Mechanism of XiJiaQi in the treatment of chronic heart failure: Integrated analysis by pharmacoinformatics, molecular dynamics simulation, and SPR validation.

OBJECTIVE: Chronic heart failure (CHF) is a complicated clinical syndrome with a high mortality rate. XiJiaQi (XJQ) is a traditional Chinese medicine used in the clinical treatment of CHF, but its bioactive components and their modes of action remain unknown. This study was designed to unravel the molecular mechanism of XJQ in the treatment of CHF using multiple computer-assisted and experimental methods. METHODS: Pharmacoinformatics-based methods were used to explore the active components and targets of XJQ in the treatment of CHF. ADMETlab was then utilized to evaluate the pharmacokinetic and toxicological properties of core components. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were to explore the underlying mechanism of XJQ treatment. Molecular docking, surface plasmon resonance (SPR), and molecular dynamics (MD) were employed to evaluate the binding of active components to putative targets. RESULTS: Astragaloside IV, formononetin, kirenol, darutoside, periplocin and periplocymarin were identified as core XJQ-related components, and IL6 and STAT3 were identified as core XJQ targets. ADME/T results indicated that periplocin and periplocymarin may have potential toxicity. GO and KEGG pathway analyses revealed that XJQ mainly intervenes in inflammation, apoptosis, diabetes, and atherosclerosis-related biological pathways. Molecular docking and SPR revealed that formononetin had a high affinity with IL6 and STAT3. Furthermore, MD simulation confirmed that formononetin could firmly bind to the site 2 region of IL6 and the DNA binding domain of STAT3. CONCLUSION: This study provides a mechanistic rationale for the clinical application of XJQ. Modulation of STAT3 and IL-6 by XJQ can impact CHF, further guiding research efforts into the molecular underpinnings of CHF.

Fluorescence-guided photoimmunotherapy using targeted nanotechnology and ML7710 to manage peritoneal carcinomatosis.

Fluorescence-guided intervention can bolster standard therapies by detecting and treating microscopic tumors before lethal recurrence. Tremendous progress in photoimmunotherapy and nanotechnology has been made to treat metastasis. However, many are lost in translation due to heterogeneous treatment effects. Here, we integrate three technological advances in targeted photo-activable multi-agent liposome (TPMAL), fluorescence-guided intervention, and laser endoscopy (ML7710) to improve photoimmunotherapy. TPMAL consists of a nanoliposome chemotherapy labeled with fluorophores for tracking and photosensitizer immunoconjugates for photoimmunotherapy. ML7710 is connected to Modulight Cloud to capture and analyze multispectral emission from TPMAL for fluorescence-guided drug delivery (FGDD) and fluorescence-guided light dosimetry (FGLD) in peritoneal carcinomatosis mouse models. FGDD revealed that TPMAL enhances drug delivery to metastases by 14-fold. ML7710 captured interpatient variability in TPMAL uptake and prompted FGLD in >50% of animals. By combining TPMAL, ML7710, and fluorescence-guided intervention, variation in treatment response was substantially reduced and tumor control improved without side effects.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

A case of treatment of multidrug-resistant intracranial Klebsiella pneumoniae infection by multichannel colistin sulfate.

The management of severe neurologic infections due to multidrug-resistant (MDR) Klebsiella pneumoniae infection remains a challenge. Limited antibiotic treatment regimens make treatment of severe MDR K. pneumoniae infection more difficult. We describe a patient who developed severe meningitis and ventriculitis after craniotomy caused by MDR K. pneumoniae and was effectively treated with the administration of multichannel applications (intravenous, intrathecal and aerosol inhalation) of colistin sulfate. This case provides clinical evidence that the intrathecal, intravenous and aerosol inhalation of colistin sulfate by multichannel application can be a last resort in refractory intracranial infection by MDR K. pneumoniae.

Barley Leaf Ameliorates Citrobacter-rodentium-Induced Colitis through Arginine Enrichment.

