Comparative single-cell RNA sequencing analysis of immune response to inactivated vaccine and natural SARS-CoV-2 infection.

Uncovering the immune response to an inactivated SARS-CoV-2 vaccine (In-Vac) and natural infection is crucial for comprehending COVID-19 immunology. Here we conducted an integrated analysis of single-cell RNA sequencing (scRNA-seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In-Vac compared with those from COVID-19 patients. Our study reveals that In-Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In-Vac modestly upregulates IFN-α but downregulates NF-κB pathways, while natural infection triggers hyperactive IFN-α and NF-κB pathways. Both In-Vac and natural infection alter T/B cell receptor repertoires, but COVID-19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL-15RA/IL-15 receptor pathway after In-Vac boost, suggesting its potential role in enhancing In-Vac-induced immunity. Collectively, our study illuminates multifaceted immune responses to In-Vac and natural infection, providing insights for optimizing SARS-CoV-2 vaccine efficacy.

Diagnostic Significance of DCE-MRI-Related Quantitative Parameters for Nasal Cavity and Sinus Tumors.

Objective: Our aim was to explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-related quantitative parameters for benign and malignant nasal cavity and sinus tumors. Methods: A total of 78 patients with nasal sinus tumors admitted to People's Hospital of Qingdao Chengyang District in China were enrolled in our study, Of the patients, 41 were diagnosed as having benign tumors and 37 as having malignant tumors by pathological diagnosis. All patients received DCE-MRI scans before surgery to derive time-intensity curves (TICs) and related quantitative parameters (flux rate constant [Kep], transfer constant [Ktrans], extravascular volume fraction [Ve]). The diagnostic surgical pathology results were used as the gold standard to analyze the diagnostic effect of TIC and related quantitative parameters of DCE-MRI, and the receiver operating characteristic (ROC) curves were plotted to determine the values of each parameter in predicting nasal sinus tumors. Results: The percentage of class I in the benign group was significantly higher than in the malignant group (P < .05); the percentage of class III in the benign group was significantly lower than in the malignant group (P < .05); the percentage of class II in the 2 groups was comparable (P > .05). Kep, Ktrans and Ve in the benign group were 0.338±0.124, 0.061±0.035 and 0.532±0.138, respectively; Kep, Ktrans and Ve in the malignant group were 0.785±0.211, 0.441±0.125 and 0.327±0.048, respectively. The levels of Kep and Ktrans were significantly lower in the benign group than in the malignant group (all P < .05); the levels of Ve were significantly higher in the benign group than in the malignant group (P < .05). The optimal Kep cut-off value for predicting malignant nasal sinus tumors was 0.510 min-1, with a sensitivity of 81.4% and specificity of 89.5%; the optimal Ktrans cut-off value for predicting malignant nasal sinus tumors was 0.206 min-1, with a sensitivity of 84.3% and specificity of 89.7%; the optimal Ve cut-off value for predicting malignant nasal sinus tumors was 0.384 min-1, with a sensitivity of 71.8% and specificity of 82.4%. Conclusion: DCE-MRI-related quantitative parameters are ideal for the diagnosis of benign and malignant nasal sinus tumors. This modality provides more data for the identification of the nature of the tumor, and thus merits clinical promotion and application.

Comparison of short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis in laparoscopic total gastrectomy.

BACKGROUND: To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy. METHODS: This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed. RESULTS: Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group. CONCLUSIONS: Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.

C0818, a novel curcumin derivative, induces ROS-dependent cytotoxicity in human hepatocellular carcinoma cells in vitro via disruption of Hsp90 function.

