Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Preparation of Rehmanniae Radix Praeparata polysaccharide iron(III) complex and evaluation of its biological activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron(III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

OMA1 competitively binds to HSPA9 to promote mitophagy and activate the cGAS-STING pathway to mediate GBM immune escape.

BACKGROUND: Immunotherapy with checkpoint inhibitors, especially those targeting programmed death receptor 1 (PD-1)/PD-1 ligand (PD-L1), is increasingly recognized as a highly promising therapeutic modality for malignancies. Nevertheless, the efficiency of immune checkpoint blockade therapy in treating glioblastoma (GBM) is constrained. Hence, it is imperative to expand our comprehension of the molecular mechanisms behind GBM immune escape (IE). METHODS: Protein chip analysis was performed to screen aberrantly expressed OMA1 protein in PD-1 inhibitor sensitive or resistant GBM. Herein, public databases and bioinformatics analysis were employed to investigate the OMA1 and PD-L1 relation. Then, this predicted relation was verified in primary GBM cell lines through distinct experimental methods. To investigate the molecular mechanism behind OMA1 in immunosuppression, a series of experimental methods were employed, including Western blotting, co-immunoprecipitation (Co-IP), mass spectrometry (MS), immunofluorescence, immunohistochemistry, and qRT-PCR. RESULTS: Our findings revealed that OMA1 competitively binds to HSPA9 to induce mitophagy and mediates the IE of GBM. Data from TCGA indicated a significant correlation between OMA1 and immunosuppression. OMA1 promoted PD-L1 levels in primary cells from patients with GBM. Next, the results of Co-IP and MS conducted on GBM primary cells revealed that OMA1 interacts with HSPA9 and induces mitophagy. OMA1 promoted not only cGAS-STING activity by increasing mitochondrial DNA release but also PD-L1 transcription by activating cGAS-STING. Eventually, OMA1 has been found to induce immune evasion in GBM through its regulation of PD-1 binding and PD-L1 mediated T cell cytotoxicity. CONCLUSIONS: The OMA1/HSPA9/cGAS/PD-L1 axis is elucidated in our study as a newly identified immune therapeutic target in GBM.

Effect of pre-admission "quasi-collective" education on health education for patients with ophthalmic day surgery.

BACKGROUND: Day surgery is a new surgical model in which patients complete the admission, surgery, and discharge on the same day. OBJECTIVE: The present study aimed to explore the effect of pre-admission "quasi-collective" health education for patients with ophthalmic day surgery. METHODS: For this study, a total of 200 patients undergoing ophthalmic day surgery from February 2019 to December 2019 were enrolled as the research subjects. The patients were divided randomly into the observation group and the control group, with 100 cases in each group. For the control group, conventional health education was conducted after admission. On the day of admission, the admission education and peri-operative health education were performed. For the observation group, pre-admission health education was provided to the patients, and detailed education on the admission instructions, pre-operative precautions, and simulation of the intra-operative process were given by the medical staff. On the day of admission, the understanding of the education was evaluated, and any weaknesses in the health education were addressed. The anxiety status, method of handwashing, method of administering the drug to the eye, preoperative preparations, intra-operative training, preoperative medication, diet guidance, and postoperative care were compared between the two groups of patients. RESULTS: Before discharge, there were significant differences in the anxiety scores, impact, and satisfaction of health education between the two groups of patients, all of which were statistically significant (P< 0.05). CONCLUSION: The pre-admission "quasi-collective" health education for patients undergoing day surgery in ophthalmology was better than conventional health education.

Effects of clinical nursing pathway on surgical site wound infection in patients undergoing acute appendicitis surgery: A meta-analysis.