Inflammatory bowel disease (IBD) has become a global public health challenge. Our previous study showed that barley leaf (BL) significantly reduces Citrobacter-rodentium (CR)-induced colitis, but its mechanism remains elusive. Thus, in this study, we used non-targeted metabolomics techniques to search for potentially effective metabolites. Our results demonstrated that dietary supplementation with BL significantly enriched arginine and that arginine intervention significantly ameliorated CR-induced colitis symptoms such as reduced body weight, shortened colon, wrinkled cecum, and swollen colon wall in mice; in addition, arginine intervention dramatically ameliorated CR-induced histopathological damage to the colon. The gut microbial diversity analysis showed that arginine intervention significantly decreased the relative abundance of CR and significantly increased the relative abundance of Akkermansia, Blautia, Enterorhabdus, and Lachnospiraceae, which modified the CR-induced intestinal flora disorder. Notably, arginine showed a dose-dependent effect on the improvement of colitis caused by CR.

Development of a new and facile method for determination of chlorpyrifos residues in green tea by dispersive liquid-liquid microextraction.

In this work a simple, rapid, and environmentally friendly method has been established for the determination of chlorpyrifos residue in green tea by dispersive liquid-liquid microextraction and gas chromatography-flame photometric detection. Some experimental parameters that influence extraction efficiency, such as the kind and volume of disperser solvents and extraction solvents, extraction time, addition of salt and pH, were investigated. And the optimal experimental conditions were obtained, quantitative analysis was carried out using external standard method. The correlation coefficient of the calibration curves was 0.999 with in 0.05 mg/kg to 5 mg/kg. The results showed that under the optimum conditions, the enrichment factors of the chlorpyrifos was about 554.51, the recoveries for standard addition fell in the range from 91.94 to 104.70% and the relative standard deviations was 4.61%. The limit of quantification of chlorpyrifos in green tea was 0.02 µg/mL at the signal/noise ratio of 3.

Modified Qing' e Pills exerts anti-osteoporosis effects and prevents bone loss by enhancing type H blood vessel formation.

Objective: To explore whether the modified Qing' e Pills (MQEP) exerts anti-osteoporotic effects and prevents bone loss by enhancing angiogenesis. Methods: Network pharmacology was used to assess whether MQEP has a pro-angiogenic capacity and to predict its potential targets. Human umbilical vein endothelial cells were treated with glucocorticoids and MQEP to assess cell viability. The expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor, and angiotensin converting enzyme, which are associated with the activation of the renin-angiotensin-aldosterone system, and the expression of vascular endothelial growth factor and hypoxia-inducible factor 1 alpha, which are associated with the formation of type H blood vessels, were examined by western blot and RT-qPCR. Thereafter, the glucocorticoid-induced osteoporosis model was established and intervened with MQEP. Femur scanning was performed with micro-computed tomography; trabecular spacing, trabecular thickness, and trabecular number were observed and calculated; the expression of nuclear factor-kappa B ligand and osteoprotegerin was detected by ELISA, and the ratio was calculated to evaluate the degree of bone resorption. Finally, type H blood vessels that were highly coupled to osteogenic cells were identified by immunohistochemistry staining and flow cytometry. Results: This is the first study to reveal and confirm that MQEP could prevent bone loss in glucocorticoid-induced osteoporosis by promoting the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, which are highly associated with type H blood vessel formation. In vitro experiments confirmed that MQEP could effectively promote the proliferation of vascular endothelial cells and alleviate glucocorticoids-induced activation of the renin-angiotensin-aldosterone system, thereby reducing vascular injury. Conclusion: MQEP exerts anti-osteoporosis effects and prevents bone loss by alleviating vascular injury caused by renin-angiotensin-aldosterone system activation and promoting type H blood vessel formation.

Advances in Our Understanding of the Mechanism of Action of Drugs (including Traditional Chinese Medicines) for the Intervention and Treatment of Osteoporosis.

