Serum albumin and atrial fibrillation: insights from epidemiological and mendelian randomization studies.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Low serum albumin level is linked to the emergence of many cardiovascular diseases, including AF. In this study, we aim to characterize the nature and magnitude of the prospective association between serum albumin and incident AF in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them. ARIC Study is a population-based, prospective, cohort study of cardiovascular risk factors in four US communities, initially consisting of 15,792 participants, aged 45-64 years, recruited between 1987 and 1989 (visit 1). The final sample size was 12,833 in this study. Baseline (visit 1) characteristics were compared between groups using one-way ANOVA test, Chi square test, or Kruskal-Wallis test as appropriate. We used multivariable Cox' hazard regression models to assess the association between albumin and incident AF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies was used to estimate the causal influence of the serum albumin and incident AF. During a median follow-up of 25.1 years, 2259 (17.6%) participants developed incident AF. After multiple adjustment, serum albumin was inversely associated with incidence of AF [HR = 0.90, 95% CI 0.86-0.94, per SD (0.27 g/dL) increase; HR = 0.80, 95% CI 0.71-0.91, Q4 vs. Q1]. In MR analysis, we detected no evidence for a causal relation between serum albumin level and AF in inverse-variance weighted (IVW) method (odds ratio: 0.996, 95% CI 0.980-1.012, per 1 g/dL increase of albumin; P = 0.620) without evidence of heterogeneity between estimates from individual SNPs (Pheterogeneity = 0.981 [MR-Egger] and Pheterogeneity = 0.860 [IVW]) nor pleiotropy effect (Ppleiotropy = 0.193). The serum albumin level is independently inverse associated with incident AF in a linear pattern. However, MR analyses did not support a causal role of serum albumin in the etiology of AF.

Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study.

BACKGROUND AND AIMS: Evidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data. METHODS AND RESULTS: Network MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. 's consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118-1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087-1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125-1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD. CONCLUSIONS: Using a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG.

Gefitinib with or without Transarterial Infusion Chemotherapy (Cisplatin) for Large Nonsmall Cell Lung Cancer with Epidermal Growth Factor Receptor Mutations.

PURPOSE: To retrospectively investigate the safety and benefit of gefitinib plus transarterial infusion (TAI) therapy as a first-line treatment compared to gefitinib alone for patients with large (>7 cm) nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. MATERIALS AND METHODS: Between January 2010 and December 2013, 92 consecutive treatment-naïve patients with large NSCLC with EGFR mutations, who were treated using gefitinib plus TAI (G+T, n = 42) or gefitinib alone (G, n = 50) were reviewed. The primary endpoints were the objective response rate (ORR) and tumor reduction rate. The secondary endpoints were progression-free survival (PFS) and overall survival (OS), and safety was also assessed. RESULTS: The baseline characteristics of the 2 groups were balanced, and no patients experienced treatment-related death. Toxicity outcomes did not differ between the G+T and G groups. The tumor reduction rate in the G+T group was significantly higher than that in the G group (42.9 vs 31.9%, P = .028). The ORR was 83% in the G+T group and 72% in the G group (P = .197). The median PFS was significantly longer in the G+T group than in the G group (14.0 vs 10.0 months, P = .023). The median OS was 30.0 months in the G+T group and 27.0 months in the G group (P = .235). CONCLUSIONS: This study suggests that compared with gefitinib alone, combination therapy with gefitinib plus TAI was well tolerated and potentially improved the tumor reduction rate and PFS in patients with large NSCLC with EGFR mutations.

Comparison of α-Fetoprotein Criteria and Modified Response Evaluation Criteria in Solid Tumors for the Prediction of Overall Survival of Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization.