This study aimed to explore the impact of clinical nursing pathway applied to acute appendicitis surgery on patients' postoperative wound infections and complications. A computerised search of PubMed, Cochrane Library, Web of Science, EMBASE, Wanfang, Chinese Biomedical Literature Database and China National Knowledge Infrastructure was conducted and supplemented by a manual search, from database inception to October 2023, to collect randomised controlled trials (RCTs) on the application of clinical nursing pathways to acute appendicitis surgery. Literature screening, data extraction and quality assessment of the included literature were carried out independently by two researchers. RevMan 5.4 software was applied for data analysis. Twenty-one RCTs with a total of 2408 patients were finally included. The analysis revealed the implementation of clinical nursing pathway could effectively reduce the incidence of wound infection (OR = 0.26, 95% CI: 0.15-0.46, p < 0.001) and postoperative complications (OR = 0.20, 95% CI: 0.15-0.27, p < 0.001), as well as shorten the hospital length of stay (MD = -3.26, 95% CI: -3.74 to -2.79, p < 0.001) and accelerated the time to first ventilations (MD = -14.85, 95% CI: -21.56 to -8.13, p < 0.001), as well as significantly improved patient satisfaction (OR = 5.52, 95% CI: 3.52-8.65, p < 0.001) in patients undergoing surgery for acute appendicitis. The application of clinical nursing pathway in acute appendicitis surgery can significantly reduce postoperative wound infection and complications, and at the same time can shorten the hospital length of stay as well as improve the satisfaction of patients.

Steroidal Saponins from Solanum lyratum Thunb.

Four undescribed steroidal compounds along with twenty known compounds were isolated from n-butanol extracted fraction of the whole plants of Solanum lyratum Thunb (SLNF). Their structures were assigned based on analyses of the extensive spectroscopic data (including MS, 1D/2D NMR, and ECD) or comparisons of the NMR data with those reported. Among the knowns, three compounds were isolated from Solanum plants for the first time, while one compound was isolated from S. lyratum for the first time. In addition, the cytotoxicities of these isolates against human colon SW480 and hepatoma Hep3B cells were evaluated by a MTT assay. And, nine of them and SLNF exhibited significant activities against both SW480 and Hep3B cells, while twelve of them significantly inhibited the activities of SW480 cells. This study allows for the exploitation of chemical markers with potential significance in discrimination of Solanum plants, and uncovers the diverse steroidal constituents from S. lyratum dedicated for its future application in cancer treatment.

Application of contrast-enhanced ultrasound in the surgical treatment of vesicoureteral reflux in children.

BACKGROUND: To determine the utility of contrast-enhanced voiding urography (CeVUS) in the treatment of vesicoureteral reflux (VUR) through ureterovesical reimplantation in children. METHODS: A total of 159 children with recurrent urinary tract infections were selected for CeVUS and voiding cystourethrography (VCUG) from December 2018 to December 2020, among whom 78 patients were eventually diagnosed with VUR. Overall, 60 pyelo-ureteric units (PUUs) were operated according to surgical indications. Accordingly, we determined the general clinical characteristics of all children, obtained two-dimensional ultrasound images, assessed the reflux status of children using the contrast-enhanced technique, and compared the obtained results via CeVUS and VCUG. Both imaging modalities were reperformed at 6, 12, and 18 months after surgery to evaluate postoperative outcomes. In particular, we assessed the consistency of the evaluation and calculated the diagnostic efficacy of CeVUS for different levels of reflux at different time points. RESULTS: CeVUS showed considerable efficacy in the diagnosis of children with VUR. Notably, the diagnostic results of both CeVUS and VCUG achieved high agreement, with a kappa value of 0.966 (P < 0.001). The results of our follow-up at different stages and evaluation of postoperative efficacy revealed that CeVUS possessed substantial diagnostic efficacy and good consistency with VCUG. CONCLUSION: CeVUS is an accurate and safe examination, with considerable clinical significance for diagnosing VUR in children, determining the treatment approach, conducting follow-up during treatment, and evaluating subsequent treatment outcomes.

Prevention of STAT3-related pathway in SK-N-SH cells by natural product astaxanthin.