Osteoporosis (OP) is known as a silent disease in which the loss of bone mass and bone density does not cause obvious symptoms, resulting in insufficient treatment and preventive measures. The losses of bone mass and bone density become more severe over time and an only small percentage of patients are diagnosed when OP-related fractures occur. The high disability and mortality rates of OP-related fractures cause great psychological and physical damage and impose a heavy economic burden on individuals and society. Therefore, early intervention and treatment must be emphasized to achieve the overall goal of reducing the fracture risk. Anti-OP drugs are currently divided into three classes: antiresorptive agents, anabolic agents, and drugs with other mechanisms. In this review, research progress related to common anti-OP drugs in these three classes as well as targeted therapies is summarized to help researchers and clinicians understand their mechanisms of action and to promote pharmacological research and novel drug development.

Blueberry Anthocyanins Extract Attenuates Acrylamide-Induced Oxidative Stress and Neuroinflammation in Rats.

Acrylamide (AA) is a widespread environmental and dietary-derived neurotoxin, which can induce oxidative stress and associated inflammation in the brain. Anthocyanins widely occur as natural antioxidant and anti-inflammatory phytochemicals. Herein, the protective effects of blueberry anthocyanins extract (BAE) against AA-induced neurotoxicity were investigated in rats. The rats were pretreated with BAE (175 mg/kg body weight/day) by oral gavage for the first 7 days, followed by the co-administration of BAE and AA (35 mg/kg body weight/day) by oral gavage for the next 12 days. Results showed that BAE significantly decreased the malondialdehyde (MDA) production, and increased glutathione (GSH) and antioxidant enzyme levels; and it also suppressed microglial activation, astrocytic reaction, and pro-inflammatory cytokine expressions. Furthermore, BAE elevated the extracellular signal-related kinase (ERK)/cAMP response elements binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway, and relieved the accumulation of amyloid beta (Aß) 1-42 and 1-40 after AA exposure. Consequently, AA-induced neuronal necrosis and downregulation of synaptosomal-associated protein 25 (SNAP-25) were attenuated by BAE in the hippocampus and cerebral cortex. In conclusion, BAE can exert a protective function on neurons and synapses against AA-induced oxidative stress and neuroinflammation.

Comparative Analysis of Polycyclic Aromatic Hydrocarbons and Halogenated Polycyclic Aromatic Hydrocarbons in Different Parts of Perilla frutescens (L.) Britt.

Perilla frutescens (L.) Britt., a medicinal herb and edible plant, is very popular among East Asian countries. The perilla leaves, stems and seeds can be used as traditional medicines and foods. Polycyclic aromatic hydrocarbons (PAHs) and halogenated PAHs (HPAHs) are organic pollutants that are widely present in the environment, such as in water, air and soil, and are harmful to humans. In this study, the contents of 16 PAHs and 4 HPAHs in perilla leaves, stems and seeds were determined by gas chromatography tandem mass spectrometry (GC-MS). A total of 12 PAHs were detected in all samples, and no HPAHs were detected. The total contents of PAHs in perilla leaves, stems and seeds varied from 41.93 to 415.60 ng/g, 7.02 to 51.52 ng/g and 15.24 to 180.00 ng/g, respectively. The statistical analyses showed that there were significant differences in the distribution of PAHs in perilla leaves, stems and seeds. On the basis of the toxic equivalent quantity (TEQ) and incremental lifetime cancer risk (ILCR) model, the cancer risks of the intake of perilla leaves, stems and seeds were assessed to be from 3.30 × 10-8 to 2.11 × 10-5, 5.52 × 10-9 to 5.50 × 10-8 and 1.20 × 10-8 to 1.41 × 10-7, respectively. These were lower than 10-4 (the priority risk level of the EPA) and suggested that there may be almost no cancer risk from the intake of these traditional Chinese medicines (TCMs).

Mechanism of Zhen Wu Decoction in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking.

Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research.

Effects of dietary guanidinoacetic acid on growth performance, guanidinoacetic acid absorption and creatine metabolism of lambs.