PURPOSE: To evaluate the value of α-fetoprotein (AFP) classification criteria in predicting tumor response and patient survival and to discuss the agreement between AFP criteria and modified Response Evaluation Criteria In Solid Tumors (mRECIST). MATERIALS AND METHODS: Between January 2011 and December 2014, 147 patients with unresectable hepatocellular carcinoma (HCC) with baseline AFP levels ≥ 400 ng/mL who underwent transarterial chemoembolization as initial treatment were retrospectively enrolled for AFP/imaging correlation analysis. AFP-based response was classified as complete response (CR) in cases of AFP level normalization, partial response (PR) in cases of > 50% decrease vs baseline, stable disease (SD) in cases of -50% to +30% change vs baseline, or progressive disease (PD) in cases of > 30% increase vs baseline. Intermethod agreement between the 2 methods was assessed by Cohen κ coefficient. Response rates according to AFP and mRECIST were compared, and the association between response rate and overall survival (OS) was evaluated. RESULTS: The κ value for agreement between AFP criteria and mRECIST was 0.549 (ie, moderate), with objective response and disease control rates of 36.1% and 63.3% per AFP criteria and 34.7% and 46.3% per RECIST (P = .807 and P = .003), respectively. Although AFP criteria and mRECIST showed significantly prognostic strata for CR, PR, SD, and PD after chemoembolization (P < .001 for both), some overlap in radiologic PD survival curves was observed. The OS of AFP-based disease control (ie, CR/PR/SD) was significantly longer than that of AFP-based PD among patients with radiologic PD (9.0 vs 6.0 mo; P < .001). CONCLUSIONS: The defined AFP response moderately correlated with mRECIST response and yielded accurate prognostic prediction in patients with HCC and AFP levels ≥ 400 ng/mL treated with chemoembolization.

Is Emergency Transcatheter Hepatic Arterial Embolization Suitable for Spontaneously Ruptured Hepatocellular Carcinoma in Child-Pugh C Cirrhosis?

PURPOSE: To evaluate the utility of emergent transcatheter arterial embolization for spontaneously ruptured hepatocellular carcinoma (HCC) in patients with Child-Pugh class C (CPC) liver cirrhosis presenting hemorrhagic shock. MATERIALS AND METHODS: A study of all 94 patients was retrospectively conducted from January 2006 to January 2016. Sixty patients underwent conservative treatment (control group) and 34 underwent embolization. RESULTS: Embolization provided better stabilization of hemodynamic status than conservative treatment (91.2% vs 61.7%), with greater overall survival (OS) rates at 30, 60, and 120 days (73.5%, 52.9%, and 29.4% vs 33.3%, 13.3%, and 0%, respectively). Mean follow-up duration was 51.07 days (range, 3-237 d). Median survival time was longer for the embolization group than the control group, specifically for patients with a shock index (SI) of ≥ 0.6 to < 1 (106.0 d ± 39.4 vs 34.0 d ± 4.7) or ≥ 1 (18.0 d ± 7.5 vs 11.0 d ± 3.2), those with CPC scores 10 or 11 (88.0 d ± 29.4 vs 28.0 d ± 4.5), and those with segmental (165.0 d ± 20.6 vs 34.0 d ± 9.7) or lobar (54.0 d ± 7.9 vs 26.0 d ± 3.4) portal vein tumor thrombus (PVTT). SI ≥ 1, Child-Pugh score of 12/13, tumor size ≥ 10 cm, and PVTT were independent factors in poor prognosis for OS. CONCLUSIONS: Emergent transcatheter arterial embolization is an effective intervention for ruptured HCC in patients with CPC liver function in hemorrhagic shock, particularly those with a SI ≥ 1, Child-Pugh scores of 10/11, and first- or lower-order PVTT.

Initial Experience: Alleviation of Pain with Percutaneous CT-Guided Cryoablation for Recurrent Retroperitoneal Soft-Tissue Sarcoma.

