ABSTRACT
Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Diterpenes , Drug Resistance, Neoplasm , Epoxy Compounds , Hedgehog Proteins , Hepatocyte Nuclear Factor 1-alpha , Lung Neoplasms , Paclitaxel , Phenanthrenes , Epoxy Compounds/pharmacology , Epoxy Compounds/therapeutic use , Humans , Phenanthrenes/pharmacology , Phenanthrenes/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Diterpenes/pharmacology , Diterpenes/therapeutic use , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Drug Resistance, Neoplasm/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Hedgehog Proteins/metabolism , Hepatocyte Nuclear Factor 1-alpha/metabolism , Hepatocyte Nuclear Factor 1-alpha/genetics , Animals , Cell Line, Tumor , Signal Transduction/drug effects , Mice, Nude , ATP Binding Cassette Transporter, Subfamily B/metabolism , ATP Binding Cassette Transporter, Subfamily B/genetics , Mice , Mice, Inbred BALB C , A549 CellsABSTRACT
BACKGROUND: The health effects of different weight loss strategies vary greatly, and the relationship between weight loss strategies, especially the combination of multiple strategies, and death is still unclear. We aimed to examine the associations of various numbers and combinations of weight loss strategies with all-cause and specific-cause mortality and to further evaluate the associations of different total weight loss volumes with mortality. METHODS: Using data from NHANES (1999-2018) with 48,430 participants aged 20 and above, we collected fourteen self-reported weight loss strategies and identified five clusters using latent class analysis. Cox proportional hazards models were used to examine the association between the amounts and clusters of weight loss strategies and mortality. RESULTS: During a median follow-up of 9.1 years of 48,430 participants, 7,539 deaths were recorded (including 1,941 CVDs and 1,714 cancer). Participants who adopted 2, 3-4, and ≥ 5 weight loss strategies had a lower risk of all-cause mortality, with HRs of 0.88 (95% CI, 0.81 to 0.97), 0.89 (95% CI, 0.81 to 0.96) and 0.71 (95% CI, 0.61 to 0.82). Regardless of weight loss or weight gain categories, there was a significant trend toward reduced mortality as the number of weight loss strategies increased (P trend < 0.05). Participants who adopted cluster-1 (four strategies), cluster-2 (five strategies) and cluster-3 (three strategies) had a significantly lower risk of all-cause mortality, with HRs of 0.71 (95% CI, 0.60 to 0.84), 0.70 (95% CI, 0.55 to 0.89) and 0.81 (95% CI, 0.70 to 0.94). Among them, cluster-1 and cluster-2 are both characterized by eating less food, exercising, drinking plenty of water, lowering calories and eating less fat. Conversely, cluster-4 (five strategies) and cluster-5 (four strategies) had marginally significant effects, and they both had actual higher total energy intakes. Similar associations were observed for CVDs and cancer mortality. CONCLUSIONS: Employing two or more weight loss strategies was associated with a lower risk of death, even among those who gained weight. Eating less food, exercising, drinking plenty of water, lowering calories and eating less fat is a better combination of strategies. On this basis, limiting the actual intake of total energy is necessary.
Subject(s)
Cause of Death , Weight Loss , Humans , Male , Female , Prospective Studies , Middle Aged , Adult , Nutrition Surveys , Mortality/trends , Aged , Proportional Hazards Models , Neoplasms/mortality , Young AdultABSTRACT
An efficient silver-mediated [2 + 2 + 1] cyclization protocol of ortho-propioloylbenzonitriles with elemental selenium for the synthesis of 4H-indeno[1,2-c][1,2]selenazol-4-ones has been developed. One C-Se bond, one N-Se bond, and one C-C bond were rapidly constructed in one step. The reaction might proceed via the formation of a highly reactive selenoketene intermediate, followed by intramolecular cyclization.
ABSTRACT
An efficient and atom-economical silver-mediated [2 + 2 + 1] cyclization protocol for the selective synthesis of 2,4- or 3,4-dicarbonylselenophenes has been developed. Readily accessible substrates, commercially available elemental selenium, and good functional group tolerance make this procedure attractive for the selective synthesis of dicarbonylselenophenes. Preliminary mechanistic investigations indicated that silver acetylene species are possible intermediates for the formation of 3,4-dicarbonylselenophenes.