Guanidinoacetic acid (GAA) is the only precursor for the creatine synthesis of vertebrates. Creatine (Cr) and phosphocreatine (PCr) are able to provide energy for the rapid growth and development of the muscle tissue. This study evaluated the effects of dietary different levels GAA on growth performance, GAA absorption and creatine metabolism of lambs. Twenty-four 3-month-old healthy Kazakh male lambs (body weight = 27.35± 0.58 kg) were randomly divided into four groups with 6 lambs in each group. The lambs were fed with the basal diets supplemented with 0 (0 mg/kg group), 500 (500 mg/kg group), 1000 (1000 mg/kg group) and 1500 mg (1500 mg/kg group) GAA per kg diet (DM basis), respectively. The results showed that, as the GAA content of the diet increased, there was a quadratic change in DMI, with the lowest in the 500 mg/kg group and the highest in the 0 mg/kg group. The CK enzyme activity and ATP content in quadriceps muscle increased linearly with increasing levels of diary GAA in the diet. PCr levels and ADP levels in the longest dorsal muscle increased linearly with increasing levels of GAA in the diet. The relative expression of SLC6A6 and SLC6A8 mRNA in the jejunum and ileum mucosa showed a quadratic change as the dietary GAA level increased, with the lowest relative expression in both the 1500 mg/kg group. With the increase of dietary GAA level, both Cr concentration in hepatic vein plasma and the portal plasma GAA concentration shows a quadratic change, with the highest concentration in the 500 mg/kg group and the lowest concentration in the 0 mg/kg group. Therefore, dietary supplementation with 500~1000 mg/kg DM GAA is recommended for lambs.

A pH-targeted and NIR-responsive NaCl-nanocarrier for photothermal therapy and ion-interference therapy.

Transport ions into cells through nanocarrier to achieve ion-interference therapy provides new inspiration for cancer treatment. In this work, a pH-targeted and NIR-responsive NaCl-nanocarrier is prepared using surfactant Vitamin E-O(EG2-Glu) and modified with polydopamine (PDA) and pH-sensitive zwitterionic chitosan (ZWC). The NaCl-nanocarrier is decorated with NH4HCO3 and IR-780 to introduce near-infrared (NIR)-responsive performance and imaging. Once the NaCl-nanocarrier is exposed to NIR laser, the temperature rises rapidly because of the excellent photothermal conversion ability of PDA, then NH4HCO3 is decomposed into NH3 and CO2, which burst the nanocarrier, resulting in Cl- and Na+ "bomb-like" release. This pH-targeted nanocarrier accumulates more at tumor site and when irradiating the site with NIR light, the temperature rises and excessive Cl- and Na+ are released to destroy the ion homeostasis and inhibit tumor growth effectively. Through this strategy, the unique combination of ion interference therapy and photothermal therapy is achieved.

Deep learning-based auto-segmentation of clinical target volumes for radiotherapy treatment of cervical cancer.

OBJECTIVES: Because radiotherapy is indispensible for treating cervical cancer, it is critical to accurately and efficiently delineate the radiation targets. We evaluated a deep learning (DL)-based auto-segmentation algorithm for automatic contouring of clinical target volumes (CTVs) in cervical cancers. METHODS: Computed tomography (CT) datasets from 535 cervical cancers treated with definitive or postoperative radiotherapy were collected. A DL tool based on VB-Net was developed to delineate CTVs of the pelvic lymph drainage area (dCTV1) and parametrial area (dCTV2) in the definitive radiotherapy group. The training/validation/test number is 157/20/23. CTV of the pelvic lymph drainage area (pCTV1) was delineated in the postoperative radiotherapy group. The training/validation/test number is 272/30/33. Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) were used to evaluate the contouring accuracy. Contouring times were recorded for efficiency comparison. RESULTS: The mean DSC, MSD, and HD values for our DL-based tool were 0.88/1.32 mm/21.60 mm for dCTV1, 0.70/2.42 mm/22.44 mm for dCTV2, and 0.86/1.15 mm/20.78 mm for pCTV1. Only minor modifications were needed for 63.5% of auto-segmentations to meet the clinical requirements. The contouring accuracy of the DL-based tool was comparable to that of senior radiation oncologists and was superior to that of junior/intermediate radiation oncologists. Additionally, DL assistance improved the performance of junior radiation oncologists for dCTV2 and pCTV1 contouring (mean DSC increases: 0.20 for dCTV2, 0.03 for pCTV1; mean contouring time decrease: 9.8 min for dCTV2, 28.9 min for pCTV1). CONCLUSIONS: DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.