PURPOSE: To evaluate the pain-alleviating effect of computed tomography (CT)-guided percutaneous cryoablation for recurrent retroperitoneal soft-tissue sarcomas (RPSs). MATERIALS AND METHODS: Data from 19 men and 20 women (median age, 50.3 y) with recurrent malignant RPS who underwent percutaneous cryoablation were reviewed retrospectively. A total of 50 tumors were treated by cryoablation, including a single tumor in 29 patients, 2 tumors in 9, and 3 tumors in 1. Adverse events and analgesic outcomes were compared as a function of tumor size (< 10 cm and ≥ 10 cm). Efficacy was assessed based on modified Response Evaluation Criteria In Solid Tumors and progression-free survival (PFS). RESULTS: Grade 1/2 adverse events included fever (n = 17), emesis (n = 7), frostbite (n = 5), and local pain (n = 4). The median follow-up period and PFS were 18.5 months (range, 12-42 mo) and 13.4 months ± 6.2, respectively. At the end of follow-up, 13 patients had died and 26 were living. The mean severe local pain scores on pretreatment day 1 and posttreatment days 1, 5, 10, 15, 20, and 25 were 7.49, 7.40, 6.51, 5.81, 5.35, 5.04, and 5.44, respectively, and significant differences versus pretreatment (P < .001) were reported for posttreatment days 5-25. Immediate relief occurred more frequently in the small-tumor group (4 of 7; 57.1%; P = .018), whereas delayed relief occurred more frequently in the large-tumor group (17 of 22; 77.3%; P = .030). CONCLUSIONS: Minimally invasive percutaneous cryoablation improves local pain and is a feasible treatment for recurrent RPSs.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Population persistence of a Tertiary relict tree Tetracentron sinense on the Ailao Mountains, Yunnan, China.

The persistence of the Tertiary relict tree Tetracentron sinense Oliv. on the eastern slope of the Ailao Mountains, Yunnan, SW China, was here studied in terms of population structure (size, age) and regeneration patterns. T. sinense occurred in unstable habitats by stream banks, on steep slopes, on scree slopes, or on roadsides near streams in narrow valleys, all places subject to frequent natural disturbances, whereas none were found on stable gentle slopes free of major disturbances at similar altitudes. Further, no established saplings of T. sinense were found in forests having high bamboo (Yushania crassicollis Yi) coverage in their understory. The size and age structure of T. sinense were multimodal. The reproduction of the tree was either by means of abundant minute wind-dispersed seeds or by resprouts in unstable habitats. These populations depended on disturbance or gap regeneration to survive. T. sinense, along with other tree life-forms including evergreen broad-leaved species and conifers, dominated in the forest canopy layer, even reaching the emergent layer in places. Results of the study provide insight into the ecological characteristics and survival mechanisms of this East Asian paleoendemic tree species. The study will provide a scientific basis for recommendations for the conservation of this species and for other Tertiary relict plants having similar regeneration dynamics.

[The analysis of the efficacy and safety of combined transarterial chemoembolization with sorafenib in patients with large hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of combined transarterial chemoembolization with sorafenib in patients with large hepatocellular carcinoma. METHODS: 79 patients with large HCC(larger than 10 cm in diameter)were enrolled from July 2008 to June 2012 for this retrospective study. 24 patients undertaken TACE combined with sorafenib as T + S group. 35 patients undertaken TACE alone as T group, and other 20 patients treated with sorafenib alone as S group. RESULTS: The median survival time was 15 months in T + S group, 10 months in T group, and 5 months in S group, respectively (P = 0.000). The median time of tumor progress was 6 months, 3 months and 2.5 months, respectively (P = 0.000). The most common adverse events related to sorafenib in group T + S group and S group alone were hand foot skin reaction, diarrhea and alopecia. The incidence rate of adverse events related to sorafenib was no significant difference between two groups. There was no 4 or more grade adverse event occurred in each group. The most common complications related to interventional treatment in group T + S group and T group alone were mild jaundice, ascites, inguinal region hematoma. The incidence rate of complications related to interventional treatment was no significant difference between two groups. CONCLUSION: The combination of TACE and sorafenib in patients with large HCC is well tolerated and safe, which is available to delay tumor progression and prolong survival.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Multi-residue analysis of pesticides in tea by online SEC-GC/MS.