ABSTRACT
BACKGROUND: Right hemi-hepatectomy plus total caudate lobectomy is the appropriate procedure for type IIIa or partial type II pCCA. However, the laparoscopic implementation of this procedure remains technically challenging, especially hilar vascular dissection and en bloc resection of the total caudate lobe. Augmented reality navigation can provide intraoperative navigation to enhance visualization of invisible hilar blood vessels and guide the parenchymal transection plane. METHODS: Eleven patients who underwent laparoscopic right hemi-hepatectomy plus total caudate lobectomy from January 2021 to January 2023 were enrolled in this study. Augmented reality navigation technology and the anterior approach were utilized in this operation. Routine operative and short-term postoperative outcomes were assessed to evaluate the feasibility of the novel navigation method in this operation. RESULTS: Right hemi-hepatectomy plus total caudate lobectomy was successfully performed in all 11 enrolled patients. Among the 11 patients, the mean operation time was 454.5 ± 25.0 min and the mean estimated blood loss was 209.1 ± 56.1 ml. Negative surgical margins were achieved in all patients. The postoperative course of all the patients was uneventful, and the mean length of postoperative hospital stay was 10.5 ± 1.2 days. CONCLUSION: Laparoscopic right hemi-hepatectomy plus total caudate lobectomy via the anterior approach may be feasible and safe for pCCA with the assistance of augmented reality navigation.
Subject(s)
Augmented Reality , Bile Duct Neoplasms , Cholangiocarcinoma , Klatskin Tumor , Laparoscopy , Liver Neoplasms , Humans , Klatskin Tumor/surgery , Hepatectomy/methods , Feasibility Studies , Liver Neoplasms/surgery , Laparoscopy/methods , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/surgeryABSTRACT
Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-ß1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-ß1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.
Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Rats , Animals , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Transforming Growth Factor beta1/metabolism , Lipid Metabolism , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/pharmacology , Silybin/pharmacology , Silybin/therapeutic use , Silybin/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucose/metabolism , Liposomes/metabolism , Liposomes/pharmacology , Disease Models, Animal , Liver/metabolism , Lipids/pharmacology , Glycolipids/metabolism , Glycolipids/pharmacologyABSTRACT
Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.
Subject(s)
Prediabetic State , Proto-Oncogene Proteins c-akt , Animals , Mice , Phosphatidylinositol 3-Kinases , Vascular Endothelial Growth Factor A , Interleukin-6 , Transcriptome , Tumor Suppressor Protein p53 , Insulin , CholesterolABSTRACT
Hydrazine is widely used in industrial and agricultural production, but excessive hydrazine possesses a serious threat to human health and environment. Here two new ratiometric fluorescence probes, DDP and DDC, with the hydroxyl coumarin chalcone unit as the sensing site are developed, which can achieve colorimetric and ratiometric recognition for hydrazine with good sensitivity, excellent selectivity, and anti-interference. The calculated fluorescence limits of detections are 0.26 µM (DDC) and 0.14 µM (DDP). The ratiometric fluorescence response to hydrazine is realized through the adjustment of donor and receptor units in coumarin conjugate structure terminals, accompanied by fluorescence peak shift about 200 nm (DDC, 188 nm; DDP, 229 nm). Stronger electropositivity in the carbon-carbon double bond is helpful to the first phase addition reaction between the probe and hydrazine. Higher phenol activity in the hydroxyl coumarin moiety will facilitate the following dihydro-pyrazole cyclization reaction. In addition, both of these probes realized the convenient detection of hydrazine vapor. The probes were also successfully applied to detect hydrazine in actual water samples, different soils, and living cells.
