signaling pathway in bovine endometrial epithelial cells to resist LPS-induced apoptosis.

Berberine exerts many beneficial effects on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (BEECs). Recently, we also found that berberine shows significant antiapoptotic and autophagy-promoting activities, but the underlying mechanism has not been elucidated. This research explored the association between the antiapoptotic and autophagy-promoting activities of berberine in LPS-treated BEECs. BEECs were first preconditioned with an inhibitor of autophagic flux (chloroquine [CQ]) for 1 h, treated with berberine for 2 h, and then incubated with LPS for 3 h. Cell apoptosis was assessed by flow cytometry, and autophagy activities were assessed by immunoblot analysis of LC3II and p62. The results indicated that the antiapoptotic activity of berberine was notably inhibited in LPS-treated BEECs after preconditioning with CQ for 1 h. Furthermore, to determine whether berberine promoted autophagy by activating the nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, we assessed autophagy in LPS-treated BEECs after preconditioning with a signaling pathway inhibitor of Nrf2 (ML385). The results indicated that the enhanced autophagy activity induced by berberine was partially reversed in LPS-treated BEECs after the Nrf2 signaling pathway was disturbed by ML385. In conclusion, berberine enhances autophagic flux to allow resistance to LPS-induced apoptosis by activating the Nrf2 signaling pathway in BEECs. The present study may provide new insight into the antiapoptotic mechanism of berberine in LPS-induced BEECs.

Identification and antibiotic susceptibility of microorganisms isolated from diabetic foot ulcers: A pathological aspect.

Diabetic foot ulcers infected with microorganisms increase the risk of amputation. The presence of drug-resistant bacteria in diabetic foot ulcers creates a big challenge during the treatment. The objective of the present study was to determine the bacterial prevalence and antibiotic resistance among bacteria isolated from Chinese patients with diabetic foot ulcers. The present study studied the microbial colonization of diabetic foot ulcers of patients from a single center in China. Wound swabs from 89 patients with diabetic foot ulcers were collected and the presence of microorganisms detected. The isolated microorganisms were subjected to antibiotic susceptibility testing by the disk diffusion method. Of 89 patients, 56 (62.9%) were male and 33 (37.1%) were female, the mean age of patients was 53.2±5.4 years, the mean duration of diabetes was 14.8±2.9 years, the mean random blood sugar was 301±87 mg/dl, mean HbA1c was 7.9±1.4%. Patients with Wanger ulcer grade III (36.0%; P=0.034) and patients within the weight range of 51-75 kg (59.6%; P=0.012) were significantly higher. The prevalence rate of diabetic foot ulcers was 11.3%. Among 153 microorganisms, gram-positive bacteria (52.3%) were more prevalent than gram-negative bacteria (44.4%). Most of the patients with polymicrobial infection were classified to have Wanger III ulcer grade diabetic foot ulcers. Staphylococcus aureus (38.2%) was the most predominant bacteria isolated followed by Staphylococcus epidermidis (29.2%) and Escherichia coli (28.1%). Most of the gram-positive and gram-negative bacteria were resistant to dicloxacillin (73.8%, P=0.021) and cefotaxime (50%), respectively and ~53.4% of the isolates were multi-drug resistance isolates, 61.8% of the Staphylococcus aureus were identified as methicillin-resistant Staphylococcus aureus and 61.8% of the gram-negative bacteria were extended-spectrum ß-lactamase producers. Staphylococcus aureus and Escherichia coli were the predominant gram-positive and gram-negative bacteria isolated, respectively. Penicillin resistance was significantly higher among the gram-negative bacteria (P=0.019). Staphylococcus aureus and Escherichia coli were the predominant gram-positive and gram-negative bacteria isolated and levofloxacin and nitrofurantoin were the most effective antibiotics among the gram-positive and gram-negative bacterial isolates, respectively.

Awareness and practice of preventive measures among healthcare workers in medical institutions in Beijing during influenza season on the eve of COVID-19 epidemic: A cross-sectional survey.

