Palladium-Catalyzed Synthesis of Indanone via C-H Annulation Reaction of Aldehydes with Norbornenes.

A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o-bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.

Helicobacter pylori intragastric colonization and migration: Endoscopic manifestations and potential mechanisms.

After being ingested and entering the human stomach, Helicobacter pylori (H. pylori) adopts several effective strategies to adhere to and colonize the gastric mucosa and move to different regions of the stomach to obtain more nutrients and escape from the harsher environments of the stomach, leading to acute infection and chronic gastritis, which is the basis of malignant gastric tumors. The endoscopic manifestations and pathological features of H. pylori infection are diverse and vary with the duration of infection. In this review, we describe the endoscopic manifestations of each stage of H. pylori gastritis and then reveal the potential mechanisms of bacterial intragastric colonization and migration from the perspective of endoscopists to provide direction for future research on the effective therapy and management of H. pylori infection.

An Efficient Nomogram for Discriminating Intrahepatic Cholangiocarcinoma From Hepatocellular Carcinoma: A Retrospective Study.

Objective: This study aims to establish a nomogram and provide an effective method to distinguish between intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: A total of 1,591 patients with HCC or ICC hospitalized at Shandong Provincial Hospital between January 2016 and August 2021 were included and randomly divided into development and validation groups in a ratio of 3:1. Univariate and multivariate analyses were performed to determine the independent differential factors between HCC and ICC patients in the development cohort. By combining these independent differential factors, the nomogram was established for discriminating ICC from HCC. The accuracy of the nomogram was estimated by using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Furthermore, the predictive nomogram was assessed in the internal testing set. Results: Through multivariate analysis, independent differential factors between HCC and ICC involved hepatitis B virus (HBV), logarithm of alpha-fetoprotein (Log AFP), logarithm of protein induced by vitamin K absence or antagonist-II (Log PIVKA-II), logarithm of carbohydrate antigen 199 (Log CA199), and logarithm of carbohydrate antigen 125 (Log CA125). A nomogram was finally established by incorporating these five independent differential factors. Comparing a model of conventional tumor biomarkers including AFP and CA199, the nomogram showed a better distinction between ICC and HCC. The area under the ROC curve (AUC) of ICC diagnosis was 0.951 (95% CI, 0.938-0.964) for the nomogram. The results were consistent in the validation cohort with an AUC of 0.958 (95% CI, 0.938-0.978). After integrating patient preferences into the analysis, the DCA showed that using this nomogram to distinguish ICC and HCC increased more benefit compared with the conventional model. Conclusion: An efficient nomogram has been established for the differential diagnosis between ICC and HCC, which may facilitate the detection and diagnosis of ICC. Further use of the nomogram in multicenter investigations will confirm the practicality of the tool for future clinical application.

Value of AFP and PIVKA-II in diagnosis of HBV-related hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation.

BACKGROUND: To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HBV-related hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. METHODS: A total of 433 participants were enrolled in this study including 266 cases with HBV-related HCC, 87 cases with HBV DNA positive benign liver disease and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HBV-related HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HBV-related HCC patients with and without vascular invasion. RESULTS: The level of AFP and PIVKA-II in HBV-related HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P < 0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HBV-related HCC diagnosis were 0.765 (95% CI, 0.713 ~ 0.8170) for AFP, 0.901 (95% CI, 0.868 ~ 0.935) for PIVKA-II, and 0.917 (95% CI, 0.886 ~ 0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was significantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level > 64.4 ng/ml or PIVKA-II level > 957.61mAU/ml was the best critical value to predict the presence of vascular invasion. CONCLUSION: Our results validate that AFP and PIVKA-II play a significant role in the diagnosis of HBV-related HCC. The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. Moreover, their concentration has important clinical value in judging tumor size, tumor cell differentiation and vascular invasion.

Expression of microRNA-184 in glioma.