PURPOSE: Neuroblastoma (NB) is the most common solid malignancy in children. Despite current intensive treatment, the long-term event-free survival rate is less than 50% in these patients. Thus, patients with NB urgently need more valid treatment strategies. Previous research has shown that STAT3 may be an effective target in high-risk NB patients. However, there are no effective inhibitors in clinical evaluation with low toxicity and few side effects. Astaxanthin is a safe and natural anticancer product. In this study, we investigated whether astaxanthin could exert antitumor effects in the SK-N-SH neuroblastoma cancer cell line. METHOD: MTT and colony formation assays were used to determine the effect of astaxanthin on the proliferation and colony formation of SK-N-SH cells. Flow cytometry assays were used to detect the apoptosis of SK-N-SH cells. The migration and invasion ability of SK-N-SH cells were detected by migration and invasion assays. Western blot and RT-PCR were used to detect the protein and mRNA levels. Animal experiments were carried out and cell apoptosis in tissues were assessed using a TUNEL assay. RESULT: We confirmed that astaxanthin repressed proliferation, clone formation ability, migration and invasion and induced apoptosis in SK-N-SH cells through the STAT3 pathway. Furthermore, the highest inhibitory effect was observed when astaxanthin was combined with si-STAT3. The reason for this may be that the combination of astaxanthin and si-STAT3 can lower STAT3 expression further than astaxanthin or si-STAT3 alone. CONCLUSION: Astaxanthin can exert anti-tumor effect on SK-N-SH cells. The inhibitory effect was the higher when astaxanthin was combined with si-STAT3.

Two-Fold ND5 Genes, Three-Fold Control Regions, lncRNA, and the "Missing" ATP8 Found in the Mitogenomes of Polypedates megacephalus (Rhacophridae: Polypedates).

In prior research on the mitochondrial genome (mitogenome) of Polypedates megacephalus, the one copy of ND5 gene was translocated to the control region (CR) and the ATP8 gene was not found. Gene loss is uncommon among vertebrates. However, in this study, we resequenced the mitogenomes of P. megacephalus from different regions using a "primer bridging" approach with Sanger sequencing technologies, which revealed the "missing" ATP8 gene in P. megacephalus as well as three other previously published Polypedates. The mitogenome of this species was found to contain two copies of the ND5 genes and three copies of the control regions. Furthermore, multiple tandem repeats were identified in the control regions. Notably, we observed that there was no correlation between genetic divergence and geographic distance. However, using the mitogenome, gene expression analysis was performed via RT-qPCR of liver samples and it was thus determined that COIII, ND2, ND4, and ND6 were reduced to 0.64 ± 0.24, 0.55 ± 0.34, 0.44 ± 0.21 and 0.65 ± 0.17, respectively, under low-temperature stress (8 °C) as compared with controls (p < 0.05). Remarkably, the transcript of long non-coding RNA (lncRNA) between positions 8029 and 8612 decreased significantly with exposure to low-temperature stress (8 °C). Antisense ND6 gene expression showed a downward trend, but this was not significant. These results reveal that modulations of protein-coding mitochondrial genes and lncRNAs of P. megacephalus play a crucial role in the molecular response to cold stress.

[The Latest Research Progress of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients --Review].

Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Bone marrow mesenchymal stem cells (MSC) play an important role in the progression of MM. Compared with normal donor derived MSC (ND-MSC), MM patients derived MSC (MM-MSC) exhibit abnormalities in genes, signaling pathways, protein expression levels and cytokines secreted by themselves. Moreover, the exosomes of MM-MSC can interact with the bone marrow microenvironment. The above reasons can lead to MM cell proliferation, chemoresistance, impaired osteogenic differentiation of MM-MSC, and affect the immunomodulatory capacity of MM patients. In order to further understand the pathogenesis and related influencing factors of MM, this paper reviews the latest research progress of MM-MSC.

SGK3 overexpression correlates with a poor prognosis in endoscopically resected superficial esophageal squamous cell neoplasia: A long-term study.

