Association of magnetic resonance imaging-derived sarcopenia with outcomes of patients with hepatocellular carcinoma after hepatectomy.

PURPOSE: To evaluate whether sarcopenia, diagnosed by magnetic resonance imaging (MRI) protocol, constitutes a prognosis-associated risk factor in patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: One hundred and ninety-three patients who underwent hepatectomy for HCC were retrospectively enrolled. The areas of the total skeletal muscle (SM) and psoas muscle (PM) were evaluated at the third lumbar vertebra in the preoperative MR images, and divided by the square of height in order to obtain the skeletal muscle index (SMI) and psoas muscle mass index (PMI). Sarcopenia was diagnosed respectively on the definitions based on the SMI or PMI. The potential of muscle-defined sarcopenia as a prognostic factor for overall survival (OS) and recurrence-free survival (RFS) was investigated in these patients. RESULTS: The areas of SM and PM, and SMI and PMI were significantly higher in the men than in the women (all p < 0.05). Notably, SMI-defined sarcopenia displayed a significant sex difference (p = 0.003), while PMI-defined sarcopenia did not (p = 0.370). Through univariate and multivariate analyses, PMI-defined sarcopenia remained an independent predictor for OS and RFS (HR = 3.486, 95% CI: 1.700-7.145, p = 0.001 and HR = 1.993, 95% CI: 1.246-3.186, p = 0.004), even after adjusting for other clinical variables. Moreover, Kaplan-Meier analysis demonstrated significantly poorer OS and RFS for patients with sarcopenia defined by using PMI, but not SMI, compared to those without sarcopenia (p < 0.001 and p = 0.006, respectively). CONCLUSION: MRI-derived, sarcopenia defined by using PMI, not SMI, may serve as a significant risk factor for RFS and OS in patients with HCC after hepatectomy.

Efficacy of polysaccharide iron complex in IDA rats: A comparative study with iron protein succinylate and ferrous succinate.

Iron deficiency anemia (IDA) is the most common nutrient-related health problem in the world. There is still a lack of comprehensive comparative study on the efficacies of commonly used iron supplements such as polysaccharide iron complex (PIC), iron protein succinylate (IPS) and ferrous succinate (FS) for IDA. In this study, we compared the PIC, IPS and FS efficacies in IDA rats via intragastric administration. The results showed that the three iron supplements had similar efficacies. PIC/IPS/FS at a dose of 15 mg Fe/kg/d for 10 d increased the hematological and serum biochemical parameters to 2.15/2.12/2.18 (Hb), 1.71/1.67/1.69 (RBC), 2.10/2.11/2.12 (HCT), 1.26/1.22/1.22 (MCV), all 1.34 (MCH), 1.15/1.15/1.14 (MCHC), 1.94/1.82/1.91 (SF), 9.75/9.67/9.53 (SI), and 23.30/22.68/21.64 (TS) times, and reduced TIBC to 0.42/0.43/0.44 times, compared to untreated IDA rats. PIC performed slightly better than IPS and FS in restoring MCV level. Meanwhile, the heart, spleen and kidney coefficients reduced to 67%/74%/65% (heart), all 59% (spleen) and 87%/88%/88% (kidney), and the liver coefficient increased to 116%/115%/116%, compared to untreated IDA rats. The liver iron content was found to be more affected by IDA than the spleen iron content. PIC/IPS/FS at 15 mg Fe/kg/d increased organ iron contents to 4.20/3.97/4.03 times (liver) and 1.36/1.24/1.41 times (spleen) within 10 d compared to untreated IDA rats, and PIC-H and FS were slightly better than IPS in restoring spleen iron content. The results of this study can provide useful data information for the comparison of three iron supplements, PIC, IPS and FS.

Experiences of doctors and nurses offering fertility guidance to young breast cancer patients: A qualitative study.

