Controlling Nutritional Status (CONUT) score is a prognostic marker in III-IV NSCLC patients receiving first-line chemotherapy.

BACKGROUND: To investigate the prognostic impact of the controlling nutritional status (CONUT) score in non-small-cell lung cancer (NSCLC) patients receiving first-line chemotherapy. METHODS: We retrospectively reviewed 278 consecutive patients undergoing chemotherapy for stage III-IV NSCLC between May 2012 and July 2020. CONUT score was calculated by incorporating serum albumin, total cholesterol, and total lymphocyte count. The patients were divided into two groups: CONUT ≥ 3 and CONUT < 3, according to receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. RESULTS: A high CONUT score was significantly associated with older age(P = 0.003), worse ECOG-PS(P = 0.018), advanced clinical stage(P = 0.006), higher systematic inflammation index (SII) (P < 0.001)and lower prognostic nutritional index (PNI) (P < 0.001).The high CONUT group had a significantly shorter progression-free survival(PFS) and overall survival(OS) than the low CONUT group. In the univariate analysis, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse PFS (Pall < 0.05). Worse ECOG-PS, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse OS (Pall < 0.05). In multivariate analysis, CONUT(HR, 2.487; 95%CI 1.818 ~ 3.403; P < 0.001) was independently associated with PFS, while PNI(HR, 0.676; 95%CI 0.494 ~ 0.927; P = 0.015) and CONUT(HR, 2.186; 95%CI 1.591 ~ 3.002; P < 0.001)were independently associated with OS. In ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 24-month PFS and OS than the SII or PNI. When the time-dependent AUC curve was used to predict PFS and OS, CONUT tended to maintain its predictive accuracy for long-term prognosis at a significantly higher level for an extended period after chemotherapy when compared with the other markers tested. The CONUT score showed better accuracy of predicting OS (C-index: 0.711) and PFS(C-index: 0.753). CONCLUSION: CONUT score is an independent prognostic indicator of poor outcomes for patients with stage III-IV NSCLC and is superior to the SII and PNI in terms of prognostic ability.

Absent atherosclerotic risk factors are associated with carotid stiffening quantified with ultrafast ultrasound imaging.

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

Carotid stiffness and atherosclerotic risk: non-invasive quantification with ultrafast ultrasound pulse wave velocity.

OBJECTIVES: To evaluate the value of ultrafast pulse wave velocity (ufPWV) for the quantitative assessment of carotid stiffness and its associated with atherosclerosis (AS) risk. METHODS: The present study included 233 patients with hyperlipoidaemia (AS risk group) and 114 healthy adults as the control group. The carotid (n = 694) intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS) and pulse wave velocity-end of systole (PWV-ES) were measured on sample images. Differences, distributive characteristics and correlation evaluation were assessed in patients (ages 18-29, 30-39, 40-49, 50-59, 60-69 and ≥70) and carotids (control group vs AS risk group). RESULTS: The cIMT, PWV-BS and PWV-ES increased with age; PWV-ES and cIMT showed an early significant increase in the 30-39 years group, whereas PWV-BS displayed a significant increase at 40-49 years compared with the 18- to 29-years group. Besides, PWV-ES correlated well with age compared with PWV-BS and cIMT. For carotid level, cIMT, PWV-BS and PWV-ES measurements were higher in the AS risk group compared with control. To compare the value of ufPWV and cIMT in early AS assessment, we subdivided groups into cIMT subgroups using a cut-off thickness of 0.050 cm. PWV-ES measurements were higher in the AS risk group compared with the control in the 0.040-0.050 cm (not thickened) and 0.051-0.060 cm (thickened) cIMT subgroups. CONCLUSIONS: Carotid ufPWV measurement at PWV-ES is a novel modality for the early diagnosis and quantitative assessment of arterial stiffness associated with atherosclerotic risk. KEY POINTS: • ufPWV technique is real-time and well repeatable for assessing carotid stiffness • ufPWV measurements increase and correlate well with age • PWV-ES is a quantitative predictor for the early assessment of AS.

Chemical shift magnetic resonance imaging for distinguishing minimal-fat renal angiomyolipoma from renal cell carcinoma: a meta-analysis.

OBJECTIVES: To determine the performance of chemical shift signal intensity index (CS-SII) values for distinguishing minimal-fat renal angiomyolipoma (mfAML) from renal cell carcinoma (RCC) and to assess RCC subtype characterisation. METHODS: We identified eligible studies on CS magnetic resonance imaging (CS-MRI) of focal renal lesions via PubMed, Embase, and the Cochrane Library. CS-SII values were extracted by lesion type and evaluated using linear mixed model-based meta-regression. RCC subtypes were analysed. Two-sided p value <0.05 indicated statistical significance. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Eleven articles involving 850 patients were included. Minimal-fat AML had significantly higher CS-SII value than RCC (p < 0.05); there were no significant differences between mfAML and clear cell RCC (cc-RCC) (p = 0.112). Clear cell RCC had a significantly higher CS-SII value than papillary RCC (p-RCC) (p < 0.001) and chromophobe RCC (ch-RCC) (p = 0.045). The methodological quality was relatively high, and Begg's test data points indicated no obvious publication bias. CONCLUSIONS: The CS-SII value for differentiating mfAML from cc-RCC remains unproven, but is a promising method for differentiating cc-RCC from p-RCC and ch-RCC. KEY POINTS: • RCC CS-SII values are significantly lower than those of mfAML overall. • CS-SII values cannot aid differentiation between mfAML and cc-RCC. • CS-SII values might help characterise RCC subtypes.