Heat shock protein 90 (Hsp90) is the most common molecular chaperone that controls the maturation of many oncoproteins critical in tumor development. Hsp90 has been considered as a promising target for cancer treatment, but the clinical significance of Hsp90 and the mechanisms of Hsp90 regulating the tumor-promoting effects in hepatocellular carcinoma (HCC) remain obscure. Previous studies have shown that curcumin, a polyphenol derived from the plant turmeric (Curcuma longa), inhibits tumor growth, which may provide an effective alternative therapy for HCC. Compared to curcumin, a novel derivative of curcumin, 3,5-(E)-Bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride (C0818) that is more potent in Hsp90 inhibition and antitumor activity. In this study, we investigated the effect of C0818 on HCC cells in vitro and its relation to Hsp90 inhibition. We showed that C0818 concentration-dependently inhibited the proliferation, the colony formation and induced apoptosis in HepG2 and Sk-Hep-1 cells. C0818 concentration-dependently inhibited DNA synthesis and induced G2/M phase arrest in HepG2 and Sk-Hep-1 cells. We further demonstrated that C0818 induced ROS- and caspase-dependent apoptosis in HCC cells through the mitochondrial-mediated pathway. C0818 induced the degradation of Hsp90 client proteins as RAS, C-Raf, P-C-Raf, Erk, P-ERK, MEK, P-MEK, Akt and P-Akt, which led to subsequent inhibition of the RAS/RAF/MEK/ERK and PI3K/AKT pathways. We revealed that C0818 could inhibit the binding of Hsp90 with its clients without affecting their transcription, which subsequently induced the degradation of Hsp90 clients by the proteasome rather than the lysosome. These results are of potential importance for elucidating a novel Hsp90 inhibitor targeting HCC.

Success and Safety of Needle Knife Papillotomy and Fistulotomy Based on Papillary Anatomy: A Prospective Controlled Trial.

BACKGROUND: Needle knife papillotomy (NKP) and fistulotomy (NKF) are the two most commonly used rescue techniques for patients with difficult biliary cannulation (DBC). Anatomy of the major duodenal papillae (MDP) influences the optimal precut technique for biliary access. However, comparative studies of the success and safety of NKP and NKF based on the anatomy of MDP have been scarce. METHODS: Patients with intact MDPs for therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) in our center were enrolled. Early needle knife precuts were uniformly applied to patients with DBC. Difficult MDPs were classified into one of five types based on their endoscopic anatomy. Each type of MDP was allocated to NKP or NKF treatment. Patients with types 1 and 2 papillae always received NKF, 3 and 4 received NKP, and 5 could receive either. The safety and efficacy were analyzed between NKP and NKF, and among different types of MDPs. RESULTS: A total of 188 out of 1674 patients undergoing ERCP satisfied the criteria for early precutting: 75 patients were assigned to the NKP group and 113 to the NKF group. The total initial success rate of biliary cannulation (ISRBC) of the precut techniques (both NKP and NKF) for patients with DBC was 91.5%. The ISRBC of patients of the NKP group was similar to that of the NKF group (90.7% vs 92.0%, P > 0.05). The ISRBC of the patients in the swollen MDP subgroup (96.1%) was higher than that of patients in the distorted MDP subgroup (81.8%, P = 0.030). The total and specific complications of the patients of the NKP group were similar to those of the NKF group (P > 0.05). CONCLUSIONS: NKP and NKF, as selected on the basis of MDP anatomy, are equally safe and highly efficient for patients with DBC to allow biliary cannulation. Patients with swollen MDPs had a higher ISRBC than patients with distorted MDPs. Selecting a precut method based on MDP anatomy is an effective and safe strategy for patients with DBC.

BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis.

B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19+ B cells, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20-CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ B cells, CD19+ BCMA+ B cells, and CD19+ TACI+ B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA.

Hsp70 Gene Polymorphisms Are Associated With Disease Susceptibility and HRQOL Improvement in Chinese Han Population With Systemic Lupus Erythematosus.

OBJECTIVES: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

Molecular mechanism whereby paraoxonase-2 regulates coagulation activation through endothelial tissue factor in rat haemorrhagic shock model.