PURPOSE: Existing qualitative studies on young breast cancer patients' fertility have explored patients' perspectives rather than those of doctors and nurses. With the goal of presenting a scientific basis for the design of high-quality fertility guidance programs, this study examines the advantages and disadvantages of providing fertility guidance, as well as the obstacles perceived by doctors and nurses. METHODS: Purposive sampling was used to select 16 doctors and nurses from a Class III Grade A cancer hospital in Hunan Province, China, from March to May 2023. Face-to-face in-depth interviews were conducted. The interview data were analyzed and organized using Colaizzi's seven-step analysis method and NVivo software, respectively. RESULTS: Three themes and nine sub-themes were extracted from the data: (1) Attitude: maintain patients' fertility hope, respect patients' fertility wishes; (2) Obstacles: patient factors, family factors, healthcare worker factors; (3) Suggestions: enhance the professional confidence of doctors and nurses, ensure two-way communication between doctors and patients, promote interdisciplinary knowledge sharing, and establish a whole-process fertility guidance model. CONCLUSIONS: When carrying out fertility guidance for young breast cancer patients, doctors and nurses should fully respect and safeguard the patients' fertility wishes and hope, continuously strengthen their own knowledge reserve, promote interdisciplinary cooperation and improve their communication abilities, rationally analyze the hindrances, and provide continuous and personalized fertility guidance considering factors related to the patient and their family.

Experiences and management needs of endocrine therapy-related symptoms in patients with breast cancer: a systematic review and qualitative evidence synthesis protocol.

INTRODUCTION: Patients with breast cancer and endocrine therapy-related symptoms often experience pain, self-denial, anxiety, fear of recurrence and despair, which can be extremely physically and psychologically traumatising for the patients. Failure to receive effective support and management reduces adherence to medications, leading to a higher risk of relapse and mortality. Clearly, it is paramount to identify what support these patients may need and how to meet their symptom management needs. This paper outlines a protocol to synthesise qualitative evidence on endocrine therapy symptom experiences, management expectations and preferences of patients with breast cancer. METHODS AND ANALYSIS: The following databases were searched in November 2023 with no date restriction applied: The Cochrane Library, PubMed, Embase, Web of Science, Scopus, CINAHL and OpenGrey. Published studies on qualitative or mixed-method on symptom experiences and management needs during endocrine therapy in patients with breast cancer will be retrieved. We will also search for reference lists and perform a forward citation search. Before inclusion in this review, two reviewers will independently apply the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research to ensure methodological validity. Any disagreements regarding the evaluation of the articles will be resolved through discussion with or by a third reviewer. Data will be extracted using the standardised data extraction tool EndNote20 for unified management, assessment, and review of information. The common sense model of self-regulation will guide data extraction and synthesis. The final synthesised findings will be graded according to the GRADE-CERQual approach to establish confidence. ETHICS AND DISSEMINATION: This systematic review addressed previously published studies without personally identifiable participant information. Ethical approval from the research committee was not required. The findings of this systematic review will be disseminated to various key stakeholders and published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023406987.

Preoperative prediction of microvascular invasion in hepatocellular carcinoma using diffusion-weighted imaging-based habitat imaging.