Continuous infusion of a large dose of CF (folinic acid) and 5-FU combined with CDDP in the treatment of advanced esophageal cancer.

5-fluorouracil (5-FU) and cisplatin (CDDP) are common chemotherapy drugs used in the treatment of patients with advanced esophageal cancer. We investigated the efficacy of adding a continuous infusion of a large dose of a common adjuvant, citrovorumfactor (CF), to the traditional 5-FU/wCDDP regimen. 50 patients with advanced esophageal cancer were treated with a continuous infusion of CF, 5-FU, and CDDP, and the short-term effects, adverse reactions, and survival periods after treatment were analyzed. Overall, the treatment was effective in 58% of patients, and the therapeutic effects of the first-line of chemotherapy were significantly better than the second-line (u = 4.121, p < 0.05). Patients experienced severe nausea and vomiting in 18.7% of the treatment cycles and experienced severe hair loss or leucopenia in 1.9% of the treatment cycles. The majority of the treatment cycles produced only mild side effects. The median survival period following chemotherapy treatment was 10.6 months (95% confidence interval was 8.146 ~ 13.054 months), with the median survival time of patients with a Karnofsky Performance Status (KPS) score ≥ 80 being significantly longer than that of patients with KPS scores < 80 (χ2 = 41.595, p < 0.05). The median survival time of patients with metastasis to the lymph nodes and surrounding tissue was significantly longer than that of patients with visceral metastasis (χ2 = 32.246, p < 0.05). Cox regression analysis showed that KPS scores before the treatment < 80 (relative risk (RR= = 1.635) and the incidence of visceral metastasis (RR = 1.875) were associated with survival time (p < 0.05). These results suggest that the continuous infusion of a large dose of CF, 5-FU, and CDDP as chemotherapy treatment of advanced esophageal cancer can produce promising short-term results and decrease adverse reactions.

Evidence of motor injury due to damaged corticospinal tract following acute hemorrhage in the basal ganglia region.

The integrity of the corticospinal tract (CST) is significantly affected following basal ganglia haemorrhage. We aimed to assess the local features of CST and to effectively predict motor function by diffusion characteristics of CST in patients with motor injury following acute haemorrhage in the acute basal ganglia region. We recruited 37 patients with paresis of the lateral limbs caused by acute basal ganglia haemorrhage. Based on the automated fiber quantification method to track CST, assessed the character of each CST segment between the affected and contralateral sides, and correlated these with the Fugl-Meyer (FM) and Barthel Index (BI) scores at 6 months after onset. The fractional anisotropy (FA) values of the injured side of CST showed a significantly lower FA than the contralateral side along the tract profiles (p < 0.05, corrections for multiple comparisons). The FA values of each site at the internal capsule, closed corona radiata were positively correlated with the FM and BI score at 6 months after onset (p < 0.001, respectively). Our findings assessed the character of CST vividly in detail and dementated the primary sites of CST can predict the long-term outcome of motor function. This study may facilitate future clinical and cognitive studies of acute haemorrhage.

Hysterosalpingo-contrast-sonography vs. magnetic resonance-hysterosalpingography for diagnosing fallopian tubal patency: A systematic review and meta-analysis.

PURPOSE: To compare hysterosalpingo-contrast-sonography (HyCoSy) and magnetic resonance-hysterosalpingography (MR-HSG) in the diagnosis of fallopian tubal patency. MATERIALS AND METHODS: The databases of PubMed, Embase, and the Cochrane Library were searched for records up to November 30, 2019. Studies involved in the diagnostic detection of HyCoSy or MR-HSG for fallopian tubal patency using conventional HSG or laparoscopy as the reference test were included. Data was analyzed by meta-analysis. We compared sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (sROC) plots of both HyCoSy and MR-HSG. Quality was assessed using the QUADAS-2 tool. RESULTS: The analysis included 24 articles involving 1340 patients. HyCoSy was studied in 17 studies, and MR-HSG was studied in seven studies. For HyCoSy in diagnosis of fallopian tubal patency, pooled sensitivity was 89 % (95 % confidence interval [CI], 87 %-91 %), and specificity was 93 % (95 % CI, 91 %-94 %). For MR-HSG in diagnosis of fallopian tubal patency, pooled sensitivity was 100 % (95 % CI, 98 %-100 %), and specificity was 82 % (95 % CI, 74 %-89 %). The sROC showed similar diagnostic accuracy for MR-HSG and HyCoSy. 3D/4D HyCoSy with ultrasound microbubbles had equal sensitivity (95 % vs. 100 %, P = 0.186) and significantly higher specificity (94 % vs. 82 %, P = 0.005) compared with MR-HSG. CONCLUSIONS: HyCoSy and MR-HSG showed similar overall diagnostic performance for diagnosing fallopian tubal patency. 3D/4D HyCoSy with ultrasound microbubbles could significantly improve the diagnostic specificity of HyCoSy.

Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves.

To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784-0.923; AUC: 0.758-0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment.

Gene expression profile of human esophageal squamous carcinoma cell line TE-1.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly causes of cancer worldwide. However, to date, the mechanisms underlying its pathogenesis remain unclear. The present study investigated the gene expression profile of human esophageal cancer cell line TE-1, a cell model for ESCC, to gain insight to the genetic regulation of this disease. Human esophageal cancer TE-1 cells and normal esophageal HET-1A cells were cultured for isolation of total RNA. Differential expression of RNA transcripts was assessed using the Agilent 4×44 K microarray, combined with real-time PCR (qRT-PCR) for validation. Classification and function of the differential genes were illustrated by bioinformatics processing including hierarchical clustering and gene ontology (GO) analysis. We identified 4,986 transcripts with differential expression (fold-change ≥1.5, P<0.05), including 2,368 up-regulated and 2,618 down-regulated transcripts. GO analysis showed that the dysregulated transcripts were associated with biological process, cellular component, and molecular function. After bioinformatic analysis of significantly regulated signaling pathways, we found these transcripts may target 35 gene pathways, including p53 signaling, glioma, ubiquitin-mediated proteolysis, insulin signaling, cell cycle, inositol phosphate metabolism, mTOR signaling, and MAPK signaling. The differentially expressed transcripts were screened between the esophageal cancer cell line TE-1 and normal esophageal cell line HET-1A, as well as their target gene pathways. Further data mining is related to prevention and treatment of esophageal cancer.

Calcium/calmodulin-dependent serine protein kinase is involved in exendin-4-induced insulin secretion in INS-1 cells.

OBJECTIVE: Exendin-4 (Ex-4) is an anti-diabetic drug that is a potent agonist of the glucagon-like peptide-1 (GLP-1) receptor. It has already been approved for the treatment of type 2 diabetes mellitus, but its underlying mechanisms of action are not fully understood. Calcium/calmodulin-dependent serine protein kinase (CASK), which plays a vital role in the transport and release of neurotransmitters in neurons, is expressed in pancreatic islet cells and ß-cells. This study aimed to investigate whether CASK is involved in the insulin secretagogue action induced by Ex-4 in INS-1 cells. MATERIAL/METHODS: A glucose-stimulated insulin secretion (GSIS) assay was performed with or without siRNA treatment against CASK. The expression level and location of CASK were evaluated by real-time PCR, western blotting and immunofluorescence. With the use of a protein kinase A (PKA) inhibitor or an exchange protein directly activated by cAMP-2 (Epac2) agonist, immunoblotting was performed to establish the signaling pathway through which Ex-4 alters CASK expression. RESULTS: Knock-down of CASK significantly attenuated the Ex-4-enhanced insulin release, and we showed that Ex-4 could increase transcription of CASK mRNA and expression of CASK protein but did not change the cellular location of CASK. A PKA inhibitor reduced the ability of Ex-4 to stimulate CASK expression, but an Epac2 agonist had no effect suggesting that regulation was mediated by the cAMP/PKA pathway. CONCLUSION: Our study suggests that the stimulation of ß-cell insulin secretion by Ex-4 is mediated, at least in part, by CASK via a novel signaling mechanism.

Reversion of multidrug resistance by SKI-II in SGC7901/DDP cells and exploration of underlying mechanisms.

In order to investigate whether SKI-II could reverse drug resistance and its possible mechanisms, we treated SGC7901/DDP cells with SKI-II or SKI-II in combination with DDP. Then cell growth, apoptosis, micro- morphological changes, and expression of SphK1, P-gp, NF-kB, Bcl-2 and Bax were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western blot assay respectively. SGC7901/DDP cells were insensitive to cisplatin 2.5 mg/L, but when pretreated with SKI-II, their proliferation was inhibited by cisplatin 2.5mg/L significantly, the inhibition rate increasing with time and dose. The apoptosis rate was also significantly elevated. Expression of SphK1 and P-gp was decreased significantly, Pearson correlation analysis showing significant correlation between the two (r=0.595, P<0.01). Expression of NF-kB and Bcl-2 was decreased significantly, while that of Bax was increased, compared to the control group. There were significant correlations between SphK1 and NF-kB(r=0.723, P<0.01), and NF-kB and Bcl-2(r=0.768, P<0.01). All these data indicated that SKI-II could reverse drug resistance of SGC7901/DDP to cisplatin by down-regulating expression of P-gp and up-regulating apoptosis through down-regulation of SphK1. The increased apoptotic sensitivity of SGC7901/ DDP to cisplatin was due to the decreasing proportion of Bcl-2/Bax via down-regulating NF-kB.