We investigated the molecular mechanism of paraoxonase-2 (PON-2) in regulating blood coagulation activation in rats with haemorrhagic shock through endothelial tissue factor (TF). Thirty adult Sprague Dawley rats were randomly divided into three groups: healthy control group (group A), the haemorrhagic shock PON-2 treatment group (group B), and the haemorrhagic shock group (group C). After the model was established, blood was withdrawn from the inferior vena cava of all rats. The difference in plasma thrombomodulin (TM) levels of the three groups was determined by Western blotting. The expression of transcription factors Egr-1 and Sp1 was detected by Western blotting assays. reverse transcription-polymerase chain Reaction (RT-PCR) was used to determine the mRNA expression of t-PA, PAI-1, TM, and PON-2 in the serum of three groups of rats. Endothelial TF was measured by enzyme linked immunosorbent assay (ELISA), and coagulation assay was used to detect the activity of coagulation factor VIII. Histopathological examination of the arteries of the rats was performed. The molecular mechanism of PON-2 in regulating blood coagulation activation in haemorrhagic shock model rats by endothelial tissue factor was analysed. The expression of thrombin was determined by electrophoresis. Compared with the healthy control group, the expression of TM in groups B and C decreased, both 188.64 ± 12.47 and 137.48 ± 9.72, respectively, with a significant difference. The mRNA expression of TM and PON was determined by RT-PCR. The mRNA expression of TM and PON in group B was 0.97 ± 0.07 and 1.14 ± 0.09, compared with the control group, and the mRNA expression of TM and PON in group C was 0.86 ± 0.38 and 1.12 ± 0.41, both of which increased, and there were significant differences. By measuring the expression of endothelial TF, the expression of TF in groups B and C was elevated to 12.69 ± 1.07 and 11.59 ± 0.87, with significant differences. The enzyme activities of PON-2 in groups B and C, which were 110.34 ± 14.37 and 52.37 ± 8.06, respectively, were increased compared with the healthy control group and there were significant differences. PON-2 regulates the activation of coagulation in rats with haemorrhagic shock by regulating the expression of endothelial tissue-related genes such as plasma TM and endothelial TF under hypoxic and ischaemic conditions.

Innate immune molecule surfactant protein D attenuates sepsis-induced acute kidney injury through modulating apoptosis and NFκB-mediated inflammation.

The objective of this study is to investigate the mechanism whereby innate immune molecule surfactant protein D (SP-D) attenuates sepsis-induced acute kidney injury (AKI) through modulating apoptosis and nuclear factor kappa-B (NFκB)-mediated inflammation. In the present study, a mouse sepsis model was established by cecal ligation and puncture in SP-D knockout (KO) mice and wild-type (WT) mice. A sham-operated group was included as the control. The experimental materials were extracted 6 and 24 hours postoperatively. The plasma levels of tumour necrosis factor alpha (TNF-α) and MCP-1 were determined by enzyme-linked immunosorbent assay (ELISA). Apoptosis was measured by double staining with Annexin V/propidium iodide and flow cytometry. The levels of NFκB in renal tissues were measured by ELISA and Western blotting assay. Apoptosis was detected by TUNEL assays. There were no significant differences in plasma TNF-α levels between the WT sham group and the KO sham group at 6 and 24 hours postoperatively (P < .05), but the levels of TNF-α in the WT sepsis and KO sepsis groups were significantly higher than those in controls (P < .05). The levels of TNF-α in the KO sepsis group were significantly higher than those of the WT sepsis group (P < .05). TNF-α levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The levels of MCP-1 in the WT sepsis group and the KO sepsis group at 6 and 24 hours postoperatively were significantly higher than those in the control group (P < .05), and MCP-1 levels in the KO sepsis group were significantly higher than those in the WT sepsis group (P < .05). MCP-1 levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The expression of SP-D in WT kidneys was significantly lower at 6 and 24 hours postoperatively (P < .05). The number of TUNEL-positive cells in the kidneys from septic SP-D KO mice was significantly higher (P < .05). The levels of NFκB in septic mice were significantly increased at 6 and 24 hours after induction of sepsis compared with the sham-operated group compared with those of septic SP-D KO mice and WT mice (P < .05). Innate immune molecule SP-D significantly decreased plasma levels of inflammatory cytokines in mice and attenuated sepsis-induced AKI by inhibiting NFκB activity and apoptosis.

Osteoporosis Self-Assessment Tool As a Screening Tool for Predicting Osteoporosis in Elderly Chinese Patients With Established Rheumatoid Arthritis.