OBJECTIVES: Habitat imaging allows for the quantification and visualization of various subregions within the tumor. We aim to develop an approach using diffusion-weighted imaging (DWI)-based habitat imaging for preoperatively predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). METHODS: Sixty-five patients were prospectively included and underwent multi-b DWI examinations. Based on the true diffusion coefficient (Dt), perfusion fraction (f), and mean kurtosis coefficient (MK), which respectively characterize cellular density, perfusion, and heterogeneity, the HCCs were divided into four habitats. The volume fraction of each habitat was quantified. The logistic regression was used to explore the risk factors from habitat fraction and clinical variables. Clinical, habitat, and nomogram models were constructed using the identified risk factors from clinical characteristics, habitat fraction, and their combination, respectively. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curves (AUCs). RESULTS: MVI-positive HCC exhibited a significantly higher fraction of habitat 4 (f4) and a significantly lower fraction of habitat 2 (f2) (p < 0.001), which were selected as risk factors. Additionally, tumor size and elevated alpha-fetoprotein (AFP) were also included as risk factors for MVI. The nomogram model demonstrated the highest diagnostic performance (AUC = 0.807), followed by the habitat model (AUC = 0.777) and the clinical model (AUC = 0.708). Decision curve analysis indicated that the nomogram model offered more net benefit in identifying MVI compared to the clinical model. CONCLUSIONS: DWI-based habitat imaging shows clinical potential for noninvasively and preoperatively determining the MVI of HCC with high accuracy. CLINICAL RELEVANCE STATEMENT: The proposed strategy, diffusion-weighted imaging-based habitat imaging, can be applied for preoperatively and noninvasively identifying microvascular invasion in hepatocellular carcinoma, which offers potential benefits in terms of prognostic prediction and clinical management. KEY POINTS: • This study proposed a strategy of DWI-based habitat imaging for hepatocellular carcinoma. • The habitat imaging-derived metrics can serve as diagnostic markers for identifying the microvascular invasion. • Integrating the habitat-based metric and clinical variable, a predictive nomogram was constructed and displayed high accuracy for predicting microvascular invasion.

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

OBJECTIVES: Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. METHODS: Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. RESULTS: The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679). CONCLUSIONS: CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Magnetic resonance elastography-derived stiffness: potential imaging biomarker for differentiation of benign and malignant pancreatic masses.

OBJECTIVE: This study sought to determine the diagnostic performance of magnetic resonance elastography (MRE) for pancreatic solid masses, compared with diffusion-weighted imaging (DWI) and serum CA19-9, to establish a threshold for differentiating between pancreatic ductal adenocarcinoma (PDAC) and benign tumors in pancreas. MATERIALS AND METHODS: Between July 2021 to January 2023, 75 adult patients confirmed with pancreatic solid tumors were enrolled in this prospective and consecutive study. All patients underwent MRE and DWI examinations that were both performed with a spin echo-EPI sequence. Stiffness maps and apparent diffusion coefficient (ADC) maps were generated, with MRE-derived mass stiffness and stiffness ratio (computing as the ratio of mass stiffness to the parenchyma stiffness) and DWI-derived ADC values obtained by placing regions of interest over the focal tumors on stiffness and ADC maps. Further analysis of comparing diagnostic performances was assessed by calculating the area under ROC curves. RESULTS: PDAC had significantly higher tumor stiffness [3.795 (2.879-4.438) kPa vs. 2.359 (2.01-3.507) kPa, P = 0.0003], stiffness ratio [1.939 (1.562-2.511) vs. 1.187 (1.031-1.453), P < 0.0001] and serum CA19-9 level [276 (31.73-1055) vs. 10.45 (7.825-14.15), P < 0.0001] than other pancreatic masses. Mass stiffness, stiffness ratio and serum CA19-9 showed good diagnostic performance for differentiation with AUC of 0.7895, 0.8392 and 0.9136 respectively. The sensitivity/specificity/positive predictive value/negative predictive value for differentiating malignant from benign pancreatic tumors with mass stiffness (cutoff, > 2.8211 kPa) and stiffness ratio (cutoff, > 1.5117) were 78.4/66.7/82.9/60% and 77.8/83.3/90.3/65.2% respectively. The combined performance of Mass stiffness, stiffness ratio and serum CA19-9 got an AUC of 0.9758. CONCLUSION: MRE holds excellent clinical potential in discriminating pancreatic ductal adenocarcinoma from other pancreatic solid masses according to their mechanical properties.

Computed tomography imaging features to evaluate the severity of portal hypertension and predict the rebleeding risk after endoscopic treatment in cirrhotic patients with variceal hemorrhage.