BACKGROUND: Influenza is an acute respiratory infectious disease caused by the influenza virus, which poses a certain threat to humans due to its short incubation period, fast transmission and strong infectivity. OBJECTIVES: To evaluate the awareness and prevention behavior against influenza among healthcare workers on the eve of the coronavirus disease 2019 (COVID-19) epidemic in Beijing, China. MATERIAL AND METHODS: Using the cross-sectional research design based on the principle of convenience sampling, an online questionnaire survey on the knowledge of flu, vaccination, medical protection behavior, and flu medication was conducted between January and February 2020. Healthcare workers from different healthcare facilities and different job positions in Beijing participated in this survey. RESULTS: A total of 1910 healthcare workers from different medical institutions and jobs were included in the study. The mean age of the participants was 32.69 ±8.72 years (range: 18-64 years). There were significant differences in knowledge about clinical signs about flu and prevention approaches among different age groups, individuals with different work experience and job titles (χ2 = 8.903-32.839; p < 0.05). Personnel with different job positions and education levels differed only in the knowledge about clinical signs of flu and identification of high-risk populations. A multivariate logistic regression analysis revealed that age (odds ratio (OR) = 0.979, 95% confidence interval (95% CI): 0.966-0.992) and education level (OR = 0.736, 95% CI: 0.588-0.921) were risk factors for hand hygiene practices, whereas job position (OR = 1.757, 95% CI: 1.146-2.695) and awareness of high-risk populations (OR = 1.405, 95% CI: 1.096-1.800) were protective factors influencing hand hygiene practices (p < 0.05). The only factor influencing mask wearing was the education level (OR = 0.610, 95% CI: 0.450-0.828). CONCLUSION: The knowledge level and preventive behavior of healthcare workers before the outbreak of COVID-19 has been insufficient.

Research landscape on 3D printing applications in healthcare within Southeast Asian countries: a systematic scoping review protocol.

INTRODUCTION: Three-dimensional (3D) printing plays a significant role as a promising technological advancement in modern healthcare settings. 3D printing has been incorporated by many sectors worldwide including in Southeast Asian countries. However, there is a paucity of research, especially in the healthcare pertaining to 3D printing activity in the Southeast Asian region. Thus, a scoping review is conducted to gain insight into 3D printing healthcare research landscape in the Southeast Asian region. METHODS AND ANALYSIS: The methodology draws on Arksey and O'Malley's seminal framework for the scoping review. The literature search will be conducted by using keywords to find suitable published literature. The existing literature will be searched using selected electronic databases such as PubMed/MEDLINE, CINAHL, Scopus, ProQuest and Web of Science from the years 2011 and 2021. The selected publications will focus on 10 Southeast Asian countries: Malaysia, Indonesia, Singapore, Thailand, Brunei, Philippines, Laos, Vietnam, Cambodia and Myanmar. Two reviewers will be performing title and abstract screening for the criteria of each publication, in which they will be working independently of each other. The included publication will undergo a full-text review and references cited will be examined for relevance using the same inclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram will guide throughout the process. Data will be extracted, analysed and charted within each category from the selected publications for each Southeast Asian country. ETHICS AND DISSEMINATION: The results of this scoping review will illustrate an overview of the 3D printing healthcare research in the Southeast Asian context, which can be a guide for the advancement of 3D printing that can be accentuated in future research. The results will undergo dissemination which will be submitted for publication in a scientific journal.

Hypertrophic Obstructive Cardiomyopathy with SAM Phenomenon: A Case Report and Literature Review.