The risk factors for Graves' ophthalmopathy.

PURPOSE: This review aimed to provide an overview of current research into the risk factors for Graves' ophthalmopathy (GO). METHODS: To find information about the risk factors for GO, the research database PubMed was searched and relevant articles were obtained to extract information about risk factors. RESULTS: Smoking has been widely accepted as an important risk factor and cigarette smoking cessation has been shown to improve the outcome and decrease the onset of GO. Radioactive iodine on the thyroid may induce hyperthyroidism and increase the occurrence of GO. Selenium deficiency is a risk factor for GO and the supplementation of selenium has been an adjuvant therapy. Decreasing stressful life events (SLE) may help improve GO. Imbalance in intestinal flora is essential to GO, with Yersinia enterocolitica and Escherichia coli both increased in the digestive tract of the individual with GO. In addition, controlling serum cholesterol may help improve GO since adipogenesis is an important pathological change in its pathogenesis. Considering the correlation between Graves' disease and GO, maintaining normal thyroid function hormone level is the first-line therapeutic strategy to prevent progression of GO. An increase in antibodies such as TSHR and IGF-1R is the main predictor of GO. Besides, gender and gene polymorphism are also risk factors towards GO. CONCLUSIONS: Risk factors for GO arise from five sources: physical and chemical environment, social-psychological environment, biological environment, the human organism, and genetic codes. Risk factors within these categories may interact with each other and their mechanisms in promoting the development of GO are complex. Research into risk factors for GO may promote emerging fields related to GO such as control of autoantibodies and intestinal microbiota.

[The health benefits of the active ingredients and whole food components of natural plants through regulating the flora].

With the cooperation of bacteria and the human body, the nutrients in food are deeply digested, utilized, and shared. In addition, symbiosis is formed between microorganisms and hosts. Such a delicate combination makes the microorganisms form the inherent flora in the human body. They obtain the biological basis for survival, and provide the necessary regulation and support for the host in terms of immunity and nutrition, through their functional metabolism and population signals. At present, most of the researches focus on the isolation and evaluation of the functional components of plants, such as plant polysaccharides, polyphenols, flavonoids, and other active functional components. However, in traditional Chinese medicine, plants are often used with whole food components. To date, studies have found that the dynamics of flora affecting human health are not fixed, nor dependent on the change of a single strain. The ecological competition and metabolic regulation between microorganisms are usually coevolved with the host. The regulatory effect of natural plants for both medicine and food mainly depends on their whole food components. This provides evidence to support the role of whole food components played in promoting the efficacy of traditional Chinese medicine from the perspective of microenvironment. Therefore, the development and utilization of medicinal and edible natural plant activities should be fully understood and evaluated with flora regulation.

Clinical outcome of chronic myeloid leukemia patients who switch from first-line therapy with a second generation tyrosine kinase inhibitor to an alternative TKI.

While second generation tyrosine kinase inhibitors (2GTKIs) are highly effective therapies for chronic myeloid leukemia (CML), a significant minority of patients who initiate a 2GTKI will require a switch to an alternative TKI. The long-term outcomes of those who require a change in therapy after front-line 2GTKI therapy are largely undescribed. Here we describe the clinical outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4-90.6 %). Amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2-80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Approximately 25 % of patients who initiate first-line 2GTKI in a real world setting will ultimately switch to an alternate TKI due to intolerance. Patients who switch for intolerance continue to enjoy excellent clinical outcomes.

Quantitative Proteomics Analysis of Berberine-Treated Colon Cancer Cells Reveals Potential Therapy Targets.