The aim of the present study was to examine the expression of microRNA (miRNA)-184 in gliomas with different pathological grades, and its effect on survival prognosis. For the present study, 40 participants were selected with different pathological grades of glioma tissues with grade I (n=10), grade II (n=8), grade III (n=16), and grade IV (n=6). In addition, 10 cases of normal brain tissue (obtained by decompression because of traumatic brain injury) were selected. RT-PCR and immunohistochemical techniques were used to detect the expression level and intensity of miRNA-184 in different grades of glioma tissues. The length of survival of miRNA-184-positive patients was analyzed. miRNA-184 mRNA expression was found in normal tissues and tumor tissues, and the expression in tumor tissues was significant (P<0.05). Statistically significant differences of miRNA-184 expression were observed among different grades (P<0.05). miRNA-184 expression increased with the increase of grade level. The differences in expression across grade levels was statistically significant (P<0.05). A positive expression was not related to the pathological types of glioma cells. The median survival time of patients with miRNA-184-positive expression was significantly shorter than that of the negative expression group (P<0.05). miRNA-184 is highly expressed in gliomas, which is positively correlated with pathological grade, and is not correlated with pathological type, and negatively correlated with survival time. Thus, miRNA-184 is a potentially important molecular marker for glioma.

Statistics of velocity and temperature fluctuations in two-dimensional Rayleigh-Bénard convection.

We investigate fluctuations of the velocity and temperature fields in two-dimensional (2D) Rayleigh-Bénard (RB) convection by means of direct numerical simulations (DNS) over the Rayleigh number range 10^{6}≤Ra≤10^{10} and for a fixed Prandtl number Pr=5.3 and aspect ratio Γ=1. Our results show that there exists a counter-gradient turbulent transport of energy from fluctuations to the mean flow both locally and globally, implying that the Reynolds stress is one of the driving mechanisms of the large-scale circulation in 2D turbulent RB convection besides the buoyancy of thermal plumes. We also find that the viscous boundary layer (BL) thicknesses near the horizontal conducting plates and near the vertical sidewalls, δ_{u} and δ_{v}, are almost the same for a given Ra, and they scale with the Rayleigh and Reynolds numbers as ∼Ra^{-0.26±0.03} and ∼Re^{-0.43±0.04}. Furthermore, the thermal BL thickness δ_{θ} defined based on the root-mean-square (rms) temperature profiles is found to agree with Prandtl-Blasius predictions from the scaling point of view. In addition, the probability density functions of turbulent energy ɛ_{u^{'}} and thermal ɛ_{θ^{'}} dissipation rates, calculated, respectively, within the viscous and thermal BLs, are found to be always non-log-normal and obey approximately a Bramwell-Holdsworth-Pinton distribution first introduced to characterize rare fluctuations in a confined turbulent flow and critical phenomena.

Interleukin-18 synergism with interleukin-2 in cytotoxicity and NKG2D expression of human natural killer cells.

Natural killer (NK) cells play an important role in anti-tumor immunity. Interleukin (IL)-18 is an immunoregulatory cytokine that induces potent NK cell-dependent anti-tumor responses when administrated with other cytokines. In this study, we explored the effects of combining IL-18 and IL-2 on NK cytotoxicity as well as expression levels of the NK cell receptor NKG2D in vitro. Freshly isolated PBMCs were incubated for 48 h with IL-18 and IL-2, then CD107a expression on CD3-CD56+ NK cells was determined by three-colour flow cytometry to evaluate the cytotoxicity of NK cells against human erythroleukemia K562 cells and human colon carcinoma HT29 cells. Flow cytometric analysis was also employed to determine NKG2D expression on NK cells. The combined use of IL-18 and IL-2 significantly increased CD107a expression on NK cells compared with using IL-18 or IL-2 alone, suggesting that the combination of these two cytokines exerted synergistic enhancement of NK cytotoxicity. IL-18 also enhanced NKG2D expression on NK cells when administered with IL-2. In addition, blockade of NKG2D signaling with NKG2D-blocking antibody attenuated the up-regulatory effect of combining IL-18 and IL-2 on NK cytolysis. Our data revealed that IL-18 synergized with IL-2 to dramatically enhance the cytolytic activity of human NK cells in a NKG2D-dependent manner. The results appear encouraging for the use of combined IL-18 and IL-2 in tumor immunotherapy.

Killer cell immunoglobulin-like receptor genotypes and haplotypes with susceptibility to pulmonary tuberculosis infection.