A multi-residue method for the analysis of pesticides in tea was developed by online size exclusion chromatography (SEC)-GC/MS with full scan mode. The sample was fortified with chlorpyrifos-d(10) isotope internal standard and extracted by acetonitrile. After purification by primary secondary amine sorbent and solvent exchange by SEC mobile phase, the sample was detected by online SEC-GC/MS. The purification result of the online system was evaluated by comparing the correlation between Chinese cabbage and tea matrix. The factors for method optimization included sample preparation, matrix effects and the instrument parameters of each online component. Scatter plot was introduced in this study to directly illustrate the results of the condition optimization and matrix effects in the online system. For most of the pesticides, the average recoveries ranged from 70 to 130% and the RSD were below 15%. The feasibility of the application of full scan mode in multi-residue determination of trace amounts of pesticides (LODs below 0.01 mg/kg) in a complex matrix was discussed.

[Radiological progression and life quality analysis in ankylosing spondylitis patients using etanercept/methotrexate combination therapy].

OBJECTIVE: To analyze the relationship between the radiological progression and quality of life in ankylosing spondylitis (AS) patients using etanercept/methotrexate (MTX) combination therapy. METHODS: A total of 153 AS cases fulfilling the 1984 modified New York diagnostic criteria were reviewed. All patients received radiological evolution at baseline and during a follow-up period. Radiological progression, clinical remission and life quality were recorded and analyzed for their relations. RESULTS: The radiological assessments of mSASSS (modified Stoke ankylosing spondylitis spine score) were recorded at baseline, 3, 6 & 12 months after treatment. Life quality assessments were recorded with SF (short-form)-36 simultaneously. No significant radiological improvement was observed at the end points. However, most patients reported a significant improvement of life quality after a combination therapy of etanercept/MTX. BASDAI (Bath ankylosing spondylitis disease activity index), C-reactive protein and erythrocyte sedimentation rate demonstrated similar trends. With no relevance with mSASSS, life quality was significantly correlated with disease activity and pain control. CONCLUSION: The combination therapy of etanercept/MTX greatly improves life quality in AS patients. Yet clinical remission and pain control offer no hint of a suspension of radiological progression. Routine radiological assessment is required throughout the follow-up period of AS even if life quality index reaches a high level.

[Protein expression and significance of survivin and NF-κB in hepatocellular carcinoma].

OBJECTIVE: To detect the protein expressions of survivin and NF (nuclear factor)-κB and investigate their roles in the pathogenesis of hepatocellular carcinoma. METHODS: A total of 206 cases were diagnosed as hepatocellular carcinoma, and immunohistochemical technique was used to detect the protein expressions of survivin and NF-κB in hepatocellular carcinoma samples and normal liver tissue specimens. Statistical analysis was performed to analyze the relationship of protein expressions of survivin and NF-κB and clinico-pathological parameters and prognosis. RESULTS: The expression of survivin was predominant in cytoplasm while that of NF-κB was in nucleolus. The positive rate of survivin protein was 78.2% in hepatocellular carcinoma and that of NF-κB was 81.1%. The positive rate of survivin and NF-κB was higher in hepatocellular carcinoma than that in benign hepatic tissue (11.7% and 15.5%). Significant differences existed in the expressions of survivin and NF-κB between hepatocellular carcinoma and normal hepatic tissue (P < 0.01). The expression of survivin was related to amicula invasion, portal vein tumor thrombus, lymph node metastasis and clinical stage in hepatocellular carcinoma (P < 0.01). The expression of NF-κB was also related to portal vein tumor thrombus, lymph node metastasis and clinical stage in hepatocellular carcinoma (P < 0.05). There was an obviously positive correlation between the expressions of survivin and NF-κB in hepatocellular carcinoma (r = 0.52, P < 0.01). Survival rate of patients for 1, 3 year of positive expression of survivin and NF-κB in hepatocellular carcinoma was 70.3% and 30.4%, respectively. And it was obviously lower than that of those of negative expression (88.5% and 61.5%). There was significant difference in the expressions of survivin and NF-κB between positive and negative subjects in 1, 3 year (P < 0.05). CONCLUSION: Protein expressions of survivin and NF-κB are higher in hepatocellular carcinoma. And they play mutually promoting roles in the development of hepatocellular carcinoma. Thus, an important prognostic indicator may be adopted.