Background: Hypertrophic cardiomyopathy (HCM) is defined by the presence of left ventricular hypertrophy (LVH) in the absence of other potentially causative cardiac, systemic, syndromic, or metabolic diseases [1]. It is the most common genetic abnormality of the myocardium, with an anaesthetized prevalence ranging from 1:500 to as high as 1:200 [2-4]. It is the primary cause of sudden cardiac death (SCD) among teenagers and athletes. Patient: A 56-year-old man presented with chest tightness and palpitations which had been occurring post-activity for the previous 6 months. The patient was advised to be admitted. He underwent echocardiography, cardiac magnetic resonance (CMR), coronary angiography (CAG) examination, and left ventriculography. He was diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) with systolic anterior motion (SAM) phenomenon. Results: Echocardiography results showed that the interventricular septal thickness was 14-16 mm and that there were 2 degrees of SAM of the mitral valve. This resulted in severe stenosis of the left ventricular outflow tract (LVOT) and moderate to severe mitral insufficiency. Left ventriculography confirmed mitral regurgitation (MR) associated with HOCM with SAM phenomenon. Under the protection of a permanent pacemaker, the patient was treated with alcohol septal ablation (ASA). After discharge, the symptoms of chest tightness and palpitation did not recur. Conclusion: Beneficial effects were observed when patients with HOCM and SAM were treated with ASA under the condition of a permanent pacemaker.

Two New Eremophilane-Type Sesquiterpenoids from Ligularia sagitta.

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.

Que Zui tea ameliorates hepatic lipid accumulation and oxidative stress in high fat diet induced nonalcoholic fatty liver disease.

In this study, the protective effects of hot water (QW) and aqueous-ethanol extracts (QA) from Que Zui tea on non-alcoholic fatty liver disease (NAFLD) were investigated. Quantitative and qualitative analysis revealed that QW and QA were rich in polyphenols, especially 6'-O-caffeoylarbutin. Both QW and QA significantly reduced body weight and liver index, increased serum levels of high density lipoprotein cholesterol (HDL-C), and decreased the levels of total cholesterol (TC), triglyceride (TG), nonesterified free fatty acids (NEFA) and low density lipoprotein cholesterol (LDL-C) in NAFLD rats induced high fat diet. Furthermore, the contents of TC, TG, NEFA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the liver tissues were inhibited after QW and QA administration. Histopathological examination showed that QW and QA significantly reduced liver lipid accumulation of NAFLD rats. In addition, QW and QA could enhance increase the activity of antioxidant (glutathione, superoxide dismutase and catalase) in the liver by regulation Nrf2 signaling pathway, thereby alleviating liver damage caused by lipid peroxidation. QW and QA activated AMPK/PPAR-α signaling pathway by increasing the expression of adiponectin and its receptor AdipoR2, thereby reducing fat production and enhancing fatty acid ß oxidation. These data suggested that QW and QA had the potential to in the prevention and treatment of NAFLD.

6'-O-Caffeoylarbutin from Que Zui tea ameliorates acetaminophen-induced liver injury via enhancing antioxidant ability and regulating the PI3K signaling pathway.

Que Zui tea (QT), a traditional herbal tea in China, has a significant hepatoprotective effect. 6'-O-Caffeoylarbutin (CA) is the most abundant chemical compound in the QT. However, the hepatoprotective effect of CA has not been investigated. This study is aimed to evaluate the protective effect of CA on acetaminophen (APAP) induced hepatotoxicity in vivo and in vitro and its possible underlying mechanism. In APAP-induced HepG-2 cells, CA inhibited intracellular ROS accumulation and cell apoptosis, and improved the expression of antioxidants including SOD, CAT and GSH. In APAP-administrated mice, CA pretreatment remarkably ameliorated the histopathological damage and inflammatory response, and antioxidant enzyme activity in the serum and liver tissues. Moreover, the immunohistochemistry and immunofluorescence assay results revealed that the CA markedly reduced ROS production and apoptosis, and activated antioxidant transcription factor Nrf2 in the liver. Meanwhile, molecular docking results showed that the strong binding force of CA and PI3K was due to the higher number of hydrogen- and π-bonds with active site residues. Notably, CA pretreatment significantly regulated the expression of PI3K, Akt, Nrf2, NQO1, HO-1, Bcl-2, Bax, caspase-3, and caspase-9 proteins in APAP-treated liver tissues. These data demonstrated that CA had a protective effect against APAP-induced hepatotoxicity via regulating the PI3K/Akt and Nrf2 signaling pathway.

Anti-leukemic effect and molecular mechanism of 11-methoxytabersonine from Melodinus cochinchinensis via network pharmacology, ROS-mediated mitochondrial dysfunction and PI3K/Akt signaling pathway.