PURPOSE: To investigate the association of computed tomography (CT) imaging features and severity of portal hypertension (PH) and develop a nomogram to predict high-risk PH in cirrhotic patients with gastroesophageal variceal hemorrhage (GVH). METHODS: The study retrospectively enrolled 158 cirrhotic patients with a history of endoscopic treatment for GVH. Hepatic vein pressure gradient (HVPG) was measured and the patients were classified into high-risk (HVPG > 16 mmHg) or low-risk (HVPG ≤ 16 mmHg) PH group. Pre-treatment CT features, including cavernous transformation of portal vein (CTPV), hilar periportal space (a distance between right portal vein and posterior edge of segment IV of the liver), and depth of right posterior hepatic notch sign (a sharp indentation in the right medial posterior liver surface), were evaluated. Risk factors associated with high-risk PH were analyzed, and a nomogram based on the imaging features was developed. RESULTS: High-risk PH group showed a higher rebleeding rate after treatment than that of the low-risk (P = 0.029). Multivariate analysis indicated that larger hilar periportal space (P < 0.001), less frequencies of CTPV (P = 0.044) and deeper right posterior hepatic notch (P < 0.001) were independent risk factors associated with high-risk PH. A nomogram based on the three CT imaging features was established to predict high-risk PH with an excellent discrimination (c-statistic 0.854). CONCLUSION: The nomogram based on CT features of hilar periportal space, depth of right posterior hepatic notch and CTPV can help to distinguish cirrhotic patients with high-risk PH, who are more vulnerable of variceal rebleeding after endoscopic treatment.

Preoperative assessment of microvascular invasion of hepatocellular carcinoma using non-Gaussian diffusion-weighted imaging with a fractional order calculus model: A pilot study.

PURPOSE: To assess the clinical potential of a set of new diffusion parameters (D, ß, and µ) derived from fractional order calculus (FROC) diffusion model in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between January 2019 to November 2020, a total of 63 patients with HCC were enrolled in this study. Diffusion-weighted images were acquired by using ten b-values (0-2000 s/mm2). The FROC model parameters including diffusion coefficient (D), fractional order parameter (ß), a microstructural quantity (µ) together with a conventional apparent diffusion coefficient (ADC) were calculated. Intraclass coefficients were calculated for assessing the agreement of parameters quantified by two radiologists. The differences of these values between the MVI-positive and MVI-negative HCC groups were compared by using independent sample t-test or the Mann-Whitney U test. Then the parameters showing significant differences between subgroups, including the ß and D, were integrated to develop a comprehensive predictive model via binary logistic regression. The diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Among all the studied diffusion parameters, significant differences were found in D, ß, and ADC between the MVI-positive and MVI-negative groups. MVI-positive HCCs showed significantly higher ß values (0.65 ± 0.17 vs. 0.51 ± 0.13, P = 0.001), along with lower D values (0.84 ± 0.11 µm2/ms vs. 1.03 ± 0.13 µm2/ms, P < 0.001) and lower ADC values (1.38 ± 0.46 µm2/ms vs. 2.09 ± 0.70 µm2/ms, P < 0.001) than those of MVI-negative HCCs. According to the ROC analysis, the combination of D and ß demonstrated the largest area under the ROC curve (0.920) compared with individual parameters (D: 0.912; ß: 0.733; and ADC: 0.831) for differentiating MVI-positive from MVI-negative HCCs. CONCLUSIONS: The FROC parameters can be used as noninvasive quantitative imaging markers for preoperatively predicting the MVI status of HCCs.

Preoperative identification of cytokeratin 19 status of hepatocellular carcinoma based on diffusion kurtosis imaging.