BACKGROUND: The expression status of serum and glucocorticoid-induced protein kinase 3 (SGK3) in superficial esophageal squamous cell neoplasia (ESCN) remains unknown. AIM: To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection. METHODS: A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled. Immunohistochemistry was used to evaluate SGK3 expression. RESULTS: SGK3 was overexpressed in 55 (59.8%) patients with ESCN. SGK3 overexpression showed a significant correlation with death (P = 0.031). Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group (P = 0.013 and P = 0.004, respectively). Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients (hazard ratio 4.729; 95% confidence interval: 1.042-21.458). CONCLUSION: SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival. Thus, it might be a new prognostic factor for ESCN.

Phytochemistry, data mining, pharmacology, toxicology and the analytical methods of Cyperus rotundus L. (Cyperaceae): a comprehensive review.

Cyperus rotundus L. has been widely used in the treatment and prevention of numerous diseases in traditional systems of medicine around the world, such as nervous, gastrointestinal systems diseases and inflammation. In traditional Chinese medicine (TCM), its rhizomes are frequently used to treat liver disease, stomach pain, breast tenderness, dysmenorrheal and menstrual irregularities. The review is conducted to summarize comprehensively the plant's vernacular names, distribution, phytochemistry, pharmacology, toxicology and analytical methods, along with the data mining for TCM prescriptions containing C. rotundus. Herein, 552 compounds isolated or identified from C. rotundus were systematically collated and classified, concerning monoterpenoids, sesquiterpenoids, flavonoids, phenylpropanoids, phenolics and phenolic glycosides, triterpenoids and steroids, diterpenoids, quinonoids, alkaloids, saccharides and others. Their pharmacological effects on the digestive system, nervous system, gynecological diseases, and other bioactivities like antioxidant, anti-inflammatory, anti-cancer, insect repellent, anti-microbial activity, etc. were summarized accordingly. Moreover, except for the data mining on the compatibility of C. rotundus in TCM, the separation, identification and analytical methods of C. rotundus compositions were also systematically summarized, and constituents of the essential oils from different regions were re-analyzed using multivariate statistical analysis. In addition, the toxicological study progresses on C. rotundus revealed the safety property of this herb. This review is designed to serve as a scientific basis and theoretical reference for further exploration into the clinical use and scientific research of C. rotundus. Supplementary Information: The online version contains supplementary materials available at 10.1007/s11101-023-09870-3.

Anti-apoptotic effect of HeidihuangWan in renal tubular epithelial cells via PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Heidihuang Wan (HDHW) is a classic Chinese herbal formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used clinically for the treatment of kidney diseases and its curative effect is stable. Previous animal experiments have confirmed that HDHW can effectively improve renal fibrosis. However, the underlying pharmacological mechanism remains unclear. AIMS OF THIS STUDY: Renal tubular epithelial cell (RTEC) apoptosis is one of the main pathological features of renal fibrosis. This study aimed to observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to further explore the pathological mechanism of HDHW against renal fibrosis. MATERIALS AND METHODS: We examined the HDHW composition in rat serum. In vitro, we first screened out the optimal intervention concentration of HDHW on RTECs using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of RTECs was detected using flow cytometry and protein expression was detected by western blotting. The 5/6 nephrectomy rat model was constructed and divided into the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western blotting was used to detect protein expression. RESULTS: HDHW downregulated the expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling pathway, and reversed the early apoptosis of RTECs, thereby resisting the apoptosis of RTECs. CONCLUSION: HDHW inhibits apoptosis of RTECs by modulating the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its pharmacological mechanism of action.

[Application of metronidazole combined with minocycline in reducing infection after dental implant in patients with localized periodontitis].