Melodinus cochinchinensis (Lour.) Merr. is a Yunnan endemic folk medicine. Our previous study showed that 11-methoxytabersonine (11-MT) isolated from M. cochinchinensis has strong cytotoxicity on human T-ALL cells, but its molecular mechanism has not been studied. In current study, the cytotoxicity and possible mechanism of 11-MT on T-cell acute lymphoblastic leukemia was explored using network pharmacology and molecular biology techniques. 11-MT significantly inhibited the cell proliferations on different four human T-ALL cells (MOLT-4, Jurkat, CCRF-CEM, and CEM/C1 cells). 11-MT triggered ROS accumulation, calcium concentration and cell apoptosis, and decreased the mitochondrial membrane potential (MMP) in human T-ALL cells, especially MOLT-4 cells. Western blot analysis showed that it can induce MOLT-4 cell apoptosis by up-regulating PI3K/Akt signaling pathway. Therefore, 11-MT induces human T-ALL cells apoptosis via up-regulation of ROS-mediated mitochondrial dysfunction and down-regulation of PI3K/Akt/mTOR signaling pathway.

Hypoglycemic and hypolipidemic effects of Epigynum auritum in high fat diet and streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Epigynum auritum is mainly distributed in Southwest China, and has been used as a "dai" folk medicine with promising Besides, the leaves and barks of E. auritum have detoxifying, analgesic and relieving swelling effects. Previous studies evidenced that E. auritum was rich in pregnanes and their glycosides. However, the hypoglycemic and hypolipidemic effects of the extract from E. auritum (EAE) and its molecular mechanism are still not studied. AIM OF THE STUDY: The aim of this study is to investigate the hypoglycemic and hypolipidemic effects of EAE on high-fat diet and streptozocin-induced type 2 diabetic rats. MATERIALS AND METHODS: The high-fat diet and streptozocin induced type 2 diabetic model was established. The diabetic rats were treated with 70% ethanol extract of E. auritum (100 and 300 mg/kg/d) or metformin (DMBG, 100 mg/kg/d) every day for 4 weeks. Fasting blood glucose was recorded weekly. The phenotypic changes were evaluated by the measurement of biochemical indexes and immunohistochemical. The expressions of signaling-related proteins were explored by western blotting. RESULTS: EAE could effectively regulate the metabolism of glucose and lipids in diabetic rats by increasing insulin sensitivity. In addition, EAE ameliorated the oxidative stress damage and further mitigated the liver, kidney, and pancreatic damage. Mechanism research results show that EAE treatment increased the phosphorylation of Akt, AMPK and GSK-3ß, up-regulated the expression of GLUT-2, GLUT-4 and PPAR-α, and reduced PPAR-γ and FAS expressions. CONCLUSION: EAE exhibited significant hypoglycemic and hypolipidemic effects in HFD/STZ-induced diabetes rats. The mechanism may be related to the effective upregulation of AMPK/Akt/GSK-3ß pathway and the decreased expression of PPAR-γ and FAS. It could be a promising natural product with potential value for the development of drugs to prevent or treat type 2 diabetic.

Tanshinone â ¡A inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition and protects bovine endometrial epithelial cells from pyolysin-induced damage by modulating the NF-κB/Snail2 signaling pathway.

Mixed infection with Escherichia coli and Trueperella pyogenes (T. pyogenes) leads to purulent endometritis, but the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the effect of tanshinone ⅡA (Tan ⅡA) on E. coli and T. pyogenes -induced purulent endometritis and explore the underlying mechanism. First, lipopolysaccharide (LPS) isolated from E. coli and bacteria-free filtrates (BFFs) isolated from T. pyogenes were used to induce a model of bovine endometrial epithelial cell (bEEC) damage in vitro. bEECs were pretreated with or without Tan ⅡA for 2 h, before LPS and BFFs were introduced to induce damage to investigate the protective effect of Tan IIA. Then, the cytolytic activity and inflammatory response in bEECs were examined using CCK-8, LDH and RT-qPCR assays. Furthermore, we confirmed the molecular mechanism by which Tan ⅡA reversed the damaged phenotypes in LPS- and BFFs-induced bEECs via the NF-κB/Snail2 pathway using qPCR and Western blotting. Tan ⅡA significantly decreased the cytolytic activity and inflammatory response in LPS- and BFFs-induced bEECs. In addition, Tan ⅡA reversed the dysregulation of E-cadherin, N-cadherin and vimentin. Moreover, Tan ⅡA significantly inhibited the activation of the NF-κB signaling pathway and decreased the expression level of Snail2, which is the main regulator of the epithelial-mesenchymal transition (EMT). In summary, Tan ⅡA inhibits the LPS-induced EMT and protects bEECs from pyolysin-induced damage by modulating the NF-κB/Snail2 signaling pathway.