Subject(s)
Chalcone , Chalcones , Carbon , Coumarins/chemistry , Fluorescent Dyes/chemistry , Humans , Hydrazines/chemistry , Hydroxyl Radical , Phenols , Pyrazoles , Soil , Spectrometry, Fluorescence , WaterABSTRACT
BACKGROUND: Minimally invasive (robotic or laparoscopic-assisted) nipple-sparing mastectomy combined with prosthesis breast reconstruction (NSM-PBR) is associated with smaller scars and greater patient satisfaction. However, the oncological safety of minimally invasive NSM-PBR remains controversial. PATIENTS AND METHODS: This was a retrospective study of patients with breast cancer who underwent breast reconstruction between 1 January 2006 and 20 February 2021. Demographic and clinicopathological characteristics, operation information, postoperative complications, and survival outcomes were analyzed. RESULTS: In all, 292 patients underwent minimally invasive NSM-PBR and 205 underwent open NSM-PBR for breast cancer. In the minimally invasive NSM-PBR group, 268 (91.8%) patients underwent laparoscopy and 24 (8.2%) patients underwent robot-assisted NSM-PBR. Mean operation time in the minimally invasive NSM-PBR group was significantly longer than that in the open NSM-PBR group (P = 0.023). Mean intraoperative blood loss was significantly less in the minimally invasive NSM-PBR group (P < 0.05). There was no significant between-group difference in total complications. Similarly, there were no significant between-group differences in overall survival, recurrence-free survival, and local recurrence rate (P = 0.450, P = 0.613, and P = 0.679, respectively). CONCLUSIONS: The complication, recurrence, and mortality rates in minimally invasive NSM-PBR group were comparable to those in open NSM-PBR group. Our preliminary results are encouraging and suggest that minimally invasive NSM-PBR affords good cosmetic results and its oncological safety is comparable to that of open surgery.
ABSTRACT
We propose the inverse design of ultracompact, broadband focusing spectrometers based on adaptive diffractive optical networks (a-DONs). Specifically, we introduce and characterize two-layer diffractive devices with engineered angular dispersion that focus and steer broadband incident radiation along predefined focal trajectories with the desired bandwidth and nanometer spectral resolution. Moreover, we systematically study the focusing efficiency of two-layer devices with side length L=100µ m and focal length f=300µ m across the visible spectrum and demonstrate accurate reconstruction of the emission spectrum from a commercial superluminescent diode. The proposed a-DONs design method extends the capabilities of efficient multi-focal diffractive optical devices to include single-shot focusing spectrometers with customized focal trajectories for applications to ultracompact spectroscopic imaging and lensless microscopy.
ABSTRACT
We propose an efficient inverse design approach for multifunctional optical elements based on adaptive deep diffractive neural networks (a-D2NNs). Specifically, we introduce a-D2NNs and design two-layer diffractive devices that can selectively focus incident radiation over two well-separated spectral bands at desired distances. We investigate focusing efficiencies at two wavelengths and achieve targeted spectral line shapes and spatial point-spread functions (PSFs) with optimal focusing efficiency. In particular, we demonstrate control of the spectral bandwidths at separate focal positions beyond the theoretical limit of single-lens devices with the same aperture size. Finally, we demonstrate devices that produce super-oscillatory focal spots at desired wavelengths. The proposed method is compatible with current diffractive optics and doublet metasurface technology for ultracompact multispectral imaging and lensless microscopy applications.
Subject(s)
Optical Devices , Microscopy , Neural Networks, Computer , Optics and PhotonicsABSTRACT
OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with kidney injury, manifested as ANCA-associated glomerulonephritis (AAGN), often portends a poor prognosis of renal function and life survival in long term. METHODS: A cohort of 339 AAGN patients were enrolled retrospectively. These patients survived and were followed up for at least 12 months after diagnosis in our centre. Multivariate Cox regression analysis and nomogram models were performed to determine the risk factors associated with renal survival and patient survival. RESULTS: The median follow-up time of all 339 patients was 65.2 (IQR 45.1, 91.3) months and the median age was 61(IQR 53, 69) years. In order to analyse the impact of the factors on renal survival, we divided the patients into 2 groups: non-dialysis group (204 patients without dialysis at the final visit) and dialysis group (135 patients with maintaining dialysis). The patients in dialysis group had lower haemoglobin level, lower eGFR level, lower platelets count, more daily urine protein, and higher Birmingham Vasculitis Activity Score (BVAS) at admission than those in non-dialysis group. Multivariate Cox regression revealed that low haemoglobin (HR=0.977, 95%CI 0.965-0.990, p<0.001), low eGFR (HR=0.957, 95%CI 0.941-0.973, p<0.001) and high proteinuria (HR=1.139, 95%CI 1.055-1.230, p=0.001) at admission were independent risk factors for developing maintaining dialysis. A nomogram was established based on the