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are expressed on natural killer (NK) cells and T cells and organized in highly polymorphic families. Genetic diversity is an important characteristic of KIR genes. The aim of the study was to investigate the influence of KIR genotypes and halotypes on the risk of pulmonary tuberculosis (PTB). METHODS: A sequence specific primer polymerase chain reaction (SSP-PCR) was employed to amplify the KIR genes and pseudogenes in 139 pulmonary tuberculosis (PTB) patients and 30 healthy controls. The innovative point of our study was the subdivision of the patient group according to sputum smear test (positive and negative). KIR genotype and haplotype frequencies were compared between the PTB group and the control group by Chi-square test, and p < 0.05 was regarded as statistically significant. RESULTS: The genotype AH and FZ14 may be associated with the clearance of Mycobacterium. In addition, haplotype B may be the susceptive haplotype that facilitated the clearance of Mycobacterium and haplotype A may be protective haplotype of PTB. CONCLUSIONS: Therefore, the diversity of genotypes and haplotypes induced an inflammatory reaction that resulted in continuous infection.

[A preliminary study on the relationship between HLA-Cw polymorphism and susceptibility to pulmonary tuberculosis].

OBJECTIVE: To analyze the relationship between HLA-Cw polymorphism and susceptibility to pulmonary tuberculosis (PTB), and therefore to explore the susceptible or resistant genes of PTB. METHODS: A hundred and twelve patients who were confirmed to have secondary PTB in Shandong Chest Hospital from May 2010 to May 2011 were selected as the PTB group, including 62 males and 50 females aged 19 - 69 years (mean 41.7). According to the acid-fast staining results, PTB patients were divided into a smear-negative group (SN group, 77 cases) and a smear-positive group (SP group, 35 cases). A hundred and ten subjects who underwent physical examination in Shandong Chest Hospital at the same period were selected as the control group, including 59 males and 51 females aged 21 - 67 years (mean 38.3). After genomic DNA was extracted, genotyping of HLA-Cw was conducted by sequence specific primer polymerase chain reaction (PCR-SSP) method. Then Hardy-Weinberg (H-W) equilibrium was tested, and gene frequencies(%) were estimated = 1-(1-phenotype frequencies)(1/2). Gene frequencies were compared between the PTB group and the control group, and between the SN group and SP group by χ(2) test. According to Bonferroni's principle, α was divided by the number of alleles (n = 8), and P < 0.006 25 was regarded as statistically significant. RESULTS: The frequency of HLA-Cw08 was significantly higher in PTB patients (43.6%, 75/112) compared with the controls (27.4%, 52/110), χ(2) = 8.790, P < 0.006 25. Among PTB patients, HLA-Cw04 had a significantly higher frequency in the SP group (20.7%, 13/35) than in the SN group (4.7%, 7/77), while HLA-Cw08 had a significantly lower frequency in the SP group (22.5%, 14/35) than in the SN group (54.4%, 61/77), χ(2) = 12.909, 16.732, both P < 0.006 25. CONCLUSIONS: HLA-Cw polymorphism is related to susceptibility to PTB. HLA-Cw08 may be one of the susceptible genes for PTB, and HLA-Cw04 and 08 may be related to MTB infectious status and clinical outcomes.

Rapid detection of the hepatitis B virus YMDD mutant using AllGlo™ probes.

BACKGROUND: The early detection of hepatitis B virus (HBV) mutants in clinical samples is important when monitoring chronic HBV patients with lamivudine-resistant mutations during lamivudine therapy. METHODS: The AllGlo™ probes were designed to distinguish between wild-type (YMDD) and mutant (YVDD and YIDD) strains of HBV. The sensitivity and specificity of the assay were evaluated using a series of diluted mixtures of wild-type and mutant plasmids. This assay was compared with direct sequencing and the mutation-specific primer assay. RESULTS: Each YMDD, YVDD, and YIDD probe only detected its corresponding plasmid. Moreover, the assay correctly identified negative samples from 40 non-HBV infected patients and 100 healthy controls. The detection limit of this assay was 50 copies/ml for YVDD and YIDD. The assay could detect the mutant strains when they were present at ≥10% within a mixed virus population. The assay was fully concordant with direct sequencing in 34 samples (56.7%) and partially concordant in 26 samples (43.3%), and detected more types of the HBV motif than direct sequencing. CONCLUSIONS: AllGlo™ probe assay is a novel, sensitive and specific assay to detect lamivudine-related HBV mutants, therefore, may be useful for monitoring chronic HBV patients treated with lamivudine.