PURPOSE: To explore the potential value of diffusion kurtosis imaging (DKI) for identification of cytokeratin 19 (CK19) status of HCCs. METHODS: This study was approved by the local institute review board and written informed consent was obtained. 73 patients with pathologically confirmed HCCs were included in this prospective study. All the diffusion-weighted (DW) images were acquired using a 3.0-T MR scanner with 4 b-values (0, 800, 1500 and 2000 s/mm2). The mean diffusion value (MD) and mean kurtosis coefficient (MK) from DKI, apparent diffusion coefficient (ADC) from DW imaging (b = 0, 500 s/mm2), and tumor-to-liver signal intensity ratios on ADC map (SIRADC) and DW images with b-value of 500 s/mm2 (SIRb500) were calculated and compared between CK19-positive (n = 23) and CK19-negative (n = 50) HCC groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for the positive expression of CK19. RESULTS: Increased a-fetoprotein level (p = 0.021) and SIRb500 (p = 0.006) and decreased ADC (p = 0.021) and MD (p < 0.001) were significantly correlated with CK19-positive HCCs at univariate analysis. Decreased MD value (odds ratio: 0.042, p = 0.002) and a-fetoprotein level (odds ratio: 5.139, p = 0.015) were the independent risk factors for CK19-positive HCCs at multivariate analysis. The area under the curve of MD value by receiver operating characteristic analysis was 0.823 with a sensitivity of 86.96% and a specificity of 76% for the prediction of CK19-positive HCCs. CONCLUSION: The decreased MD value derived from DKI is potential quantitative biomarker for predicting CK19-positive HCCs.

Differentiating Cytokeratin 19 expression of hepatocellular carcinoma by using multi-b-value diffusion-weighted MR imaging with mono-exponential, stretched exponential, intravoxel incoherent motion, diffusion kurtosis imaging and fractional order calculus models.

PURPOSE: To evaluate Cytokeratin 19 expression in hepatocellular carcinoma (HCC) with diffusion parameters derived from mono-exponential model (MEM), stretched exponential model (SEM), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) imaging, and fractional order calculus (FROC) model and compare their predictive performance. METHOD: 61 patients with pathologically confirmed primary HCC were included in this prospective study. All the DWIs were acquired using a 3.0 T MR scanner with 10b-values (0-2000 s/mm2). The apparent diffusion coefficient (ADC), distributed diffusion coefficient (DDC), heterogeneity index (α), apparent kurtosis coefficient (AK), apparent diffusion coefficient (AD), pseudo-diffusion coefficient (Dp), true diffusion coefficient (Dt), perfusion fraction (f), diffusion coefficient (D), fractional order parameter (ß), and a microstructural quantity (µ) were calculated. The diagnostic efficacy of various diffusion parameters for predicting CK19 expression of HCC was compared. RESULTS: ADC, DDC, Dt, Dp, AD, and D were significantly lower in CK19-positive HCCs than in CK19-negative HCCs (P ≤ 0.05). ß was significantly higher in CK19-positive group (P = 0.001). AD (AUC = 0.845) had the greatest AUC values in differentiating CK19-positive and CK19-negative HCC with individual parameters. The combination of ß, AD, and Dp generated the highest area under the ROC curve (AUC = 0.881) compared with individual parameters. CONCLUSIONS: ADC, DDC, Dt, Dp, D, and ß may serve as noninvasive and quantitative imaging markers and holds great potential in accurately accessing CK19 status of HCC. More importantly, the combination of different diffusion parameters yielded better diagnostic performance.

Progression-Free Survival Prediction in Small Cell Lung Cancer Based on Radiomics Analysis of Contrast-Enhanced CT.

Purposes and Objectives: The aim of this study was to predict the progression-free survival (PFS) in patients with small cell lung cancer (SCLC) by radiomic signature from the contrast-enhanced computed tomography (CT). Methods: A total of 186 cases with pathological confirmed small cell lung cancer were retrospectively assembled. First, 1,218 radiomic features were automatically extracted from tumor region of interests (ROIs) on the lung window and mediastinal window, respectively. Then, the prognostic and robust features were selected by machine learning methods, such as (1) univariate analysis based on a Cox proportional hazard (CPH) model, (2) redundancy removing using the variance inflation factor (VIF), and (3) multivariate importance analysis based on random survival forests (RSF). Finally, PFS predictive models were established based on RSF, and their performances were evaluated using the concordance index (C-index) and the cumulative/dynamic area under the curve (C/D AUC). Results: In total, 11 radiomic features (6 for mediastinal window and 5 for lung window) were finally selected, and the predictive model constructed from them achieved a C-index of 0.7531 and a mean C/D AUC of 0.8487 on the independent test set, better than the predictions by single clinical features (C-index = 0.6026, mean C/D AUC = 0.6312), and single radiomic features computed in lung window (C-index = 0.6951, mean C/D AUC = 0.7836) or mediastinal window (C-index = 0.7192, mean C/D AUC = 0.7964). Conclusion: The radiomic features computed from tumor ROIs on both lung window and mediastinal window can predict the PFS for patients with SCLC by a high accuracy, which could be used as a useful tool to support the personalized clinical decision for the diagnosis and patient management of patients with SCLC.