Tanshinone IIA exhibits anti-inflammatory and antioxidative effects in LPS-stimulated bovine endometrial epithelial cells by activating the Nrf2 signaling pathway.

Endometritis is a major disease in productive bovines, and is also caused by conditional pathogens after delivery. The integrity and activity of bovine endometrial epithelial cells (bEECs) determine the development of endometritis. Tanshinone IIA, a compound purified from Salvia miltiorrhiza bunge, has been reported to have anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of tanshinone IIA in the LPS-induced inflammatory response of bEECs. The results showed that tanshinone IIA inhibited the mRNA expression levels of COX-2 and iNOS, and reduced the expression levels of IL-1ß, TNF-α, IL-6 and IL-8 induced by LPS. In addition, we found that tanshinone IIA inhibited the level of MDA, but increased the activities of CAT and SOD. To evaluate the anti-inflammatory mechanism of tanshinone IIA, we examined the activation of Nrf2. The results showed that the Nrf2 signaling pathway was significantly activated by tanshinone IIA. In conclusion, these results showed that tanshinone IIA exhibited anti-inflammatory and antioxidative effects by activating the Nrf2 signaling pathway.

MiR-194-5p serves as a potential biomarker and regulates the proliferation and apoptosis of hippocampus neuron in children with temporal lobe epilepsy.

BACKGROUND: The aim of the present study is to explore the expression level and the clinical significance of miR-194-5p to the children with temporal lobe epilepsy, and investigate its functions in regulating cell behaviors of hippocampal neurons. METHODS: The expression level of miR-194-5p was detected in the serum of 59 temporal lobe epilepsy (TLE) children and 63 healthy children. To further study the role of miR-194-5p in the development of TLE in children, the epileptiform discharge model was established in rat hippocampal neurons to mimic TLE conditions in children. Receiver operator characteristic (ROC) curves and area under the ROC curve were established to evaluate the diagnostic value of serum microRNAs to the differentiation of the TLE group and healthy group. The influence of miR-194-5p on the proliferation and apoptosis of hippocampus neurons was examined by using MTT and flow cytometric apoptosis assay. Luciferase reporter assay was performed to confirm the target gene of miR-194-5p. RESULTS: The result demonstrated that miR-194-5p was significantly dysregulated in plasma of TLE patients. Analysis of ROCs showed that the miR-194-5p had high specificity and sensitivity in the diagnosis of the TLE in children. The expression of miR-194-5p was found to increase in the hippocampal cells cultured in the magnesium-free medium through quantitative real-time polymerase chain reaction. Hyper-expressed of miR-194-5p reversed TLE-induced reduction for the cell viability, and inhibited the cell apoptosis induced by TLE. Insulin-like growth factor 1 receptor (IGF1R) was proved to be a direct target gene of miR-194-5p. CONCLUSION: MiR-194-5p is a likely potential biomarker and treatment target of TLE in children. IGF1R might be involved in the regulatory role of miR-194-5p in hippocampus neuron apoptosis.

HRESIMS-guided isolation of aspidosperma-scandine type bisindole alkaloids from Melodinus cochinchinensis and their anti-inflammatory and cytotoxic activities.