[Transcriptional targeting gene therapy of double suicide gene driven by hTERT promoter in hepatic carcinoma].

OBJECTIVE: To examine the selective killing effects of pEGFP-C1-mediated double suicide gene system driven by the hTERT promoter (hTERT-CDglyTK) on hepatic carcinoma cells. METHODS: The hTERT promoter and gene fragments SV40, yCD and TKgly were amplified by PCR (polymerase chain reaction) and then inserted into pEGFP-C1. And the constructs of pEGFP-hTERT-CD, pEGFP-hTERT-TK and pEGFP-hTERT-CDglyTK were transfected to SMMC 7721 or HL7702 respectively. The transfection effects were observed and the cellular expressions of suicide genes detected by RT-PCR (reverse transcription-polymerase chain reaction), QPCR (quantitative polymerase chain reaction) and Western blot. The transfected cells were treated with 5-fluorocytosine and ganciclovir at different concentrations and the cell-killing and bystander effects evaluated by the method of MTT (3-(4,5)-dimethyl thiadiazole (-z-y1)-3,5-di-phenytetrazoliumromide). The activity of cell telomerase was detected by the method of TRAP-argentation and the apoptotic rates analyzed by flow cytometry. All results of double and single gene systems were analyzed. RESULTS: The fragments of enzyme digestion corresponded to the expectations. RT-PCR, QPCR and Western blot demonstrated the expressions of CD, TK and CDglyTK. pEGFP-hTERT-CD, pEGFP-hTERT-TK and pEGFP-hTERT-CDglyTK showed the similar transfection efficiencies in SMMC7721 (74.5%, 76.3%, 76.9%). More sensitive to the prodrugs (P = 0.020, P = 0.015), higher apoptotic rates (P = 0.023, P = 0.017) and bystander effects (P = 0.012, P = 0.001)and lower telomerase activities (P = 0.045, P = 0.038) were observed in double gene system versus those in single gene system. However, the transfection and growth of HL7702 cell could not be infected by this double suicide gene. CONCLUSION: The plasmid of CDglyTK fusion gene system driven by hTERT promoter has been successfully constructed. It has demonstrated highly specific killing effects on hepatic carcinoma cells.

[Transcatheter arterial chemoembolization plus percutaneous thermal ablation in large hepatocellular carcinoma: clinical observation of efficacy and predictors of prognostic factors].

OBJECTIVE: To explore the technical success rate, efficacy, overall survival, recurrence-free survival and prognostic factors of transcatheter arterial chemoembolization (TACE) plus thermal ablations of radiofrequency ablation (RFA) and microwave ablation (MWA) in the patients with large hepatocellular carcinoma (HCC). METHODS: Forty-five cases with Child-pugh class A, B cirrhosis and large HCC with a maximum tumor between 5.0 cm to 10.0 cm underwent TACE and thermal ablation. Twenty-five patients received TACE plus RFA while the other 20 patients underwent TACE plus MWA. Their efficacy, long-term survival and prognostic factors were statistically analyzed. RESULTS: TACE plus thermal ablation were performed in 84 tumors with a successful rate of 100% (86/86) and a complete ablation rate of 94.0% (79/84). The major complication rate was 6.7% (3/45). Local and distant recurrence rates were 66.7% (30/45) and 71.1% (32/45) respectively. The 1 and 2-year recurrence-free survival rates were 26.7% (12/45) and 13.3% (6/45). And the 1, 2 and 3-year survival rates were 80.0% (36/45), 33.3% (15/45) and 6.7% (3/45) respectively. Univariate and Cox regression analyses indicated that tumor size > 7.0 cm, multi-nodularity, incomplete necrosis and pretherapy α-fetoprotein (AFP) ≥ 200 µg/L were 4 unfavorable prognostic factors for the long-term survival. CONCLUSION: The combined procedures of TACE and percutaneous thermal ablation are both safe and effective for the unresectable large HCC (> 5.0 cm). It represents an alleviate treatment for those patients with tumor size > 7.0 cm. Tumor size, tumor number, completeness of necrosis and AFP level are all significant prognostic factors.