Effect of Suo Quan Wan on the bladder function of aging rats based on the ß-adrenoceptor.

Suo Quan Wan (SQW) has been used to treat lower urinary tract symptoms (LUTS) in elderly patients for hundreds of years in China. ß-adrenoceptors (ß-ARs), particularly ß3-adrenoceptor (ß3-AR), was reported to be important in the bladder dysfunction of the elderly. The present study was conducted to explore the effect of ß-AR, and particularly the ß3-adrenoceptor, in aging rat bladder function in vitro and to test the therapeutic effect of SQW on LUTS in an aging rat model based on the ß3-adrenoceptor. Briefly, the bladder detrusor muscles of young (age, 3 months) and aging (age, 15 months) female rats were separated. A ß-AR non-selective agonist, isoprenaline (ISO), subtype ß3-AR agonist (BRL37344A) and ß3-AR antagonist (SR59230A) were used to define the tension change of detrusor muscles between young and aging rats in vitro. For blank controls, 12 young rats were marked, and 48 aging female rats were randomly divided into four groups as follows: Model, SQW high, SQW middle and SQW low. Following oral administration of SQW for 6 weeks in aging rats, urodynamic and bladder detrusor tests were used to evaluate the therapeutic effect of SQW. The expression of ß3-AR mRNA was investigated using reverse transcription-quantitative polymerase chain reaction. Using ISO and BRL37344A in vitro, maximum relaxation (Emax), intrinsic activity (IA), and log (50% effective concentration) (PD2) were significantly decreased in aging rats compared with that in young rats (P<0.05). Significant changes were also observed in the ß3-AR antagonist experiment, which blocked ISO-induced relaxation, with significant decreases observed in Emax, IA and PD2, and a significant increase observed in PA2 for the aging rats compared with the young controls (P<0.05). SQW was demonstrated to enhance bladder control, storage and contraction ability. Furthermore, SQW was able to increase the sensitivity and expression of ß3-AR in an aging rat. In conclusion, the decrease in ß3-AR sensitivity in aging rats and the expression resulted in bladder detrusor dysfunction. In addition, the therapeutic effect of SQW against LUTS relies on the former's effect on the urethral sphincter, bladder detrusor and ß3-AR.

Genetic variants in miR-196a2 and miR-499 are associated with susceptibility to esophageal squamous cell carcinoma in Chinese Han population.

Esophageal squamous cell carcinoma (ESCC) is the dominant type of esophageal cancer in the East Asian population. MicroRNAs (miRNAs) have been studied to play important roles in tumorigenesis. Single nucleotide polymorphisms (SNPs) in miRNA lead to the aberrant expression and structural alteration of miRNA and are hypothesized to be involved in tumorigenesis and cancer development. We conducted a population-based case-control study to evaluate the association between SNPs in miRNAs and ESCC risk in 1400 ESCC cases and 2185 matched controls. Four SNPs including miR-196a2 rs11614913, miR-146a rs2910164, miR-499 rs3746444, and miR-423 rs6505162 were selected with comprehensive collection strategy and genotyped using the SNaPshot Multiplex System. Odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the strength of association. The CC genotype of miR-196a2 rs11614913 was significantly associated with an increased ESCC risk compared with the TT genotype (OR 1.11, 95 % CI 1.01-1.22, P 0.049) and the TT/TC genotypes (OR 1.09, 95 % CI 1.01-1.19, P 0.043). The association was more pronounced in non-drinkers in the recessive model (OR 1.13, 95 % CI 1.01-1.27, P 0.029). A significantly increased risk of ESCC associated with miR-499 rs3746444 polymorphism was evident among patients who never smoking and drinking. This study suggests that miR-196a2 rs11614913 and miR-499 rs3746444 are associated with an increased ESCC risk in a Chinese population.