Osteoporosis Self-Assessment Tool for Asians (OSTA) is an indicator for assessing osteoporosis in postmenopausal women. The aim of this study was to investigate the value of OSTA index on predicting osteoporosis in elderly Chinese patients with established rheumatoid arthritis (RA). A total of 320 patients with RA and 158 normal individuals were recruited from January 2015 to October 2017. Bone mineral density (BMD) at the femur and lumbar spine was measured by dual-energy X-ray absorptiometry. RA group and control group were divided into low risk (values≥-1), medium risk (values between -4 and -1), and high risk (values ≤-4) group according to the value of OSTA index. One-way analysis of variance showed that BMD at all detected regions among the 3 groups were obviously different (p < 0.0001). Incidences of osteoporosis among different OSTA groups were 21.76% (47/216), 56.41% (44/78), and 80.77% (21/26), separately (x2 = 67.389, p < 0.0001). In RA group including premenspausal or postmenspausal female subgroup, prevalences of osteoporosis among different OSTA groups were different (p < 0.05-0.0001). We also found a positive linear correlation between OSTA index and BMD (p < 0.0001) both in RA and in control groups. Logistic regression revealed OSTA index (odds ratio = 0.734, p < 0.0001, 95% confidence interval: 0.657-0.819) was a protective factor for occurrence of RA-induced osteoporosis. OSTA had the highest discriminatory power, with an estimated Area Under Curve (AUC) of 0.750 (95% confidence interval 0.694-0.807, p < 0.0001), sensitivity of 76.9% and specificity of 66.5%. Our findings indicated that OSTA index was closely associated with BMD in RA patients, the degree of correlation was much stronger than age or BMI. OSTA index was a predictor for osteoporosis in RA, but it might have little relationship with disease status in RA.

Loss of BMI-1 dampens migration and EMT of colorectal cancer in inflammatory microenvironment through TLR4/MD-2/MyD88-mediated NF-κB signaling.

Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism. We observed that the expression of BMI-1, TNF-α, and IL-1ß was significantly increased in HT29 and HCT116 cells after THP-1 Conditioned-Medium (THP-1-CM) stimulation. Additionally, inhibition of BMI-1 impeded cell invasion induced by THP-1-CM-stimulation in both HT29 and HCT116 cells. BMI-1 knockdown remarkably repressed THP-1-CM-induced EMT by regulating the expression of EMT biomarkers with an increase in E-cadherin accompanied by decrease in N-cadherin and vimentin. Furthermore, downregulation of BMI-1 dramatically impeded THP-1-CM-triggered Toll-like receptor 4(TLR4)/myeloid differentiation protein 2(MD-2)/myeloid differentiation factor 88(MyD88) activity by repressing the expression of the TLR4/MD-2 complex and MyD88. Further data demonstrated that knockout of BMI-1 also dampened NF-κB THP-1-CM-triggered activity. Taken all data together, our findings established that BMI-1 modulated TLR4/MD-2/MyD88 complex-mediated NF-κB signaling involved in inflammation-induced cancer cells invasion and EMT, and therefore, could be a potential chemopreventive agent against inflammation-associated colorectal cancer. HIGHLIGHTS: Establishment of an inflammatory microenvironment. Suppression of BMI-1 reverses THP-1-CM-induced inflammatory cytokine production in CRC. Loss of BMI-1 suppressed TLR4/MD-2/MyD88 complex-mediated NF-κB signaling.

Effects of placebo-controlled insulin-sensitizing drugs on hormonal parameters in polycystic ovary syndrome patients: A network meta-analysis.