The Melodinus species have been proved to be good resources of bisindole alkaloids. Six bisindole alkaloids were isolated from the leaves and stems of Melodinus cochinchinensis (Lour.) Merr. guided by HRESIMS data analysis. Among them, melokhanines K-M, epi-scandomelonine, and epi-scandomeline possessed aspidosperma-scandine skeleton linked by a C-C bond while meloyine II had a scandine-scandine skeleton. The structures were established by extensive spectroscopic analysis of their HRESIMS and NMR data. Melokhanines K-M were undescribed compounds, while epi-scandomelonine, epi-scandomeline and meloyine II were known compounds, which were reported from Melodinus species for the first time. The anti-inflammatory and cytotoxic activities of the isolates were also evaluated in vitro. Melokhanine K and meloyine II showed potent inhibitory activity on the production of nitric oxide, interleukin-6, and tumor necrosis factor-α in LPS-induced RAW 264.7 macrophages, whereas epi-scandomelonine and epi-scandomeline exhibited certain cytotoxic activity against MOLT-4 cells with IC50 values 5.2 and 1.5 µM, respectively.

Mitochondria autophagy: a potential target for cancer therapy.

Mitophagy is a selective form of macroautophagy in which dysfunctional and damaged mitochondria can be efficiently degraded, removed and recycled through autophagy. Selective removal of damaged or fragmented mitochondria is critical to the functional integrity of the entire mitochondrial network and cells. In past decades, numerous studies have shown that mitophagy is involved in various diseases; however, since the dual role of mitophagy in tumour development, mitophagy role in tumour is controversial, and further elucidation is needed. That is, although mitophagy has been demonstrated to contribute to carcinogenesis, cell migration, ferroptosis inhibition, cancer stemness maintenance, tumour immune escape, drug resistance, etc. during cancer progression, many research also shows that to promote cancer cell death, mitophagy can be induced physiologically or pharmacologically to maintain normal cellular metabolism and prevent cell stress responses and genome damage by diminishing mitochondrial damage, thus suppressing tumour development accompanying these changes. Signalling pathway-specific molecular mechanisms are currently of great biological significance in the identification of potential therapeutic targets. Here, we review recent progress of molecular pathways mediating mitophagy including both canonical pathways (Parkin/PINK1- and FUNDC1-mediated mitophagy) and noncanonical pathways (FKBP8-, Nrf2-, and DRP1-mediated mitophagy); and the regulation of these pathways, and abovementioned pro-cancer and pro-death roles of mitophagy. Finally, we summarise the role of mitophagy in cancer therapy. Mitophagy can potentially be acted as the target for cancer therapy by promotion or inhibition.

A pilot study of the effect of a home-based multimodal symptom-management program in children and adolescents undergoing chemotherapy.

BACKGROUND: Prevalent symptoms that affect children and adolescents throughout the process of cancer diagnosis and treatment include nausea and vomiting, fatigue, pain, mucositis, and anxiety. AIM: To examine the effect of a home-based multimodal symptom-management program for alleviation of nausea and vomiting, fatigue, pain, mucositis, and anxiety in children and adolescents undergoing chemotherapy for hematological malignancies or solid tumors. METHODS: In an exploratory pilot randomized study with qualitative interview, patients between 10 and 18 years of age were randomly assigned to either the symptom-management program plus usual care (intervention group) or usual care (control group). The program consisted of multiple nonpharmacological interventional components. The targeted symptoms were measured at baseline (after diagnosis), at the first 2 weeks of each cycle of chemotherapy, and at 6 months after baseline, using the Memorial Symptom Assessment Scale 10-18 and the State Anxiety Scale for Children. RESULTS: Fifty children (31 boys; mean age, 13.7 years) were randomized either to the intervention group or the control group (25 each) and underwent baseline assessment. A comparison between the groups showed that the intervention group had a significant less fatigue over time (P < .05). However, no differences were found with respect to nausea and vomiting, pain, mucositis, and anxiety between groups. Both children and parents reported a positive experience with the symptom-management program. CONCLUSION: The home-based symptom-management program may have helped to reduce fatigue in children and adolescents undergoing chemotherapy. In addition, qualitative data support the importance of improving children and parents' knowledge, coping skills, and psychological preparation for symptoms associated with chemotherapy.