results of multivariate Cox analysis and the internal bootstrap resampling approach showed the C-index of the nomogram was 0.83. Then we divided all patients into death group (n=99) and survival group (n=240). The patients in death group had older age, more hypertension, more chronic lung disease, lower platelets count, lower serum albumin, higher BVAS and lower eGFR at admission than those in survival group. Multivariate Cox regression revealed that the status of maintaining dialysis (HR 3.51, 95% CI 1.91-6.47, p<0.001) and old age (HR 1.07, 95% CI 1.04-1.09, p<0.001) were independent risk factors for all-cause mortality. Again, a nomogram was established and the C-index was 0.74. CONCLUSIONS: We analysed the independent risk factors for maintaining dialysis and all-cause mortality in AAGN patients with a follow-up of more than 12 months. The two proposed nomograms were of predictive value.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Glomerulonephritis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/therapy , Antibodies, Antineutrophil Cytoplasmic , Female , Follow-Up Studies , Glomerulonephritis/etiology , Glomerulonephritis/therapy , Hemoglobins/metabolism , Humans , Male , Nomograms , Retrospective StudiesABSTRACT
OBJECTIVES: Urinary luteinizing hormone (uLH) and urinary follicle-stimulating hormone (uFSH) have been shown to be useful screening and management tools for children with central precocious puberty. However, studies on uLH and uFSH reference intervals are scarce. Therefore, we aimed to establish reference intervals for uLH and uFSH, according to age, sex, and pubertal status in apparently healthy children aged 6-11 years. METHODS: We performed detection capability, precision, accuracy by recovery, linearity, agreement analysis, and stability testing to analyze the method performance of uLH and uFSH. The Clinical Laboratory Standards Institute's C28-A3 criteria was used to establish the reference intervals. RESULTS: Both uLH and uFSH were stable at 4 °C for 52.6 h and 64.8 days, respectively. The total imprecision of uFSH is within the manufacturer's claim, while the total imprecision of uLH remained within tolerable bias. Both uLH and uFSH could be measured with acceptable detection capability. The recovery rates of the hormones were 87.6-98.8% and 102.8-103.4%, respectively, and therefore within acceptable limits. There were significant correlations between the serum and urine concentrations (LH: r=0.91, p<0.001; FSH: r=0.90, p<0.001). The reference intervals of uLH and uFSH were established according to age, sex, and pubertal status. CONCLUSIONS: We established reference intervals for uLH and uFSH based on age, sex and pubertal status to provide a non-invasive clinical screening tool for precocious puberty in children aged 6-11 years.
Subject(s)
Luteinizing Hormone , Puberty, Precocious , Child , Follicle Stimulating Hormone , Gonadotropins , Humans , Puberty, Precocious/diagnosis , Reference ValuesABSTRACT
BACKGROUND: ABO blood group incompatibility, neonatal sepsis, G-6-PD deficiency, thyroid dysfunction, and hereditary spherocytosis are all probable causes of neonatal hyperbilirubinemia. However, the etiology of some hyperbilirubinemia is extremely complicated, which may be caused by multiple factors, resulting in severe jaundice. We report a case of severe jaundice due to three causes, showing the significance for the investigation of the etiology of neonatal hyperbilirubinemia. CASE PRESENTATION: At 96 h of life, a full-term and vaginal delivery male infant with yellowish discoloration of body was transferred to our hospital. When he entered neonatal intensive care unit on the fourth day after birth, he developed jaundice and the transcutaneous bilirubin was 28 mg/dl. Total bilirubin was 540.2 µmol/L, while the indirect bilirubin was 516.7 µmol/L. Both parents and the baby's blood types were O Rh(D +), and direct coomb's test was negative. But mother's indirect coomb's test was positive. Investigating for minor blood group revealed that the father's blood type of Rh was CCDee, the mather's was ccDEE, and CcDEe for the baby. After intensive phototherapy and double volume exchange transfusion, the total bilirubin remained at 303 µmol/L. At day 10, the bilirubin level was 303.5 µmol/L, intensive phototherapy was continued, and intravenous immunoglobulin was used again. The test for thyroid hormones at day 10, the TSH was 13.334mIU/L. And the screening for congenital hypothyroidism showed the TSH was 33mIU/L. Because of the palpable abdominal mass, ultrasound and MRI was done, showed a huge mass in the right adrenal gland. Brainstem auditory evoked potential was performed at day 7, which indicated hearing impairment (65db for left ear and 70db for the right). Euthyrox and intermittent phototherapy were given as following treatment. The jaundice did not subside until the 12th day. CONCLUSION: Even if their parents' ABO blood group and Rh (d) are consistent, a Coomb test is required for newborns with hyperbilirubinemia since they may have minor blood group incompatibilities. When bilirubin rises rapidly or the clinical treatment effect is inadequate, additional causes should be aggressively screened. Adrenal ultrasound should be performed on newborns with palpable abdominal mass, anemia and jaundice to determine whether there is adrenal hemorrhage.