PURPOSE: To explore the value of metronidazole combined with minocycline in reducing infection after dental implant in patients with localized periodontitis. METHODS: A total of 120 patients with localized periodontitis who underwent dental implantation in the Department of Stomatological, Shanghai Pudong New Area People's Hospital from August 2021 to September 2022 were selected. According to the way of postoperative infection prevention, the patients were divided into control group and experimental group, with 60 patients in each group. The control group was orally given roxithromycin capsules, and the experimental group was locally coated with minocycline hydrochloride ointment and metronidazole gel. The incidence of postoperative infection and complications was compared between the two groups. The modified gingival creval bleeding index (mSBI), periodontal probing depth (PD) and modified plaque index (mPLI) of the patients were examined by periodontal probe. Serum C-reactive protein (CRP) level was determined by immunoturbidimetry and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) level was determined by ELISA. SPSS 25.0 software package was used for statistical analysis of the data. RESULTS: Good healing rate of the experimental group was 91.67% higher than that of the control group 73.33%, postoperative infection rate was 8.33% and complication rate was 6.67% in the experimental group, significantly lower than that of the control group (26.67% and 20.00%), respectively (P＜0.05). After treatment, the level of CRP, TNF-α and IL-6 in the experimental group were significantly lower than those in the control group (P＜0.05). At 3 and 6 months after treatment, mSBI, mPLI and PD in the experimental group were significantly lower than those in the control group(P＜0.05). CONCLUSIONS: The administration of minocycline hydrochloride and metronidazole in patients with localized periodontitis undergoing implantation can reduce oral inflammatory response, reduce postoperative infection and other complications, and improve periodontal health.

Phytochemical and pharmacological studies on Solanum lyratum: a review.

Solanum lyratum is one of the temperate plants, broadly distributed in Korea, China, Japan, India, and South-East Asia and well-documented in those oriental ethnic medicine systems for curing cancers, jaundice, edema, gonorrhea, cholecystitis, phlogosis, rheumatoid arthritis, etc. This review systematically summarized the research progress on S. lyratum respecting the botany, traditional uses, phytochemistry, pharmacology, and toxicology to increase people's in-depth understanding of this plant, by data retrieval in a series of online or off-line electronic databases as far as we can reach. Steroidal saponins and alkaloids, terpenoids, nitrogenous compounds, and flavonoid compounds are the main chemical constituents in S. lyratum. Among them, steroidal alkaloids and saponins are the major active ingredients ever found in S. lyratum, exerting activities of anti-cancer, anti-inflammation, anti-microbial, anti-allergy, and anti-oxidation in vivo or in vitro. As a result, S. lyratum has been frequently prescribed for the abovementioned therapeutic purposes, and there are substantial traditional and modern shreds of evidence of its use.

Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis.

BACKGROUND: Proteomic signatures of Ming's infiltrative gastric cancer (IGC) remain unknown. AIM: To elucidate the molecular characteristics of IGC at the proteomics level. METHODS: Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry. The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software. The differentially expressed proteins (DEPs) were screened using |log2(Fold change)| > 1 and P-adj < 0.01 as the thresholds. The expression levels of selected proteins were verified by Western blotting. The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software. The DEPs were functionally annotated using clusterProfiler, STRING and DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. P < 0.05 was considered statistically significant. RESULTS: A total of 7361 DEPs were identified, of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues. The top 10 up-regulated proteins were MRTO4, BOP1, PES1, WDR12, BRIX1, NOP2, POLR1C, NOC2L, MYBBP1A and TSR1, and the top 10 down-regulated proteins were NDUFS8, NDUFS6, NDUFA8, NDUFA5, NDUFC2, NDUFB8, NDUFB5, NDUFB9, UQCRC2 and UQCRC1. The up-regulated proteins were enriched for 9 biological processes including DNA replication, ribosome biogenesis and initiation of DNA replication, and the cellular component MCM complex. Among the down-regulated proteins, 17 biological processes were enriched, including glucose metabolism, pyruvic acid metabolism and fatty acid ß-oxidation. In addition, the mitochondrial inner membrane, mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components, and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity, acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched. The significant KEGG pathways for the up-regulated proteins were DNA replication, cell cycle and mismatch repair, whereas 18 pathways including oxidative phosphorylation, fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins. CONCLUSION: The proteins involved in cell cycle regulation, DNA replication and mismatch repair, and metabolism were significantly altered in IGC, and the proteomic profile may enable the discovery of novel biomarkers.