Characterizing clinicopathological findings of transarterial chemoembolization for Wilms tumor.

PURPOSE: We characterized the clinicopathological changes after transarterial chemoembolization for treatment of Wilms tumor. MATERIALS AND METHODS: A total of 44 consecutive patients with Wilms tumor were randomized to undergo transarterial chemoembolization preoperatively or to undergo surgery only. We compared the clinicopathological findings of resected tumor from the 2 groups. RESULTS: Tumor-free survival at 2 years in the group undergoing transarterial chemoembolization was significantly higher compared to the control group (p <0.01), and tumor related recurrence and deaths within 1 year were significantly lower in the study group than in controls (p <0.01). Average tumor shrinkage was 48.2% in the study group. Average area of necrosis in tumor sections was 63.5% in the study group and 15% in controls (AUC 2.78, p <0.01). Percentage of tumor with moderate to severe interstitial fibrosis was 64% (14 of 22 patients) in the study group and 18% (4 of 22) in controls (AUC 2.72, p <0.01). Comparative rates of percentage of tumor demonstrating grade III to IV lymphocytic infiltration were 73% (16 of 22 patients) and 18% (4 of 22, chi-square 11.6, p <0.01), median mitotic index in tissues 1.4 and 0.19 (AUC 55.7, p <0.01), and median apoptotic index of tumor cells 28.1 and 12.8 per 10 microscopic fields (AUC 109.00, p <0.05). Expression of p53 and Bcl-2 protein did not differ between the groups, but Bax protein expression was significantly higher in the study group (85% vs 40%, p <0.05). CONCLUSIONS: Transarterial chemoembolization induces tumor cell necrosis, degeneration and apoptosis, while also boosting interstitial fibrous tissue hyperplasia and lymphocyte infiltration. These histopathological findings could help explain the basis of the better clinical outcome in patients with Wilms tumor who underwent preoperative transarterial chemoembolization.

Causal assessment of sleep on coronary heart disease.

OBJECTIVE: Sleep is an essential physiological process that protects our physical and mental health. However, the causality of the association between sleep and coronary heart disease (CHD) is unknown. Mendelian randomization (MR), using genetic variants as instrumental variables to test for causality, can infer credible causal associations. We applied a two-sample MR framework to determine the causal association between sleep (sleeplessness, sleep duration, and daytime dozing) and CHD by integrating summary-level genome-wide association study (GWAS) data. METHODS: Data included in this study were the GWAS summary statistics datasets from the C4D Consortium for CHD; Neale Lab UKB-a:13 Consortium for sleeplessness; Neale Lab UKB-a:9 Consortium for sleep duration and Neale Lab UKB-a:15 Consortium for daytime dozing. The conventional MR approach (inverse variance weighted, IVW) method and Egger method were used. Heterogeneity was calculated using each of the different MR methods where possible. Horizontal pleiotropy was evaluated by p-value of the MR-Egger intercept. RESULTS: The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval, CI) for CHD was 3.924 (1.345-11.447) per standard deviation increase in sleeplessness (p = 0.012). Results were consistent in MR-Egger method (OR, 4.654; 95% CI, 1.191-18.186; p = 0.009). The genetically predicted sleeplessness was positively casually associated with CHD. The causal association between sleep duration (or daytime dozing) and CHD was not established. CONCLUSION: Our analysis provided evidence supporting a causal relationship between sleeplessness (not sleep duration or daytime dozing) and CHD.