Subject(s)
Congenital Hypothyroidism , Hyperbilirubinemia, Neonatal , Jaundice , Bilirubin , Female , Hematoma , Humans , Hyperbilirubinemia, Neonatal/complications , Infant, Newborn , Male , ThyrotropinABSTRACT
This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.
Subject(s)
Drugs, Chinese Herbal , Prediabetic State , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Network Pharmacology , Prediabetic State/drug therapy , Prediabetic State/geneticsABSTRACT
BACKGROUND: Most end-stage renal disease patients rely on hemodialysis (HD) to maintain their life, and they face a serious financial burden and high risk of mortality. Due to the current situation of the health care system in China, a large number of patients on HD are lost to follow-up, making the identification of patients with high mortality risks an intractable problem. OBJECTIVE: This paper aims to propose a maintenance HD mortality prediction approach using longitudinal HD data under the situation of data imbalance caused by follow-up losses. METHODS: A long short-term memory autoencoder (LSTM AE) based model is proposed to capture the physical condition changes of HD patients and distinguish between surviving and nonsurviving patients. The approach adopts anomaly detection theory, using only the surviving samples in the model training and identifying dead samples based on autoencoder reconstruction errors. The data are from a Chinese hospital electronic health record system between July 30, 2007, and August 25, 2016, and 36/72/108 continuous HD sessions were used to predict mortality within prediction windows of 90/180/365 days. Furthermore, the model performance is compared to that of logistic regression, support vector machine, random forest, LSTM classifier, isolation forest, and stacked autoencoder models. RESULTS: Data for 1200 patients (survival: 1055, death: 145) were used to predict mortality during the next 90 days using 36 continuous HD sessions. The area under the PR curve for the LSTM AE was 0.57, the Recallmacro was 0.86, and the F1-scoremacro was 0.87, outperforming the other models. Upon varying the observation window or prediction window length, LSTM AE continued to outperform the other models. According to the variable importance analysis, the dialysis session length was the feature that contributed the most to the prediction model. CONCLUSIONS: The proposed approach was able to detect patients on maintenance HD with high mortality risk from an imbalanced dataset using anomaly detection theory and leveraging longitudinal HD data.
Subject(s)
Kidney Failure, Chronic , Renal Dialysis , China , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Logistic Models , Support Vector MachineABSTRACT
BACKGROUND: Preperitoneal herniation is a rare complication after transabdominal preperitoneal patch plasty (TAPP) and may be caused by inadequate peritoneal closure. We herein report two cases of postoperative small bowel obstruction due to preperitoneal herniation through a disrupted peritoneum. CASE PRESENTATION: Two men in their 70s were admitted to our center because of small bowel obstruction after TAPP. After examinations and unsuccessful conservative treatment, emergency laparoscopic exploration was performed. Preperitoneal herniation through the disrupted peritoneum was found. The herniated small bowel was reduced and the peritoneum was properly reclosed. The patients recovered and were discharged with normal bowel function. CONCLUSIONS: Inadequate peritoneal closure may cause preperitoneal herniation and lead to postoperative small bowel obstruction and even death. Hernia surgeons can avoid this complication by improving their suture technique and paying attention to the procedure details.
Subject(s)
Hernia, Inguinal , Intestinal Obstruction , Laparoscopy , Hernia, Inguinal/surgery , Herniorrhaphy/adverse effects , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Male , Peritoneum/surgery , Surgical Mesh , Suture TechniquesABSTRACT
The goal of this study was to identify and compare the main biomarkers of Taxillus chinensis from different hosts. A metabolomics approach utilizing ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS), including cluster analysis, sample correlation analysis and orthogonal partial least squares discriminant analysis, was used to explore the flavonoid metabolites of Taxillus chinensis growing on different hosts. Results: The total flavonoids content (up to 30.08 mg/g) in Taxillus chinensis from Morus alba (CSG) was significantly higher than that from growth on Liquidambar formosana (CFG) or Clausena lansium (CHG) (p < 0.01). There were 23 different metabolites between CSG and CHG, 23 different metabolites between CSG and CFG, and 19 different metabolites between CHG and CFG. The results demonstrated that different hosts exerted a large influence on the metabolites of Taxillus chinensis; it was found that CSG differed from CFG and CHG in eleven metabolic compounds, ten of which were upregulated and one of which was downregulated. Most of these metabolites derive from compounds contained in the host plant, white mulberry (Morus alba); many feature potent anti-cancer effects. Differences in host can influence the type and abundance of flavonoids in parasitic plants such as Taxillus chinensis, which is of great significance to researchers seeking to understand the formation mechanism of Taxillus chinensis metabolites. Therefore, attention should be paid to the species of host plant when studying the Taxillus chinensis metabolome. Plants grown on Morus alba offer the greatest potential for the development of new anti-cancer drugs.