[Effect of inflammation factors on endothelial function in insulin resistance SD rats].

OBJECTIVE: To test the effect of inflammation factors on endothelial dysfunction in insulin resistance SD rats. METHODS: Male SD rats were divided randomly into three groups. The rats in the NC group, OB group and OB-AS group were fed with normal chow, high-fat chow, and high fat chow plus aspirin, respectively. The perifereal insulin sensitivity was detected with hyperinsulinemic euglycemic clamp. The endothelial dependent and independent vasodilatation were evaluated by measuring blood flow through femoral artery. Serum concentrations of high-sensitivity (hs) CRP and TNF-alpha were measured. Quantitative analysis of the expression of IKKbeta and NF-kappaB was performed. RESULTS: The rats in the OB group had significantly higher levels of serum hsCRP and TNF-alpha than the rats in the NC group (P < 0.05). There was a significant difference in endothelium-dependent (Ach-mediated dilation) vascular response and serum NO level between the OB group and the NC group (P < 0.05). Meanwhile, the rats in the OB group showed higher expression of NF-kappaBp65 (P < 0.05) and IKKbeta/NF-kappaBp65 (P < 0.05) than those in the NC group. Interestingly, compared with the rats in the OB group, the serum concentrations of TNF-alpha and CRP decreased significantly in the rats in the OB-AS group, to which high dose aspirin was given (P < 0.05). Better endothelium-dependent vascular response and higher serum NO level were observed in the rats in the OB-AS group than those in the NC group (P < 0.05). The rats in the OB-AS group also had significantly lower expression of NF-kappaBp65 (P < 0.05) and IKKbeta/NF-kappaBp65 (P < 0.05) than those in the OB group. CONCLUSION: Elevated inflammation factors are involved in the endothelial dysfunction by inactivating IKKbeta-NF-kappaB pathway in rats with insulin resistance.

Association of estrogen receptor alpha gene polymorphisms with cytokine genes expression in systemic lupus erythematosus.

AIM: To analyze the association of estrogen receptor alpha (OR alpha) gene polymorphisms with cytokine genes expression in patients with systemic lupus erythematosus (SLE) and controls. METHODS: Genomic DNA was extracted and polymorphisms of XbaI, Ukrainian (XX, Xx, or xx genotype) and PvuII (PP, Pp, or pp) in intron 1 of OR alpha gene were detected by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. The messenger RNA (mRNA) levels of interleukin (IL)-10, IL-4, interferon (IFN)-gamma, and IL-2 were assessed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In patients with SLE with PpXx genotype, IL-10 and IL-4 mRNA expression was higher (P < 0.001 and P = 0.013, respectively), while in patients with SLE with Ppxx genotype IFN-gamma and IL-2 mRNA expression was lower than in controls (P < 0.001). There was no significant difference in mRNA expression of 4 cytokines among controls with various genotypes. CONCLUSION: OR alpha gene polymorphism may be associated with the expression of IL-10, IL-4, IL-2, and IFN-gamma in patients with SLE.

[The effect and pathophysiological mechanism of high free fatty acids(FfAs) on the cardiac structure and function].