Diagnostic accuracy of photodynamic diagnosis with 5-aminolevulinic acid, hexaminolevulinate and narrow band imaging for non-muscle invasive bladder cancer.

Objective: To assess the diagnostic test accuracy (DTA) of photodynamic diagnosis with 5-aminolaevulinic acid (5-ALA), hexylaminolevulinate (HAL) and narrow band imaging (NBI) for non-muscle-invasive bladder cancer (NMIBC), with white light-guided cystoscopy (WLC) as reference standard. Materials and Methods: A systematic review and narrative synthesis was performed in accordance with PRISMA. Major electronic databases were searched until 20th May 2019. All studies assessing the DTA of 5-ALA, HAL and NBI compared with WLC at patient and lesion-level were included. Relevant sensitivity analyses and risk of bias (RoB) assessment were undertaken. Results: 26 studies recruiting 3979 patients were eligible for inclusion. For patient-level analysis, NBI appeared to be the best (median sensitivity (SSY) 100%, median specificity (SPY) 68.45%, median positive predictive value (PPV) 90.75%, median negative predictive value (NPV) 100% and median false positive rate (FPR) 31.55%), showing better DTA outcomes than either HAL or 5-ALA. For lesion-level analysis, median SSY across NBI, HAL and 5-ALA were 93.08% (IQR 87.04-98.81%), 93.16% (IQR 91.48-97.04%) and 94.42% (IQR 82.37-95.73%) respectively. As for FPR, median values for NBI, HAL and 5-ALA were 20.40% (IQR 13.68-27.36%), 17.43% (IQR 12.79-22.40%) and 28.12% (IQR 22.08-42.39%), respectively. Sensitivity analyses based on studies with low to moderate RoB and studies with n>100 patients show similar findings. Conclusions: NBI appears to outperform 5-ALA and HAL in terms of diagnostic accuracy. All three modalities present high FPR, hence indicating the ability to detect additional cases and lesions beyond WLC.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study.

BACKGROUND: The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM: To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS: This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS: All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION: Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

[Experimental study of protective mechanism of Lipo-PGE(1) on hepatic ischemia-reperfusion injury].

OBJECTIVE: To explore protective mechanism of Lipo-PGE(1) on hepatic ischemia-reperfusion injury. METHOD: Twenty-one adult dogs were divided into three groups randomly: CON group, IV group and SMA group, each group includes seven dogs. Animals were occluded porta hepatis 45 min and reperfused 60 min to establish I/R injury models. Lipo-PGE(1) administration was conducted once before porta occlusion 5 min and after reperfusion 60 min in IV and SMA group, the dosage of Lipo-PGE(1) was microgxkg(-1) and rate was 0.05 microgxkg(-1)xmin(-1); and 0.9% sodium chloride administration was conducted once at same time, the rate of NS was 2 mlxkg(-1). CT perfusion imaging, free pressure of portal vein, oxygen content of portal vein and hepatic oxygen delivery, index of liver function (ALT, LDH and TB) were performed in succession and compared before and after I/R. Simultaneously, the morphology of liver samples were observed by light microscope and electron microscope. RESULTS: (1) The liver perfusion was markedly decreased in the CON group, and moderately decreased in IV group and mildly in SMA group. (2) There was no significant difference of CpvO(2) in group comparison (P > 0.05) before and after I/R, but there was an increasing tendency in SMA group after I/R. There was significant difference of HDO(2) in group comparison before and after I/R (P < 0.05), but mildly in SMA group. (3) FPP increased obviously after I/R in control group, but there were no significant differences in the other groups. (4) The serious injury of liver in CON group after I/R was detected under light microscope and electron microscope, and moderately improved in IV group and markedly improved in SMA group. CONCLUSION: The protective mechanisms of Lipo-PGE(1) on hepatic ischemia-reperfusion injury include: improving microcirculation, releasing FPP, increasing CpvO(2) and HDO(2), as well as alleviating parenchyma injury.