Binding of caffeic acid to human serum albumin by the retention data and frontal analysis.

A new mathematical model and frontal analysis were used to characterize the binding behavior of caffeic acid to human serum albumin (HSA) based on high-performance affinity chromatography. The experiments were carried out by injecting various mole amounts of the drug onto an immobilized HSA column. They indicated that caffeic acid has only one type of binding site to HSA on which the association constant was 2.75 × 10(4) /m. The number of the binding site involving the interaction between caffeic acid and HSA was 69 nm. The data obtained by the frontal analysis appeared to present the same results for both the association constant and the number of binding sites. This new model based on the relationship between the mole amounts of injection and capacity factors assists understanding of drug-protein interaction. The proposed model also has the advantages of ligand saving and rapid operation.

Exploring drug-protein interactions using the relationship between injection volume and capacity factor.

Affinity chromatography is the most widespread and widely accepted methodology for exploring drug-protein and protein-protein interactions. Despite the successful application of frontal analysis and zonal elution in affinity chromatography, research into the creation of new mathematical tools for data processing is encouraged due to these two methods' drawbacks of long analysis times and high ligand consumption. In this work, we created a novel mathematical model using the relationship between the molar amount of an injected solute and its capacity factor. We validated the method by analyzing the binding of drugs to human serum albumin (HSA) and ß2-adrenoceptor (ß2-AR). The association constants of omeprazole, propranolol and promethazine binding to HSA were determined to be (4.10±0.24)×10(4), (2.30±0.12)×10(4) and (1.24±0.14)×10(4)M(-1), respectively. These constants agreed with previously reported literature results of 4.60×10(4), 2.30×10(4) and 1.40×10(4)M(-1). Salbutamol, norepinephrine, isoprenaline, bamethane and methoxyphenamine were found to bind to ß2-AR with association constants of (1.11±0.06)×10(3), (0.95±0.03)×10(3), (1.66±0.12)×10(3), (0.47±0.04)×10(3) and (0.43±0.02)×10(3)M(-1), respectively, which positively correlated to the negative logarithm of the dissociation constants obtained via radio-ligand binding assays. The proposed model is relatively fast and conserves ligand, and it has the potential to serve as an alternative method for rapidly revealing drug-protein and protein-protein interactions.

New lignans and their biological activities.

Lignans, which are widely distributed in higher plants, represent a vast and rather diverse group of phenylpropane derivatives. They have attracted considerable attention due to their pharmacological activities. Some of the lignans have been developed approved therapeutics, and others are considered as lead structures for new drugs. This article is based on our previous review of lignans discovered in the period 2000-2004, and it provides a comprehensive compilation of the 354 new naturally occurring lignans obtained from 61 plant families between 2005 and 2011. We classified five main types according to their structural features, and provided the details of their sources, some typical structures, and diverse biological activities. A tabular compilation of the novel lignans by species is presented at the end. A total of 144 references were considered for this review.

Objective assessment of transcatheter arterial chemoembolization angiographic endpoints: preliminary study of quantitative digital subtraction angiography.