OBJECTIVE: To study the pathophysiological links between elevated circulating FFAs concentration and the cardiac structure, and their function in obese insulin resistance rat model. METHODS: 4 weeks age male SD rats were fed with high-fat chow (OB) or standard laboratory chow (NC) respectively. Whole-body insulin sensitivity, the maximum velocity of myocardial contraction (+dp/dt(max)) and the maximum velocity of myocardial diastole (-dp/dt(max)) of intracardiac pressure, and myocardiac cell diameter (MCD) were measured. The concentrations of triglyceride (TG), FFAs and angiotensin II (Ang II) both in blood and in left ventricular portions of heart and the expressions of NF-kappaB, I-kappaB and iNOS in myocardium were analyzed. RESULTS: OB group developed obesity and left ventricular hypertrophy, and their insulin sensitivity was much lower than that of control group. Obese rats had higher plasma concentrations of TG, FFAs and Ang II. Accordingly, dramatic lipid deposition occurred within cardiomyocytes of obese rats, and the value of myocardiac Ang II was also increased. High-fat diet also induced a progressive decrease in values of +dp/dt(max) and -dp/dt(max). The higher expressions of NF-kappaB and iNOS in myocardium were observed in OB group, while IkappaB lower. Intramyocardial lipid deposition was associated with plasma FFAs concentrations (r = 0.80, P < 0.01). Intramyocardial FFAs concentration was associated with myocardial Ang II concentration (r = 0.74, P < 0.05) and changes in expressions of NF-kappaB (r = 0.86, P < 0.01), iNOS (r = 0.66, P < 0.05). The contractile dysfunction was associated with intramyocardial lipid deposition (r = -0.87, P < 0.01), Ang II (r = -0.52, P < 0.05) and expressions of NF-kappaB (r = -0.57, P < 0. 01), iNOS (r = -0.70, P < 0. 01). The diastolic dysfunction was associated with intramyocardial lipid deposition ( r = -0.85, P < 0.01), Ang II (r = -0.82, P<0.01) and expressions of NF-kappaB (r = -0.75, P < 0.01), iNOS (r = -0.78, P < 0.01). CONCLUSION: In obese/insulin resistance, state ectopic lipid accumulation in myocardium as the results of elevated circulating FFAs and TG concentration impairs cardiac systolic and diastolic functions. It is logical to deduce that ectopic lipid accumulation in myocardium may increase RAS activity and expressions of NF-kappaB, iNOS in myocardium, all of them have important roles to increase the risk of congestive heart failure in obese subjects.

[The protective effects of Radix Astragali and Rhizoma Ligustici chuanxiong on endothelial dysfunction in type 2 diabetic patients with microalbuminuria].

OBJECTIVE: To evaluate the effects of traditional Chinese complex prescription of Radix Astragali and Rhizoma Ligustici Chuanxiong on urinary albumin excretion (UAE) and vascular endothelial dysfunction in type 2 diabetic patients with microalbuminuria. METHODS: Twenty-one type 2 diabetic patients with microalbuminuria were involved in this before-after study by individual informed consent. Each of the eligible subjects was given the decoction of Radix Astragali and Rhizoma Ligustici Chuanxiong per os 150 ml q.d. for six months. The following examinations were performed at baseline and after treatment: (1) high-resolution ultrasonography to measure the diameter changes of brachial artery in response to reactive hyperemia (endothelium-dependent) and on administration of glyceryl trinitrate (endothelium-independent); (2) high resolution ultrasonography to measure combined intima-media thickness (IMT) of common carotid arteries (CCA); (3) fasting plasma plasminogen activator inhibitor type 1 (PAI-1) activity, C reactive protein (CRP) and malonic aldehyde(MDA) concentration. RESULTS: The patients had impaired endothelial dependent vasodilation (EDV), elevated plasma PAI-1 activity and increased CRP and MDA concentration at baseline. After six months treatment with Radix Astragali and Rhizoma Ligustici Chuanxiong, their urinary albumin-to- creatinine ratio decreased from (86.5 +/- 53.9) microg/mg to (55.05 +/- 51.67) microg/mg (P=0.002). The EDV was improved at the end of the treatment (baseline: 7.49 +/- 2.98%, after treatment: 12.73 +/- 5.36%, P=0.001). Meanwhile, the activity of PAI-1 and the levels of MDA and CRP were significantly decreased CPAI-1: (83.49 +/- 5.11) X 10(-2) AU/ml vs. (79.7 +/- 7.8) x 10(-2) AU/ml, P=0.015; MDA: (3.20 +/- 1.13) nmol/L vs. (2.09 +/- 0.71) nmol/L, P=0.000; CRP: (7.04 +/- 2.64) mg/ L vs. (1.58 +/- 0.69) mg/L, P=0.000]. But no significant changes of the CCA IMT and endothelial independent vasodilation (EIV) were observed. Partial correlated analysis showed that MDA concentration was negatively correlated with EDV (r=-0.3736, P = 0.018). Correlated analysis also showed that CRP was negatively correlated with EDV (r=-0.348, P=0.028). CONCLUSION: Radix Astragali and Rhizoma Ligustici Chuanxiong compound medication may decrease urinary albumin excretion and improve endothelial dysfunction in type 2 diabetic patients with microalbuminuria. The mechanism may relate with the therapeutic effects of Radix Astragali and Rhizoma Ligustici Chuanxiong on anti-inflammation, anti-oxidation and alleviation of the hypo-fibrinolytic/pro-thrombotic state.