This network meta-analysis was conducted to compare effects of different placebo-controlled insulin-sensitizing drugs, including metformin, pioglitazone, rosiglitazone, and troglitazone on hormonal parameters in polycystic ovary syndrome (PCOS) patients. We searched PubMed, EMBASE, and Cochrane Library databases from their inception to July 2017. Randomized controlled trials (RCTs) met our inclusion criteria were included. We combined direct and indirect evidences to evaluate weighted mean difference (WMD) value and draw surface under the cumulative ranking curve (SUCRA). Totally 28 eligible RCTs were enrolled. The network meta-analysis results indicated that: Compared with placebo, patients treated with pioglitazone had relatively higher sex-hormone-binding globulin (SHBG) (nmol/L) level (WMD = 6.65, 95%CI = 0.57-12.98), patients treated with metformin had comparatively lower total testosterone (TT) (ng/mL) level (WMD = -0.20, 95%CI = -0.39 to -0.02); Compared with rosiglitazone, patients treated with metformin had relatively higher estradiol (E2 ) (pg/mL) level (WMD = 47.91, 95%CI = 11.44-85.55). However, there were no statistical significance among the placebo-controlled insulin-sensitizing drugs in follicle stimulating hormone (FSH) (IU/L), luteinizing hormone (LH) (IU/L), dehydroepiandrostrone-sulphate (DHEAS) (µg/dL), free testosterone (FT) (pg/mL) and androstenedione (ng/mL). The results of cluster analysis showed that rosiglitazone may be the best drug for PCOS patients regarding to DHEAS, TT, FSH, and LH, metformin may be the best drug for PCOS patients as for E2 , FT, and androstenedione. Rosiglitazone had the best effect on PCOS patients in terms of DHEAS, TT, FSH, and LH, metformin had the best effect on PCOS patients for E2 , FT, and androstenedione.

Plasmon-Enhanced Ultrasensitive Surface Analysis Using Ag Nanoantenna.

Raman scattering and fluorescence spectroscopy permeate analytic science and are featured in the plasmon-enhanced spectroscopy (PES) family. However, the modest enhancement of plasmon-enhanced fluorescence (PEF) significantly limits the sensitivity in surface analysis and material characterization. Herein, we report a Ag nanoantenna platform, which simultaneously fulfills very strong emission (an optimum average enhancement of 105-fold) and an ultrafast emission rate (∼280-fold) in PES. For applications in surface science, this platform has been examined with a diverse array of fluorophores. Meanwhile, we utilized a finite-element method (FEM) and time-dependent density functional theory (TD-DFT) to comprehensively investigate the mechanism of largely enhanced radiative decay. PES with a shell-isolated Ag nanoantenna will open a wealth of advanced scenarios for ultrasensitive surface analysis.

C1206, a novel curcumin derivative, potently inhibits Hsp90 and human chronic myeloid leukemia cells in vitro.

4-(4-Pyridinyl methylene) curcumin (C1206) is a new derivative of curcumin that is more active than curcumin in inhibition of heat shock protein 90 (Hsp90) and antitumor action. In this study we investigated the relationship between C1206-induced inhibition of Hsp90 and its anti-leukemic effects. The fluorescence quenching experiments showed that C1206 seemed to bind the middle dimerization domain of Hsp90. The interaction between C1206 and Hsp90 was driven mainly by electrostatic interaction. In in vitro enzyme activity assay, C1206 dose-dependently inhibited Hsp90 ATPase activity with an IC50 value of 4.17 µmol/L. In both imatinib-sensitive K562 chronic myeloid leukemia cells and imatinib-resistant K562/G01 chronic myeloid leukemia cells, C1206 (0.4-3.2 µmol/L) dose-dependently caused the degradation of Hsp90 client proteins and downstream proteins (AKT, MEK, ERK, C-RAF, P-AKT, P-MEK and P-ERK). Furthermore, C1206 (0.4-3.2 µmol/L) dose-dependently induced apoptosis of K562 and K562/G01 cells through triggering mitochondrial pathway. Consistent with this result, C1206 inhibited the proliferation of K562 and K562/G01 cells with IC50 values of 1.10 and 0.60 µmol/L, respectively. These results suggest that C1206 is a novel Hsp90 inhibitor and a promising therapeutic agent for chronic myeloid leukemia.

Upregulated long non-coding RNA LOC90784 promotes cell proliferation and invasion and is associated with poor clinical features in HCC.