Subject(s)
Flavonoids/metabolism , Loranthaceae/chemistry , Metabolomics , Chromatography, High Pressure Liquid , Flavonoids/analysis , Tandem Mass SpectrometryABSTRACT
Based on the research literatures of Passiflora incarnata and the theory of traditional Chinese medicine, the paper discussed the traditional Chinese medicinal properties of P. incarnate, so as to provide a theoretical basis for the compatibility and application of P. incarnata. The literature databases of CNKI, Wanfang, VIP, Web of Science, PubMed and Scopus were selected, and the literatures relating to P. incarnata were reviewed to screen out the scientific research literatures with a high credibility, rational design and reliable conclusions. Foreign pharmacopoeia was consulted, and the listed products were summarized. The traditional Chinese medicine properties of P. incarnata were studied based on 32 clinical trials, 66 pharmacological researches, 64 chemical constituents researches as well as the theory of traditional Chinese medicine. It was preliminarily concluded that the medicinal properties of P. incarnata are sweet, cool, and enter heart, liver channels. The function is mainly to calm the heart and tranquilizing the mind, and calm the liver wind. It is used for hyperactivity of liver-Yang, stagnation of liver-Qi, restlessness of mind, depression, nervousness, insomnia. This paper summarized the source, characteristics of natures, tastes and channel tropism, usage and dosage, function indications of P. incarnata, and defined its clear traditional Chinese medicine property, which lays a theoretical foundation for the compatibility and clinical application of P. incarnata and Chinese medicine.
Subject(s)
Anti-Anxiety Agents , Drugs, Chinese Herbal , Passiflora , Sleep Initiation and Maintenance Disorders , Anxiety , Humans , Medicine, Chinese Traditional , Sleep Initiation and Maintenance Disorders/drug therapyABSTRACT
BACKGROUND: Peritoneal fibrosis (PF) is a frequent complication caused by peritoneal dialysis (PD). Peritoneal mesothelial cells (PMCs), the first barrier of the peritoneum, play an important role in maintaining structure and function in the peritoneum during PD. Mesothelial-mesenchymal transition (MMT) and oxidative stress of PMCs are two key processes of PF. PURPOSE: To elucidate the efficacy and possible mechanism of asiaticoside inhibition of MMT and ROS generation in TGF-ß1-induced PF in human peritoneal mesothelial cells (HPMCs). METHODS: MMT and ROS generation of HPMCs were induced by TGF-ß1. To explain the anti-MMT and antioxidant role of asiaticoside, varied doses of asiaticoside, oxygen radical scavenger (NAC), TGF-ß receptor kinase inhibitor (LY2109761) and Nrf2 inhibitor (ML385) were used separately. Immunoblots were used to detect the expression of signaling associated proteins. DCFH-DA was used to detect the generation of ROS. Transwell migration assay and wound healing assay were used to verify the capacity of asiaticoside to inhibit MMT. Immunofluorescence assay was performed to observe the subcellular translocation of Nrf2 and expression of HO-1. RESULTS: Asiaticoside inhibited TGF-ß1-induced MMT and suppressed Smad signaling in a dose-dependent manner. Migration and invasion activities of HPMCs were decreased by asiaticoside. Asiaticoside decreased TGF-ß1-induced ROS, especially in a high dose (150 µM) for 6 h. Furthermore, ML385 partly abolished the inhibitory effect of asiaticoside on MMT, ROS and p-Smad2/3. CONCLUSIONS: Asiaticoside inhibited the TGF-ß1-induced MMT and ROS via Nrf2 activation, thus protecting the peritoneal membrane and preventing PF.