Colon cancer is one of the most lethal malignancies worldwide. Berberine has been found to exert potential anti-colon cancer activity in vitro and in vivo, although the detailed regulatory mechanism is still unclear. This study aims to identify the underlying crucial proteins and regulatory networks associated with berberine treatment of colon cancer by using proteomics as well as publicly available transcriptomics and tissue array data. Proteome profiling of berberine-treated colon cancer cells demonstrated that among 5130 identified proteins, the expression of 865 and 675 proteins were changed in berberine-treated HCT116 and DLD1 cells, respectively. Moreover, 54 differently expressed proteins that overlapped in both cell lines were mainly involved in mitochondrial protein synthesis, calcium mobilization, and metabolism of fat-soluble vitamins. Finally, GTPase ERAL1 and mitochondrial ribosomal proteins including MRPL11, 15, 30, 37, 40, and 52 were identified as hub proteins of berberine-treated colon cancer cells. These proteins have higher transcriptional and translational levels in colon tumor samples than that of colon normal samples, and were significantly down-regulated in berberine-treated colon cancer cells. Genetic dependency analysis showed that silencing the gene expression of seven hub proteins could inhibit the proliferation of colon cancer cells. This study sheds a light for elucidating the berberine-related regulatory signaling pathways in colon cancer, and suggests that ERAL1 and several mitochondrial ribosomal proteins might be promising therapeutic targets for colon cancer.

Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota.

Supplementation of dietary fiber has been proved to be an effective strategy to prevent and relieve inflammatory bowel disease (IBD) through gut microbiota modulation. However, more attention has been paid to the efficacy of soluble dietary fiber than that of insoluble dietary fiber (IDF). In the present study, we investigated whether IDF from barley leaf (BLIDF) can inhibit gut inflammation via modulating the intestinal microbiota in DSS-induced colitis mice. The mice were fed 1.52% BLIDF-supplemented diet for 28 days. Results demonstrated that feeding BLIDF markedly mitigated DSS-induced acute colitis symptoms and down-regulated IL-6, TNF-α, and IL-1ß levels in the colon and serum of colitis mice. BLIDF supplementation effectively reduced the abundance of Akkermansia and increased the abundance of Parasutterella, Erysipelatoclostridium, and Alistipes. Importantly, the anti-colitis effects of BLIDF were abolished when the intestinal microbiota was depleted by antibiotics. Furthermore, the targeted microbiota-derived metabolites analysis suggested that BLIDF feeding can reverse the DSS-induced decline of short-chain fatty acids and secondary bile acids in mice feces. Finally, BLIDF supplementation elevated the expression of occludin and mucin2, and decreased the expression of claudin-1 in colons of DSS-treated mice. Overall, our observations suggest that BLIDF exerts anti-inflammatory effects via modulating the intestinal microbiota composition and increasing the production of microbiota-derived metabolites.

The effectiveness of iron supplementation for postpartum depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Postpartum depression (PPD) is one of the most common postpartum psychiatric disorders. The prevalence of PPD ranges from approximately 10% to 30%. In recent years, iron supplementation has emerged as potential means to treat PPD, and an increasing number of studies have been published to support the effectiveness of iron supplementation for PPD. we will conduct a comprehensive systematic review and meta-analysis to evaluate the evidence of randomized controlled trials for iron supplementation treatment of PPD. METHODS: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Science, and Technology Journal Database, and Chinese Biomedical Literature Database will be searched from their inception of databases to December 31, 2020. Two reviewers will select articles, extract data and assess the risk of bias independently. Any disagreement will be resolved by discussion with the third reviewer. Review Manager 5.3 software will be used for data synthesis. The Cochrane risk of bias assessment tool will be used to assess the risk of bias. RESULTS: This study will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the effectiveness of iron supplementation for PPD. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of iron supplementation for PPD, inform our understanding of the value of iron supplementation in improving PPD symptoms, and help clinicians to make better decisions regarding the appropriate role of iron supplementation as a part of prevention and treatment routines. STUDY REGISTRATION NUMBER: INPLASY2020110007.