A growing amount of literature has indicated that long non-coding RNAs (lncRNAs) are important factors in hepatocellular carcinoma (HCC) progression. However, the significance of lncRNAs in the progression and prognosis of liver cancer is largely unknown. In the present study, upregulated lncRNA LOC90784 was identified through integrative analysis of GSE58043 and GSE55191. Furthermore, associations between LOC90784 expression and the clinicopathological characteristics of patients were analyzed with a validated cohort 1 and the Cancer Genome Atlas (TCGA) cohort 2. We investigated the mechanisms by which this highly expressed lncRNA promotes HCC proliferation, invasion and migration via qRT-PCR, fluorescence in situ hybridization (FISH) staining, siRNA transfection, cell proliferation assays, Transwell and colony formation assays, flow cytometry analysis and Western blot. The results showed that LOC90784 expression levels were significantly higher in HCC cell lines and tissues and mainly localized in the cytoplasm. Knockdown of lncRNA LOC90784 expression inhibited proliferation and induced apoptosis and cell cycle arrest by promoting Bax and repressing CDK4 and Cyclin D1 protein expression; it also inhibited invasion and migration by repressing MMP2 and MMP9 expression in HCC cells. LOC90784 overexpression was associated with poor clinical features in the two cohorts and poor overall survival rates in HCC patients with clear resection margins (R0) in cohort 2. These results indicated that LOC90784 upregulation may be a critical oncogene and potential new biomarker in HCC.

[Fluorescence Properties of Single-Trp Peptide: Response to pH and Metal Ions].

Considering the important role of metal ions including copper ions are playing in human body, a novel single-Trp peptide WDAHSS was designed and synthesized in this study to achieve sensitive detection of copper ions via fluorescence spectroscopy. The intrinsic fluorescence of a tryptophan residue in WDAHSS, which was the only source of the molecular fluorescence, could be easily quenched with copper ions. By comparing fluorescence spectra of WDAHSS with those of tryptophan molecules at different pH values, the quenching mechanism of WDAHSS was explored in detail. Research showed that the histidine in WDAHSS bound copper ions with metal coordination. With participation of peptide bond, a square planar structure was formed. It was a consequent chelation of copper ions that caused the quenching of tryptophan residue. At the same time, this study discussed how pH conditions affected the fluorescence spectra of WDAHSS. Furthermore, association constants of copper ions towards WDAHSS were calculated through fluorescence measurements and fitting analyses. To enhance the anti-jamming ability to pH variation, the amino terminal of WDAHSS was intentionally acetylized, leading to a stable fluorescence emission under physiological pH conditions. Besides, WDAHSS was designed as a special structure to enhance the selectivity and biocompatibility of its sensitive detection of copper ions. Further studies on WDAHSS may help to improve the fluorescence imaging detection in vivo.

A metal-free one-pot synthesis of benzo[c]chromen-6-ones from 3,4-dichlorocoumarins and butadienes using tandem photo-thermal-photo reactions.

An efficient, simple and versatile synthesis of biologically valuable benzo[c]chromen-6-ones is achieved using a tandem photo-thermal-photo reaction sequence starting from 3,4-dichlorocoumarins and a 1,3-butadiene. In this concise one-pot protocol, neither metal catalyst nor peroxide promoter is needed and the products can be purified through simple recrystallization in most cases. The synthesis consists of a reaction sequence of photo-induced [4 + 2] and [2 + 2] cycloadditions, silica gel promoted elimination of HCl and electrocyclic cyclobutene ring opening followed by a photo-induced 6π electrocyclization. The reactions proceed well with a range of dichlorocoumarins and some typical butadienes to provide the corresponding annulated products in 70-80% yield.

Needle-knife papillotomy and fistulotomy improved the treatment outcome of patients with difficult biliary cannulation.

BACKGROUND AND AIMS: Needle-knife papillotomy and fistulotomy (NKPF) is a new, modified technique designed for difficult biliary cannulation. The safety and efficacy of performing NKPF based on characteristics of main duodenal papilla (MDP) was evaluated. METHODS: We performed a retrospective review of consecutive patients with intact papilla who were established as candidates for therapeutic ERCP at tertiary referral center. A total of 532 patients were included in conventional endoscopic retrograde cholangiopancreatography (ERCP) group in which repeated cannulation was tried in patients with difficult bile duct cannulation; and 598 patients enrolled in early NKPF group according to predefined parameters. Based on the characteristics of MDP, different types of NKPF were performed. The endoscopic data (mean procedure time, anatomy of the main papilla), rate of cannulation success, and post-ERCP complications were collected. RESULTS: A total of 82 patients underwent NKPF. The mean procedure time of the small papilla group was longer than bulging papilla group (P < 0.05). The success rate of biliary cannulation in the small papilla group (69.3 %) was lower than in the bulging papilla group (100 %, P < 0.01). The overall successful biliary cannulation of patients in the NKPF group was significantly higher than in the conventional group (98.8 vs 90.8 %, P > 0.05). The total complication rate was 6.6 % among conventional group patients and 5.7 % among NKPF group, respectively. The overall complication rate and rates of specific complications (pancreatitis, bleeding, cholangitis, and perforation) in the two groups were similar (P > 0.05). CONCLUSION: Early NKPF based on characteristics of MDP raised the success rate of biliary cannulation when conventional cannulation failed and did not increase the complication rate post-ERCP. Clinic Trials. gov number, Hongwei-1102-12.