PURPOSE: To explore the significance of quantitative digital subtraction angiography (DSA; Q-DSA) in the assessment of chemoembolization endpoints. MATERIALS AND METHODS: Twenty patients with hepatocellular carcinoma treated with chemoembolization were included in the study. All DSA series before and after chemoembolization were postprocessed with Q-DSA. The maximal enhancement and time to peak (TTP) were measured for several homologous anatomic landmarks, including the origin and embolized site of the tumor-feeding artery, parenchyma of the tumor, and ostia of the pre- and postprocedure catheter. The TTP, tumor blood supply time, and maximal enhancement of the time density curve (TDC) were analyzed. RESULTS: Of the 20 DSA series collected, 18 were successfully postprocessed. The TTPs of the landmarks before and after treatment were 3.60 seconds±1.02 and 3.57 seconds±0.78 at the ostia of the catheter, 3.91 seconds±1.01 and 4.09 seconds±1.14 at the origin site of the tumor-feeding artery, and 4.07 seconds±1.02 and 5.60 seconds±1.56 s the embolized site of the main tumor-feeding artery, respectively. Statistical differences were detected between pre- and postprocedural TTP of the embolized site of the feeding artery (P<.01), as well as between pre- and postprocedural tumor blood supply time (P<.01). The mean maximal TDC enhancements of selected tumor spots were 3.01 units±1.04 and 0.81 units±0.35 before and after the procedure (P<.01), respectively. CONCLUSIONS: Q-DSA may provide a feasible quantitative measurement in the assessment of chemoembolization endpoints.

The interaction of telomere DNA G-quadruplex with three bis-benzyltetrahydroisoquinoline alkaloids.

Telomeres are important multifunctional nucleoprotein structures located at the ends of eukaryotic chromosomes. Telomerase regulates telomere elongation, and its activity is associated with tumorigenesis. Because the activity of telomerase can be inhibited by G-quadruplex (G4) formation (a four-stranded DNA with stacks of G-quartets formed by four guanines in a planar structure), the role of G4 in cancer therapy has attracted many research interests. We studied the effects of three natural alkaloids-tetrandrine, fangchinoline, and berbamine-on the stability and formation of telomere DNA G4 with circular dichroism melting spectroscopy (melting-CD), variable temperature ultraviolet (melting-UV), proton nuclear magnetic resonance spectroscopy ((1)H NMR), and molecular docking, and examined the relationships among the alkaloid structure and their activities. We further investigated their cytotoxicity with the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and flow cytometry (FCM). The results demonstrated that alkaloids increased G4 stability and induced its formation, which added structure diversity of G4-ligands. The results showed that -OH at R(1), -OCH(3) at R(2), and [Formula: see text] at R(3) had higher stability than other substituent groups for these alkaloids. We also found a transition of antiparallel to parallel G4 as the temperature increased. The result indicated the possible advantage of parallel G4 in adversity. In addition, the alkaloids demonstrated a moderate cytotoxicity and proved to be cell cycle blocker in the G(1) phase. These alkaloids have revealed promising potentials to be the agents for antitumor therapy.

Effect of cultivating croplands and grazing in arid grassland habitats on the conservation of melitaeine butterflies in a mountainous area in northern China.

In the study area (Yanjiaping Village, Hebei Province, China), grazing extensity varies at different locations, small and discontinuous croplands are imbedded in some arid grassland, which are habitats for the melitaeine butterflies, Euphydryas aurinia and Melitaea phoebe. These two species of butterflies coexist in this area, in which grazing and cultivation are the main disturbances. Grazing and cultivation have a reciprocal effect on E. aurinia, rather than M. phoebe. We observed that E. aurinia preferred to occupy patches with moderate grazing and imbedded with small and discontinuous croplands, where E. aurinia also has high population density. The percentage of E. aurinia larval groups in the ribbings was significantly higher than that of M. phoebe, whereas larvae of both species tended to increase in recent years. Our data also showed that the population density and the patch occupancy rate of both E. aurinia and M. phoebe were the highest under moderate grazing. It indicates that cultivation of small and discontinuous croplands within the patch has a significant effect on the population density of both species of melitaeine butterflies. Thus, to artificially create or maintain semi-natural habitats, complemented by moderate grazing, might be an ecological strategy to conserve melitaeine butterflies effectively. Considering the distinct impacts of cultivation and grazing on the population distribution and dynamics of the two different species, human disturbance in the mountainous area might be strategically involved in proposing conservation plans for the target species in the future.