[The Latest Research Progress on Myelodysplastic Syndrome Patient-derived Mesenchymal Stem Cell--Review].

Myelodysplastic syndrome (MDS) are a heterogeneous group of hematological malignancies. Currently, in addition to demethylated chemotherapy and hematopoietic stem cell transplantation, MDS patient-derived mesenchymal stem cells (MDS-MSC) play an important role in understanding the pathogenesis of MDS and related therapeutic targets. For example, abnormal expression of DICER1 gene, abnormalities of PI3K/AKT and Wnt/ß-catenin signaling pathways provide new therapeutic targets for MDS. In addition, MDS-MSC is also affected by abnormal microenvironment of the body, such as inflammatory factor S100A9, as well as hypercoagulation and iron overload. In this review, genes, signaling pathways, cytokines, hematopoietic microenvironment, and the effect of therapeutic drugs for MDS-MSC were briefly summarized.

Systematic analysis of the potential off-target activities of osimertinib by computational target fishing.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used to treat non-small cell lung cancer. However, its off-targets are obscure, and systematic analysis of off-target activities remains to be performed. Here, we identified the off-targets of osimertinib using PharmMapper and DRAR-CPI and analyzed the intersected targets using the GeneMANIA and DAVID servers. A drug-target-pathway network was constructed to visualize the associations. The results showed that osimertinib is associated with 31 off-targets, 40 Kyoto Encyclopedia of Genes and Genomes pathways, and 9 diseases. Network analysis revealed that the targets were involved in cancer and other physiological processes. In addition to EGFR, molecular docking analysis showed that seven proteins, namely Janus kinase 3, peroxisome proliferator-activated receptor alpha, renin, mitogen-activated protein kinases, lymphocyte-specific protein tyrosine kinase, cell division protein kinase 2 and proto-oncogene tyrosine-protein kinase Src, could also be potential targets of osimertinib. In conclusion, osimertinib is predicted to target multiple proteins and pathways, resulting in the formation of an action network via which it exerts systematic pharmacological effects.

Beta-blockers and 1-year clinical outcomes in hospitalized heart failure patients with atrial fibrillation.

OBJECTIVE: To assess the association between beta-blockers and 1-year clinical outcomes in heart failure (HF) patients with atrial fibrillation (AF), and further explore this association that differs by left ventricular ejection fraction (LVEF) level. METHODS: We enrolled hospitalized HF patients with AF from China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study. COX proportional hazard regression models were employed to calculate hazard ratio of beta-blockers. The primary outcome was all-cause death. RESULTS: Among 1762 HF patients with AF (756 women [41.4%]), 1041 (56%) received beta-blockers at discharge and 1272 (72.2%) had an LVEF > 40%. During one year follow up, all-cause death occurred in 305 (17.3%), cardiovascular death occurred in 203 patients (11.5%), and rehospitalizations for HF occurred in 622 patients (35.2%). After adjusting for demographic characteristics, social economic status, smoking status, medical history, anthropometric characteristics, and medications used at discharge, the use of beta-blockers at discharge was not associated with all-cause death [hazard ratio (HR): 0.86; 95% Confidence Interval (CI): 0.65-1.12; P = 0.256], cardiovascular death (HR: 0.76, 95% CI: 0.52-1.11; P = 0.160), or the composite outcome of all-cause death and HF rehospitalization (HR: 0.97, 95% CI: 0.82-1.14; P = 0.687) in the entire cohort. There were no significant interactions between use of beta-blockers at discharge and LVEF with respect to all-cause death, cardiovascular death, or composite outcome. In the adjusted models, the use of beta-blockers at discharge was not associated with all-cause death, cardiovascular death, or composite outcome across the different levels of LVEF: reduced (< 40%), mid-range (40%-49%), or preserved LVEF (≥ 50%). CONCLUSION: Among HF patients with AF, the use of beta-blockers at discharge was not associated with 1-year clinical outcomes, regardless of LVEF.