[Precise and Rapid Detection of Glutathione by Using Novel Fluorescent Ag Nanoclusters].

Glutathione (GSH) is an important three-peptide molecule, which has the functions of antioxidation and detoxification, and plays a crucial role in the fields of biology, medicine and food science. It is involved in many important biochemical reactions in cells and body fluid, and the changes of GSH content reflect the specific health problems of human body. Current methods of GSH detection are always complicated, time-consuming and expensive instrument depended, such as surface enhanced Raman spectroscopy (SERS), electrochemical analysis, high performance liquid chromatography (HPLC) and so on. The probe's photochemical properties can be modified by the reaction between GSH and nanoclusters, which will result in the changes of fluorescence intensity and wavelength. In this paper, a new method to realize precise and rapid GSH detection is developed by using silver na-noclusters as a fluorescent probe, and simultaneously measures the probe's fluorescence intensity and wavelength. The synthesis of the fluorescence probe reported in this paper possesses the advantages of steps-simple and pollution free, and the GSH detection method has faster response, more accurate measurement and smaller relative error over the traditional methods. The good specificity of GSH detection among other molecules with the similar structure is further proved in control group experiments by comparing the differences of their fluorescence intensities and wavelength. The measurement accuracy is fully assured due to the insensitivity of the probe to a variety of salt ions and amino acids. This technique can be further employed in the intracellular detection and imaging of GSH.

Clip closure of defect after endoscopic resection in patients with larger colorectal tumors decreased the adverse events.

BACKGROUND: Clip closure of large colorectal mucosal defects may reduce the rate of adverse events in a cost-effective manner. OBJECTIVE: To assess the adverse events and outcomes of clip closure of defects after endoscopic resection in patients with large colorectal tumors. DESIGN: Prospective, randomized, controlled study. SETTING: Single tertiary referral center. PATIENTS AND INTERVENTIONS: Patients with lesions measuring 1 to 4 cm who were scheduled for endoscopic resection between March 2012 and December 2014 were randomly assigned to a clip-closure group and a no-closure group. In the clip-closure group, the defect of the resection site was completely closed with an endoclip. In the no-closure group, the defect was left open. The following primary outcome measures were assessed: delayed postoperative bleeding, postpolypectomy coagulation syndrome, perforation, and abdominal pain. Secondary outcome measures of length of hospital stay, time required for procedure, and patient's satisfaction were also assessed. RESULTS: Patients and lesions had similar characteristics across both groups. For patients who underwent clip closure (n = 174), the rates of delayed postoperative bleeding (1.1% [2/174]) and postpolypectomy coagulation syndrome (0.6% [1/174]) were lower than those in the no-closure group (6.9% [12/174], P = .01 and 4.6% [8/174], P = .03). Two patients experienced perforation, 1 in each group. In the clip-closure group, 4 patients reported abdominal pain as opposed to 26 in the no-closure group (2.8% vs 16.7%, P < .01). The procedure took longer in the closure group (38.1 minutes vs 30.9 minutes, P = .04). The length of hospitalization was shorter in the closure group (3.1 days vs 4.7 days, P = .03). Total medical expense was similar between the 2 groups. Patients who underwent closure reported greater satisfaction. LIMITATION: This was a single-center analysis. CONCLUSIONS: Clip closure of endoscopic resection defects in patients with large colorectal tumors decreased the rate of procedure-related adverse events and did not increase the cost of hospitalization.